Elevation of plasma leptin concentrations in obese hyperinsulinaemic hypothyroidism before and after treatment

Background Plasma leptin is considered to play a role in maintenance of ene rgy balance and body weight by neuroendocrine mechanisms. Thyroid hormones are permissive for adrenergic activation, which in turn has been shown to d ecrease leptin expression. This study was therefore designed to test the hy pothesis that hyperthyroidism results in lower leptin concentrations, where as hypothyroidism leads to higher plasma leptin concentrations. In addition , the effects of normalization of thyroid function on plasma leptin were in vestigated. Materials and methods Pasting plasma leptin concentrations and body fat mas s (total body electrical conductivity) were measured in patients with overt hypothyroidism and hyperthyroidism before and after successful treatment. Plasma leptin, glucose, insulin and free fatty acid concentrations were mon itored during an oral glucose tolerance test (OGTT 75 g). Results Fasting plasma leptin concentrations were similar in lean patients, independently of their thyroid function (hyperthyroid 12.5 +/- 2 ng mL(-1) , hypothyroid 10.2 +/- 2 ng mL(-1), euthyroid 12.7 +/- 3 ng mL(-1)). In obe se hypothyroid patients, plasma leptin was threefold higher (P < 0.0005) th an in lean hypothyroid patients, twofold higher (P < 0.005) than in obese h yperthyroid patients matched for fat mass and 30% increased (P < 0.01) comp ared with obese euthyroid subjects. There were no differences between fasti ng and post-prandial (OGTT) leptin concentrations in any group. Normalizati on of thyroid function did not affect plasma leptin, which remained elevate d (P < 0.005) in formerly obese hypothyroid patients. Plasma leptin was not associated with serum thyroid hormones but highly correlated with body mas s index and body fat mass in all patients (r = 0.85, P < 0.001). Plasma lep tin correlated with plasma insulin concentration only in hyperthyroid patie nts (P < 0.01, r = 0.64), who presented with blunted stimulation of insulin release and higher plasma glucose (P < 0.05) than hypothyroid subjects. Conclusion The results indicate that (a) the correlation of leptin with bod y fat mass is preserved in thyroid dysfunction, (b) plasma leptin is marked ly increased in obese hypothyroid hyperinsulinaemic patients and (c) plasma leptin is not affected by oral glucose loading.