High circulating thyrotropin levels in obese women are reduced after body weight loss induced by caloric restriction

Context: Previous clinical studies concerning the impact of body weight loss on single plasma TSH concentration measurements or the TSH response to TRH in obese humans have shown variable results. Objective: The objective of this study was to investigate the effect of weight loss induced by caloric restriction on diurnal TSH concentrations and secretion in obese humans. Design: This was a clinical, prospective, crossover study. Setting: The study was conducted at the Clinical Research Center of Leiden University Medical Center. Participants: Eleven obese premenopausal women (body mass index, 33.3 +/- 0.7 kg/m(2)) were studied. Intervention: The study intervention was weight loss (50% reduction overweight by caloric restriction). Main Outcome Measure(s): Twenty-four-hour plasma TSH concentrations (10-min intervals) and the 24-h TSH secretion rate, calculated by a waveform-independent deconvolution technique (Pulse), were determined. Results: The 24-h TSH secretion rate was significantly higher in obese women than in normal weight controls, and weight loss was accompanied by diminished TSH release ( before weight loss, 43.4 +/- 6.4 mU/liter (.) 24 h; after weight loss, 34.4 +/- 5.9 mU/liter (.) 24 h; P = 0.02). Circulating free T(3) levels decreased after weight loss from 4.3 +/- 0.19 to 3.8 +/- 0.14 pmol/liter (P = 0.04). Differences in 24-h TSH release correlated positively with the decline of circulating leptin (r(2) = 0.62; P < 0.01). Conclusions: Elevated TSH secretion in obese women is significantly reduced by diet-induced weight loss. Among various physiological cues, leptin may be involved in this phenomenon. The decreases in TSH and free T(3) may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.