The Role of the Adrenal Cortex in Glucose and Pyruvic Acid Metabolism in Man Including the Use of Intravenous Hydrocortisone in Acute Hypoglycemia

Abstract

l1.e EndocrineMetabolic Clinic, Albany Hospital, iilbany, N . V . I n froductionWith Thomas Addison's observations, in 1855, of the disease which now bears his name, great interest was generated in determining its cause and treatment. The synthesis of the first adrenal steroid, desoxycorticosterone, by Reichstein in 1937, with its strong electrolyte-regulating effects, prolonged the lives of Addisonians and led to a search for other compounds with which to correct the remaining metabolic disturbances characteristic of the adrenal deficient state. Newly isolated steroids from natural sources were shown to exert profound carbohydrate effects such as hyperglycemia, glycosuria, and hepatic glycogenesis. Inglel observed glycosuria in normal, force-fed rats given 17-hydroxycort icosterone, 11-dehydro-1 7-hydroxycorticosterone,2 ~orticosterone,~ and adrenocort icotropin h~r m o n e .~ Forshamb and Perera,6 using ll-dehydrocorticosterone, prevented hypoglycemia in fasted Addison disease patients without producing any significant increase in the fasting blood sugar or glucose tolerance. Eventually, a hierarchy of steroids was established which graded the steroids according to their electrolyte-effects on the one hand, and their carbohydrate effects on the other. Interestingly, the steroids possessed opposite degrees of potency when compared by these two standards of biological activity.The effect of certain of the adrenal steroids upon the glycogen content of the liver is very marked. According to Pabst, Sheppard, and Kuizenga? 17-hydroxycorticosterone is the most potent in causing deposition of liver glycogen, followed by 1 l-dehydro-l7-hydroxycorticosterone, corticosterone, and 11-dehydrocorticosterone. The compound 11-desoxycorticosterone is only weakly glycogenic, although it is the most potent in its effect upon electrolyte balance.With this knowledge, there developed an interest in determining other sites of action of the carbohydrate-active steroids. The ameliorating effect of adrenalectomy in diabetes of animals was shown by Long and Lukens.x The Cork suggested an inhibitory action of these steroids on the glucokinase reaction of carbohydrate synthesis. Cortical hormones participate in the synthesis of carbohydrate from proteins (gluconeogenesis), in which certain amino acids are deaminated and then combined into six-carbon chains to form glucose. A second function is to influence the reaction glucose F! glycogen towards the right, increasing the storage of glycogen in the liver at the expense of the blood sugar. In this reaction, many other hormones have an influence: insulin likewise promotes glycogen storage, while thyroxin and epinephrine mobilize glucose for use in the tissues. Anterior pituitary growth hormone antagonizes ' These studies were made possible. in part, through the help and cooperation of the Upjohn Company, lialamazoo, blirh.; Armour Laboratories, New York, N . Y.; and Ciba Pharmaceutical Produrts, Inc., Summit, N . J. 464

Predicting and Defining Steroid Resistance in Pediatric Nephrotic Syndrome Using Plasma Metabolomics

“…32,33 Pyruvate-metabolizing enzymes, including pyruvate carboxylase, are also regulated by GC. 34,35 Pyruvate also may be an important mediator or marker of kidney injury, as has been reported in acute kidney injury 36 and diabetic nephropathy models. 37,38 There are therefore reasonable mechanisms by which GC treatment may regulate [pyruvate] and kidney function, and conversely where a lack of response to GC may prevent recovery of [pyruvate] and kidney function.…”

The acute effect of hydrocortisone, deoxycorticosterone and aldosterone upon the excretion of sodium, potassium and acid by the human kidney

“…In night experiments the drop in phosphate excretion after cortisol injection was small and could hardly account for a difference of l9,uequiv/min in hydrion output, nor could lack of available buffer easily explain the greater over-all increase in cation exchange observed after cortisol injection. Bartter & Fourman (1957), whose observations resembled our own, ascribed the kaliuresis after cortisol to a rise in plasma potassium concentration, due perhaps to increased tissue break-down; Knight, Kornfeld, Glaser & Bondy (1955) also found a rise of plasma potassium concentration after giving cortisol, but other workers have found the concentration to remain unchanged or to fall (Frawley, 1955;Raisz, McNeely, Saxon & Rosenbaum, 1957;Mills & Thomas, 1957). Figure 9 of Mills & Thomas (1957) includes plasma potassium concentrations for subjects M and F in the cortisol experiments here recorded, so that rising excretion and falling plasma concentration have been observed simultaneously.…”

Circadian excretory rhythms in night workers

“…Phosphate excretion normally falls on waking, and since cortisol and other glucocorticoids are known to lower plasma phosphate concentration (Ingbar, Kass, Burnett, Relman, Burrows, and Sisson, 1951;Frawley, 1955;Kupperman, Persky, Linsk, Isaacs, and Rosenbluth, 1955;Mills andThomas, 1957a, 1959), and hence renal excretion of phosphate, the hypothesis of a causal connexion is plausible. In many subjects the adrenal rhythm was out of phase with the sleeping habits, and the plasma steroid concentration was not high around the time of waking; we have therefore examined the data for phosphate excretion.…”