Twenty adult patients with Cushing's disease treated with long term reserpine administration in combination with a single course of external pituitary irradiation were followed. Eleven patients experienced long term remissions of 15.5 +/- 8.9 (mean +/- SD) yr (55%) after a mean irradiation dose of 53.9 +/- 11.4 Gy and a mean duration of reserpine administration of 24.3 +/- 9.3 months. The long term remission rates of the patients irradiated with 50 Gy or less (n = 9; 45.0 +/- 7.1 Gy) and those with more than 50 Gy (n = 10; 61.3 +/- 3.3 Gy; excluding 1 irradiated with 66 Gy who developed brain necrosis) were 56% (5 of 9) and 60% (6 of 10), respectively, and did not differ significantly. There were no significant differences between the 2 groups with regard to the duration of reserpine administration or pretreatment clinical features. At the latest examination, regardless of the irradiation dose, all 9 patients with long term remission showed a higher level of plasma cortisol or 11-hydroxycorticosteroids in the morning than in the evening, normal suppressibility of plasma cortisol with overnight 1 mg dexamethasone (9 of 10), and well preserved responses of other pituitary hormones to various loading tests: normal responses of plasma ACTH to CRH (6 of 9), TSH (7 of 8), and PRL (5 of 8) to TRH and age-related normal responses of GH to GRH (4 of 8), LH (6 of 8), and FSH (6 of 8) to GnRH. These findings suggest that long term reserpine administration in combination with a conventional dose of pituitary irradiation is useful in the treatment of Cushing's disease.

Serum concentrations of thyroglobulin in healthy subjects were measured by a solid-phase immunoradiometric assay. The mean concentration of serum thyroglobulin in 53 healthy males was 5.0 ng/ml (1.0-25.9 ng/ml) and that of 57 healthy females was 5.2 ng/ml (1.0-27.7 ng/ml). Neither sex-related nor age-related change in the serum thyroglobulin level was observed.

Abstract. Effects of reserpine treatment, not associated with pituitary irradiation, on the pituitaryadrenocortical axis in a total of 37 untreated patients with Cushing's disease were evaluated. With short-term treatment (2 mg daily for 2 weeks, n=36), basal excretion of urinary 17-OHCS significantly decreased from 11.2±5.2 mg/day/m2 (body surface area) (mean ± SD) to 9.6±4.4 mg/day/m2 (P<0.01), and metyrapone-induced incremental responses of urinary 17-OHCS decreased from 58.4±41.4 mg/3 days/m2 to 45.9±29.8 mg/3 days/m2 (P<0.05). Long-term treatment (1.7±0.3 mg/day for a mean of 15.8± 19.9 weeks) induced a marked reduction in plasma cortisol, and 24-h urinary 17-OHCS and/or free cortisol in 4 of 8 patients examined. Long-term reserpine administration caused normal suppression of plasma cortisol (or 11-OHCS) in 3 of 9 patients with 1 mg, and in all of 5 patients with an 8 mg overnight dexamethasone suppression test. Plasma ACTH response to CRH was evidently decreased in one patient evaluated one month after the initiation of reserpine. The circadian rhythm of plasma cortisol was normal in one patient when the basal glucocorticoid level became normal with reserpine treatment. The present findings suggest that reserpine itself contributes in a causal fashion to the effectiveness of our regimen, reserpine and pituitary irradiation, for some Cushing's disease patients in whom it is effective.

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