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High Circulating Thyrotropin Levels in Obese Women Are Reduced after Body Weight Loss Induced by Caloric Restriction

Departments of General Internal Medicine (P.K., J.G.L., A.E.M.), Endocrinology and Metabolic Diseases (F.R., H.P.), and Clinical Chemistry (M.F.), and Center for Human Drug Research (J.B.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: Dr. Hanno Pijl, Leiden University Medical Center, Department of Internal Medicine (C4-83), P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: h.pijl{at}lumc.nl.

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/m²) 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 T₃ 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 (r² = 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 T₃ may blunt energy expenditure in response to long-term calorie restriction, thereby frustrating weight loss attempts of obese individuals.

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