L-thyroxine therapy in subclinical hypothyroidism - effect on cardiovascular risk factors, endothelial function and patient-reported outcomes /

Abstract

Context: It is controversial whether the treatment of subclinical hypothyroidism (SCH) with L-thyroxine improves cardiovascular (CV) risk factors and quality of life (QoL). Objective: To determine whether CV risk factors, endothelial function and patient-reported outcomes improve in people with SCH with L-thyroxine treatment. Design: Randomised double blind, cross-over study. Setting: Patients from primary care practices identified from laboratory database. Patients: One hundred patients (81 females) with mild SCH, and no existing thyroid or vascular disease, mean (SD) age 53.8 (12) years, thyrotropin (TSH) of 6.6 (1.3) mIU/L. One patient withdrew due to perceived side-effects. Intervention: Oral 100 meg of L-thyroxine or matching placebo daily for twelve weeks each. Main outcome measures: Powered to detect significant improvements in two primary parameters: total cholesterol (TQ levels and endothelial function (brachial artery flow mediated dilatation-FMD), the earliest marker of atherosclerosis. Results: L-thyroxine treatment reduced (mean difference, 95% Q TSH (5.64 mIU/L, 4.11 to 7.17), increased FT4 and FT3 levels (6.98 pmol/L, 5.97 to 7.98 and 0.6 pmol/L, 0.37 to 0.82, respectively), FMD improved (1.65%, 1.2 to 2.1) and TC levels reduced (435 mmol/L, -0.52 to -0.16). Increase in FT4 levels was the only significant determinant of the improvement in TC and FMD. Sexlife and overall QoL were less negatively impacted by SCH during L-thyroxine treatment. Symptom bother scores did not benefit by L-thyroxine but there was a significant improvement in the frequency of tiredness - from 89% to 78%, p<0.05. Health status and treatment satisfaction did not show any significant change. Conclusion: SCH treated by L-thyroxine leads to a significant improvement in CV risk factors and some patient-reported outcomes. The benefit of CV risk reduction is related to the increased level of achieved FT-4 concentration.