L-thyroxine did not improve symptoms or tiredness in older patients with subclinical hypothyroidism

Patients who were treated with thyroid medication instead of placebo did not experience significantly greater improvement in symptoms or quality of life regardless of the severity of their symptoms before treatment.


In older adults with subclinical hypothyroidism and high symptom burden, L-thyroxine did not improve symptoms or relieve tiredness compared with placebo, a study found.

The study included 638 patients ages 65 years or older with persistent subclinical hypothyroidism in a secondary analysis of TRUST (Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial), a randomized, placebo-controlled trial conducted in Europe and the U.K. In addition to persistent subclinical hypothyroidism, patients had a thyroid-stimulating hormone level of 4.60 to 19.9 mIU/L for more than three months and a normal free thyroxine level.

Researchers examined the one-year change in hypothyroid symptoms and tiredness scores (range, 0 to 100; higher scores indicate more symptoms) on the Thyroid-Related Quality-of-Life Patient-Reported Outcome Questionnaire in participants with high symptom burden (baseline hypothyroid symptoms score >30 or tiredness score > 40) versus lower symptom burden. The study results were published May 5 by Annals of Internal Medicine.

In the study, 132 participants had hypothyroid symptoms scores greater than 30, and 133 had tiredness scores greater than 40. The hypothyroid symptoms score improved similarly in those receiving L-thyroxine (mean within-group change, −12.3; 95% CI, −16.6 to −8.0) and those receiving placebo (mean within-group change, −10.4; 95% CI, −15.3 to −5.4) at one year. The adjusted between-group difference was −2.0 (95% CI, −5.5 to 1.5; P=0.27).

Improvements in tiredness scores were also similar in those receiving L-thyroxine (mean within-group change, −8.9; 95% CI, −14.5 to −3.3) and those receiving placebo (mean within-group change, −10.9; 95% CI, −16.0 to −5.8). The adjusted between-group difference was 0.0 (95% CI, −4.1 to 4.0; P=0.99). There was no evidence that baseline hypothyroid symptoms score (P=0.20 for interaction) or tiredness score (P=0.82 for interaction) modified the effects of L-thyroxine versus placebo.

The authors noted that their post hoc analysis had a small sample size and only one year of outcome data. Still, they wrote, “In the absence of another randomized clinical trial specifically designed for persons with SCH [subclinical hypothyroidism] and high symptom burden, these results do not support routine L-thyroxine therapy among older adults with SCH, including those with greater hypothyroid symptom burden and tiredness.”