[Cushing's disease--pathophysiology and treatment].

We followed up 21 Cushing's disease patients (16 females and 5 males) aged 15 to 46 years, treated with reserpine (R) plus pituitary irradiation (PI). Mean duration of R administration and mean dose of PI were 24.5 +/- 10.8 (mean +/- SD) months and 54.0 +/- 9.8 Gy, respectively. Of them, four patients did not respond, one who received 66 Gy had brain necrosis and panhypopituitarism, and the other 16 patients (78%, 16/21) achieved initial remission. Of these 16 patients, there were 10 (aged 15 to 46 years) who were irradiated with 50 Gy or less (mean, 45.5 +/- 6.9 Gy), and 7 of them had initial response. As previously demonstrated effectiveness of the present regimen (R plus PI) could be evaluated by subjecting the patients to R-test, higher rate of remission was obtained among R-test responders (J. Clin. Endocrinol. Metab. 41:511, 1975). Eleven of our R-test responders in the present study showed an early onset of remission (6.9 +/- 5.7 months) as compared with 5 R-test non-responders (17.0 +/- 9.1, p less than 0.05). In addition, the response time positively correlated with the ratio of the difference between basal plasma cortisol (11-OHCS) levels before and after midnight administration of 8 mg dexamethasone (delta D8) divided by the difference between 24-h urinary excretion of 17-OHCS for 3 successive days before, during metyrapone (3.0 g/day, 6 divided dose, 2 days) administration and one day after (delta M). The sixteen patients were followed up until 1990 for a mean of 12.4 years (2.2 to 25.2 years). Among them, one died of unrelated illness with this regimen 4 years after achieving remission, 4 relapsed between 5 to 7 years follow-up, and the remaining 11 (52%, 11/21) had long-term remission for a mean of 15.7 +/- 9.0 years (2.2 to 25.2 years). Of them, there were 5 patients who were treated with PI with 50 Gy or less, and had long-term remission (5.8 to 24.4 with a mean of 17.6 +/- 7.6 years). During the long-term follow-up period of these 11 patients, endocrine assessment was carried out while off therapy. Basal urinary excretion of cortisol or 17-OHCS were were normal in all of the 11 patients, and 8 of 9 showed normal diurnal rhythm of plasma cortisol. Nine of 10 patients tested showed normal suppressibility by overnight 1 mg dexamethasone test and 6 of 9 showed normal response to CRH.(ABSTRACT TRUNCATED AT 400 WORDS)