1University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; 2Queen Elizabeth Hospital, Gateshead, United Kingdom.
Objective
It is controversial whether subclinical hypothyroidism (SCH) always reflects mild thyroid failure and if treatment is beneficial. The arguments in favour of treatment are prevention of progression, reducing cholesterol levels and improving symptoms. The consequence of SCH on body weight and its response to treatment has never been studied in a systematic manner.
Methods
Unselected population-based studies of SCH and randomised controlled trials (RCTs) that have assessed weight (BMI) as an outcome were systematically studied and meta-analysed. A prospective double-blind crossover RCT of L-thyroxine (100 mcg) versus placebo was performed in 100 SCH patients. BMI and waist circumference was measured as well as body composition assessed by bio-impedance method. Adipokines (leptin, resistin and adiponectin) were measured in patients at baseline and after therapy with L-thyroxine. Ethical approval was obtained from the local committee.
Results
Systematic review identified 10 population-based studies and 7 RCTs. BMI was not significantly higher in people with SCH as compared to euthyroid individuals in population-based studies, with a random weighted mean difference (95%CI) of 0.16 kg/m2 (−0.1 to 0.43), P=0.22. Meta-analysis of previous RCTs of L-thyroxine therapy showed a significant random weighted mean reduction in BMI of 0.38 kg/m2 (0.15 to 0.60), P=0.001. In the RCT of 100 patients, L-thyroxine reduced BMI by 0.20 kg/m2 (0.03 to 0.37), P<0.02; waist circumference reduced by 1.13 cm (0.23 to 2.0), P<0.01. Bio-impedance revealed that there was reduction in body fat by 0.60 kg (0.21 0.93), P< 0.03. Adiponectin and leptin levels did change but resistin levels increased on L-thyroxine, P<0.05.
Conclusions
People with SCH are not significantly heavier than euthyroid individuals but L-thyroxine therapy reduces weight, as borne out in meta-analysis. In a large RCT, L-thyroxine reduced weight, central adiposity and fat mass. L-thyroxine treatment leads to an unexpected increase in resistin levels, which requires further research.