Abbie I. Knowlton

Cardiac failure in Addison's disease

In an average 30 years of follow-up study, seven of 22 patients with primary adrenal insufficiency have had cardiac failure. Comparison of these seven with the 15 who remain free of this complication revealed that the former group were somewhat older and had higher incidences of unrelated cardiac disease and of nonsteroid-dependent hypertension, but that their replacement regimens, with respect to sodium supplementation and sodium-retaining steroids, were identical with the latter. Coincident with the appearance of cardiac failure, all seven patients had a decrease in sodium requirements. Adequate control of the adrenal disease was subsequently possible with elimination of mineralocorticoid support in one of the six who had initially required this therapy and a reduction in dosage in the other five. In all seven, dietary sodium supplements were no longer required. In three patients with severe failure, sodium restriction was imposed and diuretics were added, although the latter therapy has required close monitoring to avoid sodium depletion.

Depletion of Carcass Potassium in Rats Made Hypertensive With Desoxycorticosterone Acetate (DCA) and With Cortisone

The hypertension which can be induced experimentally in rats by the administration of desoxycorticosterone acetate (DCA) differs from that which develops in rats given cortisone acetate in its dependence upon a liberal sodium intake (1). Not only is DCA-hypertension made more severe by providing the animals with excess sodium (2), but it fails to develop if the available supply of this cation be sufficiently restricted (3). In contradistinction, the capacity of cortisone (1) or of hydrocortisone (4) to elevate the blood pressure is independent of sodium intake. It seemed of interest, therefore, to determine whether the mechanisms underlying the dissimilar actions of these two groups of steroids would be reflected in the electrolyte composition of the tissues of animals given one or the other compound under conditions of sodium loading as well as of sodium restriction. A preliminary study analyzing pooled samples of tissue indicated that the hypertension induced by DCAwas accompanied by an increase in carcass sodium, whereas this did not obtain in the carcasses of rats made hypertensive with cortisone (5).

The effect of cortisone on the urinary excretion of 17-ketosteroids in patients with Cushing's syndrome.

The administration of cortisone to patients with virilism associated with adrenal hyperplasia results in a marked decrease in urinary 17-ketosteroid excretion (1-3) whereas no significant fall occurs in those patients whose virilism is due to an adrenal tumor (4, 5). The administration of cortisone inhibits pituitary adrenocorticotropin secretion causing secondary atrophy of the adrenals (6, 7); hence a decrease in 17-ketosteroid excretion ensues in those patients in whom the normal pituitary-adrenal interrelationship is preserved. The data obtained in patients with adrenogenital syndrome (4) as a result of the injection of cortisone stimulated a similar investigation of patients suffering from an allied disease, Cushings syndrome. It is generally agreed that the manifestations of Cushings syndrome are due to excessive 11-oxygenated corticosteroid secretion by the adrenal cortex, although the pituitary (8) and the hypothalamus (9) as well as the adrenal (10) have been postulated as the site primarily involved. If either an adrenal or pituitary tumor is present, it seems reasonable that the source of excessive secretion responsible for the disease picture lies in the neoplastic tissue and in such patients because of the autonomous nature of the tumor no fall in 17-ketosteroids would be anticipated following the injection of exogenous cortisone. On the other hand if no tumor exists, the bilateral adrenal hyperplasia may arise de novo and be independent of pituitary control, or the normal pituitary-adrenal interrelationships may still be operating. If the latter obtains, then the administration

THE COMBINED EFFECT OF CORTISONE ACETATE AND DESOXYCORTICOSTERONE ACETATE IN ADRENAL-ECTOMIZED RATS ON A LOW SODIUM DIET

In a previous report the authors have described the response of young adrenalectomized rats to desoxycorticosterone acetate (DCA) and to cortisone acetate (CA) when maintained on a diet severely restricted in sodium content (1). Daily injections of 2.5 mg. of DCAresulted in progressive weight gain and maintenance of normal blood pressure, while similar doses of CA were accompanied by rapid weight loss and arterial hypertension. With both steroids terminal serum sodium values were within normal range. The present experiments describe the results obtained over a wide range of dosages of DCA2 and CA,8 given singly and in varying combinations, and were undertaken in an attempt to determine to what extent the individual action of each steroid was modified by concomitant administration of the other.