The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial

J Clin Endocrinol Metab. 2007 May;92(5):1715-23. doi: 10.1210/jc.2006-1869. Epub 2007 Feb 13.


Context: 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.

Objective: The objective of the study was to assess CV risk factors and patient-reported outcomes after treatment.

Design: This was a randomized, double-blind, crossover study of L-thyroxine and placebo.

Setting: The study was conducted with community-dwelling patients.

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: Intervention consisted of 100 microg L-thyroxine or placebo daily for 12 wk each.

Measurements: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anthropometry
  • Body Mass Index
  • Body Weight / physiology
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / drug effects
  • Brachial Artery / physiology
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol / blood
  • Cross-Over Studies
  • Double-Blind Method
  • Endothelium, Vascular / drug effects*
  • Female
  • Health Status
  • Humans
  • Hypothyroidism / complications
  • Hypothyroidism / drug therapy*
  • Hypothyroidism / psychology*
  • Linear Models
  • Male
  • Middle Aged
  • Quality of Life*
  • Risk Factors
  • Sample Size
  • Thyroxine / therapeutic use*
  • Treatment Outcome
  • Ultrasonography
  • Vasodilation / physiology


  • Cholesterol
  • Thyroxine