Isolation of 17-hydroxycorticosterone from the urine in a case of Cushing's syndrome associated with severe diabetes mellitus.

Many of the features of Cushing’s syndrome are those that would be expected to result from an oversupply of adrenal cortical hormones. Indeed, Albright (1) has attributed the development of this syndrome to overproduction by the adrenal cortex of the carbohydrate-active hormones (S hormone), while Kenyon (2) and Kepler and his associates (3) have explained some of the features of the syndrome, including the diabetes, by the action of these steroids, and other features by the action of other adrenal steroids. Evidence in support of these views has been found in an increased excretion of carbohydrate-active material in the urine as measured by stimulation of glycogenesis in the liver of the adrenalectomized animal (4), and also as measured by less specific chemical methods (5). It was therefore a matter of considerable interest to attempt to isolate the active material from the urine when a case of Cushing’s syndrome presented itself in which the associated diabetes mellitus was unusually severe. In this case the excretion of corticosteroid-like substances varied between 14 and 19 mg. (in terms of ll-dehydrocorticosterone),per day. The patient, a boy 14 years of age, was found at surgical exploration, and later at necropsy, to have hyperplastic adrenal cortices? The method for the determination of corticosteroid-like substances was based on the procedure of Lowenstein, Corcoran, and Page (6), in which the amount of formaldehyde generated by the action of periodic acid is determined. The amount of formaldehyde is taken as a measure of the amount of the groups -COCH,OH and -CHOHCH20H, the former group being an essential characteristic of the cortical hormones. In order to avoid interference by the steroid residues and impurities the formaldehyde was distilled prior to the calorimetric procedure. The urine was collected daily, acidified to pH 1, and extracted with chloroform after standing 1 to 3 days at room temperature. The extracts were pooled and worked up when enough had been accumulated. It was