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


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


METHODS
The study was conducted with community-dwelling patients.


METHODS
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.


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


METHODS
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.


CONCLUSIONS
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.
Razvi
Salman
S
Department of Endocrinology, Queen Elizabeth Hospital, Gateshead, United Kingdom.
Ingoe
Lorna
L
Keeka
Gill
G
Oates
Crispian
C
McMillan
Carolyn
C
Weaver
Jolanta U
JU
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000886:Anthropometry; D015992:Body Mass Index; D001835:Body Weight / Q000502:physiology; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000502:physiology; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006304:Health Status; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy* / Q000523:psychology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011788:Quality of Life; D012307:Risk Factors; D018401:Sample Size; D013974:Thyroxine / Q000627:therapeutic use*; D016896:Treatment Outcome; D014463:Ultrasonography; D014664:Vasodilation / Q000502:physiology
D002784:Cholesterol; D013974:Thyroxine