No Benefit of Levothyroxine Treatment in High-Burden Subclinical Hypothyroidism

Hypothyroid symptoms and tiredness in patients with high-burden subclinical hypothyroidism are not improved with levothyroxine (LT₄) treatment, according to study results published in the Annals of Internal Medicine.

The benefit of LT₄ for patients with subclinical hypothyroidism has been debated and may depend on disease burden. In a secondary analysis of the randomized placebo-controlled Thyroid Hormone Replacement for Untreated Older Adults with Subclinical Hypothyroidism Trial (TRUST), investigators aimed to evaluate whether LT₄ therapy improves symptoms in older patients (aged ≥65 years) with high symptom burden.

Symptom burden was evaluated using the Thyroid-Related Quality-of-Life Patient-Reported Outcome (ThyPRO; range, 0-100) and EuroQol Group 5-Dimension (EQ-5D; range, 0.00-1.00) questionnaires, as well as performance on a handgrip test. Patients with a high symptom burden were defined as those with a hypothyroid symptoms score >30 or a tiredness score >40 on the ThyPRO questionnaire, an EQ-5D Health Utility score <0.75, or a handgrip strength <20 kg. The primary outcomes for the analysis were changed in hypothyroid symptoms and tiredness scores at 1 year.

Of the 638 patients included in the study, 132 (20.7%) had a hypothyroid symptoms score >30 and 133 (20.8%) had a tiredness score >40. Within these high-burden groups, there was no statistically significant difference in the proportion of patients who achieved normal thyrotropin (TSH) levels in the treatment and placebo groups at 1 year.

Compared with the placebo group, similar levels of improvement were observed in LT₄-treated patients with regard to hypothyroid symptoms score (between-group difference, -2.0; 95% CI, -5.5 to 1.5; P =.27) and tiredness score (between-group difference, 0.0; 95% CI, -4.1 to 4.0; P =.99). Baseline hypothyroid symptoms and tiredness scores did not modify the effects of LT₄ treatment (P_interaction = .20 and .81, respectively).

Similar results were seen in patients with EQ-5D scores <0.75 (n=152) and handgrip strength <20 kg (n=125).

The researchers noted that the secondary analysis was not prespecified in the original TRUST trial protocol. In addition, the mean TSH level after 1 year of therapy was 3.6 mIU/L in all groups; more aggressive LT₄ therapy may have led to increased benefit.

“[LT₄] therapy, as compared with placebo, was not associated with an improvement in hypothyroid symptoms or tiredness in older adults with persistent [subclinical hypothyroidism] and high symptom burden at baseline,” the study authors concluded. “[T]hese results do not support routine [LT₄] therapy among older adults with [subclinical hypothyroidism], including those with greater hypothyroid symptom burden and tiredness.”

Disclosure: Support for the study was partially provided by Merck.

Reference

de Montmollin M, Feller M, Beglinger S, et al. L-thyroxine therapy for older adults with subclinical hypothyroidism and hypothyroid symptoms: secondary analysis of a randomized trial [published online May 5, 2020]. Ann Intern Med. doi:10.7326/M19-3193