Circulating nitric oxide is modulated by recombinant human TSH administration during monitoring of thyroid cancer remnant.

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.