Subclinical Hypothyroidism: To Screen or Not to Screen?

By Addie Peretz, MD

Faculty Peer Reviewed

Despite the ease of screening for hypothyroidism with hormone assays and the availability of thyroxine replacement therapy, no recommendations regarding routine screening for hypothyroidism in adults are universally accepted. The American Academy of Family Physicians [1] and the American Association of Clinical Endocrinologists [2] recommend periodic assessment of thyroid function in older women.  The American Thyroid Association advocates for more frequent earlier screening, recommending measurement of thyroid stimulating hormone (TSH) beginning at age 35 and every 5 years thereafter.[3]

Whereas screening adults for hypothyroidism is controversial, screening infants for congenital hypothyroidism is routinely done.  The reasons for the universal acceptance of congenital hypothyroidism screening include its high prevalence (1:4000 births), the severity of the consequences if even mild hypothyroidism is left untreated, and the efficacy of treatment with levothyroxine replacement.  Adults have a lower prevalence of overt disease, and the necessity, efficacy, and cost -effectiveness of treating subclinical hypothyroidism are uncertain.[4]

Subclinical hypothyroidism (SCH) is defined as a normal serum free thyroxine (T4) concentration in the presence of an elevated serum thyrotropin (TSH) concentration.[5]  In the United States National Health and Examination Survey (NHANES III), 4.3% of the 16 533 people studied, excluding those subjects with known thyroid disease, were found to have SCH.[6] Other population-based studies report the prevalence of subclinical hypothyroidism to be as high as 15%.  A higher prevalence has been reported among women, Caucasian populations, those over 50 years of age, and men and women with a family history of thyroid disease.

One of the most compelling reasons to screen for hypothyroidism is to reduce the risk of the  potential consequences of SCH.  In a prospective study of patients with subclinical hypothyroidism with 10-20 years of follow-up, approximately 33-55% of patients went on to develop overt hypothyroidism.  The risk of progression tended to correlate with the initial serum TSH concentration and the presence of antithyroid peroxidase antibodies.[7]

Another clinically relevant potential consequence of SCH is cardiovascular disease.  While data are inconsistent, some observational studies have reported an increased risk of cardiovascular disease among subjects with SCH.[8]  This increased risk may be related to the reported association between elevated TSH and elevated total and LDL-cholesterol concentrations.[9]  Other proposed mechanisms point to the link between SCH and other cardiovascular risk factors, including markers of inflammation, vascular reactivity, endothelial function, and carotid intima media thickness.[10]

While the development of overt hypothyroidism or cardiovascular disease are two of the more severe potential consequences of SCH, the disease also has an impact on quality of life and has been associated with neuropsychiatric disease.  SCH has been linked to defects in verbal memory and executive function, defects which improve upon treatment with levothyroxine.[11]  In addition, the lifetime frequency of depression has been found to be higher in subjects who have SCH compared with those who do not.[12]

Though the potential consequences of SCH can be severe, standardized treatment recommendations are lacking. Levothyroxine replacement therapy is recommended for all patients with a TSH greater than 10 mlU/L; however, treatment recommendations are controversial for those patients with a serum TSH level between 5 and 10 mIU/L.  Large-scale randomized trials establishing a benefit of treatment of SCH have yet to be conducted.  Studies are necessary to confirm that detection of SCH will allow physicians to implement effective interventions with levothyroxine therapy.

Despite the lack of randomized trials, screening is nonetheless important.  Until these trials are conducted, clinicians ought to have an especially low threshold for screening higher risk populations, including women with vague symptoms suggestive of hypothyroidism (such as fatigue or depression), women who are pregnant or anticipate becoming pregnant, those with a strong family history of autoimmune thyroid disease,[13] and patients with type 1 diabetes.[14],[15]

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