Long term follow-up of Cushing's disease treated with reserpine and pituitary irradiation.

Abstract

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.

Long Term Follow-up of Cushing's Disease Treated with Reserpine and Pituitary Irradiation Followed by Subtotal Adrenalectomy.

“…All of 5 (patients 3-6 and 9) patients in the arginine infusion test and 3 (patients 3, 6 and 7) of 5 in the insulin-induced hypoglycemia test showed normal responses during the early remission period as already described in our previous paper (Miura et al 1975). In addition, as in the patients who achieved long term remission with our regimen alone in our previous reports (Miura et al 1975;Murayama et al 1992), normal suppressibility of plasma cortisol was observed in the present group of patients, even though some of them relapsed subsequently. According to our most recent study, reserpine treatment alone, not combined with pituitary irradiation, sometimes improved suppressibility of plasma cortisol with low and high dose dexamethasone, and restored the normal diurnal rhythm of plasma cortisol, and normal response of plasma GH to 1-arginine or insulin-induced hypoglycemia tests in Cushing's disease (Minamori et al 1993).…”

“…Our recent follow-up results, however, also revealed a problem that the regimen required a long period of 2 to 28 months with a mean of 10.4 + 7.5 months to obtain the initial remission in the 11 patients with long term remission (Murayama et al 1992). In this study we had no way to determine how long additional treatments should be withheld or performed in patients with critical conditions or no apparent response on the therapeutic course.…”

“…Of them, follow-up results of 20 patients without further treatment were previously reported (Murayama et al 1992), and the remaining 10 patients (1 man and 9 women, patients 1.10), aged 15 to 59 years (mean±s.D., 32.7+14.2 years) with further treatment are reported here. Eight (1 man and 7 women) of these 10 patients were the same patients described in our previous report (Miura et al 1975),…”

“…Factors predictive of response to the regimen Excepting 2 patients whose outcome was difficult to evaluate because one developed brain necrosis and panhypopituitarism 2 years after achieving an initial remission and another died of a disorder unrelated to the original disease during remission (Murayama et al 1992), 28 patients with Cushing's disease treated with our therapeutic regimen-reserpine plus pituitary irradiation-were divided into 3 groups: 11 patients achieving long term remission, 7 patients showing failure with our regimen including 3 nonresponders and 4 patients relapsing after initial success (Murayama et al 1992) and the presently enrolled 10 patients who underwent an additional subtotal adrenalectomy during the early course of our regimen. To facilitate prediction of long term response or failure to the regimen, pretreatment clinical characteristics such as age, duration of disease before the treatment, pretreatment endocrine characteristics such as basal plasma and/or urine glucocorticoids levels, % AD, %AM, total dose and duration of reserpine treatment, and pituitary irradiation dose of the initial course were compared and analyzed between the above mentioned 3 groups.…”

“…There were no significant factors predictive of response to our regimen. et al In 1975, we proposed a new treatment regimen consisting of reserpine and pituitary irradiation for Cushing's disease (Miura et al 1975), and recently summarized clinically favorable long term follow-up results in 20 Cushing's disease patients treated with this regimen (Murayama et al 1992). In fact, 11 of the 20 patients (55%) thus treated have been well for a mean of 15.5+8.9 (mean± S.D.)…”