THYROTROPIN WITH DECREASED BIOLOGICAL-ACTIVITY, A DELAYED CONSEQUENCEOF CRANIAL IRRADIATION FOR NASOPHARYNGEAL CARCINOMA

Patients with TSH of decreased bioactivity have had previous surgery o r no known cause (idiopathic). We describe eight patients with nasopha ryngeal carcinoma treated with irradiation alone more than 5 yr ago. A ll had hypothalamic hypothyroidism with low FT4 and normal TSH. Iv TRH gave an exaggerated ISH response, with 60 min greater than 20 min val ues, without any FT4 or TT3 response at 24 h to the hypersecreted TSH. Radioiodine uptake in 2 patients before and after 3 days of bovine TS H increased from 13 to 31%, and 11 to 28%, respectively. Oral TRH give n for 20 days to 5 patients showed a distinctive pattern in serum TSH, FT4 and TT3. Serum TSH rose markedly in the initial few days, dropped to moderate levels for a few days and finally dropped further towards normal values. In contrast, the FT4 and TT3 remained unchanged at hyp othyroid levels in the first few days, despite the very elevated TSH; but increased to euthyroid levels and remained higher even white the s erum TSH declined further. Direct measurement of TSH bioactivity in FR TL-5 cells in 3 patients showed low values of bioactivity to immunoact ivity ratios: 0.4, <0.2, and 0.35 (NR 0.6-2.1) which increased in 2 pa tients to 0.9 and 0.8 after 20 days TRH. Serum free alpha-subunit leve ls were low and unchanged (0.3 to 1.1 mu g/L) with prolonged TRH. Thes e observations suggest that cranial irradiation may cause hypothalamic hypothyroidism with TSH with decreased bioactivity, and that prolonge d TRH administration may restore normal bioactivity.