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

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 mIU and 10 mIU per liter, repeat the test as 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/L. (LOE = 1b)

Stott DJ, Rodondi N, Kearney PM, et al, for the TRUST Study Group. Thyroid hormone therapy for older adults with subclinical hypothyroidism. N Engl J Med 2017;376(26):2534-2544.  [PMID:28402245]

Randomized controlled trial (double-blinded)

Government

Concealed

Outpatient (any)

Whether to treat patients with subclinical hypothyroidism (slightly elevated thyrotropin, normal T4, and no or minimal symptoms) remains controversial. The authors of this study recruited 737 such adults, 65 years and older, and randomized them to receive thyroid replacement or matching placebo. The mean baseline thyrotropin level was 6.4 mIU/L (normal range: 0.4 to 4.59 mIU/L), and few had a value greater than 10.0 mIU/L. The groups were balanced, allocation was appropriately concealed, and analysis was by intention to treat. Patients were followed up for 1 year, and the primary outcomes were the 4-item ThyPRO thyroid symptom score and a 7-item Tiredness Score. The treatment dose 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 "dose"). The final achieved average thyrotropin level was just over 3.0, which is a bit higher than the target 2.5 mIU/L recommended by some guidelines (Eur Thyroid J 2013;2:215-28). At the end of the study period, there was no difference in any clinical outcomes. A subset of slightly more than half the patients in each group had extended follow-up for a median of 2 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.