Michael L. LeFevre, MD, MSPH; on behalf of the U.S. Preventive Services Task Force *
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Disclosures: Dr. Gillman reports royalties from UpToDate and Cambridge University Press outside the submitted work. Authors not named here have disclosed no conflicts of interest. Authors followed the policy regarding conflicts of interest described at www.uspreventiveservicestaskforce.org/Page/Name/methods-and-processes. Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterest Forms.do?msNum=M15-0483.
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Update of the 2004 U.S. Preventive Services Task Force (USPSTF) recommendation on screening for thyroid disease.
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 effects of treatment on intermediate and final health outcomes.
This recommendation applies to nonpregnant, asymptomatic adults.
The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for thyroid dysfunction in nonpregnant, asymptomatic adults. (I statement)
Screening for thyroid dysfunction: clinical summary of U.S. Preventive Services Task Force recommendation.
Appendix Table 1. What the USPSTF Grades Mean and Suggestions for Practice
Appendix Table 2. USPSTF Levels of Certainty Regarding Net Benefit
James V. Hennessey MD, Jeffrey R. Garber MD
On behalf of the American Association of Clinical Endocrinologists Thyroid Scientific Committee.
March 29, 2015
USPSTF Throid Screening Recommendation
The USPSTF statement on screening for Thyroid Dysfunction and literature review address whether thyroid function tests should be performed as a clinical preventive service in adults without symptoms of thyroid disease. Utilizing a well-defined and rigid, analytical approach, the task force concluded that the level of evidence to support identifying asymptomatic disease was insufficient to assess either the benefits or harms of doing so. Symptoms of thyroid dysfunction are often subtle and, non-specific and vary substantially from individual to individual [3, 4]. Even those with overt hypothyroidism may not have features that reliably distinguish them from euthyroid individuals . From a clinician’s perspective, the narrowly focused USPSTF process and the rigid definition of the term screening is not used in daily interactions with patients .More recently ATA/AACE has recommended aggressive case finding (ACF) rather than general population screening for those with specific clinical features making it more likely to have thyroid dysfunction and to benefit from diagnosis. For hypothyroidism these include: family history of thyroid disease, autoimmune disorders, anemias, chromosomal disorders, prior neck radiation or thyroid surgery, hyperprolactinemia and treatment with medications like amiodarone, lithium, tyrosine kinase inhibitors, interferon α and interleukin-2. Randomized controlled trials have yet to address whether some of the cardiovascular benefits of treating overt thyroid dysfunction apply to subclinical thyroid disease. However substantial evidence suggests that it does, thereby lending further support for ACF for hyperthyroidism as well as hypothyroidism. [7-13].We agree with the USPSTF that strong data do not exist to justify screening non-pregnant adult populations for thyroid disease. However the data called for by the USPSTF is unlikely forthcoming  and thyroid dysfunction can be readily diagnosed and treated in a safe and cost effective manner. Accordingly, in the interim thyroid dysfunction should be considered when evaluating many of the non-specific complaints that physicians face daily  particularly in those persons most likely to have thyroid disease who benefit from treatment. 1. LeFevre, M.L., Screening for Thyroid dysfunction: U. S. Preventative Services Task Force Recommendation Statement. Ann Intern Med, 2015.2. Rugge, J.B., C. Bougatsos, and R. Chou, Screening and treatment of thyroid dysfunction: an evidence review for the u.s. Preventive services task force. Ann Intern Med, 2015. 162(1): p. 35-45.3. Canaris, G.J., J.F. Steiner, and E.C. Ridgway, Do traditional symptoms of hypothyroidism correlate with biochemical disease? J Gen Intern Med, 1997. 12(9): p. 544-50.4. Carle, A., et al., Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study. Eur J Endocrinol, 2014. 171(5): p. 593-602.5. Garber, J.R., et al., Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid, 2012. 22(12): p. 1200-35.6. Brenta, G., et al., Clinical practice guidelines for the management of hypothyroidism. Arq Bras Endocrinol Metabol, 2013. 57(4): p. 265-91.7. McQuade, C., et al., Hypothyroidism and moderate subclinical hypothyroidism are associated with increased all-cause mortality independent of coronary heart disease risk factors: a PreCIS database study. Thyroid, 2011. 21(8): p. 837-43.8. Razvi, S., et al., The incidence of ischemic heart disease and mortality in people with subclinical hypothyroidism: reanalysis of the Whickham Survey cohort. J Clin Endocrinol Metab, 2010. 95(4): p. 1734-40.9. Rhee, C.M., et al., Subclinical hypothyroidism and survival: the effects of heart failure and race. J Clin Endocrinol Metab, 2013. 98(6): p. 2326-36.10. Nanchen, D., et al., Subclinical thyroid dysfunction and the risk of heart failure in older persons at high cardiovascular risk. J Clin Endocrinol Metab, 2012. 97(3): p. 852-61.11. Ochs, N., et al., Meta-analysis: subclinical thyroid dysfunction and the risk for coronary heart disease and mortality. Ann Intern Med, 2008. 148(11): p. 832-45.12. Rodondi, N., et al., Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA, 2010. 304(12): p. 1365-74.13. Danzi, S. and I. Klein, Thyroid disease and the cardiovascular system. Endocrinol Metab Clin North Am, 2014. 43(2): p. 517-28.
Robert A. Stern PhD (1), James V. Hennessey MD (2)
Boston University School of Medicine (1), Harvard Medical School (2), Boston MA
Neuro-psychiatric aspects of the USPSTF Recomendation
The USPSTF[1, 2] utilized a well-defined, rigid, approach, of literature review to conclude that the evidence supporting identification of asymptomatic disease is insufficient. We are concerned that clinicians will conclude that thyroid function testing is unwarranted in all but the most symptomatic patients. Symptoms of thyroid dysfunction are subtle, non-specific, vary substantially from individual to individual and are unreliable[3, 4]. The USPSTF concludes no effect of subclinical hypothyroidism (SCHypo) and L-thyroxine (LT4) replacement on mood and neuro-psychiatric function based on 2 controlled studies which, based on design, USPSTF rated as fair and good quality. The first study diagnosed SCHypo when a confirmed TSH was greater than 3.5 mIu/L (57% had TSH 3.5 to 4.99), likely included many euthyroid individuals and then specifically excluded SCHypo subjects with symptoms by a standard questionnaire. These asymptomatic SCHypo subjects tested no differently than euthyroid controls who were not similarly excluded for symptoms. After 1 year of LT4 treatment, no improvement in function of these asymptomatic subjects was observed, a finding not unexpected since it would be difficult to detect improvement in individuals who, by design, are asymptomatic. The second study enrolled subjects as SCHypo with a single elevated TSH. By 6 months 35% of the controls on placebo were euthyroid. At the end of 1 year, only 84% on LT4 and fully 50% of those on placebo had a normal TSH. This trial had additional statistical (power) short comings, baseline cognitive function was essentially normal, and fully one half of the control group was not hypothyroid by study end, making it impossible to demonstrate an effect of treatment ( . Clearly the evidence rating system missed clinically relevant defects which would lead a clinician to dismiss the data. This further underscores the lack of good data to demonstrate an effect of screening but simultaneously creates the illusion that there is “Fair and Good” quality studies that do not support the treatment of subclinical hypothyroidism. Moreover, there are additional randomized controlled trials of LT4 that were not included in the USPSTF review that did show significant, albeit modest, improvement of treatment on neurocognitive and neuropsychiatric functioning. We agree with Cappola and Cooper that it seems inconceivable to propose a placebo controlled prospective study in subjects with overt but potentially “asymptomatic hypo or hyperthyroidism but do think more can be learned about subclinical dysfunction . If all generally accepted practices were subject to the standard of randomized placebo-controlled trials prior to implementation, it is likely that incision and drainage of abscesses and the use of parachutes by airborne troops would not be recommended. Since the performance of large scale, controlled clinical trials of overt hypothyroidism are highly unlikely, we recommend aggressive case finding to identify those most likely to benefit from diagnosis and treatment.
1. LeFevre, M.L., Screening for Thyroid dysfunction: U. S. Preventative Services Task Force Recommendation Statement. Ann Intern Med, 2015.
2. Rugge, J.B., C. Bougatsos, and R. Chou, Screening and treatment of thyroid dysfunction: an evidence review for the u.s. Preventive services task force. Ann Intern Med, 2015. 162(1): p. 35-45.
3. Canaris, G.J., J.F. Steiner, and E.C. Ridgway, Do traditional symptoms of hypothyroidism correlate with biochemical disease? J Gen Intern Med, 1997. 12(9): p. 544-50.
4. Carle, A., et al., Hypothyroid symptoms and the likelihood of overt thyroid failure: a population-based case-control study. Eur J Endocrinol, 2014. 171(5): p. 593-602.
5. Jorde, R., et al., Neuropsychological function and symptoms in subjects with subclinical hypothyroidism and the effect of thyroxine treatment. J Clin Endocrinol Metab, 2005.
6. Parle, J., et al., A randomized controlled trial of the effect of thyroxine replacement on cognitive function in community-living elderly subjects with subclinical hypothyroidism: the Birmingham Elderly Thyroid study. J Clin Endocrinol Metab, 2010. 95(8): p. 3623-32.
7. Joffe, R.T., et al., Subclinical hypothyroidism, mood, and cognition in older adults: a review. Int J Geriatr Psychiatry, 2013. 28(2): p. 111-8.
8. Cappola, A.R. and D.S. Cooper, Screening and Treating Subclinical Thyroid Disease: Getting Past the Impasse. Ann Intern Med, 2015.
Bangladesh Institute of Family Medicine and research
April 2, 2015
TSH should be included in routine screening for patients with cardiometabolic diseases
I agree with the recommendation that routine thyroid screening in asymptomatic nonpregnant individuals should be discouraged but at least TSH testing should be included in the routine laboratory investigation for patients with cardiometabolic diseases. Patients with cardiometabolic diseases frequently require statin therapy and statin induced myopathy is common even in asymptomatic hypothyroid or subclinical hypothyroid patients. Decision for levothyroxine therapy may be taken later but a physician should be vigilant during prescription of statin in patients with higher TSH level.
Albert Siu, MD, MSPH, Kirsten Bibbins-Domingo, PhD, MD, MAS, David Grossman, MD, MPH
Chair, USPSTF, Vice Chair, USPSTF
July 29, 2015
Drs. Hennessey and Stern appear to misunderstand our recommendation process, including the methods underlying our systematic evidence reviews, and we welcome the opportunity to clarify. The U.S. Preventive Services Task Force (USPSTF) makes recommendations that apply to average-risk individuals without signs or symptoms of disease; “aggressive case finding” falls outside of the scope of our work. An “I statement” is not a recommendation against screening; it is an acknowledgement that the requisite evidence is lacking, so that the balance of benefits and harms cannot be determined (1). The systematic evidence review employed a standardized, validated approach to assess all included studies. Quality ratings (good, fair, or poor) apply to the internal validity of studies, and include such factors as randomization or intention-to-treat analysis (2). Issues such as excluding symptomatic subjects (a goal of the review) or enrolling subjects after a single abnormal thyroid-stimulating hormone level relate to external validity. The strength of evidence is based on an assessment of information from all studies. Drs. Hennessey and Stern note additional randomized, controlled trials (RCTs) of levothyroxine treatment showing “significant” improvements in neurocognitive function. They cite their own review (3) of 10 treatment studies, 2 of which were in our report. The rest were either not RCTs, comprised of symptomatic participants, or did not assess neurocognitive function (e.g., asked about self-report of energy level). Drs. Hennessey and Stern concluded that “more research is required to determine…whether thyroid hormone therapy is appropriate and effective in treating subclinical hypothyroidism-associated neurobehavioral impairments” (3). We agree. Our call for treatment trials of asymptomatic overt thyroid dysfunction is ethical and needed. The benefits of screening for and treatment of asymptomatic thyroid dysfunction are uncertain and, if they exist, likely only occur in a smaller proportion of the population than would be screened and treated. Harms also occur to many throughout the screening and treatment cascade. This is the exact situation when a trial is most useful, and the proper course of action in the absence of certainty of net benefit. Sincerely,Albert Siu, MD, MSPH, Chair, USPSTFKirsten Bibbins-Domingo, PhD, MD, MAS, Vice Chair, USPSTFDavid Grossman, MD, MPH, Vice Chair, USPSTFReferences1. U.S. Preventive Services Task Force. Screening for thyroid dysfunction: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162:641-50.2. Rugge JB, Bougatsos C, Chou R. Screening for and treatment of thyroid dysfunction: an evidence review for the U.S. Preventive Services Task Force. Evidence synthesis no. 118. AHRQ publication no. 15-05217-EF-1. Rockville, MD. Agency for Healthcare Research and Quality; 2014. Accessed at: http://www.ncbi.nlm.nih.gov/books/NBK285869/ on July 1, 2015.3. Joffe RT, Pierce EN, Hennessey J, et al. Subclinical hypothyroidism, mood, and cognition in the elderly: a review. Int J Geriatr Psychiatry. 2013;28:111-8.
LeFevre ML, on behalf of the U.S. Preventive Services Task Force. Screening for Thyroid Dysfunction: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2015;162:641–650. doi: https://doi.org/10.7326/M15-0483
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Published: Ann Intern Med. 2015;162(9):641-650.
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