Treatment of Cushing's Disease with Reserpine and Pituitary Irradiation†

Abstract

Eighteen patients with Cushing's disease were treated with reserpine and pituitary irradiation. Complete remission was obtained in 9 out of 18 patients after reserpine treatment of 1-2 mg per day for a mean period of 20.4 months, and pituitary irradiation with a mean of 5,865 rads. In another 9 patients, reserpine 0.8-2 mg per day for a mean period of 22.5 months, and pituitary irradiation with a mean of 6,650 rads, were employed. Of these 9 patients, an additional subtotal adrenalectomy was carried out in 6 patients who are now in complete remission. Because of severe psychic symptoms resulted from the original disease in 2 of the remaining 3 patients, subtotal adrenalectomy was performed first and pituitary irradiation and reserpine treatment followed. Remission was eventually obtained in these 2 cases. One patient refused the operation, and thus had little clinical remission. All of the 17 cases in remission were followed up for periods of 6 months to 10 yr. During this time, only one case which had responded to reserpine and pituitary irradiation relapsed, but regained remission following resumption of therapy. Another died of cerebral glioblastoma 4 yr after remission of the disease. It was noteworthy that endocrinologic data including: plasma levels of ACTH and 11-OHCS, suppressibility by dexamethasone, responses of plasma GH to arginine and to insulin loads, and diurnal rhythm of plasma 11-OHCS were nearly normal in a considerable number of the cases in remission. Effectiveness of the combined therapy with reserpine and pituitary irradiation for treating Cushing's disease may support a working hypothesis that reserpine acts through some as yet unknown mechanism to correct a presumed central nervous disorder, while suitable pituitary irradiation probably corrects the pituitary dysfunction directly.

Combined Reserpine and Pituitary Irradiation Therapy for Cushing's Disease Patients Following Unsuccessful Transsphenoidal Microsurgery.

“…The observation that case 1 and 3 remained in remission even after reserpine was discontinued is in agreement with the observation reported by Miura et al(1975), although its explanation remains unclear.…”

“…In the present study, the combination therapy with reserpine irradiation, initially reported by Miura et al(1975), was effective in obtaining complete remission in patients whose surgical treatment was disappointing . In case 1, aminoglutethimide and metyrapone were temporally effective in reducing steroid secretion by their anti-adrenocortical action .…”

“…combined therapy with reserpine and irradiation, initially described by Miura et al (1975), used to be one of the treatments for Cushing's disease, transsphenoidal pituitary microsurgery (TPM) has become the vogue in this decade because of its high cure rate (Hardy, 1982;Boggan et al, 1983;Tagliaferri et al, 1986). However, recent reports (Burch, 1983;Guilhaume et al, 1988) …”

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

“…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),…”

“…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.)…”