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An Alteration in Cortisol Metabolism in Patients with Cushing's Syndrome and Bilateral Adrenal Hyperplasia12

1963; Oxford University Press; Volume: 23; Issue: 12 Linguagem: Inglês

10.1210/jcem-23-12-1271

1945-7197

JAQUELINE A. GUIGNARD-DE MAEYER, John F. Crigler, Norman I. Gold,

Hormonal Regulation and Hypertension

Quantitative estimations of the urinary cortisol metabolites, ATHF, THF and THE, were obtained in 12 patients with Cushing's syndrome and surgically demonstrated bilateral adrenal hyperplasia. Ten of these patients (7 studied before and 3 from 2 months to 6 years after initial therapy) showed a marked proportional decrease in the excretion of the 5α-reduced metabolite, ATHF, indicating a significant alteration in the metabolism of cortisol. Two of the patients (both with active disease although previously treated) showed normal proportions of these 3 urinary cortisol metabolites. Thus, 2 groups of patients with Cushing's syndrome are distinguished by differences in cortisol metabolism. Two of the patients excreting a low proportion of ATHF prior to treatment were studied subsequently 1 and 2 years after adrenalectomy. The described alteration in cortisol metabolism had persisted in both individuals in the absence of clinical or laboratory evidence of excess cortisol. In an effort to determine the significance of the observations in patients with Cushing's syndrome, the same urinary cortisol metabolites were determined in normal adults and children and in subjects with either exogenously induced or spontaneously occurring alterations in adrenal function associated with variations in ACTH and steroid production. Only in 3 subjects administered long-term ACTH (63–98 days) were low proportions of urinary ATHF observed. In these subjects, however, the proportion of cortisol excreted as THE (representing the degree of 11-oxidation taking place) was significantly less than that observed in the patients with Cushing's syndrome who had comparable total excretions of the 3 cortisol metabolites. Normal children, who excrete proportionately larger amounts of THE than adults (increased 11-oxidation), showed a significant proportional decrease in urinary ATHF when given ACTH for only 2 days. Long-term (6 months to 6 years) glucocorticoid administration, per se, was not associated with any alteration in the proportional urinary excretion of these cortisol metabolites. The possible significance of these observations in understanding the pathogenesis of Cushing's syndrome is discussed.