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Salman Razvi, Lorna Ingoe, Gill Keeka, Crispian Oates, Carolyn McMillan, Jolanta U. Weaver, The Beneficial Effect of l-Thyroxine on Cardiovascular Risk Factors, Endothelial Function, and Quality of Life in Subclinical Hypothyroidism: Randomized, Crossover Trial, The Journal of Clinical Endocrinology & Metabolism, Volume 92, Issue 5, 1 May 2007, Pages 1715–1723, https://doi.org/10.1210/jc.2006-1869
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Abstract
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 μg 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 T4 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 T4 concentration.
