Adrenal suppression with aminoglutethimide. I. Differential effects of aminoglutethimide on glucocorticoid metabolism as a rationale for use of hydrocortisone

R. J. Santen, S. A. Wells, S. Runic, C. Gupta, John Kendall, E. B. Rudy, E. Samojlik

Research output: Contribution to journalArticle

67 Citations (Scopus)

Abstract

The morbidity resulting from surgical adrenalectomy in patients with metastatic breast carcinoma has limited the use of this procedure to highly selected patients. Consequently, a chemical method of adrenal inhibition was developed which used aminoglutethimide to block cholesterol to pregnenolone conversion and dexamethasone as replacement glucocorticoid. This regimen effectively lowered urinary free cortisol excretion but was complicated by a drug interaction in which aminoglutethimide accelerated the metabolism of dexamethasone and reduced its bioavailability. Theoretically, replacement of dexamethasone with a glucocorticoid not subject to drug altered degradation would eliminate this drug interaction and simplify therapy. In order to determine whether hydrocortisone could be used, the metabolism and biological activity of this glucocorticoid was evaluated before and during aminoglutethimide administration. The plasma half-life, volume of distribution and metabolic clearance rate of hydrocortisone as determined by the single injection technique were not significantly altered by aminoglutethimide. The biopotency of hydrocortisone as reflected by its ability to suppress ACTH below basal levels was also retained during aminoglutethimide administration while that of dexamethasone was not. In order to evaluate the effectiveness of hydrocortisone in the aminoglutethimide regimen, a method was required for monitoring adrenal cortical function which was independent of glucocorticoid secretion. Plasma dehydroepiandrosterone-sulfate (DHA-S) levels were highly correlated (r-0.79, P

Original languageEnglish (US)
Pages (from-to)469-479
Number of pages11
JournalJournal of Clinical Endocrinology and Metabolism
Volume45
Issue number3
StatePublished - 1977
Externally publishedYes

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Aminoglutethimide
Metabolism
Glucocorticoids
Hydrocortisone
Dexamethasone
Drug interactions
Drug Interactions
Metabolic Clearance Rate
Plasmas
Pregnenolone
Dehydroepiandrosterone Sulfate
Adrenalectomy
Bioactivity
Adrenocorticotropic Hormone
Biological Availability
Half-Life
Cholesterol
Breast Neoplasms
Morbidity
Degradation

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Adrenal suppression with aminoglutethimide. I. Differential effects of aminoglutethimide on glucocorticoid metabolism as a rationale for use of hydrocortisone. / Santen, R. J.; Wells, S. A.; Runic, S.; Gupta, C.; Kendall, John; Rudy, E. B.; Samojlik, E.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 45, No. 3, 1977, p. 469-479.

Research output: Contribution to journalArticle

Santen, R. J. ; Wells, S. A. ; Runic, S. ; Gupta, C. ; Kendall, John ; Rudy, E. B. ; Samojlik, E. / Adrenal suppression with aminoglutethimide. I. Differential effects of aminoglutethimide on glucocorticoid metabolism as a rationale for use of hydrocortisone. In: Journal of Clinical Endocrinology and Metabolism. 1977 ; Vol. 45, No. 3. pp. 469-479.
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