Abstract Dr. Frederick K. Heath: While the endocrine glands are not essential to living processes, they do coordinate these in the complex organism and so render it more adaptable to stress. Without an endocrine system the organism can survive often only under special conditions. About one hundred years ago Addison first reported death following total destruction of the adrenal glands but the importance of the cortical tissue was not emphasized until almost fifty years later and then by the failure of epinephrine to support life in the total absence of the whole glands. Now, with some thirty different cortical steroids isolated, it is possible in part to correlate cortical functions with specific chemical structure. Substances having effects upon salt and water exchange, and carbohydrate and protein metabolism are found in the pregnane group of steroids with 21 carbon atoms. The androgenic substances fall into the class with no side chain at C-17 and therefore belong to the etiocholane group with 19 carbon atoms. Estrogenic materials are found in the phenols with 18 carbon atoms. Control of the electrolyte balance, so far best understood of the cortical functions, was in large part worked out before the active steroids were available. It is now known that desoxycorticosterone (and to a small extent 11-dehydrocorticosterone) act upon the renal tubular cells so as to promote the reabsorption of sodium and the excretion of potassium. Individuals with Cushing's syndrome may have high serum sodium and low serum potassium levels and tend toward hydremia and hypertension. The Addisonian, on the other hand, tends toward low sodium and high potassium concentrations in the serum, dehydration and hypotension; as the tubules fail to reabsorb sodium and retain potassium, there is a loss of chloride and/or bicarbonate, nitrogen retention and a fall in urinary ammonia. The administration of salt and water with or without DCA usually reverses this trend and relieves the accompanying symptoms. Hypoglycemia occurs in the adrenalectomized animal. Conversely, the diabetic animal is relieved by adrenalectomy and is made worse by the administration of either cortical extract or the 11-oxysteroids, particularly 11 -hydro-17-hydroxycorticosterone (Compound E of Kendall). Cori offers an explanation of these findings, which are associated with decreased phosphorylation of glucose, by the in vitro demonstration that cortical extract increases the inhibitory effect of anterior pituitary extract on hexokinase, an inhibition antagonized by insulin. Low blood sugar, episodes of hypoglycemia and insulin sensitivity may occur in the Addisonian patient. Yet to date, except in hypoadrenalism with diabetes or diabetes alone, no significant effects upon carbohydrate metabolism have followed the use of any adrenal cortical substance in humans. In contrast, ACTH does exert an appreciable effect in normal man. Diabetes and insulin resistance may be seen in instances of hyperadrenalism. The effect of the adrenal cortex upon protein metabolism is obscure. The gluconeogenic effect appears to be less than that upon carbohydrate utilization. In small animals the 11-oxysteroids seem to cause inhibition of growth during the growing phase and weight loss in mature animals. Decreased excretion of the urinary corticoids and 17-ketosteroids occurs after adrenalectomy and in Addison's disease. Increased excretion of these compounds may be found in hyperadrenalism. There is a marked increase in 17-ketosteroid excretion in the adrenogenital syndrome which may represent the formation of abnormal steroids. In this connection the increased urinary excretion of corticosteroids of the 11-oxy group following exposure of normal animals to stress, substances which serve to protect an adrenalectomized animal under similar conditions, introduces the concept of the “alarm” reaction, “general adaptation syndrome” and the “diseases of adaptation” of Selye. The opinion was expressed that these hypotheses required more verification. The effect of adrenal cortical materials on antibodies is probably small. No question exists as to the reduction in circulatory lymphocytes, fragmentation of tissue lymphocytes and reduction in the size of lymph nodes and thymus following the exhibition of cortical substances. On the other hand, no conclusive evidence establishes the lymphocyte per se as an important source of antibodies. Furthermore, adrenalectomized animals appear to form antibody as well as normal controls and no changes in immunity have been noted in Addison's disease or Cushing's syndrome.