Significance of Adrenocortical Atrophy in the Carbohydrate Metabolism of Hypophysectomized Dogs

Abstract

Evaluation of the relative significance of the adrenocortical steroids and of anterior pituitary hormones (other than ACTH) in the endocrine control of normal carbo-hydrate metabolism was undertaken. Hypophysectomized dogs (85-502 days post-hypophysectomy) manifesting an extreme insulin sensitivity, an abnormal secondary hypoglycemia during the glucose tolerance test, and a slight adrenaline hyperglycemia were used. Attempts were made to produce "physiological" steroid levels in these dogs by (a) stimulation of the atrophic adrenal cortices with potent ACTH prepns. (3-20 IU/mg.) and (b) adequate steroid replacement therapy. Correlations were made between the anatomic changes in the adrenal glands and the changes in carbohydrate metabolism induced by ACTH. Prolonged admn. of ACTH not only corrected many of the abnormalities in carbohydrate metabolism but also produced signs of hypercorticalism, viz., resistance to insulin, diabetes, and abnormally high blood sugar rises in response to adrenaline. Most dogs had adrenal gland wts. within the normal range, but histological evidence for adrenocortical hyperplasia was present. Thus "physiological" steroid levels were not attained in the ACTH studies. Prolonged admn. of either cortisone or hydro-cortisone, in dosages (0.83-1.35 mg./kg./day) sufficient to correct the disturbed carbohydrate metabolism of adrenalectomized dogs, only diminished but never abolished the insulin hyper-sensitivity of the hypophysectomized dogs. By the use of such "physiological" steroid levels, it is concluded that the adrenocortical atrophy is but 1 factor responsible for the abnormalities in carbohydrate metabolism of hypophysectomized dogs. In addition, absence of anterior pituitary hormone(s) other than ACTH contributes to the production of these abnormalities. These anterior pituitary hormone(s) participate in the hormonal regulation of normal carbohydrate metabolism.