The Journal of Family Practice

Subclinical hypothyroidism (SCH) is a biochemical state in which the thyroid-stimulating hormone (TSH) is elevated while the free thyroxine (T4) level is normal. Overt hypothyroidism is not diagnosed until the free T4 level is decreased, regardless of the degree of TSH elevation.

The overall prevalence of SCH in iodine-rich areas is 4% to 10%, with a risk for progression to overt hypothyroidism of between 2% and 6% annually.¹ The prevalence of SCH varies depending on the TSH reference range used.¹ The normal reference range for TSH varies depending on the laboratory and/or the reference population surveyed, with the range likely widening with increasing age.

SCH is most common among women, the elderly, and White individuals.² The discovery of SCH is often incidental, given that usually it is detected by laboratory findings alone without associated symptoms of overt hypothyroidism.³

The not-so-significant role of symptoms in subclinical hypothyroidism

Symptoms associated with overt hypothyroidism include constipation, dry skin, fatigue, slow thinking, poor memory, muscle cramps, weakness, and cold intolerance. In SCH, these symptoms are inconsistent, with around 1 in 3 patients having no symptoms at all.⁴

One study reported that roughly 18% of euthyroid individuals, 22% of SCH patients, and 26% of those with overt hypothyroidism reported 4 or more symptoms classically thought to be related to hypothyroidism.⁴ A large Danish cohort study found that hypothyroid symptoms were no more common in patients with SCH than in euthyroid individuals in the general population.⁵ These studies question the validity of attributing symptoms to SCH.

Adverse health associations

Observational data suggest that SCH is associated with an increased risk for dyslipidemia, coronary heart disease, heart failure, and cardiovascular mortality, particularly in those with TSH levels ≥ 10 mIU/L.^6,7 Such associations were not found for most adults with TSH levels between 5 and 10 mIU/L.⁸ There are also potential associations of SCH with obesity, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.^9,10 Despite thyroid studies being commonly ordered as part of a mental health evaluation, SCH has not been statistically associated with depressive symptoms.^11,12

Caveats with laboratory testing

There are several issues to consider when performing a laboratory assessment of thyroid function. TSH levels fluctuate considerably during the day, as TSH secretion has a circadian rhythm. TSH values are 50% higher at night and in the early morning than during the rest of the day.¹³ TSH values also may rise in response to current illness or stress. Due to this biologic variability, repeat testing to confirm TSH levels is recommended if an initial test result is abnormal.¹⁴

Continue to: An exact reference range...

Supplements containing biotin should be withheld for several days before assessing thyroid function.

An exact reference range for TSH is not widely agreed upon—although most laboratories regard 4.0 to 5.0 mIU/L as the high-end cutoff for normal. Also, “normal” TSH levels appear to differ by age. Accordingly, some experts have recommended an age-based reference range for TSH levels,¹⁵ although this is not implemented widely by laboratories. A TSH level of 6.0 mIU/L (or even higher) may be more appropriate for adults older than 65 years.¹

Biotin supplementation has been shown to cause spurious thyroid testing results (TSH, T3, T4) depending on the type of assay used. Therefore, supplements containing biotin should be withheld for several days before assessing thyroid function.¹⁶Patients with SCH are often categorized as having TSH levels between 4.5 and 10 mIU/L (around 90% of patients) or levels ≥ 10 mIU/L.^8,17 If followed for 5 years, approximately 60% of patients with SCH and TSH levels between 4 and 10 mIU/L will normalize without intervention.¹⁸ Normalization is less common in patients with a TSH level greater than 10 mIU/L.¹⁸

The risk for progression to overt hypothyroidism also appears to be higher for those with certain risk factors. These include higher baseline TSH levels, presence of thyroid peroxidase antibodies (TPOAbs), or history of neck irradiation or radioactive iodine uptake.¹ Other risk factors for eventual thyroid dysfunction include female sex, older age, goiter, and high iodine intake.¹³

Evidence for treatment varies

Guidelines for the treatment of SCH (TABLE 1^8,14,19,20) are founded on the condition’s risk for progression to overt hypothyroidism and its association with health consequences such as cardiovascular disease. Guidelines of the American Thyroid Association (ATA) and European Thyroid Association (ETA), and those of the United Kingdom–based National Institute for Health and Care Excellence (NICE), prioritize treatment for individuals with a TSH level > 10 mIU/L^a and for those with TSH values < 10 mIU/L but still elevated and apparent symptoms of hypothyroidism.^14,19,20 The strength of evidence behind this guidance is challenged by a lack of data from prospective randomized controlled trials (RCTs) demonstrating health benefits following treatment of SCH. The British Medical Journal (BMJ) Guideline cites this lack of evidence and recommends against treating SCH at any TSH level, regardless of symptoms.⁸

There are few large RCTs of treatment outcomes for SCH. A 2017 RCT (the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism, or TRUST, trial) of 737 adults older than 65 years with SCH evaluated the ability of levothyroxine to normalize TSH values compared with placebo. At 1 year, there was no difference in hypothyroid symptoms or tiredness scale scores with levothyroxine treatment compared with placebo.²¹ This finding was consistent even in the subgroup with a higher baseline symptom burden.²²

Continue to: Two small RCTs evaluated...

Two small RCTs evaluated treatment of SCH with depressive symptoms and cognitive function, neither finding benefit compared with placebo.^12,23 A 2018 systematic review and meta-analysis of 21 studies and 2192 adults did not show a benefit to quality of life or thyroid-specific symptoms in those treated for SCH compared with controls.²⁴

RCT support also is lacking for a reduction in cardiovascular mortality following treatment for SCH. A large population-level retrospective cohort from Denmark showed no difference in cardiovascular mortality or myocardial infarction in those treated for SCH compared with controls.²⁵ Pooled results from 2 RCTs (for patients older than 65 years, and those older than 80 years) showed no change in risk for cardiovascular outcomes in older adults treated for SCH.²⁶ Older adults treated for SCH in the TRUST trial showed no improvements in systolic or diastolic­ function on echocardiography.^27­ Two trials showed no difference in carotid intima-media thickness with treatment of SCH compared with placebo.^28,29

While most of the RCT data come from older adults, a retrospective cohort study in the United Kingdom of younger (ages 40-70 years; n = 3093) and older (age > 70 years; n = 1642) patients showed a reduction in cardiovascular mortality among treated patients who were younger (hazard ratio [HR] = 0.61; 4.2% vs. 6.6%) but not those who were older (HR = 0.99; 12.7% vs. 10.7%).³⁰ There is also evidence that thyroid size in those with goiter can be reduced with treatment of SCH.³¹

A measured approach to treating subclinical hypothyroidism

Consider several factors when deciding whether to treat SCH. For instance, RCT data suggest a lack of treatment benefit in relieving depression, improving cognition, or reducing general hypothyroid symptoms. Treatment of SCH in older adults does not appear to improve cardiovascular outcomes. The question of whether long-term treatment of SCH in younger patients reduces cardiovascular morbidity or mortality lacks answers from RCTs. Before diagnosing SCH or starting treatment, always confirm SCH with repeat testing in 2 to 3 months, as a high percentage of those with untreated SCH will have normal thyroid function on repeat testing.

Before diagnosing subclinical hypothyroidism (SCH) or starting treatment, always confirm SCH with repeat testing in 2 to 3 months.

In the event you and your patient elect to treat SCH, guidelines and trials generally support a low initial daily dose of 25 to 50 mcg of levothyroxine (T4), followed with dose changes­ every 4 to 8 weeks and a goal of normalizing TSH to within the lower half of the reference range (0.4-2.5 mIU/L).¹⁴ This is generally similar to published treatment goals for primary hypothyroidism and is based on studies suggesting the lower half of the reference range is normal for young, healthy, euthyroid individuals.³² Though full replacement doses (1.6-1.8 mcg/kg of ideal body weight) can be started for those who are elderly or who have ischemic heart disease or angina, this approach should be avoided in favor of low-dose initial therapy.³³ Thyroid supplements are best absorbed when taken apart from food, calcium, or iron supplements. The ATA suggests taking thyroid medication 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal).³³

Continue to: Screening guidelines differ

Lacking population-level screening data from RCTs, most organizations do not recommend screening for thyroid dysfunction or they note insufficient evidence to make a screening recommendation (TABLE 2^17,19,20,34). In their most recent recommendation statement on the subject in 2015, the US Preventive Services Task Force (USPSTF) concluded the current evidence was insufficient to recommend for or against thyroid dysfunction screening in nonpregnant, asymptomatic adults.¹⁷ This differs from the ATA and the American Association of Clinical Endocrinology (AACE; formerly known as the American Association of Clinical Endocrinologists), which both recommend targeted screening for thyroid dysfunction based on symptoms or risk factors.²⁰

What about subclinical hypothyroidism in pregnancy?

Overt hypothyroidism is associated with adverse events during pregnancy and with subsequent neurodevelopmental complications in children, although the effects of SCH during pregnancy remain less certain. Concerns have been raised over the potential association of SCH with pregnancy loss, placental abruption, premature rupture of membranes, and neonatal death.³⁵ Historically, the prevalence of SCH during pregnancy has ranged from 2% to 2.5%, but using lower trimester-based TSH reference ranges, the prevalence of SCH in pregnancy may be as high as 15%.³⁵

Guided by a large RCT that failed to find benefit (pregnancy outcomes, neurodevelopmental outcomes in children) following treatment of SCH in pregnancy,³⁶ the American College of Obstetricians and Gynecologists (ACOG) recommends against routine screening for thyroid disease in pregnancy.³⁴ The ATA notes insufficient evidence to rec-ommend universal screening for thyroid dysfunction in pregnancy but recommends targeted screening of those with risk factors.³⁷ Data are conflicting on the benefit of treating known or recently detected SCH on pregnancy outcomes including pregnancy loss.^35,38 As such, the American Society of Reproductive Medicine and the ATA both generally recommend treatment of SCH in pregnant patients, particularly when the TSH is ≥ 4.0 mIU/L and TPOAbs are present.^37,39

^a The ATA, ETA, and NICE have slightly different recommendations when a TSH level = 10 mIU/L. ETA and NICE recommend prioritizing treatment for individuals with this level, while ATA recommends treatment when individual factors are also considered.

ACKNOWLEDGEMENT
The authors thank Family Medicine Medical Librarian Gwen Wilson, MLS, AHIP, for her assistance with literature searches.

CORRESPONDENCE
Nicholas LeFevre, MD, Family and Community Medicine, University of Missouri–Columbia School of Medicine, One Hospital Drive, M224 Medical Science Building, Columbia, MO 65212; [email protected]

Subclinical hypothyroidism (SCH) is a biochemical state in which the thyroid-stimulating hormone (TSH) is elevated while the free thyroxine (T4) level is normal. Overt hypothyroidism is not diagnosed until the free T4 level is decreased, regardless of the degree of TSH elevation.

The overall prevalence of SCH in iodine-rich areas is 4% to 10%, with a risk for progression to overt hypothyroidism of between 2% and 6% annually.¹ The prevalence of SCH varies depending on the TSH reference range used.¹ The normal reference range for TSH varies depending on the laboratory and/or the reference population surveyed, with the range likely widening with increasing age.

SCH is most common among women, the elderly, and White individuals.² The discovery of SCH is often incidental, given that usually it is detected by laboratory findings alone without associated symptoms of overt hypothyroidism.³

The not-so-significant role of symptoms in subclinical hypothyroidism

Symptoms associated with overt hypothyroidism include constipation, dry skin, fatigue, slow thinking, poor memory, muscle cramps, weakness, and cold intolerance. In SCH, these symptoms are inconsistent, with around 1 in 3 patients having no symptoms at all.⁴

One study reported that roughly 18% of euthyroid individuals, 22% of SCH patients, and 26% of those with overt hypothyroidism reported 4 or more symptoms classically thought to be related to hypothyroidism.⁴ A large Danish cohort study found that hypothyroid symptoms were no more common in patients with SCH than in euthyroid individuals in the general population.⁵ These studies question the validity of attributing symptoms to SCH.

Adverse health associations

Observational data suggest that SCH is associated with an increased risk for dyslipidemia, coronary heart disease, heart failure, and cardiovascular mortality, particularly in those with TSH levels ≥ 10 mIU/L.^6,7 Such associations were not found for most adults with TSH levels between 5 and 10 mIU/L.⁸ There are also potential associations of SCH with obesity, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.^9,10 Despite thyroid studies being commonly ordered as part of a mental health evaluation, SCH has not been statistically associated with depressive symptoms.^11,12

Caveats with laboratory testing

There are several issues to consider when performing a laboratory assessment of thyroid function. TSH levels fluctuate considerably during the day, as TSH secretion has a circadian rhythm. TSH values are 50% higher at night and in the early morning than during the rest of the day.¹³ TSH values also may rise in response to current illness or stress. Due to this biologic variability, repeat testing to confirm TSH levels is recommended if an initial test result is abnormal.¹⁴

Continue to: An exact reference range...

Supplements containing biotin should be withheld for several days before assessing thyroid function.

An exact reference range for TSH is not widely agreed upon—although most laboratories regard 4.0 to 5.0 mIU/L as the high-end cutoff for normal. Also, “normal” TSH levels appear to differ by age. Accordingly, some experts have recommended an age-based reference range for TSH levels,¹⁵ although this is not implemented widely by laboratories. A TSH level of 6.0 mIU/L (or even higher) may be more appropriate for adults older than 65 years.¹

Biotin supplementation has been shown to cause spurious thyroid testing results (TSH, T3, T4) depending on the type of assay used. Therefore, supplements containing biotin should be withheld for several days before assessing thyroid function.¹⁶Patients with SCH are often categorized as having TSH levels between 4.5 and 10 mIU/L (around 90% of patients) or levels ≥ 10 mIU/L.^8,17 If followed for 5 years, approximately 60% of patients with SCH and TSH levels between 4 and 10 mIU/L will normalize without intervention.¹⁸ Normalization is less common in patients with a TSH level greater than 10 mIU/L.¹⁸

The risk for progression to overt hypothyroidism also appears to be higher for those with certain risk factors. These include higher baseline TSH levels, presence of thyroid peroxidase antibodies (TPOAbs), or history of neck irradiation or radioactive iodine uptake.¹ Other risk factors for eventual thyroid dysfunction include female sex, older age, goiter, and high iodine intake.¹³

Evidence for treatment varies

Guidelines for the treatment of SCH (TABLE 1^8,14,19,20) are founded on the condition’s risk for progression to overt hypothyroidism and its association with health consequences such as cardiovascular disease. Guidelines of the American Thyroid Association (ATA) and European Thyroid Association (ETA), and those of the United Kingdom–based National Institute for Health and Care Excellence (NICE), prioritize treatment for individuals with a TSH level > 10 mIU/L^a and for those with TSH values < 10 mIU/L but still elevated and apparent symptoms of hypothyroidism.^14,19,20 The strength of evidence behind this guidance is challenged by a lack of data from prospective randomized controlled trials (RCTs) demonstrating health benefits following treatment of SCH. The British Medical Journal (BMJ) Guideline cites this lack of evidence and recommends against treating SCH at any TSH level, regardless of symptoms.⁸

There are few large RCTs of treatment outcomes for SCH. A 2017 RCT (the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism, or TRUST, trial) of 737 adults older than 65 years with SCH evaluated the ability of levothyroxine to normalize TSH values compared with placebo. At 1 year, there was no difference in hypothyroid symptoms or tiredness scale scores with levothyroxine treatment compared with placebo.²¹ This finding was consistent even in the subgroup with a higher baseline symptom burden.²²

Continue to: Two small RCTs evaluated...

Two small RCTs evaluated treatment of SCH with depressive symptoms and cognitive function, neither finding benefit compared with placebo.^12,23 A 2018 systematic review and meta-analysis of 21 studies and 2192 adults did not show a benefit to quality of life or thyroid-specific symptoms in those treated for SCH compared with controls.²⁴

RCT support also is lacking for a reduction in cardiovascular mortality following treatment for SCH. A large population-level retrospective cohort from Denmark showed no difference in cardiovascular mortality or myocardial infarction in those treated for SCH compared with controls.²⁵ Pooled results from 2 RCTs (for patients older than 65 years, and those older than 80 years) showed no change in risk for cardiovascular outcomes in older adults treated for SCH.²⁶ Older adults treated for SCH in the TRUST trial showed no improvements in systolic or diastolic­ function on echocardiography.^27­ Two trials showed no difference in carotid intima-media thickness with treatment of SCH compared with placebo.^28,29

While most of the RCT data come from older adults, a retrospective cohort study in the United Kingdom of younger (ages 40-70 years; n = 3093) and older (age > 70 years; n = 1642) patients showed a reduction in cardiovascular mortality among treated patients who were younger (hazard ratio [HR] = 0.61; 4.2% vs. 6.6%) but not those who were older (HR = 0.99; 12.7% vs. 10.7%).³⁰ There is also evidence that thyroid size in those with goiter can be reduced with treatment of SCH.³¹

A measured approach to treating subclinical hypothyroidism

Consider several factors when deciding whether to treat SCH. For instance, RCT data suggest a lack of treatment benefit in relieving depression, improving cognition, or reducing general hypothyroid symptoms. Treatment of SCH in older adults does not appear to improve cardiovascular outcomes. The question of whether long-term treatment of SCH in younger patients reduces cardiovascular morbidity or mortality lacks answers from RCTs. Before diagnosing SCH or starting treatment, always confirm SCH with repeat testing in 2 to 3 months, as a high percentage of those with untreated SCH will have normal thyroid function on repeat testing.

Before diagnosing subclinical hypothyroidism (SCH) or starting treatment, always confirm SCH with repeat testing in 2 to 3 months.

In the event you and your patient elect to treat SCH, guidelines and trials generally support a low initial daily dose of 25 to 50 mcg of levothyroxine (T4), followed with dose changes­ every 4 to 8 weeks and a goal of normalizing TSH to within the lower half of the reference range (0.4-2.5 mIU/L).¹⁴ This is generally similar to published treatment goals for primary hypothyroidism and is based on studies suggesting the lower half of the reference range is normal for young, healthy, euthyroid individuals.³² Though full replacement doses (1.6-1.8 mcg/kg of ideal body weight) can be started for those who are elderly or who have ischemic heart disease or angina, this approach should be avoided in favor of low-dose initial therapy.³³ Thyroid supplements are best absorbed when taken apart from food, calcium, or iron supplements. The ATA suggests taking thyroid medication 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal).³³

Continue to: Screening guidelines differ

Lacking population-level screening data from RCTs, most organizations do not recommend screening for thyroid dysfunction or they note insufficient evidence to make a screening recommendation (TABLE 2^17,19,20,34). In their most recent recommendation statement on the subject in 2015, the US Preventive Services Task Force (USPSTF) concluded the current evidence was insufficient to recommend for or against thyroid dysfunction screening in nonpregnant, asymptomatic adults.¹⁷ This differs from the ATA and the American Association of Clinical Endocrinology (AACE; formerly known as the American Association of Clinical Endocrinologists), which both recommend targeted screening for thyroid dysfunction based on symptoms or risk factors.²⁰

What about subclinical hypothyroidism in pregnancy?

Overt hypothyroidism is associated with adverse events during pregnancy and with subsequent neurodevelopmental complications in children, although the effects of SCH during pregnancy remain less certain. Concerns have been raised over the potential association of SCH with pregnancy loss, placental abruption, premature rupture of membranes, and neonatal death.³⁵ Historically, the prevalence of SCH during pregnancy has ranged from 2% to 2.5%, but using lower trimester-based TSH reference ranges, the prevalence of SCH in pregnancy may be as high as 15%.³⁵

Guided by a large RCT that failed to find benefit (pregnancy outcomes, neurodevelopmental outcomes in children) following treatment of SCH in pregnancy,³⁶ the American College of Obstetricians and Gynecologists (ACOG) recommends against routine screening for thyroid disease in pregnancy.³⁴ The ATA notes insufficient evidence to rec-ommend universal screening for thyroid dysfunction in pregnancy but recommends targeted screening of those with risk factors.³⁷ Data are conflicting on the benefit of treating known or recently detected SCH on pregnancy outcomes including pregnancy loss.^35,38 As such, the American Society of Reproductive Medicine and the ATA both generally recommend treatment of SCH in pregnant patients, particularly when the TSH is ≥ 4.0 mIU/L and TPOAbs are present.^37,39

^a The ATA, ETA, and NICE have slightly different recommendations when a TSH level = 10 mIU/L. ETA and NICE recommend prioritizing treatment for individuals with this level, while ATA recommends treatment when individual factors are also considered.

ACKNOWLEDGEMENT
The authors thank Family Medicine Medical Librarian Gwen Wilson, MLS, AHIP, for her assistance with literature searches.

CORRESPONDENCE
Nicholas LeFevre, MD, Family and Community Medicine, University of Missouri–Columbia School of Medicine, One Hospital Drive, M224 Medical Science Building, Columbia, MO 65212; [email protected]

Subclinical hypothyroidism (SCH) is a biochemical state in which the thyroid-stimulating hormone (TSH) is elevated while the free thyroxine (T4) level is normal. Overt hypothyroidism is not diagnosed until the free T4 level is decreased, regardless of the degree of TSH elevation.

The overall prevalence of SCH in iodine-rich areas is 4% to 10%, with a risk for progression to overt hypothyroidism of between 2% and 6% annually.¹ The prevalence of SCH varies depending on the TSH reference range used.¹ The normal reference range for TSH varies depending on the laboratory and/or the reference population surveyed, with the range likely widening with increasing age.

SCH is most common among women, the elderly, and White individuals.² The discovery of SCH is often incidental, given that usually it is detected by laboratory findings alone without associated symptoms of overt hypothyroidism.³

The not-so-significant role of symptoms in subclinical hypothyroidism

Symptoms associated with overt hypothyroidism include constipation, dry skin, fatigue, slow thinking, poor memory, muscle cramps, weakness, and cold intolerance. In SCH, these symptoms are inconsistent, with around 1 in 3 patients having no symptoms at all.⁴

One study reported that roughly 18% of euthyroid individuals, 22% of SCH patients, and 26% of those with overt hypothyroidism reported 4 or more symptoms classically thought to be related to hypothyroidism.⁴ A large Danish cohort study found that hypothyroid symptoms were no more common in patients with SCH than in euthyroid individuals in the general population.⁵ These studies question the validity of attributing symptoms to SCH.

Adverse health associations

Observational data suggest that SCH is associated with an increased risk for dyslipidemia, coronary heart disease, heart failure, and cardiovascular mortality, particularly in those with TSH levels ≥ 10 mIU/L.^6,7 Such associations were not found for most adults with TSH levels between 5 and 10 mIU/L.⁸ There are also potential associations of SCH with obesity, nonalcoholic fatty liver disease, and nonalcoholic steatohepatitis.^9,10 Despite thyroid studies being commonly ordered as part of a mental health evaluation, SCH has not been statistically associated with depressive symptoms.^11,12

Caveats with laboratory testing

There are several issues to consider when performing a laboratory assessment of thyroid function. TSH levels fluctuate considerably during the day, as TSH secretion has a circadian rhythm. TSH values are 50% higher at night and in the early morning than during the rest of the day.¹³ TSH values also may rise in response to current illness or stress. Due to this biologic variability, repeat testing to confirm TSH levels is recommended if an initial test result is abnormal.¹⁴

Continue to: An exact reference range...

Supplements containing biotin should be withheld for several days before assessing thyroid function.

An exact reference range for TSH is not widely agreed upon—although most laboratories regard 4.0 to 5.0 mIU/L as the high-end cutoff for normal. Also, “normal” TSH levels appear to differ by age. Accordingly, some experts have recommended an age-based reference range for TSH levels,¹⁵ although this is not implemented widely by laboratories. A TSH level of 6.0 mIU/L (or even higher) may be more appropriate for adults older than 65 years.¹

Biotin supplementation has been shown to cause spurious thyroid testing results (TSH, T3, T4) depending on the type of assay used. Therefore, supplements containing biotin should be withheld for several days before assessing thyroid function.¹⁶Patients with SCH are often categorized as having TSH levels between 4.5 and 10 mIU/L (around 90% of patients) or levels ≥ 10 mIU/L.^8,17 If followed for 5 years, approximately 60% of patients with SCH and TSH levels between 4 and 10 mIU/L will normalize without intervention.¹⁸ Normalization is less common in patients with a TSH level greater than 10 mIU/L.¹⁸

The risk for progression to overt hypothyroidism also appears to be higher for those with certain risk factors. These include higher baseline TSH levels, presence of thyroid peroxidase antibodies (TPOAbs), or history of neck irradiation or radioactive iodine uptake.¹ Other risk factors for eventual thyroid dysfunction include female sex, older age, goiter, and high iodine intake.¹³

Evidence for treatment varies

Guidelines for the treatment of SCH (TABLE 1^8,14,19,20) are founded on the condition’s risk for progression to overt hypothyroidism and its association with health consequences such as cardiovascular disease. Guidelines of the American Thyroid Association (ATA) and European Thyroid Association (ETA), and those of the United Kingdom–based National Institute for Health and Care Excellence (NICE), prioritize treatment for individuals with a TSH level > 10 mIU/L^a and for those with TSH values < 10 mIU/L but still elevated and apparent symptoms of hypothyroidism.^14,19,20 The strength of evidence behind this guidance is challenged by a lack of data from prospective randomized controlled trials (RCTs) demonstrating health benefits following treatment of SCH. The British Medical Journal (BMJ) Guideline cites this lack of evidence and recommends against treating SCH at any TSH level, regardless of symptoms.⁸

There are few large RCTs of treatment outcomes for SCH. A 2017 RCT (the Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism, or TRUST, trial) of 737 adults older than 65 years with SCH evaluated the ability of levothyroxine to normalize TSH values compared with placebo. At 1 year, there was no difference in hypothyroid symptoms or tiredness scale scores with levothyroxine treatment compared with placebo.²¹ This finding was consistent even in the subgroup with a higher baseline symptom burden.²²

Continue to: Two small RCTs evaluated...

Two small RCTs evaluated treatment of SCH with depressive symptoms and cognitive function, neither finding benefit compared with placebo.^12,23 A 2018 systematic review and meta-analysis of 21 studies and 2192 adults did not show a benefit to quality of life or thyroid-specific symptoms in those treated for SCH compared with controls.²⁴

RCT support also is lacking for a reduction in cardiovascular mortality following treatment for SCH. A large population-level retrospective cohort from Denmark showed no difference in cardiovascular mortality or myocardial infarction in those treated for SCH compared with controls.²⁵ Pooled results from 2 RCTs (for patients older than 65 years, and those older than 80 years) showed no change in risk for cardiovascular outcomes in older adults treated for SCH.²⁶ Older adults treated for SCH in the TRUST trial showed no improvements in systolic or diastolic­ function on echocardiography.^27­ Two trials showed no difference in carotid intima-media thickness with treatment of SCH compared with placebo.^28,29

While most of the RCT data come from older adults, a retrospective cohort study in the United Kingdom of younger (ages 40-70 years; n = 3093) and older (age > 70 years; n = 1642) patients showed a reduction in cardiovascular mortality among treated patients who were younger (hazard ratio [HR] = 0.61; 4.2% vs. 6.6%) but not those who were older (HR = 0.99; 12.7% vs. 10.7%).³⁰ There is also evidence that thyroid size in those with goiter can be reduced with treatment of SCH.³¹

A measured approach to treating subclinical hypothyroidism

Consider several factors when deciding whether to treat SCH. For instance, RCT data suggest a lack of treatment benefit in relieving depression, improving cognition, or reducing general hypothyroid symptoms. Treatment of SCH in older adults does not appear to improve cardiovascular outcomes. The question of whether long-term treatment of SCH in younger patients reduces cardiovascular morbidity or mortality lacks answers from RCTs. Before diagnosing SCH or starting treatment, always confirm SCH with repeat testing in 2 to 3 months, as a high percentage of those with untreated SCH will have normal thyroid function on repeat testing.

Before diagnosing subclinical hypothyroidism (SCH) or starting treatment, always confirm SCH with repeat testing in 2 to 3 months.

In the event you and your patient elect to treat SCH, guidelines and trials generally support a low initial daily dose of 25 to 50 mcg of levothyroxine (T4), followed with dose changes­ every 4 to 8 weeks and a goal of normalizing TSH to within the lower half of the reference range (0.4-2.5 mIU/L).¹⁴ This is generally similar to published treatment goals for primary hypothyroidism and is based on studies suggesting the lower half of the reference range is normal for young, healthy, euthyroid individuals.³² Though full replacement doses (1.6-1.8 mcg/kg of ideal body weight) can be started for those who are elderly or who have ischemic heart disease or angina, this approach should be avoided in favor of low-dose initial therapy.³³ Thyroid supplements are best absorbed when taken apart from food, calcium, or iron supplements. The ATA suggests taking thyroid medication 60 minutes before breakfast or at bedtime (3 or more hours after the evening meal).³³

Continue to: Screening guidelines differ

Lacking population-level screening data from RCTs, most organizations do not recommend screening for thyroid dysfunction or they note insufficient evidence to make a screening recommendation (TABLE 2^17,19,20,34). In their most recent recommendation statement on the subject in 2015, the US Preventive Services Task Force (USPSTF) concluded the current evidence was insufficient to recommend for or against thyroid dysfunction screening in nonpregnant, asymptomatic adults.¹⁷ This differs from the ATA and the American Association of Clinical Endocrinology (AACE; formerly known as the American Association of Clinical Endocrinologists), which both recommend targeted screening for thyroid dysfunction based on symptoms or risk factors.²⁰

What about subclinical hypothyroidism in pregnancy?

Overt hypothyroidism is associated with adverse events during pregnancy and with subsequent neurodevelopmental complications in children, although the effects of SCH during pregnancy remain less certain. Concerns have been raised over the potential association of SCH with pregnancy loss, placental abruption, premature rupture of membranes, and neonatal death.³⁵ Historically, the prevalence of SCH during pregnancy has ranged from 2% to 2.5%, but using lower trimester-based TSH reference ranges, the prevalence of SCH in pregnancy may be as high as 15%.³⁵

Guided by a large RCT that failed to find benefit (pregnancy outcomes, neurodevelopmental outcomes in children) following treatment of SCH in pregnancy,³⁶ the American College of Obstetricians and Gynecologists (ACOG) recommends against routine screening for thyroid disease in pregnancy.³⁴ The ATA notes insufficient evidence to rec-ommend universal screening for thyroid dysfunction in pregnancy but recommends targeted screening of those with risk factors.³⁷ Data are conflicting on the benefit of treating known or recently detected SCH on pregnancy outcomes including pregnancy loss.^35,38 As such, the American Society of Reproductive Medicine and the ATA both generally recommend treatment of SCH in pregnant patients, particularly when the TSH is ≥ 4.0 mIU/L and TPOAbs are present.^37,39

^a The ATA, ETA, and NICE have slightly different recommendations when a TSH level = 10 mIU/L. ETA and NICE recommend prioritizing treatment for individuals with this level, while ATA recommends treatment when individual factors are also considered.

ACKNOWLEDGEMENT
The authors thank Family Medicine Medical Librarian Gwen Wilson, MLS, AHIP, for her assistance with literature searches.

CORRESPONDENCE
Nicholas LeFevre, MD, Family and Community Medicine, University of Missouri–Columbia School of Medicine, One Hospital Drive, M224 Medical Science Building, Columbia, MO 65212; [email protected]

Meet Dr. A and Dr. M

Dr. A is a 50-year-old family physician who provides prenatal care in a busy practice. She sees patients in eight 4-hour clinic sessions per week and is on inpatient call 1 week out of every 2 months. Dr. A has become disillusioned with her practice. She typically works until 7 pm and arrives home exhausted, with little energy to interact with her family. She spends hours in the evenings and on weekends completing charts and answering phone calls. Dr. A is concerned because she recently gained weight and lacks an established fitness routine. The COVID-19 pandemic made life more difficult as she dealt with the risk of getting infected and the changing recommendations for treatment and prevention. After 20 years of practice, Dr. A wonders whether she should leave clinical medicine.

Dr. M is a single, 32-year-old family physician working at an academic medical center. Dr. M is unhappy in his job, is trying to grow his practice, and views himself as having little impact or autonomy. He finds himself lost while navigating the electronic health record (EHR) and struggles to be efficient in the clinic. Dr. M has multiple administrative responsibilities that require him to work evenings and weekends. Debt from medical school loans also motivates him to moonlight several weekends per month. Over the past few months, Dr. M has become frustrated and discouraged, making his depression more difficult to manage. He feels drained by the time he arrives home, where he lives alone. He has stopped exercising, socializing with friends, and dating. Dr. M often wonders if he is in the wrong profession.

Defining burnout, stress, and wellness

Dr. A and Dr. M are experiencing symptoms of burnout, common to physicians and other health care professionals. Recent studies showed an increase in burnout during the COVID-19 pandemic.^1,2 In a survey using the Maslach Burnout Inventory (MBI), approximately 44% of physicians reported at least one symptom of burnout.³ After adjusting for age, gender, relationship status, and hours worked per week, physicians were found to be at greater risk for burnout than nonphysician workers.³ The latest Medscape physician burnout survey found an increase in burnout among US physicians from 42% in 2021 to 47% in 2022 during the COVID-19 pandemic.¹ Rates of burnout were even higher among family physicians and other frontline (eg, emergency, infectious disease, and critical care) physicians.¹

Burnout has 3 key dimensions: (1) overwhelming exhaustion; (2) feelings of cynicism and detachment from the job; and (3) a sense of ineffectiveness and lack of accomplishment.⁴ The MBI is considered the standard tool for research in the field of burnout and has been repeatedly assessed for reliability and validity.⁴ The original MBI includes such items as: “I feel emotionally drained from my work,” “I feel like I’m working too hard on my job,” and “I worry that this job is hardening me emotionally.”⁵

According to the World Health Organization, burnout is an occupational phenomenon associated with chronic work-related stress that is not successfully managed.⁶ This definition emphasizes work stress as the cause of burnout, thus highlighting the importance of addressing the work environment.⁷ Physician burnout can affect physician health and wellness and the quality of patient care.^8-13 Because of the cost of burnout to individuals and the health care system, it is important to understand stressors that can lead to physician burnout.

Stress has been described as “physical, mental, or emotional strain or tension … when a person perceives that demands exceed the personal and social resources the individual is able to mobilize.”¹⁴ Work-related sources of stress affecting practicing physicians include long workdays, multiple bureaucratic tasks, lack of autonomy/control, and complex patients.^1,15

The COVID-19 pandemic is a stressor that increased physicians’ exposure to patient suffering and deaths and physicians’ vulnerability to disease at work.¹⁶ Physicians taking care of patients with COVID-19 risk infection and the possibility of infecting others.Online health records are another source of stress for many physicians.^17,18 Access to online health records on personal devices can blur the line between work and home. For each hour of direct patient contact, a physician spends an additional 2 hours interacting with an EHR.¹⁹ Among family physicians and other primary care physicians, increased EHR interaction outside clinic hours has been associated with decreased workplace satisfaction and increased rates of burnout.^11,19,20 Time spent on non-patient-facing clinical tasks, such as peer-to-peer reviews and billing queries, contributes more to burnout than clinic time alone.¹⁷

Continue to: These and other organizational factors...

A physician burnout survey found an increase in burnout among US physicians from 42% in 2021 to 47% in 2022 during the COVID-19 pandemic.

These and other organizational factors contribute to the stress experienced by physicians. Many describe themselves as feeling consumed by their work. At the beginning of the COVID-19 pandemic, physicians (and the rest of the health care team) had to quickly­ learn how to conduct virtual office visits. Clerical responsibilities increased as patients relied more on patient portals and telephone calls to receive care.

Who is predisposed to burnout? Although burnout is a work-related syndrome, studies have shown an increase in burnout associated with individual (ie, personal) factors. For example, female physicians have been shown to have higher rates of burnout compared with male physicians.^1,3 The stress of balancing the demands of the profession can begin during medical school and residency, with younger physicians having nearly­ twice the risk for stress-related symptoms when compared with older colleagues.^15,20-23 Having a child younger than 21 years old, and other personal factors related to balancing family and life demands, increases the likelihood of burnout.^11,21,22

Physicians with certain personality types and predispositions are at increased risk for burnout.^23-25 For example, neuroticism on the Big Five Personality Inventory (one of the most well-known of the psychology inventories) is associated with an increased risk for burnout. Neuroticism may manifest as sadness or related emotional dysregulation (eg, irritability, anxiety).²⁶ Other traits measured by the Big Five Personality Inventory include extraversion, agreeableness, conscientiousness, and openness to experience.²⁶

Physicians who were depressed were more likely to experience burnout symptoms (87.5%); however, only 26.2% of physicians experiencing burnout were diagnosed as having depression.

A history of depression is also associated with an increased risk for burnout.²⁷ Although depression and burnout are separate conditions, a 2016 study found significant overlap between the two.²⁷ Physicians in this study who were depressed were more likely to experience burnout symptoms (87.5%); however, only 26.2% of physicians experiencing burnout were diagnosed as having depression.²⁷ Rates of depression are higher among physicians when compared with nonphysicians, yet physicians are less likely to seek help due to fear of stigma and potential licensing concerns.^28,29 Because of this, when physicians experience depressive symptoms, they may respond by working harder rather than seeking professional counseling or emotional support. They might believe that “asking for help is a sign of weakness,” thus sacrificing their wellness.

Wellness encompasses a sense of thriving characterized by thoughts and feelings of contentment, joy, and fulfillment—and the absence of severe distress.³⁰ Wellness is a multifaceted condition that includes physical, psychological, and social aspects of an individual’s personal and professional life. Individuals experience a sense of wellness when they nurture their physical selves, minds, and relationships. People experience a sense of wellness when they balance their schedules, eat well, and maintain physical activity. Making time to enjoy family and friends also contributes to wellness.

Continue to: The culture of medicine often rewards...

The culture of medicine often rewards physician attitudes and behaviors that detract from wellness.³¹ Physicians internalize the culture of medicine that promotes perfectionism and downplays personal vulnerability.³² Physicians are reluctant to protect and preserve their wellness, believing self-sacrifice makes them good doctors. Physicians may spend countless hours counseling patients on the importance of wellness, but then work when ill or neglect their personal health needs and self-care—potentially decreasing their resilience and increasing the risk for burnout.³¹

Two paths to managing stress and preventing burnout

Patel and colleagues distinguish between 2 burnout intervention categories: (1) those that focus on individual physicians and (2) those that focus on the organizational environment.³³ We find these distinctions useful and offer strategies for enhancing individual physician wellness (TABLE 1^34-41). Similar to West and colleagues,¹¹ we offer strategies for addressing organizational sources of stress (TABLE 2^42-48). The following text describes these burnout intervention categories, emphasizing increasing self-care and changes that enable physicians to adapt effectively.

The recommendations outlined in this article are based on published stress and burnout literature, as well as the experiences of the authors. However, the number of randomized controlled studies of interventions aimed at reducing physician stress and burnout is limited. In addition, strategies proposed to reduce burnout in other professions may not address the unique stressors physicians encounter. Hence, our recommendations are limited. We have included interventions that seem optimal for individual physicians and the organizations that employ them.

Individual strategies target physical, psychological, and social wellness

Physician wellness strategies are divided into 3 categories: physical, psychological, and social wellness. Most strategies to improve physical wellness are widely known, evidence based, and recommended to patients by physicians.^34-36 For example, most physicians advise their patients to eat healthy balanced meals, avoid unhealthy foods and beverages, maintain a healthy body weight, get daily exercise and adequate sleep, avoid excessive alcohol use, and abstain from tobacco use. However, discrepancies between physicians’ advice to patients and their own behaviors are common. Simply stated, physicians are well advised to follow their own advice regarding physical self-care.

CBT and mindfulness are key to psychological wellness. Recommendations for enhancing psychological wellness are primarily derived from cognitive behavioral therapy (CBT) and mindfulness principles and practices.^37,38 CBT has been called the “gold standard” of psychotherapy, based on the breadth of research demonstrating that “no other form of psychotherapy has been shown to be systematically superior to CBT.”³⁹

Continue to: CBT is based on the premise...

CBT is based on the premise that individuals’ thoughts and beliefs largely determine how they feel (emotions) and act (behaviors). Certain thoughts lead to positive feelings and effective behaviors, while others lead to negative feelings and less effective behaviors. For example, when a physician has self-critical or helpless thoughts (eg, “I’m just no good at managing my life”), they are more likely to feel unhappy and abandon problem-solving. In contrast, when a physician has self-affirming or hopeful thoughts (eg, “This is difficult, but I have the personal resources to succeed”), they are more likely to feel confident and act to solve problems.

Physicians vacillate between these thoughts and beliefs, and their emotions and behaviors follow accordingly. When hyper-focused on “the hassles of medicine,” physicians feel defeated, depressed, and anxious about their work. In contrast, when physicians recognize and challenge problematic thoughts and focus on what they love about medicine, they feel good and interact with patients and coworkers in positive and self-reinforcing ways.

Mindfulness can help reduce psychological stress and increase personal fulfillment. Mindfulness is characterized as being in the present moment, fully accepting “what is,” and having a sense of gratitude and compassion for self and others.⁴⁰ In practice, mindfulness involves being intentional.

Dahl and colleagues⁴¹ describe a framework for human flourishing that includes 4 core dimensions of well-being (awareness, insight, connection, and purpose) that are all closely linked to mindful, intentional living. Based on their work, it is apparent that those who maintain a “heightened and flexible attentiveness” to their thoughts and feelings are likely to benefit by experiencing “improved mental health and psychological well-being.”⁴¹

However, the utility of CBT and mindfulness practices depends on receptivity to psychological interventions. Individuals who are not receptive may be hesitant to use these practices or likely will not benefit from them. Given these limitations of behavioral interventions, it would be helpful if more attention were paid to preventing and managing physician stress and burnout, especially through research focused on organizational changes.

Continue to: Supportive relationships are powerful

Supportive relationships are powerful. Finally, to enhance social wellness, it would be difficult to overstate the potential benefits of positive, supportive, close relationships.⁴² However, the demands of a career in medicine, starting in medical school, have the potential for inhibiting (rather than enhancing) close relationships.

Placing value on relationships with friends and family members is essential. As Dr. M began experiencing burnout, he felt increasingly lonely, yet he isolated himself from those who cared about him. Dr. A felt lonely at home, even though she was surrounded by family. Physicians are often reluctant to initiate vulnerable communication with others, believing “no one wants to hear about my problems.” However, by realizing the need for help and asking friends and family for emotional support, physicians can improve their wellness. Fostering supportive relationships can help provide the resilience needed to address organizational stressors.

Tackling organizational challenges

Long hours and pressure to see large numbers of patients (production demands) are a challenge across practice settings. Limiting work hours has been effective in improving the well-being of physician trainees but has had an inconsistent effect on burnout.^43,44

Organizations can offer flexible scheduling, and physicians considering limiting work hours may switch to part-time status or shift work. However, decreasing work hours may have the unintended consequence of increased stress as some physicians feel pressure to do more in less time.⁴⁵ Therefore, it’s important to set clear boundaries around work time and when and where work tasks are completed (eg, home vs office).

How we use technology matters. Given­ technology’s ever-increasing role in medicine, organizations must identify and use the most efficient, effective technology for managing clerical processes. When physicians participate in these decisions and share their experiences, technology is likely to be more user-friendly and impose less stress.⁴⁶

Continue to: If technology contributes to stress...

When physicians recognize and challenge problematic thoughts and focus on what they love about medicine, they feel good and interact with patients and coworkers in positive ways.

If technology contributes to stress by being too complex or impractical, it’s important to identify individuals in the workplace (eg, IT support or “super-users”) to help address these challenges. Organizations can implement multidisciplinary teams to address EHR challenges and decrease physician stress and burnout by training support staff to assist with clerical duties, allowing physicians to focus on patient care.^47,48 Such organizational-­directed interventions will be most successful when physicians are included in the decision-making process.⁴⁷

Take on leadership roles to influence change. Leadership may be formal (involving a title and authority) or informal (leading by example). Health care organizations that are committed to the well-being of physicians will make the effort to improve the systems in which physicians work. Physicians working in organizations that are reluctant to change have several choices: implement individual strategies, take on leadership roles to influence change, or reconsider their fit for the organization. Physicians in solo practice might consider joining others in solo practices to share systems (call, phone triage, technical resources, etc) to implement some of these interventions.

Dr. A and Dr. M implement new wellness strategies

Dr. A and Dr. M have recently committed to addressing stressors in their lives and improving their wellness. Dr. A has become more assertive at work, highlighting her need for additional resources to function effectively. In response, her practice has hired scribes to assist in documenting visits. This success has inspired Dr. A to pay attention to her lifestyle choices. Gradually, she has begun to exercise and engage in healthy eating.

Dr. M has begun to utilize resources at his medical center to improve his EHR efficiency and patient flow. He has taken steps to address his financial concerns, developing a budget and spending judiciously. He practices mindfulness and ensures that he gets at least 7 hours of sleep per night, improving his mental and physical health. By doing so, he has more energy to connect with friends, ­exercise, and date.

CORRESPONDENCE
Margaret L. Smith, MD, MPH, MHSA, KUMC, Family Medicine and Community Health, 3901 Rainbow Boulevard – Mailstop 4010, Kansas City, KS 66160; [email protected]

Meet Dr. A and Dr. M

Dr. A is a 50-year-old family physician who provides prenatal care in a busy practice. She sees patients in eight 4-hour clinic sessions per week and is on inpatient call 1 week out of every 2 months. Dr. A has become disillusioned with her practice. She typically works until 7 pm and arrives home exhausted, with little energy to interact with her family. She spends hours in the evenings and on weekends completing charts and answering phone calls. Dr. A is concerned because she recently gained weight and lacks an established fitness routine. The COVID-19 pandemic made life more difficult as she dealt with the risk of getting infected and the changing recommendations for treatment and prevention. After 20 years of practice, Dr. A wonders whether she should leave clinical medicine.

Dr. M is a single, 32-year-old family physician working at an academic medical center. Dr. M is unhappy in his job, is trying to grow his practice, and views himself as having little impact or autonomy. He finds himself lost while navigating the electronic health record (EHR) and struggles to be efficient in the clinic. Dr. M has multiple administrative responsibilities that require him to work evenings and weekends. Debt from medical school loans also motivates him to moonlight several weekends per month. Over the past few months, Dr. M has become frustrated and discouraged, making his depression more difficult to manage. He feels drained by the time he arrives home, where he lives alone. He has stopped exercising, socializing with friends, and dating. Dr. M often wonders if he is in the wrong profession.

Defining burnout, stress, and wellness

Dr. A and Dr. M are experiencing symptoms of burnout, common to physicians and other health care professionals. Recent studies showed an increase in burnout during the COVID-19 pandemic.^1,2 In a survey using the Maslach Burnout Inventory (MBI), approximately 44% of physicians reported at least one symptom of burnout.³ After adjusting for age, gender, relationship status, and hours worked per week, physicians were found to be at greater risk for burnout than nonphysician workers.³ The latest Medscape physician burnout survey found an increase in burnout among US physicians from 42% in 2021 to 47% in 2022 during the COVID-19 pandemic.¹ Rates of burnout were even higher among family physicians and other frontline (eg, emergency, infectious disease, and critical care) physicians.¹

Burnout has 3 key dimensions: (1) overwhelming exhaustion; (2) feelings of cynicism and detachment from the job; and (3) a sense of ineffectiveness and lack of accomplishment.⁴ The MBI is considered the standard tool for research in the field of burnout and has been repeatedly assessed for reliability and validity.⁴ The original MBI includes such items as: “I feel emotionally drained from my work,” “I feel like I’m working too hard on my job,” and “I worry that this job is hardening me emotionally.”⁵

According to the World Health Organization, burnout is an occupational phenomenon associated with chronic work-related stress that is not successfully managed.⁶ This definition emphasizes work stress as the cause of burnout, thus highlighting the importance of addressing the work environment.⁷ Physician burnout can affect physician health and wellness and the quality of patient care.^8-13 Because of the cost of burnout to individuals and the health care system, it is important to understand stressors that can lead to physician burnout.

Stress has been described as “physical, mental, or emotional strain or tension … when a person perceives that demands exceed the personal and social resources the individual is able to mobilize.”¹⁴ Work-related sources of stress affecting practicing physicians include long workdays, multiple bureaucratic tasks, lack of autonomy/control, and complex patients.^1,15

The COVID-19 pandemic is a stressor that increased physicians’ exposure to patient suffering and deaths and physicians’ vulnerability to disease at work.¹⁶ Physicians taking care of patients with COVID-19 risk infection and the possibility of infecting others.Online health records are another source of stress for many physicians.^17,18 Access to online health records on personal devices can blur the line between work and home. For each hour of direct patient contact, a physician spends an additional 2 hours interacting with an EHR.¹⁹ Among family physicians and other primary care physicians, increased EHR interaction outside clinic hours has been associated with decreased workplace satisfaction and increased rates of burnout.^11,19,20 Time spent on non-patient-facing clinical tasks, such as peer-to-peer reviews and billing queries, contributes more to burnout than clinic time alone.¹⁷

Continue to: These and other organizational factors...

A physician burnout survey found an increase in burnout among US physicians from 42% in 2021 to 47% in 2022 during the COVID-19 pandemic.

These and other organizational factors contribute to the stress experienced by physicians. Many describe themselves as feeling consumed by their work. At the beginning of the COVID-19 pandemic, physicians (and the rest of the health care team) had to quickly­ learn how to conduct virtual office visits. Clerical responsibilities increased as patients relied more on patient portals and telephone calls to receive care.

Who is predisposed to burnout? Although burnout is a work-related syndrome, studies have shown an increase in burnout associated with individual (ie, personal) factors. For example, female physicians have been shown to have higher rates of burnout compared with male physicians.^1,3 The stress of balancing the demands of the profession can begin during medical school and residency, with younger physicians having nearly­ twice the risk for stress-related symptoms when compared with older colleagues.^15,20-23 Having a child younger than 21 years old, and other personal factors related to balancing family and life demands, increases the likelihood of burnout.^11,21,22

Physicians with certain personality types and predispositions are at increased risk for burnout.^23-25 For example, neuroticism on the Big Five Personality Inventory (one of the most well-known of the psychology inventories) is associated with an increased risk for burnout. Neuroticism may manifest as sadness or related emotional dysregulation (eg, irritability, anxiety).²⁶ Other traits measured by the Big Five Personality Inventory include extraversion, agreeableness, conscientiousness, and openness to experience.²⁶

Physicians who were depressed were more likely to experience burnout symptoms (87.5%); however, only 26.2% of physicians experiencing burnout were diagnosed as having depression.

A history of depression is also associated with an increased risk for burnout.²⁷ Although depression and burnout are separate conditions, a 2016 study found significant overlap between the two.²⁷ Physicians in this study who were depressed were more likely to experience burnout symptoms (87.5%); however, only 26.2% of physicians experiencing burnout were diagnosed as having depression.²⁷ Rates of depression are higher among physicians when compared with nonphysicians, yet physicians are less likely to seek help due to fear of stigma and potential licensing concerns.^28,29 Because of this, when physicians experience depressive symptoms, they may respond by working harder rather than seeking professional counseling or emotional support. They might believe that “asking for help is a sign of weakness,” thus sacrificing their wellness.

Wellness encompasses a sense of thriving characterized by thoughts and feelings of contentment, joy, and fulfillment—and the absence of severe distress.³⁰ Wellness is a multifaceted condition that includes physical, psychological, and social aspects of an individual’s personal and professional life. Individuals experience a sense of wellness when they nurture their physical selves, minds, and relationships. People experience a sense of wellness when they balance their schedules, eat well, and maintain physical activity. Making time to enjoy family and friends also contributes to wellness.

Continue to: The culture of medicine often rewards...

The culture of medicine often rewards physician attitudes and behaviors that detract from wellness.³¹ Physicians internalize the culture of medicine that promotes perfectionism and downplays personal vulnerability.³² Physicians are reluctant to protect and preserve their wellness, believing self-sacrifice makes them good doctors. Physicians may spend countless hours counseling patients on the importance of wellness, but then work when ill or neglect their personal health needs and self-care—potentially decreasing their resilience and increasing the risk for burnout.³¹

Two paths to managing stress and preventing burnout

Patel and colleagues distinguish between 2 burnout intervention categories: (1) those that focus on individual physicians and (2) those that focus on the organizational environment.³³ We find these distinctions useful and offer strategies for enhancing individual physician wellness (TABLE 1^34-41). Similar to West and colleagues,¹¹ we offer strategies for addressing organizational sources of stress (TABLE 2^42-48). The following text describes these burnout intervention categories, emphasizing increasing self-care and changes that enable physicians to adapt effectively.

The recommendations outlined in this article are based on published stress and burnout literature, as well as the experiences of the authors. However, the number of randomized controlled studies of interventions aimed at reducing physician stress and burnout is limited. In addition, strategies proposed to reduce burnout in other professions may not address the unique stressors physicians encounter. Hence, our recommendations are limited. We have included interventions that seem optimal for individual physicians and the organizations that employ them.

Individual strategies target physical, psychological, and social wellness

Physician wellness strategies are divided into 3 categories: physical, psychological, and social wellness. Most strategies to improve physical wellness are widely known, evidence based, and recommended to patients by physicians.^34-36 For example, most physicians advise their patients to eat healthy balanced meals, avoid unhealthy foods and beverages, maintain a healthy body weight, get daily exercise and adequate sleep, avoid excessive alcohol use, and abstain from tobacco use. However, discrepancies between physicians’ advice to patients and their own behaviors are common. Simply stated, physicians are well advised to follow their own advice regarding physical self-care.

CBT and mindfulness are key to psychological wellness. Recommendations for enhancing psychological wellness are primarily derived from cognitive behavioral therapy (CBT) and mindfulness principles and practices.^37,38 CBT has been called the “gold standard” of psychotherapy, based on the breadth of research demonstrating that “no other form of psychotherapy has been shown to be systematically superior to CBT.”³⁹

Continue to: CBT is based on the premise...

CBT is based on the premise that individuals’ thoughts and beliefs largely determine how they feel (emotions) and act (behaviors). Certain thoughts lead to positive feelings and effective behaviors, while others lead to negative feelings and less effective behaviors. For example, when a physician has self-critical or helpless thoughts (eg, “I’m just no good at managing my life”), they are more likely to feel unhappy and abandon problem-solving. In contrast, when a physician has self-affirming or hopeful thoughts (eg, “This is difficult, but I have the personal resources to succeed”), they are more likely to feel confident and act to solve problems.

Physicians vacillate between these thoughts and beliefs, and their emotions and behaviors follow accordingly. When hyper-focused on “the hassles of medicine,” physicians feel defeated, depressed, and anxious about their work. In contrast, when physicians recognize and challenge problematic thoughts and focus on what they love about medicine, they feel good and interact with patients and coworkers in positive and self-reinforcing ways.

Mindfulness can help reduce psychological stress and increase personal fulfillment. Mindfulness is characterized as being in the present moment, fully accepting “what is,” and having a sense of gratitude and compassion for self and others.⁴⁰ In practice, mindfulness involves being intentional.

Dahl and colleagues⁴¹ describe a framework for human flourishing that includes 4 core dimensions of well-being (awareness, insight, connection, and purpose) that are all closely linked to mindful, intentional living. Based on their work, it is apparent that those who maintain a “heightened and flexible attentiveness” to their thoughts and feelings are likely to benefit by experiencing “improved mental health and psychological well-being.”⁴¹

However, the utility of CBT and mindfulness practices depends on receptivity to psychological interventions. Individuals who are not receptive may be hesitant to use these practices or likely will not benefit from them. Given these limitations of behavioral interventions, it would be helpful if more attention were paid to preventing and managing physician stress and burnout, especially through research focused on organizational changes.

Continue to: Supportive relationships are powerful

Supportive relationships are powerful. Finally, to enhance social wellness, it would be difficult to overstate the potential benefits of positive, supportive, close relationships.⁴² However, the demands of a career in medicine, starting in medical school, have the potential for inhibiting (rather than enhancing) close relationships.

Placing value on relationships with friends and family members is essential. As Dr. M began experiencing burnout, he felt increasingly lonely, yet he isolated himself from those who cared about him. Dr. A felt lonely at home, even though she was surrounded by family. Physicians are often reluctant to initiate vulnerable communication with others, believing “no one wants to hear about my problems.” However, by realizing the need for help and asking friends and family for emotional support, physicians can improve their wellness. Fostering supportive relationships can help provide the resilience needed to address organizational stressors.

Tackling organizational challenges

Long hours and pressure to see large numbers of patients (production demands) are a challenge across practice settings. Limiting work hours has been effective in improving the well-being of physician trainees but has had an inconsistent effect on burnout.^43,44

Organizations can offer flexible scheduling, and physicians considering limiting work hours may switch to part-time status or shift work. However, decreasing work hours may have the unintended consequence of increased stress as some physicians feel pressure to do more in less time.⁴⁵ Therefore, it’s important to set clear boundaries around work time and when and where work tasks are completed (eg, home vs office).

How we use technology matters. Given­ technology’s ever-increasing role in medicine, organizations must identify and use the most efficient, effective technology for managing clerical processes. When physicians participate in these decisions and share their experiences, technology is likely to be more user-friendly and impose less stress.⁴⁶

Continue to: If technology contributes to stress...

When physicians recognize and challenge problematic thoughts and focus on what they love about medicine, they feel good and interact with patients and coworkers in positive ways.

If technology contributes to stress by being too complex or impractical, it’s important to identify individuals in the workplace (eg, IT support or “super-users”) to help address these challenges. Organizations can implement multidisciplinary teams to address EHR challenges and decrease physician stress and burnout by training support staff to assist with clerical duties, allowing physicians to focus on patient care.^47,48 Such organizational-­directed interventions will be most successful when physicians are included in the decision-making process.⁴⁷

Take on leadership roles to influence change. Leadership may be formal (involving a title and authority) or informal (leading by example). Health care organizations that are committed to the well-being of physicians will make the effort to improve the systems in which physicians work. Physicians working in organizations that are reluctant to change have several choices: implement individual strategies, take on leadership roles to influence change, or reconsider their fit for the organization. Physicians in solo practice might consider joining others in solo practices to share systems (call, phone triage, technical resources, etc) to implement some of these interventions.

Dr. A and Dr. M implement new wellness strategies

Dr. A and Dr. M have recently committed to addressing stressors in their lives and improving their wellness. Dr. A has become more assertive at work, highlighting her need for additional resources to function effectively. In response, her practice has hired scribes to assist in documenting visits. This success has inspired Dr. A to pay attention to her lifestyle choices. Gradually, she has begun to exercise and engage in healthy eating.

Dr. M has begun to utilize resources at his medical center to improve his EHR efficiency and patient flow. He has taken steps to address his financial concerns, developing a budget and spending judiciously. He practices mindfulness and ensures that he gets at least 7 hours of sleep per night, improving his mental and physical health. By doing so, he has more energy to connect with friends, ­exercise, and date.

CORRESPONDENCE
Margaret L. Smith, MD, MPH, MHSA, KUMC, Family Medicine and Community Health, 3901 Rainbow Boulevard – Mailstop 4010, Kansas City, KS 66160; [email protected]

Meet Dr. A and Dr. M

Dr. A is a 50-year-old family physician who provides prenatal care in a busy practice. She sees patients in eight 4-hour clinic sessions per week and is on inpatient call 1 week out of every 2 months. Dr. A has become disillusioned with her practice. She typically works until 7 pm and arrives home exhausted, with little energy to interact with her family. She spends hours in the evenings and on weekends completing charts and answering phone calls. Dr. A is concerned because she recently gained weight and lacks an established fitness routine. The COVID-19 pandemic made life more difficult as she dealt with the risk of getting infected and the changing recommendations for treatment and prevention. After 20 years of practice, Dr. A wonders whether she should leave clinical medicine.

Dr. M is a single, 32-year-old family physician working at an academic medical center. Dr. M is unhappy in his job, is trying to grow his practice, and views himself as having little impact or autonomy. He finds himself lost while navigating the electronic health record (EHR) and struggles to be efficient in the clinic. Dr. M has multiple administrative responsibilities that require him to work evenings and weekends. Debt from medical school loans also motivates him to moonlight several weekends per month. Over the past few months, Dr. M has become frustrated and discouraged, making his depression more difficult to manage. He feels drained by the time he arrives home, where he lives alone. He has stopped exercising, socializing with friends, and dating. Dr. M often wonders if he is in the wrong profession.

Defining burnout, stress, and wellness

Dr. A and Dr. M are experiencing symptoms of burnout, common to physicians and other health care professionals. Recent studies showed an increase in burnout during the COVID-19 pandemic.^1,2 In a survey using the Maslach Burnout Inventory (MBI), approximately 44% of physicians reported at least one symptom of burnout.³ After adjusting for age, gender, relationship status, and hours worked per week, physicians were found to be at greater risk for burnout than nonphysician workers.³ The latest Medscape physician burnout survey found an increase in burnout among US physicians from 42% in 2021 to 47% in 2022 during the COVID-19 pandemic.¹ Rates of burnout were even higher among family physicians and other frontline (eg, emergency, infectious disease, and critical care) physicians.¹

Burnout has 3 key dimensions: (1) overwhelming exhaustion; (2) feelings of cynicism and detachment from the job; and (3) a sense of ineffectiveness and lack of accomplishment.⁴ The MBI is considered the standard tool for research in the field of burnout and has been repeatedly assessed for reliability and validity.⁴ The original MBI includes such items as: “I feel emotionally drained from my work,” “I feel like I’m working too hard on my job,” and “I worry that this job is hardening me emotionally.”⁵

According to the World Health Organization, burnout is an occupational phenomenon associated with chronic work-related stress that is not successfully managed.⁶ This definition emphasizes work stress as the cause of burnout, thus highlighting the importance of addressing the work environment.⁷ Physician burnout can affect physician health and wellness and the quality of patient care.^8-13 Because of the cost of burnout to individuals and the health care system, it is important to understand stressors that can lead to physician burnout.

Stress has been described as “physical, mental, or emotional strain or tension … when a person perceives that demands exceed the personal and social resources the individual is able to mobilize.”¹⁴ Work-related sources of stress affecting practicing physicians include long workdays, multiple bureaucratic tasks, lack of autonomy/control, and complex patients.^1,15

The COVID-19 pandemic is a stressor that increased physicians’ exposure to patient suffering and deaths and physicians’ vulnerability to disease at work.¹⁶ Physicians taking care of patients with COVID-19 risk infection and the possibility of infecting others.Online health records are another source of stress for many physicians.^17,18 Access to online health records on personal devices can blur the line between work and home. For each hour of direct patient contact, a physician spends an additional 2 hours interacting with an EHR.¹⁹ Among family physicians and other primary care physicians, increased EHR interaction outside clinic hours has been associated with decreased workplace satisfaction and increased rates of burnout.^11,19,20 Time spent on non-patient-facing clinical tasks, such as peer-to-peer reviews and billing queries, contributes more to burnout than clinic time alone.¹⁷

Continue to: These and other organizational factors...

A physician burnout survey found an increase in burnout among US physicians from 42% in 2021 to 47% in 2022 during the COVID-19 pandemic.

These and other organizational factors contribute to the stress experienced by physicians. Many describe themselves as feeling consumed by their work. At the beginning of the COVID-19 pandemic, physicians (and the rest of the health care team) had to quickly­ learn how to conduct virtual office visits. Clerical responsibilities increased as patients relied more on patient portals and telephone calls to receive care.

Who is predisposed to burnout? Although burnout is a work-related syndrome, studies have shown an increase in burnout associated with individual (ie, personal) factors. For example, female physicians have been shown to have higher rates of burnout compared with male physicians.^1,3 The stress of balancing the demands of the profession can begin during medical school and residency, with younger physicians having nearly­ twice the risk for stress-related symptoms when compared with older colleagues.^15,20-23 Having a child younger than 21 years old, and other personal factors related to balancing family and life demands, increases the likelihood of burnout.^11,21,22

Physicians with certain personality types and predispositions are at increased risk for burnout.^23-25 For example, neuroticism on the Big Five Personality Inventory (one of the most well-known of the psychology inventories) is associated with an increased risk for burnout. Neuroticism may manifest as sadness or related emotional dysregulation (eg, irritability, anxiety).²⁶ Other traits measured by the Big Five Personality Inventory include extraversion, agreeableness, conscientiousness, and openness to experience.²⁶

Physicians who were depressed were more likely to experience burnout symptoms (87.5%); however, only 26.2% of physicians experiencing burnout were diagnosed as having depression.

A history of depression is also associated with an increased risk for burnout.²⁷ Although depression and burnout are separate conditions, a 2016 study found significant overlap between the two.²⁷ Physicians in this study who were depressed were more likely to experience burnout symptoms (87.5%); however, only 26.2% of physicians experiencing burnout were diagnosed as having depression.²⁷ Rates of depression are higher among physicians when compared with nonphysicians, yet physicians are less likely to seek help due to fear of stigma and potential licensing concerns.^28,29 Because of this, when physicians experience depressive symptoms, they may respond by working harder rather than seeking professional counseling or emotional support. They might believe that “asking for help is a sign of weakness,” thus sacrificing their wellness.

Wellness encompasses a sense of thriving characterized by thoughts and feelings of contentment, joy, and fulfillment—and the absence of severe distress.³⁰ Wellness is a multifaceted condition that includes physical, psychological, and social aspects of an individual’s personal and professional life. Individuals experience a sense of wellness when they nurture their physical selves, minds, and relationships. People experience a sense of wellness when they balance their schedules, eat well, and maintain physical activity. Making time to enjoy family and friends also contributes to wellness.

Continue to: The culture of medicine often rewards...

The culture of medicine often rewards physician attitudes and behaviors that detract from wellness.³¹ Physicians internalize the culture of medicine that promotes perfectionism and downplays personal vulnerability.³² Physicians are reluctant to protect and preserve their wellness, believing self-sacrifice makes them good doctors. Physicians may spend countless hours counseling patients on the importance of wellness, but then work when ill or neglect their personal health needs and self-care—potentially decreasing their resilience and increasing the risk for burnout.³¹

Two paths to managing stress and preventing burnout

Patel and colleagues distinguish between 2 burnout intervention categories: (1) those that focus on individual physicians and (2) those that focus on the organizational environment.³³ We find these distinctions useful and offer strategies for enhancing individual physician wellness (TABLE 1^34-41). Similar to West and colleagues,¹¹ we offer strategies for addressing organizational sources of stress (TABLE 2^42-48). The following text describes these burnout intervention categories, emphasizing increasing self-care and changes that enable physicians to adapt effectively.

The recommendations outlined in this article are based on published stress and burnout literature, as well as the experiences of the authors. However, the number of randomized controlled studies of interventions aimed at reducing physician stress and burnout is limited. In addition, strategies proposed to reduce burnout in other professions may not address the unique stressors physicians encounter. Hence, our recommendations are limited. We have included interventions that seem optimal for individual physicians and the organizations that employ them.

Individual strategies target physical, psychological, and social wellness

Physician wellness strategies are divided into 3 categories: physical, psychological, and social wellness. Most strategies to improve physical wellness are widely known, evidence based, and recommended to patients by physicians.^34-36 For example, most physicians advise their patients to eat healthy balanced meals, avoid unhealthy foods and beverages, maintain a healthy body weight, get daily exercise and adequate sleep, avoid excessive alcohol use, and abstain from tobacco use. However, discrepancies between physicians’ advice to patients and their own behaviors are common. Simply stated, physicians are well advised to follow their own advice regarding physical self-care.

CBT and mindfulness are key to psychological wellness. Recommendations for enhancing psychological wellness are primarily derived from cognitive behavioral therapy (CBT) and mindfulness principles and practices.^37,38 CBT has been called the “gold standard” of psychotherapy, based on the breadth of research demonstrating that “no other form of psychotherapy has been shown to be systematically superior to CBT.”³⁹

Continue to: CBT is based on the premise...

CBT is based on the premise that individuals’ thoughts and beliefs largely determine how they feel (emotions) and act (behaviors). Certain thoughts lead to positive feelings and effective behaviors, while others lead to negative feelings and less effective behaviors. For example, when a physician has self-critical or helpless thoughts (eg, “I’m just no good at managing my life”), they are more likely to feel unhappy and abandon problem-solving. In contrast, when a physician has self-affirming or hopeful thoughts (eg, “This is difficult, but I have the personal resources to succeed”), they are more likely to feel confident and act to solve problems.

Physicians vacillate between these thoughts and beliefs, and their emotions and behaviors follow accordingly. When hyper-focused on “the hassles of medicine,” physicians feel defeated, depressed, and anxious about their work. In contrast, when physicians recognize and challenge problematic thoughts and focus on what they love about medicine, they feel good and interact with patients and coworkers in positive and self-reinforcing ways.

Mindfulness can help reduce psychological stress and increase personal fulfillment. Mindfulness is characterized as being in the present moment, fully accepting “what is,” and having a sense of gratitude and compassion for self and others.⁴⁰ In practice, mindfulness involves being intentional.

Dahl and colleagues⁴¹ describe a framework for human flourishing that includes 4 core dimensions of well-being (awareness, insight, connection, and purpose) that are all closely linked to mindful, intentional living. Based on their work, it is apparent that those who maintain a “heightened and flexible attentiveness” to their thoughts and feelings are likely to benefit by experiencing “improved mental health and psychological well-being.”⁴¹

However, the utility of CBT and mindfulness practices depends on receptivity to psychological interventions. Individuals who are not receptive may be hesitant to use these practices or likely will not benefit from them. Given these limitations of behavioral interventions, it would be helpful if more attention were paid to preventing and managing physician stress and burnout, especially through research focused on organizational changes.

Continue to: Supportive relationships are powerful

Supportive relationships are powerful. Finally, to enhance social wellness, it would be difficult to overstate the potential benefits of positive, supportive, close relationships.⁴² However, the demands of a career in medicine, starting in medical school, have the potential for inhibiting (rather than enhancing) close relationships.

Placing value on relationships with friends and family members is essential. As Dr. M began experiencing burnout, he felt increasingly lonely, yet he isolated himself from those who cared about him. Dr. A felt lonely at home, even though she was surrounded by family. Physicians are often reluctant to initiate vulnerable communication with others, believing “no one wants to hear about my problems.” However, by realizing the need for help and asking friends and family for emotional support, physicians can improve their wellness. Fostering supportive relationships can help provide the resilience needed to address organizational stressors.

Tackling organizational challenges

Long hours and pressure to see large numbers of patients (production demands) are a challenge across practice settings. Limiting work hours has been effective in improving the well-being of physician trainees but has had an inconsistent effect on burnout.^43,44

Organizations can offer flexible scheduling, and physicians considering limiting work hours may switch to part-time status or shift work. However, decreasing work hours may have the unintended consequence of increased stress as some physicians feel pressure to do more in less time.⁴⁵ Therefore, it’s important to set clear boundaries around work time and when and where work tasks are completed (eg, home vs office).

How we use technology matters. Given­ technology’s ever-increasing role in medicine, organizations must identify and use the most efficient, effective technology for managing clerical processes. When physicians participate in these decisions and share their experiences, technology is likely to be more user-friendly and impose less stress.⁴⁶

Continue to: If technology contributes to stress...

When physicians recognize and challenge problematic thoughts and focus on what they love about medicine, they feel good and interact with patients and coworkers in positive ways.

If technology contributes to stress by being too complex or impractical, it’s important to identify individuals in the workplace (eg, IT support or “super-users”) to help address these challenges. Organizations can implement multidisciplinary teams to address EHR challenges and decrease physician stress and burnout by training support staff to assist with clerical duties, allowing physicians to focus on patient care.^47,48 Such organizational-­directed interventions will be most successful when physicians are included in the decision-making process.⁴⁷

Take on leadership roles to influence change. Leadership may be formal (involving a title and authority) or informal (leading by example). Health care organizations that are committed to the well-being of physicians will make the effort to improve the systems in which physicians work. Physicians working in organizations that are reluctant to change have several choices: implement individual strategies, take on leadership roles to influence change, or reconsider their fit for the organization. Physicians in solo practice might consider joining others in solo practices to share systems (call, phone triage, technical resources, etc) to implement some of these interventions.

Dr. A and Dr. M implement new wellness strategies

Dr. A and Dr. M have recently committed to addressing stressors in their lives and improving their wellness. Dr. A has become more assertive at work, highlighting her need for additional resources to function effectively. In response, her practice has hired scribes to assist in documenting visits. This success has inspired Dr. A to pay attention to her lifestyle choices. Gradually, she has begun to exercise and engage in healthy eating.

Dr. M has begun to utilize resources at his medical center to improve his EHR efficiency and patient flow. He has taken steps to address his financial concerns, developing a budget and spending judiciously. He practices mindfulness and ensures that he gets at least 7 hours of sleep per night, improving his mental and physical health. By doing so, he has more energy to connect with friends, ­exercise, and date.

CORRESPONDENCE
Margaret L. Smith, MD, MPH, MHSA, KUMC, Family Medicine and Community Health, 3901 Rainbow Boulevard – Mailstop 4010, Kansas City, KS 66160; [email protected]

A 41-year-old man presented for evaluation of an extensive skin rash that had erupted more than a month earlier. The patient had received 2 doses of the Pfizer COVID-19 vaccine 3 weeks apart. Ten days after his second dose, the patient developed a rash all over his body. He described the rash as burning, itchy, and uncomfortable. The patient denied any triggers such as recent or previous infections, stressors, or drugs. The patient had no personal or family history of dermatologic disorders; his general medical history was unremarkable. The patient smoked and drank alcohol occasionally.

On physical exam, the patient had a diffuse rash, which initially had manifested on both of his hands, including the palms, and then spread to 60% to 70% of his total body surface area, including his face, ears, anterior and posterior chest, upper and lower extremities, and buttocks. The rash consisted of 10- to 15-mm white scaly plaques that did not bleed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Punch biopsies were obtained, and histopathology revealed diffuse compact hyperkeratosis with broad zones of parakeratosis. There was attenuation of the granular layer and regular elongation of the rete ridges associated with thinning of the suprapapillary epidermis and mild spongiosis. These pathologic findings were consistent with a diagnosis of psoriasis. There were no drug-related skin eruption features, such as apoptotic keratinocytes, eosinophils, or interface dermatitis. Periodic acid-Schiff stains for fungal organisms were negative. The combined clinical presentation (itchy, teardrop-shaped, scaly lesions) and histologic impression were consistent with guttate psoriasis.

Psoriasis can be seen in various forms. Subtypes of psoriasis include guttate psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and pustular psoriasis.¹ Guttate psoriasis accounts for about 2% of psoriasis cases and usually is seen in patients younger than 30 years.² Guttate psoriasis is characterized by 1- to 10-mm teardrop-shaped pink papules with fine scaling.³

One study found that the average time of new onset of psoriasis or flare-up can be between 5 to 14 days after the COVID-19 vaccination.

Triggers for psoriasis. Vaccinations, medications, and infections (eg, group A beta-hemolytic streptococcal upper respiratory infections) can trigger guttate psoriasis.³ MRNA vaccines (eg, Moderna and Pfizer/BioNTech COVID-19 vaccines) have been associated with psoriasis episodes.¹ Other vaccines such as influenza, rubella, bacillus Calmette-Guerin, tetanus-diphtheria, and pneumococcal polysaccharide also have been known to trigger psoriasis.⁴ Medications that can trigger psoriasis include beta-blockers, lithium, antimalarial drugs, and (in some cases)­ nonsteroidal anti-inflammatory drugs.⁵

The impact of COVID-19 vaccine. We are still learning about the incidence and prevalence of adverse effects (such as psoriasis) that can follow COVID-19 vaccination. One study found that the average time of new onset­ of psoriasis or flare-up can be between 5 to 14 days after COVID-19 vaccination.⁶

Psoriasis following vaccination. The pathologic mechanism for the new onset or flare of psoriasis after COVID-19 vaccination is unknown. What is known is that the dysregulation of Th-1 and Th-17 plays an important role in the pathogenesis of psoriasis.⁷ Previously, it was found that psoriasis can manifest after tetanus-diphtheria vaccines due to an increase in the production of Th-17 cells.⁷ Th-1 and Th-17 production also increases after influenza vaccine and can cause an onset or flare-up of psoriasis.⁸

Continue to: The differential includes syphilis and exfoliative dermatitis

The differential includes syphilis and exfoliative dermatitis

The differential diagnosis includes various forms of psoriasiform dermatitis, such as secondary syphilis, chronic spongiotic dermatitis, psoriasiform drug eruption, exfoliative dermatitis, and pityriasis rubra pilaris. A combination of clinical and histopathologic findings is used to zero in on the diagnosis. The summary below highlights the clinical findings.

Secondary syphilis manifests with symmetric papular eruptions primarily on the trunk and extremities with involvement on the palms and soles. Lesions are red or reddish brown, can be smooth, and are rarely pustular.

Chronic spongiotic dermatitis manifests with a shiny, glazed, cracked appearance and itchy reddish lesions on the soles.

Psoriasiform drug eruption manifests after drug administration with a psoriasis-like rash with erythematous, squamous, thick, dry, and plaque-type lesions.

Exfoliative dermatitis manifests with erythematous single or multiple pruritic patches on the trunk, head, and genitals.

Continue to: Pityriasis rubra pilaris

Pityriasis rubra pilaris manifests in various ways. Patients may have plaques that are erythematous, scaly, or follicular. Sometimes, it may manifest as erythroderma with an “island of sparing,” which is normal-looking skin in the affected areas.

How to make the diagnosis

Psoriasis can be diagnosed by physical examination. A skin biopsy is not usually necessary but can be helpful for complex cases.

There are no laboratory or genetic tests to confirm the diagnosis of psoriasis. Depending on the case, routine bloodwork (eg, complete blood count and metabolic panel) and infectious disease tests (eg, HIV, hepatitis panel, and rapid plasma reagin for syphilis) can be helpful to rule out other etiologies of skin rash.

Treatment is based on patient factors and disease severity

Starting with a low- to medium-potency steroid, such as betamethasone valerate 0.1% cream twice per day or triamcinolone acetonide 0.1% cream twice per day for 2 weeks, provides high safety and efficacy for localized disease.⁹ An appropriate-potency steroid should be chosen based on the disease severity, location, and patient’s preference and age. Topical vitamin D analogues often are used in conjunction with topical steroids to treat psoriasis.⁹

Depending on the severity, patient age, comorbidities, and availability of treatment, other treatment options for psoriasis include oral methotrexate (2.5 mg to 25 mg weekly, starting with a low dose), acitretin (10 mg to 50 mg daily), apremilast (10 mg daily, gradually increasing to 30 mg twice per day in a divided dose), biologics, and narrowband ultraviolet light.

In this case, betamethasone dipropionate 0.05% cream twice daily for 2 weeks was not sufficiently effective due to the extent of the psoriasis. Following consultation with a dermatologist, clobetasol propionate 0.05% cream twice per day and oral apremilast (10 mg once per day on the first day and 10 mg twice per day afterward) were prescribed for 2 weeks. The patient’s psoriasis improved somewhat after 2 weeks of the treatment, but many plaques remained. Therefore, apremilast was stopped and subcutaneous adalimumab was started (initial loading dose, 80 mg, then 40 mg every other week). The psoriasis lesions cleared over the next 2 to 3 months. The patient was maintained on the adalimumab to avoid a recurrence of lesions.

A 41-year-old man presented for evaluation of an extensive skin rash that had erupted more than a month earlier. The patient had received 2 doses of the Pfizer COVID-19 vaccine 3 weeks apart. Ten days after his second dose, the patient developed a rash all over his body. He described the rash as burning, itchy, and uncomfortable. The patient denied any triggers such as recent or previous infections, stressors, or drugs. The patient had no personal or family history of dermatologic disorders; his general medical history was unremarkable. The patient smoked and drank alcohol occasionally.

On physical exam, the patient had a diffuse rash, which initially had manifested on both of his hands, including the palms, and then spread to 60% to 70% of his total body surface area, including his face, ears, anterior and posterior chest, upper and lower extremities, and buttocks. The rash consisted of 10- to 15-mm white scaly plaques that did not bleed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Punch biopsies were obtained, and histopathology revealed diffuse compact hyperkeratosis with broad zones of parakeratosis. There was attenuation of the granular layer and regular elongation of the rete ridges associated with thinning of the suprapapillary epidermis and mild spongiosis. These pathologic findings were consistent with a diagnosis of psoriasis. There were no drug-related skin eruption features, such as apoptotic keratinocytes, eosinophils, or interface dermatitis. Periodic acid-Schiff stains for fungal organisms were negative. The combined clinical presentation (itchy, teardrop-shaped, scaly lesions) and histologic impression were consistent with guttate psoriasis.

Psoriasis can be seen in various forms. Subtypes of psoriasis include guttate psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and pustular psoriasis.¹ Guttate psoriasis accounts for about 2% of psoriasis cases and usually is seen in patients younger than 30 years.² Guttate psoriasis is characterized by 1- to 10-mm teardrop-shaped pink papules with fine scaling.³

One study found that the average time of new onset of psoriasis or flare-up can be between 5 to 14 days after the COVID-19 vaccination.

Triggers for psoriasis. Vaccinations, medications, and infections (eg, group A beta-hemolytic streptococcal upper respiratory infections) can trigger guttate psoriasis.³ MRNA vaccines (eg, Moderna and Pfizer/BioNTech COVID-19 vaccines) have been associated with psoriasis episodes.¹ Other vaccines such as influenza, rubella, bacillus Calmette-Guerin, tetanus-diphtheria, and pneumococcal polysaccharide also have been known to trigger psoriasis.⁴ Medications that can trigger psoriasis include beta-blockers, lithium, antimalarial drugs, and (in some cases)­ nonsteroidal anti-inflammatory drugs.⁵

The impact of COVID-19 vaccine. We are still learning about the incidence and prevalence of adverse effects (such as psoriasis) that can follow COVID-19 vaccination. One study found that the average time of new onset­ of psoriasis or flare-up can be between 5 to 14 days after COVID-19 vaccination.⁶

Psoriasis following vaccination. The pathologic mechanism for the new onset or flare of psoriasis after COVID-19 vaccination is unknown. What is known is that the dysregulation of Th-1 and Th-17 plays an important role in the pathogenesis of psoriasis.⁷ Previously, it was found that psoriasis can manifest after tetanus-diphtheria vaccines due to an increase in the production of Th-17 cells.⁷ Th-1 and Th-17 production also increases after influenza vaccine and can cause an onset or flare-up of psoriasis.⁸

Continue to: The differential includes syphilis and exfoliative dermatitis

The differential includes syphilis and exfoliative dermatitis

The differential diagnosis includes various forms of psoriasiform dermatitis, such as secondary syphilis, chronic spongiotic dermatitis, psoriasiform drug eruption, exfoliative dermatitis, and pityriasis rubra pilaris. A combination of clinical and histopathologic findings is used to zero in on the diagnosis. The summary below highlights the clinical findings.

Secondary syphilis manifests with symmetric papular eruptions primarily on the trunk and extremities with involvement on the palms and soles. Lesions are red or reddish brown, can be smooth, and are rarely pustular.

Chronic spongiotic dermatitis manifests with a shiny, glazed, cracked appearance and itchy reddish lesions on the soles.

Psoriasiform drug eruption manifests after drug administration with a psoriasis-like rash with erythematous, squamous, thick, dry, and plaque-type lesions.

Exfoliative dermatitis manifests with erythematous single or multiple pruritic patches on the trunk, head, and genitals.

Continue to: Pityriasis rubra pilaris

Pityriasis rubra pilaris manifests in various ways. Patients may have plaques that are erythematous, scaly, or follicular. Sometimes, it may manifest as erythroderma with an “island of sparing,” which is normal-looking skin in the affected areas.

How to make the diagnosis

Psoriasis can be diagnosed by physical examination. A skin biopsy is not usually necessary but can be helpful for complex cases.

There are no laboratory or genetic tests to confirm the diagnosis of psoriasis. Depending on the case, routine bloodwork (eg, complete blood count and metabolic panel) and infectious disease tests (eg, HIV, hepatitis panel, and rapid plasma reagin for syphilis) can be helpful to rule out other etiologies of skin rash.

Treatment is based on patient factors and disease severity

Starting with a low- to medium-potency steroid, such as betamethasone valerate 0.1% cream twice per day or triamcinolone acetonide 0.1% cream twice per day for 2 weeks, provides high safety and efficacy for localized disease.⁹ An appropriate-potency steroid should be chosen based on the disease severity, location, and patient’s preference and age. Topical vitamin D analogues often are used in conjunction with topical steroids to treat psoriasis.⁹

Depending on the severity, patient age, comorbidities, and availability of treatment, other treatment options for psoriasis include oral methotrexate (2.5 mg to 25 mg weekly, starting with a low dose), acitretin (10 mg to 50 mg daily), apremilast (10 mg daily, gradually increasing to 30 mg twice per day in a divided dose), biologics, and narrowband ultraviolet light.

In this case, betamethasone dipropionate 0.05% cream twice daily for 2 weeks was not sufficiently effective due to the extent of the psoriasis. Following consultation with a dermatologist, clobetasol propionate 0.05% cream twice per day and oral apremilast (10 mg once per day on the first day and 10 mg twice per day afterward) were prescribed for 2 weeks. The patient’s psoriasis improved somewhat after 2 weeks of the treatment, but many plaques remained. Therefore, apremilast was stopped and subcutaneous adalimumab was started (initial loading dose, 80 mg, then 40 mg every other week). The psoriasis lesions cleared over the next 2 to 3 months. The patient was maintained on the adalimumab to avoid a recurrence of lesions.

A 41-year-old man presented for evaluation of an extensive skin rash that had erupted more than a month earlier. The patient had received 2 doses of the Pfizer COVID-19 vaccine 3 weeks apart. Ten days after his second dose, the patient developed a rash all over his body. He described the rash as burning, itchy, and uncomfortable. The patient denied any triggers such as recent or previous infections, stressors, or drugs. The patient had no personal or family history of dermatologic disorders; his general medical history was unremarkable. The patient smoked and drank alcohol occasionally.

On physical exam, the patient had a diffuse rash, which initially had manifested on both of his hands, including the palms, and then spread to 60% to 70% of his total body surface area, including his face, ears, anterior and posterior chest, upper and lower extremities, and buttocks. The rash consisted of 10- to 15-mm white scaly plaques that did not bleed.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

Punch biopsies were obtained, and histopathology revealed diffuse compact hyperkeratosis with broad zones of parakeratosis. There was attenuation of the granular layer and regular elongation of the rete ridges associated with thinning of the suprapapillary epidermis and mild spongiosis. These pathologic findings were consistent with a diagnosis of psoriasis. There were no drug-related skin eruption features, such as apoptotic keratinocytes, eosinophils, or interface dermatitis. Periodic acid-Schiff stains for fungal organisms were negative. The combined clinical presentation (itchy, teardrop-shaped, scaly lesions) and histologic impression were consistent with guttate psoriasis.

Psoriasis can be seen in various forms. Subtypes of psoriasis include guttate psoriasis, inverse psoriasis, erythrodermic psoriasis, nail psoriasis, and pustular psoriasis.¹ Guttate psoriasis accounts for about 2% of psoriasis cases and usually is seen in patients younger than 30 years.² Guttate psoriasis is characterized by 1- to 10-mm teardrop-shaped pink papules with fine scaling.³

One study found that the average time of new onset of psoriasis or flare-up can be between 5 to 14 days after the COVID-19 vaccination.

Triggers for psoriasis. Vaccinations, medications, and infections (eg, group A beta-hemolytic streptococcal upper respiratory infections) can trigger guttate psoriasis.³ MRNA vaccines (eg, Moderna and Pfizer/BioNTech COVID-19 vaccines) have been associated with psoriasis episodes.¹ Other vaccines such as influenza, rubella, bacillus Calmette-Guerin, tetanus-diphtheria, and pneumococcal polysaccharide also have been known to trigger psoriasis.⁴ Medications that can trigger psoriasis include beta-blockers, lithium, antimalarial drugs, and (in some cases)­ nonsteroidal anti-inflammatory drugs.⁵

The impact of COVID-19 vaccine. We are still learning about the incidence and prevalence of adverse effects (such as psoriasis) that can follow COVID-19 vaccination. One study found that the average time of new onset­ of psoriasis or flare-up can be between 5 to 14 days after COVID-19 vaccination.⁶

Psoriasis following vaccination. The pathologic mechanism for the new onset or flare of psoriasis after COVID-19 vaccination is unknown. What is known is that the dysregulation of Th-1 and Th-17 plays an important role in the pathogenesis of psoriasis.⁷ Previously, it was found that psoriasis can manifest after tetanus-diphtheria vaccines due to an increase in the production of Th-17 cells.⁷ Th-1 and Th-17 production also increases after influenza vaccine and can cause an onset or flare-up of psoriasis.⁸

Continue to: The differential includes syphilis and exfoliative dermatitis

The differential includes syphilis and exfoliative dermatitis

The differential diagnosis includes various forms of psoriasiform dermatitis, such as secondary syphilis, chronic spongiotic dermatitis, psoriasiform drug eruption, exfoliative dermatitis, and pityriasis rubra pilaris. A combination of clinical and histopathologic findings is used to zero in on the diagnosis. The summary below highlights the clinical findings.

Secondary syphilis manifests with symmetric papular eruptions primarily on the trunk and extremities with involvement on the palms and soles. Lesions are red or reddish brown, can be smooth, and are rarely pustular.

Chronic spongiotic dermatitis manifests with a shiny, glazed, cracked appearance and itchy reddish lesions on the soles.

Psoriasiform drug eruption manifests after drug administration with a psoriasis-like rash with erythematous, squamous, thick, dry, and plaque-type lesions.

Exfoliative dermatitis manifests with erythematous single or multiple pruritic patches on the trunk, head, and genitals.

Continue to: Pityriasis rubra pilaris

Pityriasis rubra pilaris manifests in various ways. Patients may have plaques that are erythematous, scaly, or follicular. Sometimes, it may manifest as erythroderma with an “island of sparing,” which is normal-looking skin in the affected areas.

How to make the diagnosis

Psoriasis can be diagnosed by physical examination. A skin biopsy is not usually necessary but can be helpful for complex cases.

There are no laboratory or genetic tests to confirm the diagnosis of psoriasis. Depending on the case, routine bloodwork (eg, complete blood count and metabolic panel) and infectious disease tests (eg, HIV, hepatitis panel, and rapid plasma reagin for syphilis) can be helpful to rule out other etiologies of skin rash.

Treatment is based on patient factors and disease severity

Starting with a low- to medium-potency steroid, such as betamethasone valerate 0.1% cream twice per day or triamcinolone acetonide 0.1% cream twice per day for 2 weeks, provides high safety and efficacy for localized disease.⁹ An appropriate-potency steroid should be chosen based on the disease severity, location, and patient’s preference and age. Topical vitamin D analogues often are used in conjunction with topical steroids to treat psoriasis.⁹

Depending on the severity, patient age, comorbidities, and availability of treatment, other treatment options for psoriasis include oral methotrexate (2.5 mg to 25 mg weekly, starting with a low dose), acitretin (10 mg to 50 mg daily), apremilast (10 mg daily, gradually increasing to 30 mg twice per day in a divided dose), biologics, and narrowband ultraviolet light.

In this case, betamethasone dipropionate 0.05% cream twice daily for 2 weeks was not sufficiently effective due to the extent of the psoriasis. Following consultation with a dermatologist, clobetasol propionate 0.05% cream twice per day and oral apremilast (10 mg once per day on the first day and 10 mg twice per day afterward) were prescribed for 2 weeks. The patient’s psoriasis improved somewhat after 2 weeks of the treatment, but many plaques remained. Therefore, apremilast was stopped and subcutaneous adalimumab was started (initial loading dose, 80 mg, then 40 mg every other week). The psoriasis lesions cleared over the next 2 to 3 months. The patient was maintained on the adalimumab to avoid a recurrence of lesions.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

ILLUSTRATIVE CASE

A 32-year-old primigravida at 10 weeks’ gestation presents for an initial prenatal visit. Medical history includes hypertension that is currently well controlled on labetalol 200 mg twice daily. The patient’s blood pressure (BP) at today’s visit is 125/80 mm Hg. Should labetalol be discontinued?

Chronic hypertension in pregnancy is hypertension that predates the pregnancy or with onset prior to 20 weeks’ gestation. Diagnostic criteria include systolic BP > 140 mm Hg or diastolic BP > 90 mm Hg, use of antihypertensive medications prior to pregnancy, or pregnancy-related hypertension persisting > 12 weeks postpartum.^2,3 Chronic hypertension affects 0.9% to 5% of pregnancies and is associated with increased risk for complications, such as superimposed preeclampsia, small-for-gestational-age infant, preterm birth, cesarean delivery, and neonatal intensive care unit admission.⁴ Superimposed preeclampsia occurs in about 17% to 25% of pregnancies affected by chronic hypertension, compared with 3% to 5% of the general population.³

Historically, a higher treatment threshold of 160/110 mm Hg was preferred to avoid theoretical complications of low placental perfusion.² Practically, this often meant discontinuing antihypertensives at the onset of prenatal care if BP was well controlled. A few small trials previously demonstrated that tight BP goals reduced the risk for severe hypertension, but they did not show an improvement in pregnancy outcomes.^5-7 This larger RCT evaluated whether treatment of mild chronic hypertension in pregnancy at lower BP thresholds is associated with improved pregnancy outcomes without negative impact on fetal growth.

STUDY SUMMARY

Active BP treatment yielded better pregnancy outcomes

In a US multicenter, open-label RCT, 2419 pregnant patients with chronic hypertension and singleton fetuses at gestational age < 23 weeks were randomized to receive either active pharmacologic treatment with a BP goal of 140/90 mm Hg or standard treatment, in which BP medication was withheld unless BP reached 160/105 mm Hg (severe hypertension). If medication was initiated in the standard-treatment group, the goal was also 140/90 mm Hg. Exclusion criteria included severe hypertension or suspected intrauterine growth restriction at randomization, known secondary hypertension, certain high-risk comorbidities (eg, cardiac or renal disease), or a major fetal anomaly.

The American College of Obstetricians and Gynecologists and the Society for Maternal– Fetal Medicine have issued statements recommending a change in practice based on this trial.

First-line medications were labetalol or extended-release nifedipine in the majority of patients in the active-treatment group and in standard-treatment patients who developed severe hypertension. Patients were followed until 6 weeks after delivery. Intention­-to-treat analyses were performed. The primary outcome was a composite of fetal or neonatal death before 28 days of life, superimposed preeclampsia with severe features up to 2 weeks postpartum, placental abruption leading to delivery, and medically indicated preterm birth before 35 weeks’ gestation. Safety outcomes included birthweight < 10th and < 5th percentile for gestational age.

Primary outcome events occurred in 30.2% of the active-treatment group compared with 37% of the standard-treatment group (adjusted risk ratio [aRR] = 0.82; 95% CI, 0.74-0.92; number needed to treat [NNT] = 15). Preeclampsia with severe features (23.3% vs 29.1%; aRR = 0.80; 95% CI, 0.70-0.92) and medically indicated preterm birth before 35 weeks (12.2% vs 16.7%; aRR = 0.73; 95% CI, 0.6-0.89) occurred less often in the active-treatment group compared with the standard-treatment group. There were no differences in rates of placental abruption, fetal or neonatal death, or small-for-gestational-age infants.

WHAT’S NEW

Target BP of < 140/90 mm Hg reduced risk

This trial provides high-quality evidence that initiating or maintaining treatment at a nonsevere BP threshold (< 140/90 mm Hg) in pregnant patients with mild chronic hypertension reduces maternal and neonatal risk without increasing the risk for small-for-­gestational-age infants. The American College of Obstetricians and Gynecologists and the Society for Maternal–Fetal Medicine have issued statements recommending a change in practice based on this trial.^8,9

Continue to: CAVEATS

Patient characteristics and medication choices were limited

This trial does not identify a BP goal for patients who are at highest risk for complications of hypertension or who already have been given a diagnosis of a growth-restricted fetus, as those patients were excluded.

Most patients in the trial who required medications received labetalol or extended-­release nifedipine. It is unclear if other medications would produce similar outcomes.

CHALLENGES TO IMPLEMENTATION

Limited challenges anticipated

There should be limited challenges to implementation.

The US Preventive Services Task Force (USPSTF) had a productive year in 2022. In total, the USPSTF

• reviewed and made recommendations on 4 new topics
• re-assessed 19 previous recommendations on 11 topics
• made 24 separate recommendations, including 1 “A,” 3 “B,” 3 “C,” and 5 “D” recommendations and 12 “I” statements (see TABLE 1¹).

A note about grading. TABLE 2² outlines the USPSTF’s grade definitions and suggestions for practice. The importance of an “A” or “B” recommendation rests historically with the requirement in the Affordable Care Act (ACA) that all USPSTF-recommended services with either of these grades have to be provided by commercial health insurance plans with no co-pay or deductible applied. (The legal challenge in Texas to the ACA’s preventive care provision may change that.)

What’s new?

The USPSTF’s review of 4 new topics exceeds the entity’s output in each of the prior 4 years, when the Task Force was able to add only 1 or 2 topics annually. However, 3 of the 4 new topics in 2022 resulted in an insufficient evidence or “I” statement, which means there was not enough evidence to judge the relative benefits and harms of the intervention.

These 3 included screening for type 2 diabetes in children and adolescents younger than 18 years; screening for obstructive sleep apnea in the general adult population (ages ≥ 18 years); and screening for eating disorders in adolescents and adults. The fourth new topic, screening for anxiety in children and adolescents, resulted in a “B” recommendation and was described in a recent Practice Alert.³

Major revision to 1 prior recommendation

Only 1 of the 19 revisited recommendations resulted in a major revision: the use of daily aspirin for primary prevention of cardiovascular disease (CVD). Note that it does not apply to those who have established CVD, in whom the use of aspirin would be considered tertiary prevention or harm reduction.

In 2016, the USPSTF recommended (with a “B” grade) the use of daily low-dose aspirin for those ages 50 to 59 years who had a 10-year risk for a CVD event > 10%; no increased risk for bleeding; at least a 10-year life expectancy; and a willingness to take aspirin for 10 years. For those ages 60 to 69 years with a 10-year risk for a CVD event > 10%, the recommendation was a “C.” For those younger than 50 and older than 70, an “I” statement was issued.

In 2022, the USPSTF was much less enthusiastic about daily aspirin as a primary preventative.⁴ The recommendation is now a “C” for those ages 40 to 59 years who have a 10-year CVD risk ≥ 10%. Those most likely to benefit have a 10-year CVD risk > 15%.

Continue to: The recommendation pertains...

The recommendation pertains to the initiation of aspirin, not the continuation or discontinuation for those who have been using aspirin without complications. The ­USPSTF suggests that the dose of aspirin, if used, should be 81 mg and that it should not be continued past age 75 years. A more detailed discussion of this recommendation and some of its clinical considerations is contained in a recent Practice Alert.⁵

“D” is for “don’t”(with a few caveats)

Avoiding unnecessary or harmful testing and treatments is just as important as offering preventive services of proven benefit. Those practices listed in TABLE 1¹ with a “D” recommendation should be avoided in practice.

However, it is worth mentioning that, while postmenopausal hormone replacement therapy should not be prescribed for the prevention of chronic conditions, this does not mean it should not be used to alleviate postmenopausal vasomotor symptoms—albeit for a limited period of time.

Also, it is important to appreciate the difference between screening and diagnostic tests. When the USPSTF recommends for or against screening, they are referring to the practice in asymptomatic people. The recommendation does not pertain to diagnostic testing to confirm or rule out a condition in a person with symptoms suggestive of a condition. Thus, the recommendation against screening adults for chronic obstructive pulmonary disease applies only to those without symptoms.

Be selective with services graded “C” or “I”

The USPSTF recommendations that require the most clinical judgment and are the most difficult to implement are those with a “C.” Few individuals will benefit from these interventions, and those most likely to benefit usually are described in the clinical considerations that accompany the recommendation. These interventions are time consuming and may be subject to insurance co-pays and deductibles. All 3 “C” recommendations made in 2022 (see TABLE 1¹) pertained to the prevention of CVD, still the leading cause of death in the United States.

Continue it: As "I" statement is not the same...

An “I” statement is not the same as a recommendation against the service—but if the service is offered, both the physician and the patient should understand the uncertainty involved. The services the USPSTF has determined lack sufficient evidence of benefits and/or harms are often recommended by other­ organizations—and in fact, the use of the “I” statement distinguishes the USPSTF from other clinical guideline groups.

If good evidence does not exist, the ­USPSTF will not make a recommendation. This is the main reason that, when the USPSTF reevaluates a topic (about every 6 to 7 years), they seldom make significant changes to their previous recommendations. Good evidence tends to survive the test of time.

However, adherence to this standard can cause the USPSTF to lag behind other guideline producers for some commonly used interventions. This delay can be considered a detriment if the intervention eventually proves to be effective, but it is a benefit if the intervention proves to be nonbeneficial or even harmful.

Putting recommendations into best practice

Given the time constraints in primary care practice, the most efficient way of providing high-quality, clinical preventive services is by implementing USPSTF “A” and “B” recommendations, being very selective about who receives an intervention with a “C” recommendation or “I” statement, and avoiding interventions with a “D” recommendation. 

BREAKING NEWS

At press time, the USPSTF issued a draft recommendation statement that women begin receiving biennial mammograms starting at age 40 years (through age 74 years). For more, see: www.uspreventiveservicestaskforce.org/uspstf/draft-recommendation/breast-cancer-screening-adults#fullrecommendation start