Some extra-thyroid effects of TSH have been described in vitro and in vivo. TSH has recently been suggested to induce IL-6 secretion from adipocytes. Leptin is the main secretory protein from adipose tissue. Our aim was to evaluate the acute effect of rhTSH-induced TSH surge on serum leptin levels in differentiated thyroid carcinoma (DTC) patients. Ten patients (2 m, 8 f; age range 3166 years) with stage 1-3 DTC were evaluated during scheduled standard rhTSH testing. Leptin, thyroglobulin (Tg) and TSH were measured, before and after rhTSH administration (0.9 mg i.m. for 2 consecutive days). L-T4 therapy ranged from 575 to 1050 μg/week and f-T4 levels ranged from 8 to 23 pg/ml. According to BMI data, only 2 patients were obese. One patient presented a high HOMA-IR (>4). LDL-cholesterol levels were over 130 mg/dl in 50% of patients. Baseline leptin levels were 8.4±1.3 ng/ml. Only BMI correlated significantly (P=0.05) with baseline leptin levels. After rhTSH administration, TSH levels increased significantly (P<0.01), while thyroid hormones remained unchanged. According to Tg-stimulated levels and neck sonography, all but 2 patients were considered disease-free. Two patients were considered partially ablated after post-surgical radioiodine therapy. On average, leptin levels did not significantly change during rhTSH administration. Twenty hours after the last rhTSH administration, leptin levels were 8.6±1.4 ng/ml, maximal leptin levels being recorded after 1 week (8.9±1.5 ng/ml). No correlation between maximal TSH and leptin levels after rhTSH was noted. In conclusion our in vivo experimental model suggests that acute TSH increase after rhTSH testing is uneffective on circulating leptin. These results are in contrast with some literature data reporting an in vivo correlation between leptin and TSH in hypothyroid, hyperthyroid and obese subjects.