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Spontaneous Diurnal Thyrotropin Secretion Is Enhanced in Proportion to Circulating Leptin in Obese Premenopausal Women

Departments of General Internal Medicine (P.K., A.E.M., H.P.), Endocrinology and Metabolic Diseases (F.R.), and Clinical Chemistry (M.F.), 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: Recent evidence implicates leptin as an important modulator of thyroid axis activity.

Objective: The objective of this study was to study spontaneous 24-h TSH secretion and 24-h circulating leptin concentrations in obese and lean women.

Design: This was a prospective parallel study (2004).

Setting: This study was conducted at the Clinical Research Center (Leiden University Medical Center, Leiden, The Netherlands).

Participants: Twelve healthy obese premenopausal women (body mass index, 33.2 ± 0.9 kg/m²) and 11 lean controls (body mass index, 21.4 ± 0.5 kg/m²) were studied in the follicular phase of their menstrual cycle.

Intervention(s): There were no interventions in this study.

Main Outcome Measure(s): Spontaneous 24-h TSH concentrations (10-min time intervals) and secretion were calculated using waveform-independent deconvolution technique (pulse). Twenty-four-hour circulating leptin concentrations (20-min time intervals) were measured.

Results: Mean TSH concentration (obese, 1.9 ± 0.2 vs. lean, 1.1 ± 0.1 mU/liter; P = 0.009) and secretion rate (obese, 43.4 ± 5.5 vs. lean, 26.1 ± 2.2 mU/liter distribution volume·24 h; P = 0.011) were substantially enhanced in obesity, whereas the fasting free T₄ (fT₄) concentrations were similar (fT₄ in obese, 15.4 ± 1.5 vs. in lean, 16.4 ± 1.5 pmol/liter; P = 0.147). TSH secretion was positively related to 24-h leptin concentrations (r² = 0.31; P = 0.007).

Conclusions: TSH release is enhanced in the face of normal plasma fT₄ concentrations in obese premenopausal women, and hyperleptinemia may well be involved in this neuroendocrine alteration.

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