Annals of Internal Medicine CLINICAL GUIDELINE Screening for Thyroid Dysfunction: U.S. Preventive Services Task Force Recommendation Statement Michael L. LeFevre, MD, MSPH, on behalf of the U.S. Preventive Services Task Force* Description: Update of the 2004 U.S. Preventive Services Task Recommendation: The USPSTF concludes that the current ev- Force (USPSTF) recommendation on screening for thyroid idence is insufficient to assess the balance of benefits and harms disease. of screening for thyroid dysfunction in nonpregnant, asymptom- atic adults. (I statement) Methods: The USPSTF reviewed the evidence on the benefits and harms of screening for subclinical and “overt” thyroid dysfunction without clinically obvious symptoms, as well as the Ann Intern Med. 2015;162:641-650. doi:10.7326/M15-0483 www.annals.org effects of treatment on intermediate and final health outcomes. For author affiliation, see end of text. * For a list of USPSTF members, see the Appendix (available at www.annals Population: This recommendation applies to nonpregnant, .org). asymptomatic adults. This article was published online first at www.annals.org on 24 March 2015. he U.S. Preventive Services Task Force (USPSTF) clinicians. Thyroid dysfunction represents a continuum Tmakes recommendations about the effectiveness of from asymptomatic biochemical changes to clinically specific preventive care services for patients without re- symptomatic disease. In rare cases, it can produce life- lated signs or symptoms. threatening complications, such as myxedema coma or It bases its recommendations on the evidence of thyroid storm (1, 2). both the benefits and harms of the service and an as- Subclinical hypothyroidism is defined as an asymp- sessment of the balance. The USPSTF does not consider tomatic condition in which a patient has a serum the costs of providing a service in this assessment. thyroid-stimulating hormone (TSH) level exceeding the The USPSTF recognizes that clinical decisions in- upper threshold of a specified laboratory reference in- volve more considerations than evidence alone. Clini- terval (commonly but arbitrarily defined as 4.5 mIU/L) cians should understand the evidence but individualize but a normal thyroxine (T4) level (3). Patients with sub- decision making to the specific patient or situation. Sim- clinical hypothyroidism are often further classified as ilarly, the USPSTF notes that policy and coverage deci- having TSH levels between 4.5 and 10.0 mIU/L or sions involve considerations in addition to the evidence greater than 10.0 mIU/L. of clinical benefits and harms. Despite its name, “overt” hypothyroidism does not require the presence of symptoms and has been de- SUMMARY OF RECOMMENDATION AND fined biochemically by an elevated TSH level and a low EVIDENCE T4 level. As such, it encompasses a range of low T4 The USPSTF concludes that the current evidence is levels that may or may not be associated with a set of insufficient to assess the balance of benefits and harms relatively subtle and nonspecific clinical symptoms, of screening for thyroid dysfunction in nonpregnant, such as fatigue, feeling cold, weight gain, hair loss, and asymptomatic adults. (I statement) constipation. See the Clinical Considerations section for sugges- Subclinical hyperthyroidism is defined as an asymp- tions for practice regarding the I statement. tomatic condition in which a patient has a serum TSH See the Figure for a summary of the recommenda- level below the lower threshold of a specified labora- tion and suggestions for clinical practice. Appendix Table 1 describes the USPSTF grades, and Appendix Table 2 describes the USPSTF classifica- See also: tion of levels of certainty about net benefit (both tables are available at www.annals.org). Editorial comment .........................664 Summary for Patients.......................I-32 Related article: Ann Intern Med. 2015;162:35-45. RATIONALE Web-Only Importance CME quiz Thyroid gland disorders are among the most com- Consumer Fact Sheet mon endocrine conditions evaluated and treated by www.annals.org Annals of Internal Medicine • Vol. 162 No. 9 • 5 May 2015 641 CLINICAL GUIDELINE Screening for Thyroid Dysfunction Figure. Screening for thyroid dysfunction: clinical summary of U.S. Preventive Services Task Force recommendation. Population Nonpregnant, asymptomatic adults Recommendation No recommendation. Grade: I statement (insufficient evidence) Risk factors for an elevated thyroid-stimulating hormone (TSH) level include female sex, advancing age, white race, type 1 Risk Assessment diabetes, Down syndrome, family history of thyroid disease, goiter, previous hyperthyroidism, and external-beam radiation in the head and neck area. Risk factors for a low TSH level include female sex; advancing age; black race; low iodine intake; personal or family history of thyroid disease; and ingestion of iodine-containing drugs, such as amiodarone. The primary screening test for thyroid dysfunction is serum TSH testing. Multiple tests over 3 to 6 mo should be performed to Screening Tests confirm or rule out abnormal findings. Follow-up testing of serum thyroxine (T4) levels in persons with persistently abnormal TSH levels can differentiate between subclinical (normal T4 level) and “overt” (abnormal T4 level) thyroid dysfunction . Hypothyroidism is treated with oral T4 monotherapy (levothyroxine sodium). Consensus is lacking on the appropriate point for clinical intervention, especially for TSH levels <10.0 mlU/L. Hyperthyroidism is treated with antithyroid medications (e.g., Treatment and methimazole) or nonreversible thyroid ablation therapy (e.g., radioactive iodine or surgery). Treatment is generally recommended Interventions for patients with a TSH level that is undetectable or <0.1 mlU/L, particularly those with overt Graves disease or nodular thyroid disease. Balance of Benefits The current evidence is insufficient to assess the balance of benefits and harms of screening for thyroid dysfunction in and Harms nonpregnant, asymptomatic adults. For a summary of the evidence systematically reviewed in making this recommendation, the full recommendation statement, and supporting documents, please go to www.uspreventiveservicestaskforce.org. tory reference interval (usually 0.4 mIU/L) but normal T4 populations that do not have known signs or symptoms and triiodothyronine (T3) levels. Patients with subclini- of disease. cal hyperthyroidism are further classified as having “low but detectable” (about 0.1 to 0.4 mIU/L) or “clearly low” Detection or “undetectable” (<0.1 mIU/L) TSH levels (3). Early detection and treatment of asymptomatic Despite its name, “overt” hyperthyroidism does not persons with abnormal serum TSH levels with or with- require the presence of symptoms and has been de- out abnormal T4 levels may be beneficial because it fined biochemically by a low or undetectable TSH level may prevent longer-term morbidity and mortality from and an elevated T4 or T3 level. When present, symp- fractures, cancer, or cardiovascular disease. However, toms are often relatively nonspecific (for example, widespread screening and treatment of subclinical thy- weight loss, heart palpitations, heat intolerance, and roid dysfunction can also result in harms due to label- hyperactivity). ing, false-positive results, and overdiagnosis and For the purposes of this recommendation, thyroid overtreatment. dysfunction is defined as a spectrum of disorders re- The USPSTF found adequate evidence that screen- lated to the thyroid gland. The spectrum begins with ing can detect “abnormal” serum TSH levels in asymp- asymptomatic subclinical hypothyroidism and hyper- tomatic persons. However, what constitutes an abnor- thyroidism. In the middle of the spectrum are asymp- mal TSH level is uncertain. Laboratory reference tomatic “overt” hypothyroidism and hyperthyroidism, intervals are based on the statistical distribution of TSH defined biochemically by changes in serum TSH and T4 levels across the general population (for example, us- levels. At the end of the spectrum is thyroid disease, ing the 97.5th percentile as an upper boundary for nor- which is reserved for symptomatic “overt” hypothyroid- mal) rather than according to the association of a TSH ism and hyperthyroidism (that is, persistently abnormal level with symptoms, adverse outcomes, or particular serum TSH and T4 levels and clearly associated clinical risk factors for disease (3). There is professional dis- signs and symptoms that cannot be better explained by agreement about the appropriate cut points for the another condition). lower and upper boundaries of normal TSH levels in In making its recommendations about clinical pre- the general population and in subgroups, such as older ventive services, the USPSTF focuses on asymptomatic adults, where values differ from the overall population 642 Annals of Internal Medicine • Vol. 162 No. 9 • 5 May 2015 www.annals.org Screening for Thyroid Dysfunction CLINICAL GUIDELINE distribution (for example, shifting to a higher range of Suggestions for Practice Regarding the normal) (4–7). I Statement Accurate interpretation of serum TSH levels is fur- Potential Preventable Burden ther complicated by measurement variability and the About 5% of women and 3% of men in the United sensitivity of TSH secretion to conditions other than thy- States have subclinical hypothyroidism (4). Of note, roid dysfunction. These issues have led many profes- several studies have shown that about 37% of persons sional groups to recommend repeating thyroid func- with subclinical hypothyroidism spontaneously