The Effect of the Chronic Administration of Adrenal Medullary Hormones to Man on Adrenocortical Function and the Renal Excretion of Electrolytes

Abstract

The acute and chronic administration of adrenaline to experimental animals and its acute administration to man have been shown to increase adrenocortical activity.In 1908 Babes and Jonesco reported that repeated injections of adrenaline caused adrenocortical hypertrophy in rabbits (1). Vogt found by direct assay of adrenal venous blood of dogs and cats that there was an increased output of adrenocortical hormone following the injection of adrenaline (2). She subsequently reported that multiple injections of adrenaline produced adrenal hypertrophy in intact but not in hypophysectomized rats (3).Long and Fry described a decrease in adrenocortical cholesterol and ascorbic acid following the injection of adrenaline in intact but not in hypophysectomized rats (4). This and subsequent work by Gershberg and associates (5) indicate that adrenaline causes an increased output of adrenocorticotrophin. Using a decrease in the level of circulating eosinophils as a very sensitive measure of increased adrenocortical activity, Recant and colleagues showed that a single dose of adrenaline increases adrenocortical activity in the dog, rat, and man (6). Although they found eosinopenia in men receiving multiple injections of adrenaline over periods as long as 48 hours, there was no evidence of increased adrenocortical activity as measured by the urinary excretion of steroids and uric acid.However, Bliss, Rubin, and Gilbert (7) reported increases in urinary uric acid and 17-ketosteroids in normal men and women given 8 mg. of adrenaline in oil in a period of 12 hours.Guest and coworkers showed that sustained eosinopenia does not occur uniformly in patients given repeated injections of adrenaline (8).Adrenaline prepared from biological material contains about 85 per cent epinephrine and 15 per cent nor-epinephrine (9) unless a special process is included to remove nor-epinephrine. The adrenaline used in the present study was manufactured from biological material and did contain nor-epinephrine. Since nor-epinephrine produces little or no eosinopenia (10, 11), the increased adrenocortical function which follows the administration of adrenaline must be due primarily to its epinephrine content. However, some of the results reported in the present paper may well have been due to nor-epinephrine. The designation adrenaline is used in this communication to indicate a mixture of epinephrine and norepinephrine.The observations reported were undertaken to determine what manifestations of increased adrenocortical activity occur during the chronic administration of adrenaline to man. To this end the level of circulating eosinophils, the urinary excretion of uric acid, the urinary excretion of steroids, and the metabolism of nitrogen, sodium, chloride, potassium, phosphorus, and calcium have been studied in men receiving repeated injections of adrenaline over a period of days.Among the effects observed have been increased urinary excretion of sodium, chloride, calcium, and uric acid, and decreased urinary excretion of potassium. The changes in th...