Interrelationships among cortisol, 17-hydroxyprogesterone, and androstenendione exposures in the management of children with congenital adrenal hyperplasia

Kyriakie Sarafoglou, Cheryl L. Zimmerman, Maria T. Gonzalez-Bolanos, Brian A. Willis, Richard Brundage

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Hydrocortisone is the standard replacement therapy for children with congenital adrenal hyperplasia (CAH). Relationships between cortisol exposures and pharmacodynamic responses of 17-hydroxyprogesterone and androstenedione exposures have not been systematically evaluated. Objectives: (1) Assess individual oral hydrocortisone pharmacokinetics; (2) relate the observed cortisol exposure in each subject to the observed exposures of 17-hydroxyprogesterone and androstenedione; (3) determine potential individualized treatment regimens based on each subject's pharmacokinetic and pharmacodynamic parameters. Methods: Thirty-four patients (18 boys, 16 girls, aged 1.4 to 18.1 years) with CAH underwent 6-hour pharmacokinetic studies. Results were analyzed by noncompartmental methods to obtain the area under the curve (AUC) for cortisol, 17-hydroxyprogesterone, and androstenedione; maximum concentration and time-to-maximum concentration for cortisol; and minimum and time-to-minimum concentration for 17-hydroxyprogesterone and androstenedione. Results: Mean (SD) cortisol half-life and Cmax were 1.01 (0.20) hours and 24.4 (5.4) μg/dL, respectively. The AUCs for cortisol, 17-hydroxyprogesterone and androstenedione were 40.8 (14.5) μg hour/dL, 29, 490 (23, 539) ng hour/dL, and 680 (795) ng hour/dL, respectively. No significant relationships existed between cortisol AUCs and the AUCs of either 17-hydroxyprogesterone (P = 0.32) or androstenedione (P = 0.99); nor were there differences between the change-from-baseline concentrations for cortisol with either 17-hydroxyprogesterone (P = 0.80) or androstenedione (P = 0.40). Cortisol simulations indicated that although four daily doses decreased 24-hour hypercortisolemia and hypocortisolemia, substantial periods of each remained. Conclusions: Concentration profiles of cortisol, 17-hydroxyprogesterone, and androstenedione are highly variable in children with CAH, and knowledge of them can assist in personalizing the therapy of CAH patients. Hydrocortisone's rapid half-life and the lack of a sustained-released product make it difficult to closely approximate normal circadian profiles.

Original languageEnglish (US)
Pages (from-to)35-41
Number of pages7
JournalJournal of Investigative Medicine
Volume63
Issue number1
DOIs
StatePublished - Jan 2015

Keywords

  • Congenital adrenal hyperplasia
  • Cortisol
  • Hydrocortisone
  • Pharmacokinetics
  • Pharmacodynamics
  • 17-hydroxyprogesterone
  • Androstenedione

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