URINARY ALPHA-KETOLIC STEROID METABOLITES OF CORTICAL HORMONES ADMINISTERED TO SUBJECTS WITH ADRENAL CORTICAL INSUFFICIENCY 1

Abstract

Hydrocortisone, cortisone, 17-hydroxy-11-desoxycorticosterone, corticosterone, 11-dehydrocorticos-terone, and 11-desoxycorticosterone were given to subjects with adrenal cortical insufficiency, and the major urinary alpha-ketolic steroid metabolites identified and semi-quantitative estimations made of excretion. Identification procedures included RDOC in various solvent systems, special color reactions and infrared spectrometric analysis and spectrometry in H2SO4 or both. The tetrahydro form (3 alpha-hydroxy pregnane configuration) of each was identified as a major alpha-ketolic metabolite. However, corticosterone and 11-dehydro-corticosterone each give lesser amounts of 2 additional alpha-ketolic metabolites saturated in ring A which appear to be the 3 alpha-hydroxy allopregnane derivatives of the parent compound and its C-11 interconversion product. The interconversion of the keto and hydroxyl group at C-ll was demonstrated in the absence of a normally functioning adrenal cortex for corticosterone and 11-dehydrocorticosterone as well as for cortisone and hydro-cortisone by the identification of the appropriate conversion products and their "tetrahydro" derivatives. The general similarity of the chromatographic pattern after administration of hydro-cortisone and cortisone as well as the similarity after corticosterone and 11-dehydrocorticosterone was demonstrated. The urinary excretion of total alpha-ketolic steroid metabolites, reducing lipids extracted after glucuronidase plus acid hydrolysis and those extractable after acid hydrolysis alone, and the total 17-ketosteroids was, in general, increased by the administration of these compounds. Considerable variability was experienced in these measurements.