Pituitary, Thyroid & Adrenal Disorders

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

Patients with Cushing disease have an increased risk for new-onset autoimmune disease in the 3 years after surgical remission, according to a new retrospective study published on February 20 in Annals of Internal Medicine.

Outcomes for patients with Cushing disease were compared against those with nonfunctioning pituitary adenomas (NFPAs). New-onset autoimmune disease occurred in 10.4% with Cushing disease and 1.6% among patients with NFPA (hazard ratio, 7.80; 95% CI, 2.88-21.10).

“Understanding and recognizing new and recurrent autoimmune disease in this setting is important to avoid misclassifying such patients with glucocorticoid withdrawal syndrome, which could result in failure to treat underlying autoimmune disease, as well as erroneous diagnosis of steroid withdrawal cases,” wrote Dennis Delasi Nyanyo of Massachusetts General Hospital and Harvard Medical School, Boston, and colleagues.

Given the general population’s annual incidence of major autoimmune diseases, estimated at about 100 cases per 100,000 people, and the 3-year incidence of 10.4% found in this study’s cohort, “our findings suggest that Cushing disease remission may trigger development of autoimmune disease,” the authors wrote.
 

Monitor Patients With Family History of Autoimmune Disease?

The study results were not necessarily surprising to Anthony P. Heaney, MD, PhD, an endocrinologist and professor of medicine at the University of California, Los Angeles, because past research has raised similar questions. The authors’ suggestion that the rapid postsurgical drop in cortisol that occurs as a result of treating Cushing disease becomes some sort of autoimmune trigger is interesting but remains speculative, Dr. Heaney pointed out.

If future evidence supports that possibility, “it would suggest, in terms of managing those patients in the postoperative setting, that there may be some merit to giving them higher concentrations of glucocorticoids for a short period of time,” Dr. Heaney said, thereby bringing their levels down more gradually rather than taking them off a cliff, in a sense. Or, if more evidence bears out the authors’ hypothesis, another approach might be treating patients with medicine to bring down the cortisol before surgery, though there are challenges to that approach, Dr. Heaney said.

At the same time, those who developed new autoimmune disease remain a small subset of patients with Cushing disease, so such approaches may become only potentially appropriate to consider in patients with risk factors, such as a family history of autoimmune disease.

The researchers conducted a retrospective chart review of adult patients who underwent transsphenoidal surgery for either Cushing disease or NFPA at Massachusetts General Hospital between 2005 and 2019.

The study involved 194 patients with Cushing disease who had postsurgical remission and at least one follow-up visit with a pituitary expert and 92 patients with NFPA who were matched to patients with Cushing disease based on age and sex. The authors regarded autoimmune disease diagnosed within 36 months of the surgery to be temporally associated with Cushing disease remission. Among the autoimmune diseases considered were “rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, autoimmune thyroiditis, celiac disease, psoriasis, vitiligo, autoimmune neuropathy, multiple sclerosis, myasthenia gravis, and ulcerative colitis.”

Patients differed in average body mass index and tumor size, but family history of autoimmune disease was similar in both groups. Average BMI was 34.5 in the Cushing group and 29.5 in the NFPA group. Average tumor size was 5.7 mm in the Cushing group and 21.3 mm in the NFPA group.

Before surgery, 2.9% of patients with Cushing disease and 15.4% of patients with NFPA had central hypothyroidism, and 8% in the Cushing group and 56.8% in the NFPA group had hyperprolactinemia. Central adrenal insufficiency occurred in 11% with NFPA and in all with Cushing disease, by definition.

After surgery, 93.8% in the Cushing group and 16.5% in the NFPA group had adrenal insufficiency. In addition, patients with Cushing disease had lower postsurgical nadir serum cortisol levels (63.8 nmol/L) than those with NFPA (282.3 nmol/L).

Of the 17 patients with Cushing disease — all women — who developed autoimmune disease within 3 years, 6 had a personal history of autoimmune disease and 7 had a family history of it. In addition, 41.2% of them had adrenal insufficiency when they developed the new autoimmune disease. Among the diseases were six autoimmune thyroiditis cases, three Sjögren syndrome cases, and two autoimmune seronegative spondyloarthropathy.

Dr. Heaney said he found it interesting that more than half of the new autoimmune diseases in patients with Cushing disease were related to the thyroid. “In this kind of setting, where you have a patient who has been producing too much steroid over a period of time and then you take that away, it’s almost like you release a brake on the TSH [thyroid-stimulating hormone],” Dr. Heaney said. “So, there’s probably some rebound in TSH that occurs, and that could be driving the thyroiditis, to some extent, that we see in these patients.”

Only one patient with NFPA developed new-onset autoimmune disease, a woman who developed Graves disease 22 months after surgery. When the researchers excluded patients in both groups with central hypothyroidism, new-onset autoimmune disease was still significantly higher (11.4%) in the Cushing group than in the NFPA group (1.9%; HR, 7.02; 95% CI, 2.54-19.39).
 

Could Postoperative Adrenal Insufficiency Contribute to Risk?

Within the Cushing cohort, those who developed autoimmune disease had a lower BMI (31.8 vs 34.8) and larger tumor size (7.2 vs 5.6 mm) than those who didn’t develop new autoimmune disease. Patients who developed autoimmune disease also had a lower baseline urine free cortisol ratio (2.7 vs 6.3) before surgery and more family history of autoimmune disease (41.2% vs 20.9%) than those who didn’t develop one.

“The higher prevalence of adrenal insufficiency and the lower nadir serum cortisol levels in the Cushing disease group suggest that the postoperative adrenal insufficiency in the Cushing disease group might have contributed to autoimmune disease pathogenesis,” the authors wrote. “This finding is clinically significant because cortisol plays a pivotal role in modulating the immune system.”

Most postoperative management among patients with Cushing disease was similar, with all but one patient receiving 0.5 or 1 mg daily dexamethasone within the first week after surgery. (The one outlier received 5 mg daily prednisone.) However, fewer patients who developed autoimmune disease (17.6%) received supraphysiologic doses of glucocorticoid — equivalent to at least 25 mg hydrocortisone — compared with patients who didn’t develop autoimmune disease (41.8%).

“Although the daily average hydrocortisone equivalent replacement doses within the first month and during long-term follow-up were within the physiologic range in both subgroups, patients with Cushing disease who had autoimmune disease received slightly lower doses of glucocorticoid replacement within the first month after surgery,” the authors reported. “The immediate postoperative period might be a critical window where supraphysiologic glucocorticoids seem to be protective with regard to development of autoimmune disease,” they wrote, though they acknowledged the study’s retrospective design as a limitation in drawing that conclusion.

At the least, they suggested that new symptoms in patients with Cushing disease, particularly those with a family history of autoimmune disease, should prompt investigation of potential autoimmune disease.

Recordati Rare Diseases funded the study. The research was also conducted with support from Harvard Catalyst (the Harvard Clinical and Translational Science Center) as well as financial contributions from Harvard University and its affiliated academic healthcare centers. One author reported holding stocks in Pfizer and Amgen, and another reported receiving consulting fees from Corcept. Dr. Heaney reported receiving institutional grants for trials from Corcept, Ascendis, Crinetics, and Sparrow Pharm; serving on the advisory board for Xeris, Recordati, Corcept, Novo Nordisk, Lundbeck, and Crinetics; and serving as a speaker for Chiesi, Novo Nordisk, and Corcept.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

TOPLINE:

Selenium supplementation is associated with improvements in key thyroid measures in patients with Hashimoto thyroiditis who are not treated with thyroid hormone replacement therapy, research from a new meta-analysis showed.

METHODOLOGY:

• For the systematic review and meta-analysis, 35 randomized controlled trials were identified that included evaluation of selenium supplementation’s effects on thyroid function.
• The studies focused on a variety of key thyroid function measures, including thyroid-stimulating hormone (TSH), free and total thyroxine (fT4, T4), free and total triiodothyronine (fT3, T3), thyroid antibodies, safety, and other factors.
• Stratified analyses were conducted to evaluate key factors including the dose and duration of selenium supplementation; patients’ thyroid status, age, gender, treatment with hormone replacement, and selenium status, such as deficiency or sufficiency; and other factors.
• While patients’ selenium levels at baseline were reported in only about half of the studies, among those that did have the data, the vast majority — 89% of cohorts — were selenium deficient.
• The study populations ranged from 31 to 364 and included children, adolescents, and adults.

TAKEAWAY:

• The analysis showed selenium supplementation to be significantly associated with decreased TSH in patients who were not treated with thyroid hormone replacement therapy (standardized mean difference [SMD], −0.21 in seven cohorts, involving 869 participants).
• Improvements associated with selenium replacement were also observed regardless of whether patients were on thyroid hormone replacement therapy in terms of decreases in thyroid peroxidase antibodies (TPOAb) (SMD, −0.96 in 29 cohorts, involving 2358 participants) and malondialdehyde (SMD, −1.16 in three cohorts, involving 248 participants).
• Overall, selenium supplementation had no significant effects on other notable thyroid measures, including fT4, T4, fT3, T3, thyroglobulin antibody (TGAb), thyroid volume, interleukin 2, or interleukin 10. However, when the analysis only included adults aged 18 and older, the selenium supplementation was linked to reductions in TSH and TPOAb, as well as increases in fT4 levels.
• Importantly, no significant differences were observed in terms of adverse effects between the studies’ intervention and control groups at selenium supplementation doses ranging from 80 to 400 μg/d for up to 12 months (odds ratio, 0.89 in 16 cohorts, involving 1339 participants).
• The authors determined that the certainty of evidence, overall, was moderate.

IN PRACTICE:

The results regarding effects of selenium on TSH “add to the existing knowledge in this field by demonstrating an effect of selenium supplementation on lowering TSH levels exclusively in Hashimoto thyroiditis patients without thyroid hormone replacement therapy,” the authors wrote. Furthermore, “our study reaffirmed the results of six prior meta-analyses reporting an effect of selenium in reducing TPOAb levels,” they added. “The inclusion of 31 cohorts enhanced statistical power compared to the previous meta-analyses, which included a maximum of nine cohorts.” “Our study suggests that selenium supplementation is safe and holds potential as a disease-modifying factor for Hashimoto thyroiditis–associated hypothyroidism,” the authors reported. “Further research is needed to confirm its efficacy, fully understand its mechanism of action, and elucidate its cost-effectiveness.”

SOURCE:

The study’s first author was Valentina V. Huwiler, MSc, of the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. The study was published in Thyroid.

LIMITATIONS:

Due to variations in assays used in the different studies for measures including TPOAb and TGAb, the authors used SMD instead of the mean difference typically recommended when varying assays are used; however, only the effect size can be interpreted and not the clinical significance, the authors noted. Serum selenium concentrations may vary based on the analytical technique. Data on participants’ dietary habits and compliance with study regimens were not available.

DISCLOSURES:

The authors had no disclosures to report.

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

Primary aldosteronism (PA) is a frequently overlooked yet common cause of secondary hypertension, presenting significant risk for cardiovascular morbidity and mortality.

But fewer than 4% of at-risk patients receive the recommended screening for PA, leaving a substantial gap in early detection and management, according to Adina F. Turcu, MD, MS, associate professor in endocrinology and internal medicine at University of Michigan Health in Ann Arbor. 

In response to this clinical challenge, Dr. Turcu and her colleagues developed a best-practice advisory (BPA) to identify patients who were at risk for PA and embedded it into electronic health record at University of Michigan ambulatory clinics. Her team found that use of the tool led to increased rates of screening for PA, particularly among primary care physicians.

Over a 15-month period, Dr. Turcu and her colleagues tested the BPA through a quality improvement study, identifying 14,603 unique candidates for PA screening, with a mean age of 65.5 years and a diverse representation of ethnic backgrounds. 

Notably, 48.1% of these candidates had treatment-resistant hypertension, 43.5% exhibited hypokalemia, 10.5% were younger than 35 years, and 3.1% had adrenal nodules. Of these candidates, 14.0% received orders for PA screening, with 70.5% completing the recommended screening within the system, and 17.4% receiving positive screening results. 

The study, conducted over 6 months in 2023, targeted adults with hypertension and at least one of the following: Those who took four or more antihypertensive medications, exhibited hypokalemia, were younger than age 35 years, or had adrenal nodules. Patients previously tested for PA were excluded from the analysis. 

The noninterruptive BPA was triggered during outpatient visits with clinicians who specialized in hypertension. The advisory would then offer an order set for PA screening and provide a link to interpretation guidance for results. Clinicians had the option to use, ignore, or decline the BPA.

“Although we were hoping for broader uptake of this EHR-embedded BPA, we were delighted to see an increase in PA screening rates to 14% of identified candidates as compared to an average of less than 3% in retrospective studies of similar populations, including in our own institution prior to implementing this BPA,” Dr. Turcu told this news organization.

Physician specialty played a crucial role in the utilization of the BPA. Internists and family medicine physicians accounted for the majority of screening orders, placing 40.0% and 28.1% of these, respectively. Family practitioners and internists predominantly used the embedded order set (80.3% and 68.9%, respectively).

“Hypertension often gets treated rather than screening for [causes of] secondary hypertension prior to treatment,” said Kaniksha Desai, MD, clinical associate professor and endocrinology quality director at Stanford University School of Medicine, Stanford, California, who was not involved in the research. But “primary hyperaldosteronism is a condition that can be treated surgically and has increased long term cardiovascular consequences if not identified. While guidelines recommend screening at-risk patients, this often can get lost in translation in clinical practice due to many factors, including time constraints and volume of patients.” 

Patients who did vs did not undergo screening were more likely to be women, Black, and younger than age 35 years. Additionally, the likelihood of screening was higher among patients with obesity and dyslipidemia, whereas it was lower in those with chronic kidney disease and established cardiovascular complications.

According to Dr. Turcu, the findings from this study suggest that noninterruptive BPAs, especially when integrated into primary care workflows, hold promise as effective tools for PA screening.

When coupled with artificial intelligence to optimize detection yield, these refined BPAs could significantly contribute to personalized care for hypertension, the investigators said. 

“Considering that in the United States almost one in two adults has hypertension, such automatized tools become instrumental to busy clinicians, particularly those in primary care,” Dr. Turcu said. “Our results indicate a promising opportunity to meaningfully improve PA awareness and enhance its diagnosis.” 

Dr. Turcu reported receiving grants from the National Heart, Lung, and Blood Institute and Doris Duke Foundation, served as an investigator in a CinCor Pharma clinical trial, and received financial support to her institution during the conduct of the study. Dr. Desai reported no relevant financial disclosures. 
 

A version of this article appeared on Medscape.com.

To assess thyroid function, clinicians typically determine blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) and do not directly measure triiodothyronine (T3).

However, findings from a large observational study of a US sample of adults with normal thyroid function suggested that subclinical variation in the hypothalamic-pituitary-thyroid (HPT)–axis effector hormone T3 “is an important and overlooked factor linking socioeconomic forces, human biology, and aging,” researchers reported.

The study, with lead author Ralph I. Lawton, an MD-PhD student at Harvard Medical School, Boston, was published online on January 4, 2024, in Proceedings of the National Academy of Sciences. In this national sample of healthy adults older than 20, free T3 was negatively related to household income. At age 40 and older, free T3 was significantly linked to being employed. Among adults from age 51 to 80, free T3 levels were inversely related to mortality.

“It is important to note that the more typically measured biomarkers for thyroid function (T4 and TSH) are poorly linked to free T3 levels,” Dr. Lawton and colleagues wrote.

The ratio of TSH:T4 explained only 1.7% of variation in T3 levels, they noted, which suggested that TSH and T4 may not be accurate surrogates of free T3. Thus, “direct measurement of free T3 is likely vital to properly stratify the effects of HPT-axis variation,” they maintained. “Improved methods for measurement [of T3] and further investigation of the role of free T3 in clinical conditions may be high yield,” according to the researchers.

Further studies of the relationship between the action of deiodinase in converting T4 to T3 and social forces and aging could elucidate critical biology. “New therapeutics targeting T3/T4 ratios,” they suggested, “may be more beneficial for a significant cohort of older individuals [with hypothyroidism] currently treated with levothyroxine [(LT4)].”
 

‘Cherry on Top’

“I think this is a really important paper,” thyroidology expert Antonio Bianco, MD, PhD, professor of medicine, The University of Chicago, who was not involved with this research, told this news organization.

His research group and others “have slowly been providing evidence of the relevance of measuring T3 levels,” he said. “This paper is sort of a cherry on top. It is really the most recent strong evidence that looking at T3 levels in plasma is really important. We need to do a better job at developing a much more precise assay for T3,” he said, “because now we know T3 is a very important parameter that endocrinologists should be looking for. We know that about 20 million Americans have hypothyroidism, and are being treated with T4 (levothyroxine),” Dr. Bianco continued.

“As endocrinologists, we believe that if you treat someone with levothyroxine, you normalize T3 levels. However, many times, with standard of care with levothyroxine, T3 levels are not normalized.”
 

Larger Variations in T3

Thyroid hormones (TSH, free T4, and free T3) influence many aspects of human physiology and behavior, but it is not known how variations in these levels in a population free of thyroid disease are associated with mortality and socioeconomic factors.

The researchers analyzed data from 7626 adults over age 20 up to age 80 who participated in the National Health and Nutrition Examination Survey during 2007-2012 and had blood tests to determine TSH, free T4, and free T3 and were not being actively treated for thyroid conditions. Among the 3603 older adults (over age 50), there were 981 deaths up until the end of 2019. TSH levels were not linked to mortality, but increasing levels of free T3 and decreasing levels of free T4 were protective for mortality (hazard ratios, 0.88 and 1.26, respectively; P < .01).

There was a robust negative relationship between household income and employment and free T3 but no relationship between these factors and T4. There was a much larger variation across age in levels of free T3 than in levels of TSH or free T4. Free T4 and free T3 diverged at older ages, when free T4 increased and free T3 continually decreased.

Older adults with symptoms of hypothyroidism may have high free T4 levels despite low free T3, the researchers noted.

“In a nonclinical sample representative of the US population,” they summarized, “we find that free T3 is much more strongly related to all domains studied — age, sex, seasonality, household income, employment, and longevity — than the other molecules of the HPT axis.”

This work was supported by the Burroughs Wellcome Fund Career at Scientific Interface award, a Brain and Behavior Research Foundation young investigator award, the Howard Hughes Medical Institute, the National Institute of Aging, and the National Institute of General Medical Sciences. Dr. Bianco served as a consultant for AbbVie, Avion Pharmaceuticals, Synthonics, Synthion, and Thyron and recently published the book Rethinking Hypothyroidism: Why Treatment Must Change and What Patients Can Do.
 

A version of this article appeared on Medscape.com.

To assess thyroid function, clinicians typically determine blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) and do not directly measure triiodothyronine (T3).

However, findings from a large observational study of a US sample of adults with normal thyroid function suggested that subclinical variation in the hypothalamic-pituitary-thyroid (HPT)–axis effector hormone T3 “is an important and overlooked factor linking socioeconomic forces, human biology, and aging,” researchers reported.

The study, with lead author Ralph I. Lawton, an MD-PhD student at Harvard Medical School, Boston, was published online on January 4, 2024, in Proceedings of the National Academy of Sciences. In this national sample of healthy adults older than 20, free T3 was negatively related to household income. At age 40 and older, free T3 was significantly linked to being employed. Among adults from age 51 to 80, free T3 levels were inversely related to mortality.

“It is important to note that the more typically measured biomarkers for thyroid function (T4 and TSH) are poorly linked to free T3 levels,” Dr. Lawton and colleagues wrote.

The ratio of TSH:T4 explained only 1.7% of variation in T3 levels, they noted, which suggested that TSH and T4 may not be accurate surrogates of free T3. Thus, “direct measurement of free T3 is likely vital to properly stratify the effects of HPT-axis variation,” they maintained. “Improved methods for measurement [of T3] and further investigation of the role of free T3 in clinical conditions may be high yield,” according to the researchers.

Further studies of the relationship between the action of deiodinase in converting T4 to T3 and social forces and aging could elucidate critical biology. “New therapeutics targeting T3/T4 ratios,” they suggested, “may be more beneficial for a significant cohort of older individuals [with hypothyroidism] currently treated with levothyroxine [(LT4)].”
 

‘Cherry on Top’

“I think this is a really important paper,” thyroidology expert Antonio Bianco, MD, PhD, professor of medicine, The University of Chicago, who was not involved with this research, told this news organization.

His research group and others “have slowly been providing evidence of the relevance of measuring T3 levels,” he said. “This paper is sort of a cherry on top. It is really the most recent strong evidence that looking at T3 levels in plasma is really important. We need to do a better job at developing a much more precise assay for T3,” he said, “because now we know T3 is a very important parameter that endocrinologists should be looking for. We know that about 20 million Americans have hypothyroidism, and are being treated with T4 (levothyroxine),” Dr. Bianco continued.

“As endocrinologists, we believe that if you treat someone with levothyroxine, you normalize T3 levels. However, many times, with standard of care with levothyroxine, T3 levels are not normalized.”
 

Larger Variations in T3

Thyroid hormones (TSH, free T4, and free T3) influence many aspects of human physiology and behavior, but it is not known how variations in these levels in a population free of thyroid disease are associated with mortality and socioeconomic factors.

The researchers analyzed data from 7626 adults over age 20 up to age 80 who participated in the National Health and Nutrition Examination Survey during 2007-2012 and had blood tests to determine TSH, free T4, and free T3 and were not being actively treated for thyroid conditions. Among the 3603 older adults (over age 50), there were 981 deaths up until the end of 2019. TSH levels were not linked to mortality, but increasing levels of free T3 and decreasing levels of free T4 were protective for mortality (hazard ratios, 0.88 and 1.26, respectively; P < .01).

There was a robust negative relationship between household income and employment and free T3 but no relationship between these factors and T4. There was a much larger variation across age in levels of free T3 than in levels of TSH or free T4. Free T4 and free T3 diverged at older ages, when free T4 increased and free T3 continually decreased.

Older adults with symptoms of hypothyroidism may have high free T4 levels despite low free T3, the researchers noted.

“In a nonclinical sample representative of the US population,” they summarized, “we find that free T3 is much more strongly related to all domains studied — age, sex, seasonality, household income, employment, and longevity — than the other molecules of the HPT axis.”

This work was supported by the Burroughs Wellcome Fund Career at Scientific Interface award, a Brain and Behavior Research Foundation young investigator award, the Howard Hughes Medical Institute, the National Institute of Aging, and the National Institute of General Medical Sciences. Dr. Bianco served as a consultant for AbbVie, Avion Pharmaceuticals, Synthonics, Synthion, and Thyron and recently published the book Rethinking Hypothyroidism: Why Treatment Must Change and What Patients Can Do.
 

A version of this article appeared on Medscape.com.

To assess thyroid function, clinicians typically determine blood levels of thyroid-stimulating hormone (TSH) and thyroxine (T4) and do not directly measure triiodothyronine (T3).

However, findings from a large observational study of a US sample of adults with normal thyroid function suggested that subclinical variation in the hypothalamic-pituitary-thyroid (HPT)–axis effector hormone T3 “is an important and overlooked factor linking socioeconomic forces, human biology, and aging,” researchers reported.

The study, with lead author Ralph I. Lawton, an MD-PhD student at Harvard Medical School, Boston, was published online on January 4, 2024, in Proceedings of the National Academy of Sciences. In this national sample of healthy adults older than 20, free T3 was negatively related to household income. At age 40 and older, free T3 was significantly linked to being employed. Among adults from age 51 to 80, free T3 levels were inversely related to mortality.

“It is important to note that the more typically measured biomarkers for thyroid function (T4 and TSH) are poorly linked to free T3 levels,” Dr. Lawton and colleagues wrote.

The ratio of TSH:T4 explained only 1.7% of variation in T3 levels, they noted, which suggested that TSH and T4 may not be accurate surrogates of free T3. Thus, “direct measurement of free T3 is likely vital to properly stratify the effects of HPT-axis variation,” they maintained. “Improved methods for measurement [of T3] and further investigation of the role of free T3 in clinical conditions may be high yield,” according to the researchers.

Further studies of the relationship between the action of deiodinase in converting T4 to T3 and social forces and aging could elucidate critical biology. “New therapeutics targeting T3/T4 ratios,” they suggested, “may be more beneficial for a significant cohort of older individuals [with hypothyroidism] currently treated with levothyroxine [(LT4)].”
 

‘Cherry on Top’

“I think this is a really important paper,” thyroidology expert Antonio Bianco, MD, PhD, professor of medicine, The University of Chicago, who was not involved with this research, told this news organization.

His research group and others “have slowly been providing evidence of the relevance of measuring T3 levels,” he said. “This paper is sort of a cherry on top. It is really the most recent strong evidence that looking at T3 levels in plasma is really important. We need to do a better job at developing a much more precise assay for T3,” he said, “because now we know T3 is a very important parameter that endocrinologists should be looking for. We know that about 20 million Americans have hypothyroidism, and are being treated with T4 (levothyroxine),” Dr. Bianco continued.

“As endocrinologists, we believe that if you treat someone with levothyroxine, you normalize T3 levels. However, many times, with standard of care with levothyroxine, T3 levels are not normalized.”
 

Larger Variations in T3

Thyroid hormones (TSH, free T4, and free T3) influence many aspects of human physiology and behavior, but it is not known how variations in these levels in a population free of thyroid disease are associated with mortality and socioeconomic factors.

The researchers analyzed data from 7626 adults over age 20 up to age 80 who participated in the National Health and Nutrition Examination Survey during 2007-2012 and had blood tests to determine TSH, free T4, and free T3 and were not being actively treated for thyroid conditions. Among the 3603 older adults (over age 50), there were 981 deaths up until the end of 2019. TSH levels were not linked to mortality, but increasing levels of free T3 and decreasing levels of free T4 were protective for mortality (hazard ratios, 0.88 and 1.26, respectively; P < .01).

There was a robust negative relationship between household income and employment and free T3 but no relationship between these factors and T4. There was a much larger variation across age in levels of free T3 than in levels of TSH or free T4. Free T4 and free T3 diverged at older ages, when free T4 increased and free T3 continually decreased.

Older adults with symptoms of hypothyroidism may have high free T4 levels despite low free T3, the researchers noted.

“In a nonclinical sample representative of the US population,” they summarized, “we find that free T3 is much more strongly related to all domains studied — age, sex, seasonality, household income, employment, and longevity — than the other molecules of the HPT axis.”

This work was supported by the Burroughs Wellcome Fund Career at Scientific Interface award, a Brain and Behavior Research Foundation young investigator award, the Howard Hughes Medical Institute, the National Institute of Aging, and the National Institute of General Medical Sciences. Dr. Bianco served as a consultant for AbbVie, Avion Pharmaceuticals, Synthonics, Synthion, and Thyron and recently published the book Rethinking Hypothyroidism: Why Treatment Must Change and What Patients Can Do.
 

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Women with autoimmune disease are more likely to have perinatal depression (PND), according to findings from a new study that also suggested the reverse relationship is true: Women with a history of PND have a higher risk of developing autoimmune disease.

The research, published online on January 9, 2024, in Molecular Psychiatry, was led by Emma Bränn, PhD, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

The researchers used data from the Swedish Medical Birth Register and identified all women who had given birth in Sweden between 2001 and 2013. Out of the group of approximately 815,000 women and 1.3 million pregnancies, just more than 55,000 women had been diagnosed with depression during their pregnancy or within a year after delivery.

The researchers then compared the incidence of 41 autoimmune diseases in women who had and did not have PND. They controlled for factors including genetic makeup and childhood environment.

Results indicated that women with autoimmune disease were 30% more likely to have PND (odds ratio, 1.30; 95% CI, 1.25-1.35). Conversely, women with PND were 30% more likely than women with no PND to develop an autoimmune disease (hazard ratio, 1.30; 95% CI, 1.25-1.36).

A sibling comparison helped confirm the results by controlling for some shared genetic and early life environmental factors related to the household in which sisters grew up.
 

Potential Shared Biological Mechanisms

The association was independent of psychiatric comorbidities, suggesting there may be shared biological mechanisms.

Dr. Bränn told this news organization that the research team wanted to do the study because previous research has shown involvement of the immune system in depression, with similarities in both the symptoms of immune system–activated diseases and depression and the molecular pathways activated by the immune system.

“Adding on top of the tremendous changes in the immune system that we see in the body of the woman during the perinatal period, we hypothesized that autoimmune diseases could be associated to perinatal depression,” she said. “This had also been shown in some previous literature but not to the extent as what we have investigated in this paper.”

She said their results help make a case for counseling women at several points in healthcare interactions — before and after conception and childbirth — and in rheumatology visits to inform women with autoimmune diseases who are contemplating motherhood of the association with developing PND. The results may also demonstrate a need for monitoring women in these groups for depression or autoimmune disease.

Fred Miller, MD, PhD, retired Scientist Emeritus of the Environmental Autoimmunity Group at the National Institute of Environmental Health Sciences, who was not part of the study, said the results seem plausible as they build on early work that demonstrated selected associations between autoimmune conditions and mental illness.

“These associations may be the result of shared genetic and environmental risk factors, including stress, hormonal changes, medications, and the proinflammatory states that can lead to both,” he said.

The novelty, he said, is in the relatively strong associations of PND with autoimmune disease overall and with specific autoimmune diseases.
 

Strong Link Found With Multiple Sclerosis (MS)

According to the paper, a significant positive bidirectional link was found for autoimmune thyroid disease, psoriasis, MS, ulcerative colitis, and celiac disease.

Researchers found a particularly strong association — double the risk in both directions — between PND and MS.

Dr. Miller said though it is unclear from this study why the association of PND with MS was stronger than with other autoimmune diseases, people with MS are known to be at a high risk for depression in general. That may come from greater shared genetic and environmental risk factors, he added.

Additionally, MS is one of the more common autoimmune diseases, he noted, so the population is larger for study.

He said he was surprised the researchers didn’t investigate medication use because medications used in depression have immunologic effects and medications used in autoimmune diseases could have effects on mental conditions.

The study has implications for clinicians in a wide variety of specialties, Dr. Miller noted.

“It suggests that caregivers be more alert to the signs of developing autoimmune disease in women with perinatal depression and to the signs of developing perinatal depression in those with autoimmune disease,” Dr. Miller said, “so that appropriate screening, diagnostics, and interventions may be undertaken.”

The researchers say they will continue to examine the long-term effects of depression during pregnancy and in the year after childbirth.

“Depression during this sensitive period can have serious consequences for both the mother and the baby,” Dr. Bränn said. “We hope that our results will help decision-makers to steer funding toward maternal healthcare so that more women can get help and support in time.”

The study was financed by Karolinska Institute, Forte (the Swedish Research Council for Health, Working Life and Welfare), the Swedish Research Council, and the Icelandic Research Fund.

The researchers and Dr. Miller reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.

METHODOLOGY:

• The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
• Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
• The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.

TAKEAWAY:

• The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
• In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
• Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
• Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
• Five patients had postoperative hematoma and/or infection requiring intervention.

IN PRACTICE:

“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”

“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”

SOURCE:

This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.

LIMITATIONS:

None listed.

DISCLOSURES:

None.

TOPLINE:

In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.

METHODOLOGY:

• The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
• Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
• The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.

TAKEAWAY:

• The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
• In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
• Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
• Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
• Five patients had postoperative hematoma and/or infection requiring intervention.

IN PRACTICE:

“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”

“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”

SOURCE:

This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.

LIMITATIONS:

None listed.

DISCLOSURES:

None.

TOPLINE:

In patients with Hashimoto disease and persistent symptoms despite adequate medical treatment, total thyroidectomy had a beneficial effect up to 5 years but with a substantially higher risk for complications than initially anticipated.

METHODOLOGY:

• The 5-year follow-up of 65 participants in a randomized, open-label trial of thyroidectomy plus medical management vs medical management alone aimed at testing the hypothesis that persistent symptoms despite adequate thyroxine replacement may be related to extrathyroidal autoimmune reactions and that complete removal of thyroid tissues may attenuate autoimmune responses and relieve symptoms.
• Patients in the control group were given the option of having surgery 18 months after enrollment, depending on trial results.
• The primary outcome was patient-reported health-related quality of life measured by the dimensional general health score in the generic Short Form-36 Health Survey questionnaire.

TAKEAWAY:

• The positive treatment effect seen after 18 months was maintained throughout the 3-year follow-up.
• In the intervention group, the improved general health score remained at the same level during the 5-year follow-up.
• Results were similar for the other Short Form-36 Health Survey domains and for total fatigue and chronic fatigue.
• Short-term (<12 months) or longer-lasting complications occurred in 23 patients, including 6 with recurrent laryngeal nerve paralysis (4 were long-term) and 12 with hypoparathyroidism (6 long-term, including 3 permanent).
• Five patients had postoperative hematoma and/or infection requiring intervention.

IN PRACTICE:

“The improvements in patient-reported outcome measures reported at 18 months after surgery were maintained at 5 years after surgery in the intervention group. In contrast, no spontaneous improvement was seen during 3 years in the control group.”

“Long-term complications in 10 of 73 (14%) patients despite use of meticulous dissection to achieve total thyroidectomy is unacceptably high. Medication and compensatory mechanisms for hypoparathyroidism and unilateral recurrent nerve injury, respectively, did alleviate symptoms.”

SOURCE:

This study was published in Annals of Internal Medicine, by Geir Hoff, MD, PhD, of the Department of Research, Telemark Hospital, Skien, and the Institute of Clinical Medicine, University of Oslo, Oslo, Norway, and colleagues.

LIMITATIONS:

None listed.

DISCLOSURES:

None.

Nearly three quarters of dedicated thyroid ultrasounds don’t identify biopsy-recommended nodules, and over a third don’t identify any nodules, new research finds.

“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.

The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.

And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.

The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”

One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
 

No Current Guidelines Advise When not to Order a Thyroid Ultrasound

Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.

According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”

Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”

Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”

Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
 

Low Detection Rates for Most Indications

The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.

The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.

Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.

Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).

Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.

“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.

Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).

The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).

Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”

Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.

A version of this article appeared on Medscape.com.

Nearly three quarters of dedicated thyroid ultrasounds don’t identify biopsy-recommended nodules, and over a third don’t identify any nodules, new research finds.

“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.

The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.

And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.

The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”

One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
 

No Current Guidelines Advise When not to Order a Thyroid Ultrasound

Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.

According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”

Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”

Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”

Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
 

Low Detection Rates for Most Indications

The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.

The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.

Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.

Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).

Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.

“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.

Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).

The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).

Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”

Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.

A version of this article appeared on Medscape.com.

Nearly three quarters of dedicated thyroid ultrasounds don’t identify biopsy-recommended nodules, and over a third don’t identify any nodules, new research finds.

“The number of thyroid ultrasounds performed in the United States has increased fivefold since 2002. This substantial increase produces a significant strain on healthcare resources and leads to over-detection and overtreatment of benign thyroid nodules and small, indolent cancers with questionable clinical relevance,” wrote Elena Kennedy, MD, then a medical student in the department of surgery at the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues.

The data, published online in Thyroid, come from a retrospective chart analysis of more than 1700 people who underwent dedicated (ie, specifically to look for a nodule) thyroid ultrasounds at a tertiary academic center. The rates of detecting both nodules and biopsy-recommended nodules were highest when the indication was a nodule seen incidentally on other imaging (aka “incidentaloma”) and lowest when the ultrasound was ordered because the patient had either metabolic or compressive symptoms.

And for the most commonly listed indication, a suspected palpable nodule, nearly half of the ultrasounds found no nodule, and only one in five detected a nodule that warranted a biopsy.

The principal investigator of the study David O. Francis, MD, an otolaryngologist at the University of Wisconsin, Madison, said in an interview, “Thyroid cancer has grown in incidence three to four times over the last 30 years without a good explanation for why…It seems to be that we’re detecting smaller and smaller nodules…Why are people being referred for all these ultrasounds? We looked for the upstream factors.”

One clear clinical implication of the new data, Dr. Francis noted, is that “if someone has compressive symptoms including dysphagia, swallowing problems, voice change, or globus sensation, ultrasound should not be the first way to work them up…It would be smarter to have someone evaluate their voice or their swallowing to see if there’s another reason besides the thyroid. The thyroid would have to get pretty big to cause dysphagia or swallowing problems.”
 

No Current Guidelines Advise When not to Order a Thyroid Ultrasound

Problematically, while there are professional society guidelines for what to do when a thyroid “incidentaloma” is found and other specific situations, there are no overall guidelines addressing when it’s appropriate to order a thyroid ultrasound, Dr. Kennedy, now an otolaryngology resident at the Indiana University of Indianapolis, and colleagues, point out.

According to Dr. Francis, “Ultrasounds are low cost and low risk. Those two factors result in people ordering more tests…The problem with that is we find things, and then we have to figure out what to do with them. That leads to incidentalomas, the surveillance, worry and anxiety, and costs…It’s tricky. We don’t want to discourage people from ever ordering ultrasounds, but there need to be some guidelines around when it’s appropriate to order.”

Asked to comment, Trevor E. Angell, MD, associate medical director of Thyroid Center at Keck School of Medicine of the University of Southern California, Los Angeles, said that the study is “clinically very important.”

Dr. Angell pointed out that the current American Thyroid Association (ATA) guidelines on thyroid nodule management, of which he is an author, recommend ultrasound for a known or suspected nodule. But he added, “there certainly should be a message that obtaining ultrasound for these other reasons are less likely to identify a nodule or anything causative. Whether it’s gastroesophageal reflux or allergic rhinitis or vocal cord dysfunction, an ultrasound isn’t a good test for those either.”

Dr. Angell said that the next ATA thyroid nodule guidelines, expected out in 2024, will address this topic more fully, but he couldn’t provide more specific information because the document is still in development. He did say, however, “Addressing when not to do an ultrasound will be an important consideration in the next guidelines.”
 

Low Detection Rates for Most Indications

The retrospective observational cohort study included 1739 adults (76% women; mean age, 53 years) who underwent dedicated thyroid ultrasounds between 2017 and 2019. In most cases, the recommendation for biopsy was determined using the American College of Radiology TI-RADS system, based on nodule size and TI-RADS category.

The most common indication for thyroid ultrasound, suspected palpable nodule, accounted for 40% of those performed. Follow-up for an “incidentaloma” was the indication in 28% of patients, and referral for compressive and metabolic symptoms accounted for 13% and 6% of ultrasounds, respectively.

Among all ultrasounds performed, 62% identified a thyroid nodule. Patients referred for incidental findings had the highest percentage of ultrasounds with thyroid nodules present at 94%. By contrast, in those referred for suspected palpable nodule on exam and for compressive symptoms, nodules were identified on 55% and 39% of ultrasounds, respectively. Patients with metabolic symptoms had a nodule identified on ultrasound 43% of the time. Among those referred for high risk factors, 57% had a nodule present.

Overall, only 27% of ultrasounds identified a thyroid nodule that was recommended for a biopsy. Again, those referred because of an incidental imaging finding had the highest percentage (55%), followed by those referred for a suspected palpable nodule (21%), high risk factors (20%), combined indications (16%), metabolic symptoms (10%), and compressive symptoms (6%).

Mean nodule size was largest among the patients referred for incidentalomas (2.4 cm), whereas all the other groups had mean nodule sizes between 1.2 cm and 1.8 cm, a significant difference (P < .05). The median size of nodules among those referred to ultrasound for a suspected palpable nodule was 1.4 cm.

“That’s pretty small. It would have had to be in the front of the thyroid where they could actually touch it. I would argue that the number of clinicians who actually palpated something was smaller. We’ve done several projects looking at how small a nodule a clinician can actually feel in the thyroid gland from the neck. It turns out we’re pretty bad at physical examination of the thyroid. This paper kind of reinforces that,” Dr. Francis said in an interview.

Patients with incidental nodules were over 10 times more likely to have a nodule found on an ultrasound than those referred for a suspected palpable nodule on exam (odds ratio [OR], 10.6). Conversely, those referred for compressive symptoms were half as likely to have an identifiable nodule compared with those referred for physical exam findings (OR, 0.5).

The odds of finding a nodule increased with age, especially for those aged ≥ 65 years compared with those younger than 45 years (OR, 3.6). Women were twice as likely to have a nodule found on thyroid ultrasound (OR, 2.0). Results were similar for the biopsy-recommended nodules, except that there was no difference between sexes (female vs male OR, 1.2).

Dr. Angell called the study “a very robust comprehensive evaluation,” but also noted that the single center source is a limitation. “It would be nice to have those big databases of national healthcare settings, but getting that granular level of information about why something was done is nearly impossible in that context.”

Dr. Kennedy, Dr. Francis, and Dr. Angell have no disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.

Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.

METHODOLOGY:

• The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
• The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
• Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
• The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
• Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.

TAKEAWAY:

• Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
• The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
• The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with  biologic DMARDs (bDMARD), with an HR of 0.54.
• The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
• The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
• However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.

IN PRACTICE:

“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.

“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.

SOURCE:

The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.

LIMITATIONS:

The study lacked details on participants’ thyroid autoantibody and hormone levels.

The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.

Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.

DISCLOSURES:

The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.

Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.

METHODOLOGY:

• The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
• The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
• Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
• The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
• Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.

TAKEAWAY:

• Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
• The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
• The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with  biologic DMARDs (bDMARD), with an HR of 0.54.
• The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
• The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
• However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.

IN PRACTICE:

“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.

“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.

SOURCE:

The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.

LIMITATIONS:

The study lacked details on participants’ thyroid autoantibody and hormone levels.

The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.

Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.

DISCLOSURES:

The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with rheumatoid arthritis (RA) in a large Swedish population cohort show a reduced incidence of autoimmune thyroid diseases, such as hypothyroidism or hyperthyroidism, after being diagnosed with RA, with the effect being more pronounced among those treated with disease-modifying anti-rheumatic drugs (DMARDs), particularly TNF-inhibitors.

Although DMARDs are commonly used in the treatment of RA, the drugs are rarely used to treat autoimmune thyroid diseases. The new results support theories raised in previous smaller studies that DMARDs could have a protective effect against thyroid disease.

METHODOLOGY:

• The study involved 13,731 patients with new-onset RA who were listed in the Swedish Rheumatology Quality Register between 2006 and 2018.
• The patients were matched for sex, age, and residential area with up to five reference individuals in the general population of 63,201 comparators.
• Overall, patients with RA were 64.7% female, with a mean age of 59. They were followed up with their matched comparators until the development of autoimmune thyroid disease, death, emigration, or the end of the study period, December 2019.
• The relative risks of autoimmune thyroid disease following a diagnosis of RA and with treatment with DMARDs were compared with those risks in the general population.
• Participants with a non-autoimmune cause for thyroxine prescription were excluded, as were those with an autoimmune thyroid disease at the time of RA diagnosis.

TAKEAWAY:

• Following their RA diagnosis, 321 (2.3%) of patients developed an autoimmune thyroid disease, compared with 1838 (2.9%) in the general population comparators, representing an incidence of 3.7 vs 4.6 per 1000 person-years (hazard ratio [HR], 0.81).
• The lower incidence of autoimmune thyroid disease was more pronounced with longer RA duration. For instance, at 10-14 years after an RA diagnosis, the incidence was 2.9 vs. 4.5 autoimmune thyroid disease events per 1000 person-years, respectively (HR, 0.64).
• The decreased risk of incident autoimmune thyroid disease among RA patients compared with the general population was strongest among patients treated with  biologic DMARDs (bDMARD), with an HR of 0.54.
• The reduced incidence of autoimmune thyroid disease with bDMARD use was most pronounced among users of TNF-inhibitors (HR, 0.67).
• The lower incidence of autoimmune thyroid disease following a diagnosis of RA contrasts with previous studies showing an increased risk for thyroid disease associated with RA.
• However, the decreased risk of thyroid disease following bDMARD treatment supports the theory that immunomodulatory treatment could also have an effect of blunting the inflammatory processes that can lead to overt clinical autoimmune thyroid disease.

IN PRACTICE:

“To our knowledge, no previous study has investigated whether the risk of new-onset autoimmune thyroid disease is affected by RA treatment in early RA,” the authors report.

“Our results demonstrate that compared to the general population, patients with RA treated with bDMARDs, TNF-inhibitors in particular, are at decreased risk of developing autoimmune thyroid disease, a finding that calls for replication and may open for drug-repurposing studies,” they note.

SOURCE:

The study was conducted by first author Kristin Waldenlind, PhD, of the Department of Medicine, Solna, Division of Clinical Epidemiology, Karolinska Institutet, Stockholm, Sweden, and colleagues. It was published online November 27 in the Journal of Internal Medicine.

LIMITATIONS:

The study lacked details on participants’ thyroid autoantibody and hormone levels.

The presence of autoimmune thyroid disease was determined based on prescriptions for thyroxine, hence the authors cannot exclude the possibility of a lower threshold for thyroxine prescription among patients treated with DMARDs.

Information was not available on potential risk factors for RA and autoimmune thyroid disease that might have introduced confounding, such as smoking or obesity.

DISCLOSURES:

The study received funding from the Swedish Research Council, the Swedish Heart Lung Foundation, Vinnova, and Region Stockholm/Karolinska Institutet (ALF). The authors’ disclosures are detailed in the published study.

A version of this article appeared on Medscape.com.

New evidence points to an association between exposure to “forever chemicals” and an increased risk for thyroid cancer.

The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.

Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.

But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.

“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
 

PFAS and thyroid cancer

PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.

These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.

Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.

To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection. 

Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer. 

Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).

A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.

“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.

But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”

First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.

“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.

Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.

“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”

Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”

Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.

A version of this article appeared on Medscape.com.

New evidence points to an association between exposure to “forever chemicals” and an increased risk for thyroid cancer.

The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.

Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.

But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.

“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
 

PFAS and thyroid cancer

PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.

These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.

Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.

To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection. 

Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer. 

Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).

A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.

“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.

But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”

First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.

“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.

Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.

“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”

Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”

Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.

A version of this article appeared on Medscape.com.

New evidence points to an association between exposure to “forever chemicals” and an increased risk for thyroid cancer.

The study suggests that higher exposure to per- and polyfluoroalkyl substances (PFAS), specifically perfluorooctanesulfonic acid (n-PFOS), may increase a person’s risk for thyroid cancer by 56%.

Several news outlets played up the findings, published online in eBioMedicine. “Dangerous ‘Forever Chemicals’ in Your Everyday Items Are Causing Cancer,” Newsweek reported.

But Gideon Meyerowitz-Katz, PhD, an epidemiologist at the University of Wollongong (Australia), voiced his skepticism.

“While it’s possible that PFAS might be causing thyroid cancer, the evidence thus far is unconvincing and probably not worth worrying about,” said Dr. Meyerowitz-Katz, who was not involved in the research.
 

PFAS and thyroid cancer

PFAS are a class of widely used synthetic chemicals found in many consumer and industrial products, including nonstick cookware, stain-repellent carpets, waterproof rain gear, microwave popcorn bags, and firefighting foam.

These substances have been dubbed “forever chemicals” because they do not degrade and are ubiquitous in the environment.

Exposure to endocrine-disrupting chemicals, including PFAS, has been identified as a potential risk factor for thyroid cancer, with some research linking PFAS exposure to thyroid dysfunction and carcinogenesis.

To investigate further, the researchers performed a nested case-control study of 86 patients with thyroid cancer using plasma samples collected at or before diagnosis and 86 controls without cancer who were matched on age, sex, race/ethnicity, body weight, smoking status, and year of sample collection. 

Eighteen individual PFAS were measured in plasma samples; 10 were undetectable and were therefore excluded from the analysis. Of the remaining eight PFAS, only one showed a statistically significant correlation with thyroid cancer. 

Specifically, the researchers found that exposure to n-PFOS was associated with a 56% increased risk for thyroid cancer among people who had a high level of the chemical in their blood (adjusted odds ratio, 1.56; P = .004). The results were similar when patients with papillary thyroid cancer only were included (aOR, 1.56; P = .009).

A separate longitudinal analysis of 31 patients diagnosed with thyroid cancer 1 year or more after plasma sample collection and 31 controls confirmed the positive association between n-PFOS and thyroid cancer (aOR, 2.67; P < .001). The longitudinal analysis also suggested correlations for a few other PFAS.

“This study supports the hypothesis that PFAS exposure may be associated with increased risk of thyroid cancer,” the authors concluded.

But in a Substack post, Dr. Meyerowitz-Katz said that it’s important to put the findings into “proper context before getting terrified about this all-new cancer risk.”

First, this study was “genuinely tiny,” with data on just 88 people with thyroid cancer and 88 controls, a limitation the researchers also acknowledged.

“That’s really not enough to do any sort of robust epidemiological analysis – you can generate interesting correlations, but what those correlations mean is anyone’s guess,” Dr. Meyerowitz-Katz said.

Even more importantly, one could easily argue that the results of this study show that most PFAS aren’t associated with thyroid cancer, given that there was no strong association for seven of the eight PFAS measured, he explained.

“There are no serious methodological concerns here, but equally there’s just not much you can reasonably gather from finding a single correlation among a vast ocean of possibilities,” Dr. Meyerowitz-Katz wrote. “Maybe there’s a correlation there, but you’d need to investigate this in much bigger samples, with more controls, and better data, to understand what that correlation means.”

Bottom line, Dr. Meyerowitz-Katz explained, is that “the link between PFAS and thyroid cancer is, at best, incredibly weak.”

Funding for the study was provided by the National Institutes of Health and The Andrea and Charles Bronfman Philanthropies. One coauthor is cofounder of Linus Biotechnology and is owner of a license agreement with NIES (Japan); received honoraria and travel compensation for lectures for the Bio-Echo and Brin foundations; and has 22 patents at various stages. Dr. Meyerowitz-Katz has no relevant disclosures.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.

Patients age 65 and older who receive thyroid hormone therapy and experience low thyrotropin are at increased risk for dementia and other cognitive problems, according to new research published in JAMA Internal Medicine.

The study found that these patients with thyrotoxicosis had a higher likelihood of incident cognitive disorder (adjusted hazard ratio, 1.39; 95% confidence interval, 1.18-1.64; P < .001). Broken down between internal and external causes of thyrotoxicosis, exogenous thyrotoxicosis continued to be a significant risk factor (aHR, 1.34: 95% CI, 1.10-1.63; P = .003), while endogenous thyrotoxicosis did not show a statistically significant risk estimates (aHR, 1.38; 95% CI, 0.96-1.98; P = .08).

The study also found that women were more likely to have low levels of thyrotropin (thyroid-stimulating hormone/TSH) than men and were more likely to be overtreated.

Previous studies looking at the correlation between hyperthyroidism and cognitive disorders often did not include participants who were already taking thyroid hormones, according to Jennifer S. Mammen, MD, PhD, assistant professor of medicine at the Asthma and Allergy Center at John Hopkins University, Baltimore, and the senior author of the study.

“The fact that we see the signal both in people who are being overtreated with thyroid hormone and in people who have endogenous hyperthyroidism is one way that we think that this supports the fact that it’s not just confounding, it’s not just bias,” Dr. Mammen said. “There’s two different sources of hyperthyroidism, and they’re both showing the same relationship.”

In the study, Dr. Mammen and colleagues analyzed electronic health records for patients aged 65 years and older who received primary care in the Johns Hopkins Community Physicians Network over a 10-year period starting in 2014. Patients had to have a minimum of two visits 30 days apart. None had a history of low TSH levels or cognitive disorder diagnoses within 6 months of their first doctor visit.

More than 65,000 patients were included in the study. Slightly more than half (56%) were female, almost 70% were White, 19.3% were Black, 4.6% were Asian, and 0.4% were American Indian. Almost 25,000 low TSH measurements among 2,710 patients were recorded during the study period. The majority of low TSH measurements were exogenous (14,875), followed by origins of unknown cause (5,833), and endogenous (4,159).

During the follow-up period, 7.2% (4,779) patients received a new cognitive disorder diagnosis, which was dementia in 77% of cases.

Dr. Mammen said primary care physicians should carefully consider whether thyroid hormone therapy is necessary for older patients, and, if so, great care should be taken to avoid overtreatment.

“This is yet another reason for us to be vigilant about not overtreating people with thyroid hormone, especially in older adults,” Dr. Mammen said. “We already know that atrial fibrillation rates are increased in people who are hyperthyroid. We know that fracture and osteoporosis is affected by hyperthyroidism. And now we also have an association with higher rates of cognitive disorders.”

Taking a cautious approach to prescribing thyroid hormone therapy for older patients is paramount, according to Jean Chen, MD, partner at Texas Diabetes & Endocrinology, who was not affiliated with the study.

“All medical providers need to be aware that the 65 and older population does not need to be treated as aggressively with their thyroid hormone,” Dr. Chen said. “We are finding more and more complications from overtreatment rather than benefit in this population.”

Often, older patients may complain of symptoms such as constipation, feeling cold, or tiredness, which can be symptoms of hypothyroidism. But these symptoms could also be from anemia, vitamin deficiencies, depression, perimenopause, menopause, insulin resistance, and sleep apnea. If necessary, Dr. Chen recommended primary care physicians consult with an endocrinologist regarding a possible treatment plan and making a differential diagnosis.

In addition, Dr. Chen said other studies have shown that treating patients with thyroid hormone either did not resolve the condition or negatively impacted anxiety, muscle strength, and bone density, or it increased the risk for arrhythmia. Therefore, it’s important to weight the risks versus the benefits.

“There’s so much gray zone here,” Dr. Chen said.

The study was supported by the Richman Family Precision Medicine Center of Excellence in Alzheimer’s Disease, the Richman Family Foundation, the Rick Sharp Alzheimer’s Foundation, the Sharp Family Foundation, among others. The work was also supported by grants from the National Institutes of Health. One coauthor reported personal fees from Karuna, MapLight Therapeutics, Axsome Therapeutics, GIA, GW Research Limited, Merck, EXCIVA, Otsuka, IntraCellular Therapies, and Medesis Pharma for consulting for treatment development in Alzheimer’s disease outside the submitted work. No other disclosures were reported.

A version of this article appeared on Medscape.com.