Kinetic Aspects of Cortisol-4-C14 Metabolism in a Patient After Subtotal Adrenalectomy for Cushing's Syndrome Associated With Bilateral Adrenal Hyperplasia*

Abstract

Although the major urinary metabolites of cortisol 1 have been identified (1-9) and quantitatively estimated (1, 10-13) in man, kinetic aspects related to the formation of these metabolites have been less clearly defined. In a previous publication (14) the pathways of formation, metabolite pool sizes, and the rates of formation of the metabolites of cortisol in two normal humans have been reported. The general method was the administration of a small quantity of cortisol-4-C14 during a steady-state condition (with reference to cortisol turnover) and the determination of the specific activities of cortisol and its metabolites in consecutive 15-minute urine samples. Equations expressing turnover of cortisol and rates of metabolite formation (15) were subsequently applied to these data. * Work supported in part by U. S. Public Health Service grant A-3164 to Harvard University; in part by grants from the Medical Foundation, Inc. and the American Legion Child Welfare Foundation to the Children's Hospital; in part by a contract with the Advisory Committee on Metabolism, Office of the Surgeon General, Department of the Army; and in part by a contract with the Atomic Energy Commission to the Peter Bent Brigham Hospital, Boston, Mass.I The compounds referred to are: cortisol or F, 11p3,-17a,21-trihydroxy-4-pregnene-3,20-dione; THF, 3a,11f,-17a,21-tetrahydroxy-5p8-pregnane-20-one; allo-THF, 3a,-1l,,17a,21-tetrahydroxy-5a-pregnane-20-one; THE, 3a, cortol, 3a,,17a,20a or p, cortolone, 3a,17a,20a or ,3,21-tetrahydroxy-5j3-pregnane-11-one; cortisone or E, 17a,21-dihydroxy-4-pregnene-3,11,20-trione; 6p-hydroxycortisol or 6,-OH-F, 6fl,11,6,17a,21-tetrahydroxy-4-pregnene-3,20-dione; 6,8-hydroxycortisone or 6#- 6,p,17a,11,11,,17ca,20a,11,,17a,20,8,17a, 1lfl-OH-Etio or llfl-hydroxyetiocholanolone, 3a,11,8-dihydroxy-5,8-androstane-17-one; and 11-0-Etio or li-ketoetiocholanolone, 3a-hydroxy-5,8-androstane-11,17-dione.To aid in the interpretation and applicability of such kinetic measurements, it seemed advisable to carry out further studies in man using similar techniques in which cortisol turnover was fixed by administration of a continuous infusion so that the calculated kinetic parameters could be compared with the known turnover rate. The patient chosen for study was a 23-year-old woman who, 6 weeks before the initial study, had had a subtotal adrenalectomy as treatment for Cushing's syndrome associated with adrenal hyperplasia. From the time of subtotal adrenalectomy to the time of the studies reported, the patient required cortisone as adrenal maintenance therapy. The initial observations of cortisol metabolism were obtained 24 hours after a surgical procedure, cholecystectomy. A similar study was repeated 4 months later when the patient appeared totally recovered from the cholecystectomy. In this paper, a comparison of kinetic parameters is made with reference to the low recovery of urinary cortisol metabolites, and attention is called to the low excretion of the 5a isomer, allo-THF, which we have reported to occur in Cus...

Metabolism of 11β-Hydroxyandrostenedione, Adrenosterone and Hydrocortisone to Urinary 11-Oxy 17-Ketosteroids1

“…In four normal subjects given 32.6 XlO 6 dpm 3 H-THF, we were also unable to detect any 5a C19O3 steroids (unpublished); it would have been possible to detect less than 0.1% conversion to 5a in these studies. No measurable quantity of purified 5a C19O3 metabolites was detected in three of our subjects given hydrocortisone, in spite of the fact that allo-THF usually comprises 9 to 25% and allocortol up to 4.5% of the urinary tetrahydro compounds (29,31,34,35). The validity of this observation is strengthened by the fact that 5a metabolites of simultaneously administered 11 OHA were readily measured and that a < 1 % conversion of hydrocortisone to 5a C19O3 steroids should have been detectable.…”

Precursors of Urinary 11-Oxy-17-Ketosteroids. II. Allo-3α-tetrahydrocortisol1

“…This is indicated by the small pool size and production rate of ATHF (23), and by the estimate that F is converted to ATHF only to the extent of 7 to 15% (17). [Certain states such as infancy (24) and hyperthyroidism (25) increase the relative production of ATHF, while others, such as pregnancy (26) and Cushing's disease (27), decrease it.]…”

Eine neue Methode zur Bestimmung der hexahydrierten Cortisol-Metaboliten

“…Gold und Mitarbeiter 8 Theoretisch ließe sich das Überwiegen der Ausscheidung der Hexahydroderivate einmal dadurch erklären, daß Tetrahydroverbindungen zu einem größeren Anteil, als man bisher annahm, am C-20 noch hydriert werden, zum anderen dadurch, daß dem bisher als Nebenweg angesehenen Abbau über die 20-Dihydroverbindungen eine größere Bedeutung zukommt (s. Schema).…”