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Background: Some extra-thyroid effects of TSH have been described in vitro and in vivo. TSH has recently been suggested to induce interleukin-6 secretion by adipocytes. Leptin is the main protein secreted by adipose tissue., Objective: The aim of our study was to evaluate the acute effect of the recombinant human TSH (rhTSH)-induced TSH surge on serum leptin levels in thyroidectomized patients undergoing levothyroxine (L-T4) suppressive therapy for differentiated thyroid carcinoma (DTC)., Design: A cohort of 15 female DTC patients was evaluated. Standard rhTSH testing was performed. Leptin, TSH, thyroid hormones, and thyroglobulin were measured before and 3, 6, and 9 days after rhTSH testing. Some metabolic parameters were also evaluated at the baseline., Results: Baseline leptin levels were 12.2+/-3.2 microg/l. Only body mass index (BMI) correlated significantly (p<0.05) with leptin levels. After rhTSH administration, TSH levels increased significantly (p<0.001), while thyroid hormones remained unchanged. Twenty hours after the last rhTSH administration, leptin (11.8+/-3.0 microg/l) levels were unchanged. The maximal TSH level was negatively related with BMI (p<0.05), but no correlation between maximal TSH and leptin levels after rhTSH was noted., Conclusions: Our in vivo experimental model suggests that an acute TSH increase after rhTSH testing is ineffective in changing circulating leptin levels.

Objective: Some extra-thyroid actions of thyroid stimulating hormone (TSH), such as an in vitro action on bone, have been described. Our aim was to evaluate in vivo the acute effect of a recombinant human TSH (rhTSH)-induced TSH surge on Osteoprotegerin (OPG) and receptor activator of the nuclear factor-kappaBeta (RANK-L) levels in patients under levo-thyroxine (L-T4) therapy., Design: 24 patients with differentiated thyroid carcinoma (DTC) were studied. Standard rhTSH testing was performed. OPG, RANK-L, TSH, thyroid hormones, thyroglobulin and several parameters of bone metabolism were evaluated., Results: Baseline OPG and RANK-L levels were in the range of our reference population. An inverse correlation between OPG and spinal Z-score (p=0.029) and between RANK-L and age (p=0.018) or urinary calcium/creatinine ratio (p=0.011) was detected. After rhTSH administration, a significant (p<0.001) increase in TSH was found. No significant increase in OPG or RANK-L levels after rhTSH was observed. No correlation was detected between TSH peak value after rhTSH and maximal percentage change in OPG or RANK-L. A slight increase in urinary cross-links after rhTSH was found., Conclusions: In a small group of subjects with a history of DTC on L-T4 regimen, our study did not support an acute direct effect of TSH on OPG and RANK-L.

During the administration of recombinant human TSH (rhTSH) to monitor differentiated thyroid carcinoma, mild side effects, such as nausea and headaches, often occur. The origin of these is not clear. Since changes in TSH and thyroid hormones can modulate some endothelial-derived factors, we aimed at testing whether rhTSH administration induces changes in nitric oxide. We studied 25 patients (56.6+/-12.6 yr) who had undergone thyroidectomy followed by ablative radioiodine for papillary thyroid cancer and who were under follow-up. While L-thyroxine therapy continued, thyroglobulin (Tg), TSH, free-T3, free-T4 and nitrite-plus-nitrate (NOx) concentrations were evaluated before and after rhTSH administration (0.9 mg i.m. on 2 consecutive days). Mean TSH showed a huge increase from baseline (0.1+/-0.0 mIU/l) to day 3 (216.3+/-17.5 mIU/l, p<0.001), which was not accompanied by changes in thyroid hormones. Mean baseline NOx levels were 12.6+/-1.2 micromoles/l and showed a significant increase on day 3 (20.1+/-1.2 micromoles/l, p<0.05 vs day 0), followed by progressive reduction from day 6 (18.1+/-2.8 micromoles/l) to day 9 (10.6+/-1.3 micromoles/l, p<0.05 vs day 0). There was a significant (p=0.04) correlation between the percentage increase in TSH and the percentage increase in NOx. On the other hand, increase in TSH did not correlate with the percentage decrease in NOx from day 6 to day 9. No correlation was noted between the increase in TSH or NOx and the occurrence or severity of the symptoms. Our study shows that, during rhTSH testing, circulating nitric oxide increases. This endothelial-derived factor might, in turn, mediate the occurrence of vasomotor headache and nausea in some particularly susceptible patients.