Treatment of Subclinical Hypothyroidism Ineffective in Older Adults


Am Fam Physician. 2017 Oct 15;96(8):online.

Clinical Question

Is there a clinical benefit to treating subclinical hypothyroidism in older adults?

Bottom Line

Treatment of patients with a minimally elevated thyrotropin (thyroid-stimulating hormone) level did not result in any improvement in symptoms. If patients present with a thyrotropin level between 4.6 and 10 mIU per L, repeat the test because the levels often normalize (this occurred in 60% of the patients initially referred for the study). Only consider treatment if levels increase to above 10.0 mIU per L. (Level of Evidence = 1b)


Whether to treat patients with subclinical hypothyroidism (slightly elevated thyrotropin level, normal thyroxine [T4] level, and no or minimal symptoms) remains controversial. The authors of this study recruited 737 adults with subclinical hypothyroidism, 65 years and older, and randomized them to receive thyroid replacement or matching placebo. The mean baseline thyrotropin level was 6.4 mIU per L (normal range = 0.4 to 4.59 mIU per L), and few patients had a value greater than 10.0 mIU per L. The groups were balanced, allocation was appropriately concealed, and analysis was by intention to treat. Patients were followed for one year, and the primary outcomes were the four-item ThyPRO thyroid symptom score and a seven-item Tiredness score.

The treatment dosage of levothyroxine was started at 50 mcg daily for most patients, and gradually increased until the thyrotropin was in the normal range (the placebo group had sham titration of their dosage). The final achieved average thyrotropin level was just greater than 3.0 mIU per L, which is a bit higher than the target 2.5 mIU per L recommended by some guidelines (Eur Thyroid J. 2013;2(4):215–228). At the end of the study period, there was no difference in any clinical outcomes. A subset of slightly more than one-half of the patients in each group had extended follow-up for a median of two years, and at that time there was a slightly greater improvement in the Tiredness score in the levothyroxine group, but this was of marginal clinical and statistical significance. There was no difference in harms, including cardiovascular events, although the study was not powered to detect a difference if there was one.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (any)

Reference: Stott DJ, Rodondi N, Kearney PM, et al.; TRUST Study Group. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med. 2017;376(26):2534–2544.

POEMs (patient-oriented evidence that matters) are provided by EssentialEvidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Associate Deputy Editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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