Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: Identifying optimal monitoring times and novel disease biomarkers

Miguel Debono, Ashwini Mallappa, Verena Gounden, Aikaterini A. Nella, Robert F. Harrison, Christopher A. Crutchfield, Peter S. Backlund, Steven J. Soldin, Richard J. Ross, Deborah P. Merke

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Objectives: The treatment goal in congenital adrenal hyperplasia (CAH) is to replace glucocorticoids while avoiding androgen excess and iatrogenic Cushing's syndrome. However, there is no consensus on how to monitor disease control. Our main objectives were to evaluate hormonal circadian rhythms and use these profiles to identify optimal monitoring times and novel disease biomarkers in CAH adults on intermediate- and long-acting glucocorticoids. Design: This was an observational, cross-sectional study at the National Institutes of Health Clinical Center in 16 patients with classic CAH. Methods: Twenty-four-hour serum sampling for ACTH, 17-hydroxyprogesterone (17OHP), androstenedione (A4), androsterone, DHEA, testosterone, progesterone and 24-h urinary pdiol and 5β-pdiol was carried out. Bayesian spectral analysis and cosinor analysis were performed to detect circadian rhythmicity. The number of hours to minimal (TminAC) and maximal (TmaxAC) adrenocortical hormone levels after dose administration was calculated. Results: A significant rhythm was confirmed for ACTH (r2, 0.95; P2, 0.70; P=0.003), androstenedione (r2, 0.47; P=0.043), androsterone (r2, 0.80; P2, 0.47; P=0.042) and progesterone (r2, 0.64; P=0.006). The mean (S.D.) TminAC and TmaxAC for 17OHP and A4 were: morning prednisone (4.3 (2.3) and 9.7 (3.5) h), evening prednisone (4.5 (2.0) and 10.3 (2.4) h), and daily dexamethasone (9.2 (3.5) and 16.4 (7.2) h). AUC0-24h progesterone, androsterone and 24-h urine pdiol were significantly related to 17OHP. Conclusion: In CAH patients, adrenal androgens exhibit circadian rhythms influenced by glucocorticoid replacement. Measurement of adrenocortical hormones and interpretation of results should take into account the type of glucocorticoid and time of dose administration. Progesterone and backdoor metabolites may provide alternative disease biomarkers.

Original languageEnglish (US)
Pages (from-to)727-737
Number of pages11
JournalEuropean Journal of Endocrinology
Volume173
Issue number6
DOIs
StatePublished - Dec 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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    Debono, M., Mallappa, A., Gounden, V., Nella, A. A., Harrison, R. F., Crutchfield, C. A., Backlund, P. S., Soldin, S. J., Ross, R. J., & Merke, D. P. (2015). Hormonal circadian rhythms in patients with congenital adrenal hyperplasia: Identifying optimal monitoring times and novel disease biomarkers. European Journal of Endocrinology, 173(6), 727-737. https://doi.org/10.1530/EJE-15-0064