The Beneficial Effect of<scp>l</scp>-Thyroxine on Cardiovascular Risk Factors, Endothelial Function, and Quality of Life in Subclinical Hypothyroidism: Randomized, Crossover Trial

TLDR

Subclinical hypothyroidism is defined by elevated TSH with normal thyroid hormone levels. The study aimed to determine whether L‑thyroxine treatment improves cardiovascular risk factors and quality of life in patients with subclinical hypothyroidism. In a randomized, double‑blind, crossover trial, 100 community‑dwelling adults with subclinical hypothyroidism received 100 µg L‑thyroxine or placebo daily for 12 weeks, with total cholesterol and flow‑mediated dilation as primary outcomes. L‑thyroxine reduced total cholesterol, LDL, waist‑to‑hip ratio, and improved flow‑mediated dilation, with higher free T4 levels predicting these changes and fatigue symptoms improving, demonstrating that treatment lowers cardiovascular risk factors and alleviates tiredness.

Abstract

Subclinical hypothyroidism (SCH) is defined as raised serum TSH levels with circulating thyroid hormones within the reference range. It is uncertain whether treatment of SCH with L-thyroxine improves cardiovascular (CV) risk factors and quality of life.The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment.This was a randomized, double-blind, crossover study of L-thyroxine and placebo.The study was conducted with community-dwelling patients.One hundred patients [mean age (sd) 53.8 (12) yr, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/liter] without previously treated thyroid or vascular disease.Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each.Primary parameters were total cholesterol (TC) and endothelial function [brachial artery flow-mediated dilatation (FMD)], an early marker of atherosclerosis. Patient-reported outcomes were also assessed.L-thyroxine treatment reduced TC (vs. placebo) from 231.6 to 220 mg/dl, P < 0.001; low-density lipoprotein cholesterol from 142.9 to 131.3 mg/dl, P < 0.05; waist to hip ratio from 0.83 to 0.81, P < 0.006; and improved FMD from 4.2 to 5.9%, P < 0.001. Multivariate analysis showed that increased serum free T(4) level was the most significant variable predicting reduction in TC or improvement in FMD. Furthermore, the symptom of tiredness improved on L-thyroxine therapy, but other patient-reported outcomes were not significantly different after correction for multiple comparisons.SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and symptoms of tiredness. The CV risk factor reduction is related to the increased level of achieved free T(4) concentration.