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Over-the-Counter Arthritis Supplements Pose Adrenal Danger
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
BOSTON —
Patients who have been taking these supplements for prolonged periods must slowly taper off them with corticosteroid replacement, because abruptly stopping the supplement can precipitate AI, Kevin S. Wei, MD, said in a presentation of 12 cases — the largest such series to date of the phenomenon — at the annual meeting of the Endocrine Society.
The specific supplements used were Artri King in eight of the patients, Ardosons in two, and Ajo Rey in one. In April 2022, the US Food and Drug Administration issued a warning that Artri King contains diclofenac and dexamethasone not listed on the product label. In July 2023, the agency issued an expanded warning about that product and others including Ajo Rey.
The supplements are not believed to be sold in the United States, but they are available in Mexico and can be ordered online, said Dr. Wei, a second-year resident at the Keck School of Medicine at the University of California, Los Angeles.
“We found that quite a lot of patients after they’ve been on the Artri King or some other over the counter arthritis supplement, started developing these cushingoid features seen in the physical exam, such as rounded facial features or stretch marks of their abdomen,” he said.
And “when patients are abruptly taken off those supplements … sometimes this can cause them to go into signs or symptoms of adrenal insufficiency. That can occasionally be life-threatening if it’s not addressed in an inpatient setting,” Dr. Wei said.
In an interview, session moderator Sharon L. Wardlaw, MD, professor of medicine at Columbia University Irving Medical Center, New York, explained that when a person takes these drugs containing hidden glucocorticoids, “they won’t be picked up in a cortisol assay, but they’ll suppress the [adrenocorticotropic hormone] and the person’s own cortisol production. They look like they have Cushing, but when you measure their hormone levels, they’re undetectable. And then people wonder what’s going on. Well, their [hypothalamic-pituitary-adrenal] axis is suppressed.”
But if the product is suddenly stopped without cortisol replacement “If they get an infection they can die because they can’t mount a cortisol response.”
The takeaway message, she said, is “always ask patients to show you their supplements and look at them. In many cases, that’s why they work so well for pain relief because they have ingredients that people shouldn’t be taking.”
Twelve Patients Seen During 2022-2023
The 12 patients were seen during 2022-2023 at an endocrinology consult service in an urban safety net hospital. Their median age was 52 years, and one third were women. All had started using the supplements for joint pain, with a median of about 6 months of use prior to cessation.
Presenting symptoms included nausea/vomiting in 42%, fatigue in 42%, abdominal pain in 33%, and dizziness in 17%. Physical exam findings included moon facies in 66%, central adiposity in 66%, abdominal striae in 50%, dorsocervical fat pad in 33%, and bruising in 33%. Three required intensive care admission.
Cortisol testing was performed in 11 of the patients and was normal (≥ 16 mcg/dL) in just one. AI (≤ 3 mcg/dL) was found in three, while the rest had indeterminate results. Of those seven patients, subsequent cosyntropin-stimulation testing suggested AI (cortisol < 16 mcg/dL at 60 minutes post stimulation) in four patients, while the other two showed reduced but normal responses (cortisol 18.2-18.4 mcg/dL).
Ten of the 12 patients were prescribed glucocorticoid tapering replacements to avoid precipitating adrenal crisis, most commonly twice-daily hydrocortisone. Of those ten, eight continued to take the replacement steroids 1-2 years later, Dr. Wei said.
Dr. Wei and Dr. Wardlaw had no disclosures.
A version of this article appeared on Medscape.com.
‘Don’t Screen’ for Vitamin D: New Endo Society Guideline
BOSTON —
The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include:
- Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
- Pregnant people to lower the risk for maternal and fetal or neonatal complications
- Adults older than 75 years to lower the risk for mortality
- Adults with prediabetes to lower the risk for type 2 diabetes
In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations.
In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions.
Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”
Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”
Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”
Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].”
Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense.
“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”
Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”
However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”
In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”
Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”
Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.”
In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing:
The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.
Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
A version of this article appeared on Medscape.com.
BOSTON —
The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include:
- Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
- Pregnant people to lower the risk for maternal and fetal or neonatal complications
- Adults older than 75 years to lower the risk for mortality
- Adults with prediabetes to lower the risk for type 2 diabetes
In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations.
In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions.
Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”
Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”
Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”
Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].”
Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense.
“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”
Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”
However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”
In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”
Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”
Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.”
In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing:
The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.
Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
A version of this article appeared on Medscape.com.
BOSTON —
The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include:
- Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
- Pregnant people to lower the risk for maternal and fetal or neonatal complications
- Adults older than 75 years to lower the risk for mortality
- Adults with prediabetes to lower the risk for type 2 diabetes
In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations.
In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions.
Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”
Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”
Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”
Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].”
Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense.
“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”
Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”
However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”
In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”
Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”
Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.”
In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing:
The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.
Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
A version of this article appeared on Medscape.com.
Cortisol Test Confirms HPA Axis Recovery from Steroid Use
TOPLINE:
An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).
METHODOLOGY:
- A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
- A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
- Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
- Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.
TAKEAWAY:
- The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
- With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
- A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
- A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).
IN PRACTICE:
“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.
SOURCE:
The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.
LIMITATIONS:
Not provided.
DISCLOSURES:
Not provided.
A version of this article appeared on Medscape.com.
TOPLINE:
An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).
METHODOLOGY:
- A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
- A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
- Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
- Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.
TAKEAWAY:
- The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
- With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
- A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
- A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).
IN PRACTICE:
“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.
SOURCE:
The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.
LIMITATIONS:
Not provided.
DISCLOSURES:
Not provided.
A version of this article appeared on Medscape.com.
TOPLINE:
An early serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) has been validated as a safe and useful screening test with 100% specificity for predicting recovery of the hypothalamic-pituitary-adrenal (HPA) axis in patients on tapering regimes from long‐term chronic glucocorticoid therapy (CGT).
METHODOLOGY:
- A retrospective review of 250-µg Synacthen test (SST) results performed in patients on tapering CGT doses from a single-center rheumatology department over 12 months.
- A total of 60 SSTs were performed in 58 patients, all in the morning (7-12 AM) after withholding CGT for 48 hours.
- Peripheral blood was sampled for cortisol at baseline, 30 minutes, and 60 minutes.
- Adrenal insufficiency (AI) was defined as a peak serum cortisol concentration.
TAKEAWAY:
- The mean duration of CGT (all prednisolone) was 63 months, prescribed primarily for giant cell arteritis/polymyalgia rheumatica (48%) and inflammatory arthritis (18%), with a mean daily dose of 3.4 mg at the time of SST.
- With the investigators’ previously reported basal serum cortisol concentration of > 237 nmol/L (> 8.6 μg/dL) used to confirm an intact HPA axis, no patient with AI would have been missed, but 37 of 51 (73%) unnecessary SSTs in euadrenal patients would have been avoided.
- A basal serum cortisol concentration of > 227 nmol/L had a specificity of 100% for predicting passing the SST, while a basal serum cortisol concentration of ≤ 55 nmol/L had a 100% sensitivity for predicting failure.
- A mean daily prednisolone dosing at the time of SST in patients with AI was significantly higher than that with normal SSTs (5.7 vs 2.9 mg, respectively; P = .01).
IN PRACTICE:
“This offers a more rapid, convenient, and cost‐effective screening method for patients requiring biochemical assessment of the HPA axis with the potential for significant resource savings without any adverse impact on patient safety,” the authors wrote.
SOURCE:
The study was conducted by Ella Sharma, of the Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, UK, and colleagues and published online on May 19, 2024, as a letter in Clinical Endocrinology.
LIMITATIONS:
Not provided.
DISCLOSURES:
Not provided.
A version of this article appeared on Medscape.com.
Collaboration Tackles Steroid-Induced Adrenal Insufficiency
Endocrinologists in Europe and the United States have come together to produce joint guidance to help clinicians manage patients who have, or are a at risk for, glucocorticoid-induced adrenal insufficiency (GC-AI).
Publication of the guidance marks the first time that the European Society of Endocrinology (ESE) and the Endocrine Society have cooperated in producing a guideline.
The guideline “Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency” is published in the May 2024 issues of the societies respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism.
Felix Beuschlein, PhD, from the ESE, who cochaired the clinical committee, told this news organization: “You would hope that this leads to a common ground for a very large number of patients.”
The risk for GC-AI is dependent on the dose, duration, and potency of the glucocorticoid; route of administration; as well as susceptibility of the individual patient. Once it develops or is suspected, careful education and management of affected patients is required.
Glucocorticoids Commonly Prescribed
“Glucocorticoid-induced adrenal insufficiency is actually a potential concern for a lot of patients,” coauthor Tobias Else, MD, of the department of internal medicine at the University of Michigan, Ann Arbor, explained to this news organization. “Roughly 1% of all people are being treated with glucocorticoids at any given time.”
“That’s a tremendous number, and it gives the scale of the situation,” added Dr. Beuschlein, director of the department of endocrinology, diabetology, and clinical nutrition at University Hospital Zürich in Switzerland. “Now, fortunately, only a very small proportion of patients who are treated with glucocorticoids do have endocrine problems, and this is what this guideline is actually concentrating on.”
Glucocorticoids are effective agents for treating autoimmune and inflammatory disorders. However, they can cause adverse reactions, particularly when administered at high doses and/or for a prolonged period.
Some studies have reported that even low-dose glucocorticoid use, such as prednisone at 2.5-7.5 mg/d, can increase the risk for cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, and fractures, as well as increase overall mortality with concurrent type 2 diabetes.
Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency, the guidelines stated. In general, tapering of glucocorticoids can occur more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.
The degree and persistence of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid therapy is stopped depends on overall exposure and recovery of adrenal function. “This is a quite individual situation, as you can imagine, because it’s about sex, age, and comorbidities, the kind of glucocorticoid or other medications that you’re giving,” said Dr. Beuschlein. To cover contingencies, the paper presents tables to explain management covering various eventualities.
Leonie van Hulsteijn, MD, from the department of clinical epidemiology, Leiden University Medical Center, Leiden, the Netherlands, said: “There are so many other specialties prescribing glucocorticoids; so especially the rheumatologist, the pulmonologist, the general practitioners.”
Asked by this news organization whether the guidelines might dissuade some clinicians from offering glucocorticoids, Dr. van Hulsteijn, who contributed to the guidance, said, “I don’t think it will keep them from prescribing it, but I really hope it will make them aware if somebody, after using long-term glucocorticoids, presents with complaints of adrenal insufficiency, that they will be aware and take immediate action.”
Evidence Gaps
The review team took around 2.5 years to draw up the guidance amid some concerns about the quality of the evidence base, which they mainly rated as “low” or “very low.” “I think we all, going through the literature, were quite astonished at how bad the evidence is for a problem as global as that,” said Dr. Beuschlein. “But that’s how it is — sometimes, even in the absence of strong evidence, you have to give some kind of guidance.”
Nevertheless, the authors have called for more research to establish risk factors contributing to the development of and susceptibility to adrenal insufficiency, a greater understanding of glucocorticoid withdrawal, and identification of glucocorticoids retaining immunosuppressive and anti-inflammatory properties that have less effect on HPA axis suppression and an improved adverse effect profile.
Patient-facing materials on GC-AI are also in development and will be made available via the ESE Patient Zone this month.
Next year, the societies plan to publish a joint guideline on diabetes in pregnancy. That will be followed in 2026 by guidance on arginine vasopressin resistance and arginine vasopressin deficiency and a guideline on male hypogonadism in 2027.
Funding for the development of joint guidelines was provided by the societies and did not involve support from other bodies.
Dr. Beuschlein declared funding from the German Research Funding Agency, the Swiss National Science Foundation, University Medicine Zürich, the Vontobel Foundation, the Swiss Heart Foundation, and consultancy work for Bayer AG. Dr. Else declared membership of the advisory board of Merck and Company. Dr. van Hulsteijn declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Endocrinologists in Europe and the United States have come together to produce joint guidance to help clinicians manage patients who have, or are a at risk for, glucocorticoid-induced adrenal insufficiency (GC-AI).
Publication of the guidance marks the first time that the European Society of Endocrinology (ESE) and the Endocrine Society have cooperated in producing a guideline.
The guideline “Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency” is published in the May 2024 issues of the societies respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism.
Felix Beuschlein, PhD, from the ESE, who cochaired the clinical committee, told this news organization: “You would hope that this leads to a common ground for a very large number of patients.”
The risk for GC-AI is dependent on the dose, duration, and potency of the glucocorticoid; route of administration; as well as susceptibility of the individual patient. Once it develops or is suspected, careful education and management of affected patients is required.
Glucocorticoids Commonly Prescribed
“Glucocorticoid-induced adrenal insufficiency is actually a potential concern for a lot of patients,” coauthor Tobias Else, MD, of the department of internal medicine at the University of Michigan, Ann Arbor, explained to this news organization. “Roughly 1% of all people are being treated with glucocorticoids at any given time.”
“That’s a tremendous number, and it gives the scale of the situation,” added Dr. Beuschlein, director of the department of endocrinology, diabetology, and clinical nutrition at University Hospital Zürich in Switzerland. “Now, fortunately, only a very small proportion of patients who are treated with glucocorticoids do have endocrine problems, and this is what this guideline is actually concentrating on.”
Glucocorticoids are effective agents for treating autoimmune and inflammatory disorders. However, they can cause adverse reactions, particularly when administered at high doses and/or for a prolonged period.
Some studies have reported that even low-dose glucocorticoid use, such as prednisone at 2.5-7.5 mg/d, can increase the risk for cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, and fractures, as well as increase overall mortality with concurrent type 2 diabetes.
Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency, the guidelines stated. In general, tapering of glucocorticoids can occur more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.
The degree and persistence of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid therapy is stopped depends on overall exposure and recovery of adrenal function. “This is a quite individual situation, as you can imagine, because it’s about sex, age, and comorbidities, the kind of glucocorticoid or other medications that you’re giving,” said Dr. Beuschlein. To cover contingencies, the paper presents tables to explain management covering various eventualities.
Leonie van Hulsteijn, MD, from the department of clinical epidemiology, Leiden University Medical Center, Leiden, the Netherlands, said: “There are so many other specialties prescribing glucocorticoids; so especially the rheumatologist, the pulmonologist, the general practitioners.”
Asked by this news organization whether the guidelines might dissuade some clinicians from offering glucocorticoids, Dr. van Hulsteijn, who contributed to the guidance, said, “I don’t think it will keep them from prescribing it, but I really hope it will make them aware if somebody, after using long-term glucocorticoids, presents with complaints of adrenal insufficiency, that they will be aware and take immediate action.”
Evidence Gaps
The review team took around 2.5 years to draw up the guidance amid some concerns about the quality of the evidence base, which they mainly rated as “low” or “very low.” “I think we all, going through the literature, were quite astonished at how bad the evidence is for a problem as global as that,” said Dr. Beuschlein. “But that’s how it is — sometimes, even in the absence of strong evidence, you have to give some kind of guidance.”
Nevertheless, the authors have called for more research to establish risk factors contributing to the development of and susceptibility to adrenal insufficiency, a greater understanding of glucocorticoid withdrawal, and identification of glucocorticoids retaining immunosuppressive and anti-inflammatory properties that have less effect on HPA axis suppression and an improved adverse effect profile.
Patient-facing materials on GC-AI are also in development and will be made available via the ESE Patient Zone this month.
Next year, the societies plan to publish a joint guideline on diabetes in pregnancy. That will be followed in 2026 by guidance on arginine vasopressin resistance and arginine vasopressin deficiency and a guideline on male hypogonadism in 2027.
Funding for the development of joint guidelines was provided by the societies and did not involve support from other bodies.
Dr. Beuschlein declared funding from the German Research Funding Agency, the Swiss National Science Foundation, University Medicine Zürich, the Vontobel Foundation, the Swiss Heart Foundation, and consultancy work for Bayer AG. Dr. Else declared membership of the advisory board of Merck and Company. Dr. van Hulsteijn declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Endocrinologists in Europe and the United States have come together to produce joint guidance to help clinicians manage patients who have, or are a at risk for, glucocorticoid-induced adrenal insufficiency (GC-AI).
Publication of the guidance marks the first time that the European Society of Endocrinology (ESE) and the Endocrine Society have cooperated in producing a guideline.
The guideline “Diagnosis and therapy of glucocorticoid-induced adrenal insufficiency” is published in the May 2024 issues of the societies respective journals, the European Journal of Endocrinology and The Journal of Clinical Endocrinology & Metabolism.
Felix Beuschlein, PhD, from the ESE, who cochaired the clinical committee, told this news organization: “You would hope that this leads to a common ground for a very large number of patients.”
The risk for GC-AI is dependent on the dose, duration, and potency of the glucocorticoid; route of administration; as well as susceptibility of the individual patient. Once it develops or is suspected, careful education and management of affected patients is required.
Glucocorticoids Commonly Prescribed
“Glucocorticoid-induced adrenal insufficiency is actually a potential concern for a lot of patients,” coauthor Tobias Else, MD, of the department of internal medicine at the University of Michigan, Ann Arbor, explained to this news organization. “Roughly 1% of all people are being treated with glucocorticoids at any given time.”
“That’s a tremendous number, and it gives the scale of the situation,” added Dr. Beuschlein, director of the department of endocrinology, diabetology, and clinical nutrition at University Hospital Zürich in Switzerland. “Now, fortunately, only a very small proportion of patients who are treated with glucocorticoids do have endocrine problems, and this is what this guideline is actually concentrating on.”
Glucocorticoids are effective agents for treating autoimmune and inflammatory disorders. However, they can cause adverse reactions, particularly when administered at high doses and/or for a prolonged period.
Some studies have reported that even low-dose glucocorticoid use, such as prednisone at 2.5-7.5 mg/d, can increase the risk for cardiovascular disease, severe infections, hypertension, diabetes, osteoporosis, and fractures, as well as increase overall mortality with concurrent type 2 diabetes.
Tapering glucocorticoids can be challenging when symptoms of glucocorticoid withdrawal develop, which overlap with those of adrenal insufficiency, the guidelines stated. In general, tapering of glucocorticoids can occur more rapidly within a supraphysiological range, followed by a slower taper when on physiological glucocorticoid dosing.
The degree and persistence of hypothalamic-pituitary-adrenal (HPA) axis suppression after glucocorticoid therapy is stopped depends on overall exposure and recovery of adrenal function. “This is a quite individual situation, as you can imagine, because it’s about sex, age, and comorbidities, the kind of glucocorticoid or other medications that you’re giving,” said Dr. Beuschlein. To cover contingencies, the paper presents tables to explain management covering various eventualities.
Leonie van Hulsteijn, MD, from the department of clinical epidemiology, Leiden University Medical Center, Leiden, the Netherlands, said: “There are so many other specialties prescribing glucocorticoids; so especially the rheumatologist, the pulmonologist, the general practitioners.”
Asked by this news organization whether the guidelines might dissuade some clinicians from offering glucocorticoids, Dr. van Hulsteijn, who contributed to the guidance, said, “I don’t think it will keep them from prescribing it, but I really hope it will make them aware if somebody, after using long-term glucocorticoids, presents with complaints of adrenal insufficiency, that they will be aware and take immediate action.”
Evidence Gaps
The review team took around 2.5 years to draw up the guidance amid some concerns about the quality of the evidence base, which they mainly rated as “low” or “very low.” “I think we all, going through the literature, were quite astonished at how bad the evidence is for a problem as global as that,” said Dr. Beuschlein. “But that’s how it is — sometimes, even in the absence of strong evidence, you have to give some kind of guidance.”
Nevertheless, the authors have called for more research to establish risk factors contributing to the development of and susceptibility to adrenal insufficiency, a greater understanding of glucocorticoid withdrawal, and identification of glucocorticoids retaining immunosuppressive and anti-inflammatory properties that have less effect on HPA axis suppression and an improved adverse effect profile.
Patient-facing materials on GC-AI are also in development and will be made available via the ESE Patient Zone this month.
Next year, the societies plan to publish a joint guideline on diabetes in pregnancy. That will be followed in 2026 by guidance on arginine vasopressin resistance and arginine vasopressin deficiency and a guideline on male hypogonadism in 2027.
Funding for the development of joint guidelines was provided by the societies and did not involve support from other bodies.
Dr. Beuschlein declared funding from the German Research Funding Agency, the Swiss National Science Foundation, University Medicine Zürich, the Vontobel Foundation, the Swiss Heart Foundation, and consultancy work for Bayer AG. Dr. Else declared membership of the advisory board of Merck and Company. Dr. van Hulsteijn declared no conflicts of interest.
A version of this article appeared on Medscape.com.
Can a Risk Score Predict Kidney Injury After Cisplatin?
Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.
Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.
A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.
Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.
However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.
Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.
“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
‘Herculean Effort’
“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.
“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.
The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.
The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.
Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.
Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.
Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.
The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.
Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
‘Definitive Work’
Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”
“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”
In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”
An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.
By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.
All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”
“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
‘Certainly Useful’
Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.
As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.
“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”
Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.
Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.
Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.
Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”
If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.
Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.
A version of this article appeared on Medscape.com.
Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.
Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.
A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.
Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.
However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.
Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.
“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
‘Herculean Effort’
“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.
“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.
The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.
The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.
Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.
Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.
Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.
The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.
Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
‘Definitive Work’
Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”
“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”
In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”
An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.
By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.
All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”
“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
‘Certainly Useful’
Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.
As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.
“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”
Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.
Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.
Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.
Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”
If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.
Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.
A version of this article appeared on Medscape.com.
Cisplatin is a preferred treatment for a wide range of cancers, including breast, head and neck, lung, ovary, and more. However, its side effects — particularly nephrotoxicity — can be severe. Kidney injury on cisplatin is associated with higher mortality and can jeopardize a patient’s eligibility for other therapies.
Now, in a large study using data from six US cancer centers, researchers have developed a risk algorithm to predict acute kidney injury (AKI) after cisplatin administration.
A risk prediction calculator based on the algorithm is available online for patients and providers to determine an individual patient›s risk for kidney injury from cisplatin using readily available clinical data.
Other risk scores and risk prediction models have been developed to help clinicians assess in advance whether a patient might develop AKI after receiving cisplatin, so that more careful monitoring, dose adjustments, or an alternative treatment, if available, might be considered.
However, previous models were limited by factors such as small sample sizes, lack of external validation, older data, and liberal definitions of AKI, said Shruti Gupta, MD, MPH, director of onco-nephrology at Brigham and Women’s Hospital (BWH) and Dana-Farber Cancer Institute, and David E. Leaf, MD, MMSc, director of clinical and translational research in AKI, Division of Renal Medicine, BWH, Boston.
Dr. Gupta and Dr. Leaf believe their risk score for predicting severe AKI after intravenous (IV) cisplatin, published online in The BMJ, is “more accurate and generalizable than prior models for several reasons,” they told this news organization in a joint email.
“First, we externally validated our findings across cancer centers other than the one where it was developed,” they said. “Second, we focused on moderate to severe kidney injury, the most clinically relevant form of kidney damage, whereas prior models examined more mild forms of kidney injury. Third, we collected data on nearly 25,000 patients receiving their first dose of IV cisplatin, which is larger than all previous studies combined.”
‘Herculean Effort’
“We conceived of this study back in 2018, contacted collaborators at each participating cancer center, and had numerous meetings to try to gather granular data on patients treated with their first dose of intravenous (IV) cisplatin,” Dr. Gupta and Dr. Leaf explained. They also incorporated patient feedback from focus groups and surveys.
“This was truly a Herculean effort that involved physicians, programmers, research coordinators, and patients,” they said.
The multicenter study included 24,717 patients — 11,766 in the derivation cohort and 12,951 in the validation cohort. Overall, the median age was about 60 years, about 58% were men, and about 78% were White.
The primary outcome was cisplatin-induced AKI (CP-AKI), defined as a twofold or greater increase in serum creatinine or kidney replacement therapy within 14 days of a first dose of IV cisplatin.
Their simple risk score consisting of nine covariates — age, hypertension, type 2 diabetes, hemoglobin level, white blood cell count, platelet count, serum albumin level, serum magnesium level, and cisplatin dose — predicted a higher risk for CP-AKI in both cohorts.
Notably, adding serum creatinine to the model did not change the area under the curve, and therefore, serum creatinine, though also an independent risk factor for CP-AKI, was not included in the score.
Patients in the highest risk category had 24-fold higher odds of CP-AKI in the derivation cohort and close to 18-fold higher odds in the validation cohort than those in the lowest risk category.
The primary model had a C statistic of 0.75 (95% CI, 0.73-0.76) and showed better discrimination for CP-AKI than previously published models, for which the C statistics ranged from 0.60 to 0.68. The first author of a paper on an earlier model, Shveta Motwani, MD, MMSc, of BWH and Dana-Farber Cancer Institute in Boston, is also a coauthor of the new study.
Greater severity of CP-AKI was associated with shorter 90-day survival (adjusted hazard ratio, 4.63; 95% CI, 3.56-6.02) for stage III CP-AKI vs no CP-AKI.
‘Definitive Work’
Joel M. Topf, MD, a nephrologist with expertise in chronic kidney disease in Detroit, who wasn’t involved in the development of the risk score, called the study “a definitive work on an important concept in oncology and nephrology.”
“While this is not the first attempt to devise a risk score, it is by far the biggest,” he told this news organization. Furthermore, the authors “used a diverse population, recruiting patients with a variety of cancers (previous attempts had often used a homogenous diagnosis, putting into question how generalizable the results were) from six different cancer centers.”
In addition, he said, “The authors did not restrict patients with chronic kidney disease or other significant comorbidities and used the geographic diversity to produce a cohort that has an age, gender, racial, and ethnic distribution, which is more representative of the US than previous, single-center attempts to risk score patients.”
An earlier model used the Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI of an increase in serum creatinine of 0.3 mg/dL, he noted. “While a sensitive definition of AKI, it captures mild, hemodynamic increases in creatinine of questionable significance,” he said.
By contrast, the new score uses KDIGO stage II and above to define AKI. “This is a better choice, as we do not want to dissuade patients and doctors from choosing chemotherapy due to a fear of insignificant kidney damage,” he said.
All that said, Dr. Topf noted that neither the current score nor the earlier model included serum creatinine. “This is curious to me and may represent the small number of patients with representative elevated creatinine in the derivation cohort (only 1.3% with an estimated glomerular filtration rate [eGFR] < 45).”
“Since the cohort is made up of people who received cis-platinum, the low prevalence of eGFRs < 45 may be due to physicians steering away from cis-platinum in this group,” he suggested. “It would be unfortunate if this risk score gave an unintentional ‘green light’ to these patients, exposing them to predictable harm.”
‘Certainly Useful’
Anushree Shirali, MD, an associate professor in the Section of Nephrology and consulting physician, Yale Onco-Nephrology, Yale School of Medicine, in New Haven, Connecticut, said that having a prediction score for which patients are more likely to develop AKI after a single dose of cisplatin would be helpful for oncologists, as well as nephrologists.
As a nephrologist, Dr. Shirali mostly sees patients who already have AKI, she told this news organization. But there are circumstances in which the tool could still be helpful.
“Let’s say someone has abnormal kidney function at baseline — ie, creatinine is higher than the normal range — and they were on dialysis 5 years ago for something else, and now, they have cancer and may be given cisplatin. They worry about their chances of getting AKI and needing dialysis again,” she said. “That’s just one scenario in which I might be asked to answer that question and the tool would certainly be useful.”
Other scenarios could include someone who has just one kidney because they donated a kidney for transplant years ago, and now, they have a malignancy and wonder what their actual risk is of getting kidney issues on cisplatin.
Oncologists could use the tool to determine whether a patient should be treated with cisplatin, or if they’re at high risk, whether an alternative that’s not nephrotoxic might be used. By contrast, “if somebody’s low risk and an oncologist thinks cisplatin is the best agent they have, then they might want to go ahead and use it,” Dr. Shirali said.
Future research could take into consideration that CP-AKI is dose dependent, she suggested, because a prediction score that included the number of cisplatin doses could be even more helpful to determine risk. And, even though the derivation and validation cohorts for the new tool are representative of the US population, additional research should also include more racial/ethnic diversity, she said.
Dr. Gupta and Dr. Leaf hope their tool “will be utilized immediately by patients and providers to help predict an individual’s risk of cisplatin-associated kidney damage. It is easy to use, available for free online, and incorporates readily available clinical variables.”
If a patient is at high risk, the clinical team can consider preventive measures such as administering more IV fluids before receiving cisplatin or monitoring kidney function more closely afterward, they suggested.
Dr. Gupta reported research support from the National Institutes of Health (NIH) and the National Institute of Diabetes and Digestive and Kidney Diseases. She also reported research funding from BTG International, GE HealthCare, and AstraZeneca outside the submitted work. She is a member of GlaxoSmithKline’s Global Anemia Council, a consultant for Secretome and Proletariat Therapeutics, and founder and president emeritus of the American Society of Onconephrology (unpaid). Dr. Leaf is supported by NIH grants, reported research support from BioPorto, BTG International, and Metro International Biotech, and has served as a consultant. Dr. Topf reported an ownership stake in a few DaVita-run dialysis clinics. He also runs a vascular access center and has participated in advisory boards with Cara Therapeutics, Vifor, Astra Zeneca, Bayer, Renibus Therapeutics, Travere Therapeutics, and GlaxoSmithKline. He is president of NephJC, a nonprofit educational organization with no industry support. Dr. Shirali declared no competing interests.
A version of this article appeared on Medscape.com.
FROM THE BMJ
GLP-1 Receptor Agonists Don’t Raise Thyroid Cancer Risk
TOPLINE:
METHODOLOGY:
- A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
- Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
- Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.
TAKEAWAY:
- The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
- During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
- Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
- In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).
IN PRACTICE:
“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”
SOURCE:
This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.
LIMITATIONS:
Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.
DISCLOSURES:
The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
- Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
- Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.
TAKEAWAY:
- The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
- During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
- Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
- In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).
IN PRACTICE:
“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”
SOURCE:
This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.
LIMITATIONS:
Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.
DISCLOSURES:
The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- A cohort study using data from nationwide registers in Denmark, Norway, and Sweden between 2007 and 2021 included 145,410 patients who initiated GLP-1 RAs and 291,667 propensity score-matched patients initiating dipeptidyl peptidase 4 (DPP4) inhibitors as active comparators.
- Additional analysis included 111,744 who initiated GLP-1 RAs and 148,179 patients initiating sodium-glucose cotransporter 2 (SGLT2) inhibitors.
- Overall, mean follow-up time was 3.9 years, with 25% followed for more than 6 years.
TAKEAWAY:
- The most common individual GLP-1 RAs were liraglutide (57.3%) and semaglutide (32.9%).
- During follow-up, there were 76 incident thyroid cancer cases among GLP-1 RA users and 184 cases in DPP4 inhibitor users, giving incidence rates per 10,000 of 1.33 and 1.46, respectively, a nonsignificant difference (hazard ratio [HR], 0.93; 95% CI, 0.66-1.31).
- Papillary thyroid cancer was the most common thyroid cancer subtype, followed by follicular and medullary, with no significant increases in risk with GLP-1 RAs by cancer type, although the numbers were small.
- In the SGLT2 inhibitor comparison, there was also no significantly increased thyroid cancer risk for GLP-1 RAs (HR, 1.16; 95% CI, 0.65-2.05).
IN PRACTICE:
“Given the upper limit of the confidence interval, the findings are incompatible with more than a 31% increased relative risk of thyroid cancer. In absolute terms, this translates to no more than 0.36 excess cases per 10 000 person-years, a figure that should be interpreted against the background incidence of 1.46 per 10,000 person-years among the comparator group in the study populations.”
SOURCE:
This study was conducted by Björn Pasternak, MD, PhD, of the Karolinska Institutet, Stockholm, and colleagues. It was published online on April 10, 2024, in The BMJ.
LIMITATIONS:
Relatively short follow-up for cancer risk. Risk by individual GLP-1 RA not analyzed. Small event numbers. Observational, with potential for residual confounding and time-release bias.
DISCLOSURES:
The study was supported by grants from the Swedish Cancer Society and the Swedish Research Council. Dr. Pasternak was supported by a consolidator investigator grant from Karolinska Institutet. Some of the coauthors had industry disclosures.
A version of this article appeared on Medscape.com.
Liquid Biopsy Has Near-Perfect Accuracy for Early Pancreatic Cancer
the most common type of pancreatic cancer.
It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).
Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.
Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.
In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.
In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.
The test performed the same whether the tumor was in the head or tail of the pancreas.
“We are very excited about this data,” said Dr. Goel.
The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.
Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.
“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.
Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.
“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.
“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.
In the meantime, Dr. Goel said there’s more work to be done.
Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.
The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.
The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.
The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.
A version of this article appeared on Medscape.com.
the most common type of pancreatic cancer.
It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).
Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.
Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.
In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.
In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.
The test performed the same whether the tumor was in the head or tail of the pancreas.
“We are very excited about this data,” said Dr. Goel.
The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.
Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.
“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.
Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.
“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.
“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.
In the meantime, Dr. Goel said there’s more work to be done.
Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.
The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.
The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.
The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.
A version of this article appeared on Medscape.com.
the most common type of pancreatic cancer.
It is quite encouraging to know we have a blood test that could potentially find this disease early, said Ajay Goel, PhD, a molecular diagnostics specialist at City of Hope in Duarte, California, who presented the findings at the annual meeting of the American Association for Cancer Research (AACR).
Dr. Goel and colleagues developed a signature for pancreatic cancer based on microRNAs identified in the exomes shed from pancreatic cancers and cell-free DNA markers found in the blood of patients with the disease.
Their initial assay tested blood samples for this signature in a training cohort of 252 people in Japan, approximately 60% of whom had pancreatic cancer. The rest were healthy controls. The assay was then tested in validation cohorts of 400 subjects, half with pancreatic cancer and half controls, in China and South Korea.
In both the initial and validation tests, the microRNA assay had an accuracy of about 90% for stage I/II pancreatic cancer, already far better than commercially available assays.
In an additional validation cohort in the United States with 139 patients with pancreatic cancer and 193 controls at six centers across the country, the researchers found that adding carbohydrate antigen 19-9 — a well-known marker of pancreatic cancer — to the assay boosted the test’s accuracy to 97%.
The test performed the same whether the tumor was in the head or tail of the pancreas.
“We are very excited about this data,” said Dr. Goel.
The technology was recently licensed to Pharus Diagnostics for commercial development, which will likely include a prospective screening trial, he told this news organization.
Because pancreatic cancer is fairly uncommon, Dr. Goel did not anticipate the test being used for general screening but rather for screening high-risk patients such as those with newly diagnosed type 2 diabetes, a family history of pancreatic cancer, or predisposing genetic mutations.
“It should be a very inexpensive test; it doesn’t cost us much to do in the lab,” he added.
Study moderator Ryan Corcoran, MD, PhD, a gastrointestinal (GI) oncologist at Massachusetts General Hospital, Boston, saw the potential.
“As a GI oncologist, I know how lethal and hard to treat pancreatic cancer is,” he said. A test that could reliably detect pancreatic cancer early, with an acceptable false-positive rate, would be extremely useful.
“The cure rate is many, many times higher,” if we detect it before it has a chance to spread, he explained.
In the meantime, Dr. Goel said there’s more work to be done.
Almost 4,000 subjects have been enrolled in ongoing validation efforts, and efforts are underway to use the test to screen thousands of banked blood samples from the PLCO, a prospective cancer screening trial in healthy subjects.
The researchers also want to see if the test can distinguish benign pancreatic cysts from ones that turn cancerous.
The idea is to find the earliest possible signs of this disease to see if we can find it not “at the moment of clinical diagnosis, but possibly 6 months, 1 year, 2 years earlier” than with radiologic imaging, Dr. Goel said.
The work was funded by the National Cancer Institute and others. Dr. Goel is a consultant for Pharus Diagnostics and Cellomics. Dr. Corcoran is a consultant for, has grants from, and/or holds stock in numerous companies, including Pfizer, Novartis, Eli Lilly, and Revolution Medicines.
A version of this article appeared on Medscape.com.
FROM AACR 2024
Do Organophosphate Esters Increase Thyroid Disease Risk?
TOPLINE:
, bis(2-chloroethyl) phosphate (BCEP) being the main contributor.
METHODOLOGY:
- Prior studies have reported that OPEs — used in building materials, electronic products, furniture, and textiles — may interfere with thyroid function, hinting at a possible association of OPEs with thyroid disease.
- Researchers assessed the association between OPE exposure and the risk for thyroid disease using data from the 2011-2014 US National Health and Nutrition Examination Survey cycle.
- They included 2449 participants (mean age, 46 years; half of whom were women) who had complete values for seven OPE metabolites through urinalysis and completed questionnaires regarding the presence of thyroid disease.
- The seven OPE metabolites assessed in this study were diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, BCEP, dibutyl phosphate, dibenzyl phosphate, and 2,3,4,5-tetrabromobenzoic acid.
- Several mixed exposure models were used to investigate the associations between the risk for thyroid disease and exposure to individual and mixed OPEs.
TAKEAWAY:
- A history of thyroid disease was self-reported by 228 participants.
- In one model, the risk for thyroid disease was 57% higher in people in the highest vs the lowest tertile of BCEP exposure (P = .005).
- A newer method confirmed the positive association between exposure to mixed OPE metabolites and a higher risk for thyroid disease (odds ratio, 1.03; P = .013), with BCEP (65%) being the main contributing factor, followed by DPHP (35%).
- A model from another new method showed a J-shaped relationship between the risk for thyroid disease and increasing levels of BCEP exposure, in which the risk first dropped but then rose with increasing exposure.
IN PRACTICE:
“The three models in our study provided similar results, with exposure to mixed OPEs having a tendency to increase the risk of thyroid disease and pointing to BCEP as the most significant compound responsible for this trend,” wrote the authors.
SOURCE:
This study was led by Yuxin Lin, from the Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China, and published online in Frontiers in Endocrinology.
LIMITATIONS:
The cross-sectional design cannot establish a causal relationship between OPE exposure and thyroid disease. The study used unweighted data, which could have limited the generalizability of the findings. Moreover, urine sample measurements were performed only once.
DISCLOSURES:
The study was supported by the Fujian Natural Science Foundation Program and the Scientific Research Program of High-level Talents of Fujian Medical University. The authors declared no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
, bis(2-chloroethyl) phosphate (BCEP) being the main contributor.
METHODOLOGY:
- Prior studies have reported that OPEs — used in building materials, electronic products, furniture, and textiles — may interfere with thyroid function, hinting at a possible association of OPEs with thyroid disease.
- Researchers assessed the association between OPE exposure and the risk for thyroid disease using data from the 2011-2014 US National Health and Nutrition Examination Survey cycle.
- They included 2449 participants (mean age, 46 years; half of whom were women) who had complete values for seven OPE metabolites through urinalysis and completed questionnaires regarding the presence of thyroid disease.
- The seven OPE metabolites assessed in this study were diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, BCEP, dibutyl phosphate, dibenzyl phosphate, and 2,3,4,5-tetrabromobenzoic acid.
- Several mixed exposure models were used to investigate the associations between the risk for thyroid disease and exposure to individual and mixed OPEs.
TAKEAWAY:
- A history of thyroid disease was self-reported by 228 participants.
- In one model, the risk for thyroid disease was 57% higher in people in the highest vs the lowest tertile of BCEP exposure (P = .005).
- A newer method confirmed the positive association between exposure to mixed OPE metabolites and a higher risk for thyroid disease (odds ratio, 1.03; P = .013), with BCEP (65%) being the main contributing factor, followed by DPHP (35%).
- A model from another new method showed a J-shaped relationship between the risk for thyroid disease and increasing levels of BCEP exposure, in which the risk first dropped but then rose with increasing exposure.
IN PRACTICE:
“The three models in our study provided similar results, with exposure to mixed OPEs having a tendency to increase the risk of thyroid disease and pointing to BCEP as the most significant compound responsible for this trend,” wrote the authors.
SOURCE:
This study was led by Yuxin Lin, from the Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China, and published online in Frontiers in Endocrinology.
LIMITATIONS:
The cross-sectional design cannot establish a causal relationship between OPE exposure and thyroid disease. The study used unweighted data, which could have limited the generalizability of the findings. Moreover, urine sample measurements were performed only once.
DISCLOSURES:
The study was supported by the Fujian Natural Science Foundation Program and the Scientific Research Program of High-level Talents of Fujian Medical University. The authors declared no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
, bis(2-chloroethyl) phosphate (BCEP) being the main contributor.
METHODOLOGY:
- Prior studies have reported that OPEs — used in building materials, electronic products, furniture, and textiles — may interfere with thyroid function, hinting at a possible association of OPEs with thyroid disease.
- Researchers assessed the association between OPE exposure and the risk for thyroid disease using data from the 2011-2014 US National Health and Nutrition Examination Survey cycle.
- They included 2449 participants (mean age, 46 years; half of whom were women) who had complete values for seven OPE metabolites through urinalysis and completed questionnaires regarding the presence of thyroid disease.
- The seven OPE metabolites assessed in this study were diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate, bis(1-chloro-2-propyl) phosphate, BCEP, dibutyl phosphate, dibenzyl phosphate, and 2,3,4,5-tetrabromobenzoic acid.
- Several mixed exposure models were used to investigate the associations between the risk for thyroid disease and exposure to individual and mixed OPEs.
TAKEAWAY:
- A history of thyroid disease was self-reported by 228 participants.
- In one model, the risk for thyroid disease was 57% higher in people in the highest vs the lowest tertile of BCEP exposure (P = .005).
- A newer method confirmed the positive association between exposure to mixed OPE metabolites and a higher risk for thyroid disease (odds ratio, 1.03; P = .013), with BCEP (65%) being the main contributing factor, followed by DPHP (35%).
- A model from another new method showed a J-shaped relationship between the risk for thyroid disease and increasing levels of BCEP exposure, in which the risk first dropped but then rose with increasing exposure.
IN PRACTICE:
“The three models in our study provided similar results, with exposure to mixed OPEs having a tendency to increase the risk of thyroid disease and pointing to BCEP as the most significant compound responsible for this trend,” wrote the authors.
SOURCE:
This study was led by Yuxin Lin, from the Department of Epidemiology and Health Statistics, School of Public Health, Fujian Medical University, Fuzhou, China, and published online in Frontiers in Endocrinology.
LIMITATIONS:
The cross-sectional design cannot establish a causal relationship between OPE exposure and thyroid disease. The study used unweighted data, which could have limited the generalizability of the findings. Moreover, urine sample measurements were performed only once.
DISCLOSURES:
The study was supported by the Fujian Natural Science Foundation Program and the Scientific Research Program of High-level Talents of Fujian Medical University. The authors declared no potential conflicts of interest.
A version of this article first appeared on Medscape.com.
Is Adrenal Fatigue a Real Condition?
While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”
Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.
“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.
Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress.
Adrenal Fatigue, Burnout, or Adrenal Insufficiency?
Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”
Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.
More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.
He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.
“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.
The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.
“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.
Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.
“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said.
This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.
While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.
“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.
Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.
“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”
Recognizing and Managing Patient Frustration
The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.
Dr. Rao empathizes with the situation that many people, often young women, find themselves in.
“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”
This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.
But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.
“We truly are what we eat, and we are what we think,” she noted.
The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.”
“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”
Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.
“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”
Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.
A version of this article appeared on Medscape.com.
While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”
Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.
“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.
Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress.
Adrenal Fatigue, Burnout, or Adrenal Insufficiency?
Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”
Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.
More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.
He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.
“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.
The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.
“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.
Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.
“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said.
This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.
While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.
“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.
Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.
“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”
Recognizing and Managing Patient Frustration
The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.
Dr. Rao empathizes with the situation that many people, often young women, find themselves in.
“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”
This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.
But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.
“We truly are what we eat, and we are what we think,” she noted.
The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.”
“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”
Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.
“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”
Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.
A version of this article appeared on Medscape.com.
While TikTok overflows with images of influencers making “adrenal cocktails” to combat what they call adrenal fatigue, the Endocrine Society says “no scientific proof exists to support adrenal fatigue as a true medical condition.”
Even before influencers began touting it on social media, a 2016 systematic review concluded that there is “no substantiation that adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
Lynette Nieman, MD, Senior Investigator and Chief of the Endocrinology Consultation Service at the National Institutes of Health Clinical Center, Bethesda, Maryland, concurs.
“There is no scientific evidence that adrenal fatigue exists or causes [general] fatigue, depression, or the many common symptoms that are said to result from this condition,” she told this news organization via email.
Still, the term has gained currency among not only social media influencers who blame it for everything from cortisol surges to estrogen imbalances but also functional and integrative medical practitioners as an explanation for chronic dysfunction related to stress.
Adrenal Fatigue, Burnout, or Adrenal Insufficiency?
Rather than “adrenal fatigue,” Marcelo Campos, MD, a primary care doctor at Atrius Health, said he prefers the medical term “burnout.”
Use of “burnout” shifts attention to the brain’s role in stress-related chronic dysfunction rather than the adrenal glands, said Dr. Campos, who also teaches at Harvard Medical School, Cambridge, Massachusetts.
More specifically still, the focuses might shift to the stress-response via the hypothalamic-pituitary-adrenocortical axis and its role in reducing levels of these cortisol and dehydroepiandrosterone sulfate.
He points out that part of the reason for the misuse of the term adrenal fatigue arises from the fact that burnout is often only associated with work stress.
“Recently, the ICD-11 [International Classification of Diseases-11] recognized burnout as a disease but focused only on work stress as a cause. The truth is that people can be burned out for many other reasons,” said Dr. Campos.
The Endocrine Society notes on their webpage dedicated to the topic that “adrenal fatigue” as a term, relates to long-term mental, emotional, or physical stress.
“The problem is not the adrenals — it is the exposure to stress in the brain. The brain — only one organ — is responsible for 40% of energy consumption in the body. As you can imagine, if you are under constant stress, you run out of gas very quickly and cannot function well,” he explained.
Adrenal fatigue theory suggests that, under stress, the adrenal glands produce too many short bursts of cortisol resulting in overall reduced cortisol levels and a feeling of being drained.
“As with many other psychiatric diseases, we do not have a way to measure biomarkers in the brain. The testing for cortisol does not work because it fluctuates too much from time to time. So, it is not reliable or reproducible,” Dr. Campos said.
This leads to the ongoing question of the best way to test and diagnose adrenal fatigue, whether it should be via blood, urine and/or saliva. And even if that is determined, there are still questions about the best time to test, how often, what the normal ranges are and how reliable the tests are.
While adrenal fatigue is not a recognized condition, adrenal insufficiency is medically recognized, resulting from an inability of the adrenal glands to make the life-essential hormones aldosterone and/or cortisol, with symptoms that include fatigue, belly pain, nausea, vomiting, diarrhea, and joint aches.
“Adrenal cocktails are not an effective treatment for adrenal insufficiency because they do not replace the missing hormones,” Dr. Nieman stated, pointing out that anyone with symptoms of adrenal insufficiency needs to see an endocrinologist.
Pratibha Rao, MD, MPH, an endocrinologist at the Cleveland Clinic, Ohio, and medical director of the Adrenal Center at Cleveland Clinic, agreed, advising that if people continue to feel exhausted beyond their normal exertion, then they should get checked for signs of adrenal insufficiency.
“In primary adrenal insufficiency, you can actually start seeing darkening of the gums and of the skin on the palms of the hands or the soles of your feet. Sometimes people can feel dizzy or experience some loss of consciousness,” she said. “If it’s sudden and severe, you may crave salt or have extreme heat or cold intolerance.”
Recognizing and Managing Patient Frustration
The lack of formal diagnostic criteria and medical evidence, however, doesn’t mean that such symptoms as fatigue and depression don’t present, often causing significant distress for patients. While the symptoms might not be associated with the adrenal glands, they still need addressing — but how that is done is, in essence, a bone of contention.
Dr. Rao empathizes with the situation that many people, often young women, find themselves in.
“Patients are frustrated. They’ve gone to multiple doctors across the country, and they feel convinced they have adrenal fatigue, but no medical doctor has endorsed it. They end up coming to us with a cry that has so often gone unanswered.”
This issue also highlights that there are millions of people experiencing mental, emotional, and physical distress of unknown cause who seek help, many of whom believe it is related to their adrenal gland function.
But rather than turning to a social media cure, Dr. Rao stresses that people would benefit more from paying greater attention to following a healthy lifestyle than regularly consuming sugar-rich drinks claimed to offer a solution. Adrenal cocktails are energy-rich, frothy blends of orange juice, coconut milk, cream of tartar, and Himalayan salt.
“We truly are what we eat, and we are what we think,” she noted.
The body is a miraculous machine, but “we forget that it does need maintenance,” Dr. Rao said. “Up to age 30, the body is so forgiving with drugs, alcohol, or whatever insult we do to it, but after the third decade, slowly every cell starts to degenerate instead of growing. We start to see the ill or beneficial effects of lifestyle habits.”
“We insult the body, and then we say, ‘oh, I have fatigue’ and seek a quick fix,” she added. “Everyone wants instant gratification.”
Dr. Rao cautioned that adrenal cocktails could be dangerous for someone who has other medical conditions.
“If someone has kidney disease, uncontrolled hypertension, or diabetes, for example, then adrenal cocktails are definitely not safe,” Dr. Rao said. “Loading up with potassium and sodium, which is found in high quantities in adrenal cocktails, will actually worsen any kidney damage, while consuming so much sugar will cause an unregulated rise in blood sugar and further damage in someone with diabetes.”
Dr. Rao also stressed that nonprofessional advice given on social media could take patient people down the wrong path with associated danger.
A version of this article appeared on Medscape.com.
Thyroid Disorders and Gynecologic Cancers: Is There a Link?
TOPLINE:
METHODOLOGY:
- Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
- This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
- Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
- The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.
TAKEAWAY:
- Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
- The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
- The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
- A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.
IN PRACTICE:
The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.
SOURCE:
This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.
LIMITATIONS:
The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.
DISCLOSURES:
This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
- This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
- Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
- The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.
TAKEAWAY:
- Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
- The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
- The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
- A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.
IN PRACTICE:
The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.
SOURCE:
This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.
LIMITATIONS:
The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.
DISCLOSURES:
This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.
A version of this article appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- Thyroid disease and altered thyroid hormone expression can affect ovulation, endometrial physiology, and estrogen levels, but studies of the association with gynecologic cancer risk have conflicting results.
- This population-based cohort study used data from the Taiwan National Health Insurance Research Database to identify women (mean age, 44 years) who were diagnosed with thyroid disease between January 2000 and December 2018.
- Propensity scores were used to pair 296,872 women with hyperthyroidism and 44,852 with hypothyroidism in a 1:1 ratio with an equal number of individuals without thyroid disorders.
- The cohort was followed up from the date of first diagnosis of hypothyroidism or hyperthyroidism until the diagnosis of gynecologic cancers (endometrial cancer, uterine corpus cancer, and ovarian cancer), death, or the end of 2018.
TAKEAWAY:
- Women with hyperthyroidism had a lower risk for all gynecologic cancers than those without hyperthyroidism (adjusted hazard ratio [aHR], 0.86; P = .0084).
- The risk of developing gynecologic cancer was lower among women with hyperthyroidism aged 20-40 years (aHR, 0.72; P = .0043) but not among those aged > 40 years.
- The reduced risk for gynecologic cancers associated with hyperthyroidism persisted even beyond 6 years of follow-up (aHR, 0.75; P < .001).
- A trend toward a slightly increased risk for gynecologic cancer was observed among women with hypothyroidism; however, the association was not statistically significant.
IN PRACTICE:
The findings may alert oncologists and healthcare decision-makers toward gynecologic cancer trends and prompt further research to understand the mechanism by which thyroid hormone regulates reproductive function, the authors noted.
SOURCE:
This study was led by John Hang Leung from the Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan, and published online in Scientific Reports.
LIMITATIONS:
The study data were obtained from administrative claims databases, so there is a possibility of underestimation or overestimation. Lifestyle factors such as obesity and alcoholism are difficult to measure, so the risk for gynecologic cancers linked to thyroid dysfunction may have been underestimated. Furthermore, because of nonavailability of laboratory data, thyroid hormone status at diagnosis could not be linked to gynecological cancer risk.
DISCLOSURES:
This study was supported by An-Nan Hospital, China Medical University, Tainan, Taiwan. The authors declared no financial interests or conflicts related to the study.
A version of this article appeared on Medscape.com.