THYROID-ADRENOCORTICAL ANTAGONISM AND HISTAMINE METABOLISM.
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Thirteen patients aged 24 to 65 with Cushing's disease have been treated by transphenoidal hypophysectomy. There was one incident of meningitis and one late death from myocarditis. No radiotherapy was given. In 12 patients pituitary histology showed Crooke's changes and an adenoma was present in seven. On review of the 12 survivors two to 11 years later, 11 are in complete remission. One patient still showed some clinical features of Cushing's syndrome but steroid levels were normal. In five of the seven premenopausal women normal menstruation has returned and pregnancy has occurred in three. In four patients replacement hormone therapy is no longer required and a further four take only partial treatment. We conclude that transphenoidal hypophysectomy is an effective treatment for Cushing's disease.
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After administration of the dopamine-receptor-blocking drug, metoclopramide (10 mg orally), there is significant release of thyrotrophin (T.S.H.) in hypothyroid patients which is not evident in euthyroid subjects. This is not due to spontaneous fluctuation in basal T.S.H. levels, and it indicates inhibitory dopaminergic control of T.S.H. release in man. The lack of significant T.S.H. release in euthyroid subjects may be due to the inhibitory effects of normal circulating levels of T3 and T4 on T.S.H. release. The T.S.H. response in hypothyroidism is significantly correlated with both T3 and T4 levels, suggesting suppression of this inhibitory pathway in increasingly severe hypothyroidism.
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