External pituitary irradiation as a cause of TRH deficiency in patients with pituitary adenomas

The influence of external pituitary irradiation (XRT) on thyrotroph function and PRL secretion was studied in twenty-five patients with pituitary adenomas, of whom eight had acromegaly. Twenty-one patients had undergone subtotal operative removal of their adenomas 8-190 weeks (median 12 weeks) before XRT. Following irradiation there was a significant reduction in peak serum TSH levels in response to i.v. TRH (P less than 0.05, compared with before XRT). Peak TSH levels returned to normal at 3 months. Similarly a transient reduction in TRH-stimulated beta-TSH release was observed. Serum T3 and T4 concentrations also fell after XRT, the levels at 3 months being significantly lower than control values (P less than 0.02), though no difference was seen at 6 and 12 months. A delayed (hypothalamic) serum TSH response to TRH (60 greater than 20-min level) developed at 6 months. In contrast, PRL concentrations (basal and TRH stimulated) were not altered during the 12 months following XRT. These findings demonstrate that thyrotroph function can be transiently impaired following external pituitary irradiation. None of the patients studied required T4 replacement therapy. The development of a delayed TSH response to i.v. TRH may indicate endogenous TRH deficiency. It was not associated with supra-sellar tumour enlargement in our patients and may be due to hypothalamic damage by irradiation.