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This version published online on February 13, 2007
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1869
A more recent version of this article appeared on May 1, 2007
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*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CHOLESTEROL
*LEVOTHYROXINE

Submitted on August 24, 2006
Accepted on February 6, 2007

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

Salman Razvi MRCP, Lorna Ingoe, Gill Keeka, Crispian Oates, Carolyn McMillan PhD, and Jolanta U Weaver PhD*

Department of Endocrinology, Queen Elizabeth Hospital, Gateshead, UK; Department of Biochemistry, Queen Elizabeth Hospital, Gateshead, UK; Regional Medical Physics Department, Newcastle General Hospital, Newcastle upon Tyne, UK; Health Psychology Research, Department of Psychology, Royal Holloway, University of London, Egham, Surrey, UK; School of Clinical Medical Sciences, Department of Diabetes and Endocrinology, University of Newcastle, Newcastle upon Tyne, UK

* To whom correspondence should be addressed. E-mail: J.U.Weaver{at}ncl.ac.uk.

Context: Subclinical hypothyroidism (SCH) is defined as raised serum thyrotropin (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 (QoL).

Objective: To assess CV risk factors and patient-reported outcomes after treatment.

Design: Randomised double-blind crossover study of L-thyroxine and placebo.

Setting: Community-dwelling patients.

Patients: One hundred patients [mean age (SD) 53.8 (12) years, 81 females] with SCH [mean TSH 6.6 (1.3) mIU/L] without previously treated thyroid or vascular disease.

Intervention: 100 µg of L-thyroxine or placebo daily for twelve weeks 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 (versus placebo) from 231.6 to 220 mg/dL, p<0.001; LDL cholesterol from 142.9 to 131.3 mg/dL, p<0.05; waist-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 thyroxine (FT4) 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 FT4 concentration.

Trial registration: ISRCTN35570362 URL: http://www.controlled-trials.com/isrctn/
Key words: Subclinical hypothyroidism • cardiovascular risk factors • endothelial function • quality of life • symptoms




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