The Hypercalcemia of Adrenal Insufficiency*

An interrelationship between the adrenal glands and calcium metabolism was demonstrated in 1911 by Guleke (1), who showed that adrenalectomy ameliorates tetany in parathyroidectomized ani-mals. This observation has been repeatedly con-firmed (2). Hypercalcemia after adrenalectomy was first demonstrated in 1924 by Kisch (3) in rabbits, and soon thereafter by other workers in dogs (4-8), cats (5, 9), and in patients with Addison's disease (10-12). An early report (13) of hypercalcemia in adrenalectomized rats was based upon dubious methods of analysis; later reports indicate that plasma calcium remains constant or falls in this species after adrenalectomy (14-16). Administration of adrenocortical steroids often ameliorates spontaneous hypercalcemia (17), ex-cept when it is caused by hyperparathyroidism ( 18). Nevertheless, in rats cortisone modifies or prevents the hypercalcemic response to parathyroid extract (16, 2). This discrepancy may be a matter of dosage, since large amounts of steroids may some-times reduce plasma calcium even in hyperpara-thyroidism (19, 20). In normal subjects, adminis-tration of adrenocortical steroids has little effect on plasma calcium concentration, and Cushing's disease is not associated with hypocalcemia. A report of hypercalcemia after cortisone adm-ninistra-tion to nephrectomized dogs (21) has not been confirmed (22). Several hypotheses have been advanced to ex-plain these observations. The possibility that hemoconcentration might explain the hypercal-cemia of adrenal insufficiency was suggested by the earliest workers; however, no mneasurenments of plasma protein concentration or ultrafiltrable cal-