The ACTH-cortisol axis was studied in 15 hemodialysis patients. Basal plasma cortisol concentrations were found to be elevated and ACTH to be in the high normal range. Cortisol responded normally to exogenous ACTH, but neither cortisol nor ACTH were suppressed in response to oral dexamethasone. 11-Deoxycortisol and ACTH concentrations did not rise normally in response to either oral or iv metyrapone. We conclude that standard testing of the ACTH-cortisol axis in dialysis patients yields results suggesting Cushing's syndrome.
Approximately one-third of patients with metastatic breast carcinoma respond to surgical ablative therapy but the morbidity associated with these procedures has limited their use to highly selected patients. Consequently, a chemical method of adrenal suppression was developed using a potent inhibitor of adrenal steroid synthesis, aminoglutethimide, in combination with a synthetic glucocorticoid, dexamethasone. While this regimen effectively blocked adrenal function, it was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism and reduced the bioavailability of dexamethasone. To overcome this problem, a new regime using aminoglutethimide and hydrocortisone, a glucocorticoid less susceptible to altered metabolism, was developed. Kinetic studies confirmed that aminoglutethimide does not interact with hydrocortisone to alter its rate of metabolism. Hormone measurements established that 1000 mg of aminoglutethimide and 40 mg of hydrocartisone daily suppressed DHA-sulfate, androstenedione, estrone, estradiol and aldosterone to a greater extent than the prior protocol using aminoglutethimide and 2-3 mg of dexamethasone. Patients experienced objective tumor regression with equal frequency while receiving the aminoglutethimide-hydrocortisone regimen or aminoglutethimide and dexamethasone and the overall rate of response in 50 evaluable patients was 38%. Side effects occurred frequently in the first few weeks of treatment but disappeared nearly uniformly thereafter. The present aminoglutethimide-hydrocortisone regimen is simple, non-toxic, effective in inhibiting estradiol synthesis and capable of inducing tumor regression as frequently as previously reported with adrenalectomy.
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