Thyrotropin with decreased biological activity, a delayed consequence of cranial irradiation for nasopharyngeal carcinoma

Abstract

Patients with TSH of decreased bioactivity have had previous surgery or no known cause (idiopathic). We describe eight patients with nasopharyngeal carcinoma treated with irradiation alone more than 5 yr ago. All had hypothalamic hypothyroidism with low FT4 and normal TSH. Iv TRH gave an exaggerated TSH response, with 60 min greater than 20 min values, 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 TSH increased from 13 to 31%, and 11 to 28%, respectively. Oral TRH given 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 hypothyroid levels in the first few days, despite the very elevated TSH; but increased to euthyroid levels and remained higher even while the serum TSH declined further. Direct measurement of TSH bioactivity in FRTL-5 cells in 3 patients showed low values of bioactivity to immunoactivity ratios: 0.4, < 0.2, and 0.35 (NR 0.6-2.1) which increased in 2 patients to 0.9 and 0.8 after 20 days TRH. Serum free a-subunit levels were low and unchanged (0.3 to 1.1 μg/L) with prolonged TRH. These observations suggest that cranial irradiation may cause hypothalamic hypothyroidism with TSH with decreased bioactivity, and that prolonged TRH administration may restore normal bioactivity.