Observations on Adrenal Insufficiency

Abstract

The influence of the adrenal cortex upon electrolyte physiology and renal function has been the subject of many recent investigations (1, 2, 3). Improvement in the preparation of cortical extract has been advanced to a state where it is now possible to maintain experimental animals in perfect health indefinitely under the standard conditions of metabolism experiments. This step forward affords an opportunity to make observations over long periods of time on the same animal, and thereby to study repeatedly the results following the termination and the reestablishment of cortical extract or sodium chloride therapy. The present work employs this technique to study the gradual as well as the rapid development of adrenal insufficiency. It includes also the effects of alterations in the sodium intake upon the varying experimental states thus produced. EXPERIMENTALThe subject of these observations was a male mongrel beagle hound, apparently in middle age, who lived in the animal colony of this laboratory for two years. The right adrenal gland was removed in April, 1933, and the left in January, 1934. On December 26, 1933, the dog was placed in a metabolism cage where he remained during all the successive periods of observation and was started on a daily diet consisting of 500 grams of raw lean beef and 5 grams of a dried milk preparation in addition to one " Haliver Oil " capsule containing viosterol.' The meat was procured in weekly supplies, each new lot being analyzed for Na, Ca, Mg, Cl, P and total nitrogen. The milk was similarly analyzed. These food analyses were limited to those periods of observation in which electrolyte balance studies were made. Varying amounts of sodium chloride were added to the diet. Cortical extract, made according to the extraction method of Pfiffner and Swingle (4), was received in 95 per cent alcohol from the Parke, Davis Laboratories, and the final preparation of the extract was completed in our laboratory. The extract was given, except in a few instances, in two daily subcutaneous injections. In the course of 13 months, during which this cortical extract was employed almost continuously, three lots were obtained which "Rockefeller Foundation Fellow from the University of Strasbourg.caused severe localized necrotizing lesions. Except for these mishaps, no untoward symptoms followed its administration.In the balance studies reported,2 the same technique and precautions were followed as in previous studies, and the methods of chemical analysis employed have been described elsewhere (1). Blood samples were obtained from the jugular vein and delivered under oil. Urea clearance tests were done according to the method of Van Slyke. Despite the removal of 20 to 40 cc. of blood at approximately weekly intervals over a period of 13 months of study, the dog did not develop anemia nor was there any significant decrease in the protein content of his serunmRoutine examination of the urine showed only a very faint trace of albumin at times. No other urinary abnormalities were noted except for a mo...

Renal Function in Patients With Addison's Disease and in Patients With Adrenal Insufficiency Secondary to Pituitary Pan-Hypofunction 1

“…They ascribed the changes to a "functional depression of the kidneys caused by a failure of elaboration by the adrenals of a substance necessary for maintenance of normal kidney function." Renal function in chronic adrenal insufficiency was measured by Stahl, Atchley and Loeb (6) in an adrenalectomized dog which was maintained for 9 months with adrenal cortical extract and salt without evidence of was observed to be in good physical condition, her serum electrolytes were normal and the blood pressure was 128/82. She lived only 18 hours after the sudden onset of weakness and hyperpyrexia.…”

Studies on the Suprarenal Cortex

“…It seems very unlikely that the loss of potassium, phosphate and nitrogen following the readministration of the hormone represents a coincidental destruction of cellular tissue. On the contrary, a marked improvement appears at once in muscular function, inconsistent with a theory of destruction of protoplasm (12). The observed excretion of potassium in most experiments is approximately the amount which would be discharged if the potassium level throughout all of the body fluids were lowered to about the same extent as is its concentration in the plasma.…”

Studies in Serum Electrolytes. Xii. The Effect of Water Restriction in a Patient With Addison's Disease Receiving Sodium Chloride 1

“…In addition, the patient had a diminished urea clearance varying from 23 to 33 per cent of average normal function. It would appear noteworthy that a similar diminution occurs in adrenalectomized dogs following withdrawal of extract (14). We believe these changes must be the result of the failure of the adrenals alone, since the presence of coincidental renal disease was excluded by the absence of antecedent history, and the failure to find casts, albumin, etc., in any of the numerous specimens of urine examined.…”