The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydr
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RESEARCH ARTICLE
Open Access
The contribution of serum cortisone and glucocorticoid metabolites to detrimental bone health in patients receiving hydrocortisone therapy Rosemary Dineen1,2*† , Lucy-Ann Behan1†, Grainne Kelleher3, Mark J. Hannon2, Jennifer J. Brady4, Bairbre Rogers2, Brian G. Keevil6,7, William Tormey3, Diarmuid Smith2, Christopher J. Thompson2, Malachi J. McKenna4,5, Wiebke Arlt8,9, Paul M. Stewart10, Amar Agha2† and Mark Sherlock2†
Abstract Background: Glucocorticoid therapy is the most common cause of iatrogenic osteoporosis. Less is known regarding the effect of glucocorticoids when used as replacement therapy on bone remodelling in patients with adrenal insufficiency. Enhanced intracellular conversion of inactive cortisone to active cortisol, by 11 betahydroxysteroid dehydrogenase type 1(11β-HSD1) and other enzymes leading to alterations in glucocorticoid metabolism, may contribute to a deleterious effect on bone health in this patient group. Methods: Study design: An open crossover prospective study randomizing ten hypopituitary men, with severe ACTH deficiency, to three commonly used hydrocortisone dose regimens. Measurements: Following 6 weeks of each regimen, patients underwent 24-h serum cortisol/cortisone sampling, measurement of bone turnover markers, and a 24-h urine collection for measurement of urinary steroid metabolites by gas chromatography-mass spectrometry (GC-MS). Serum cortisone and cortisol were analysed by liquid chromatography-mass spectrometry (LC-MS). Results: Dose-related and circadian variations in serum cortisone were seen to parallel those for cortisol, indicating conversion of ingested hydrocortisone to cortisone. The median area under the curve (AUC) of serum cortisone was significantly higher in patients on dose A (20 mg/10 mg) [670.5 (IQR 621–809.2)] compared to those on dose C (10 mg/5 mg) [562.8 (IQR 520.1–619.6), p = 0.01]. A negative correlation was observed between serum cortisone and bone formation markers, OC [1–49] (r = − 0.42, p = 0.03), and PINP (r = − 0.49, p = 0.01). There was a negative correlation between the AUC of night-time serum cortisone levels with the bone formation marker, OC [1–49] (r = − 0.41, p = 0.03) but there were no significant correlations between day-time serum cortisone or cortisol with bone turnover markers. (Continued on next page)
* Correspondence: [email protected] † Rosemary Dineen, Lucy-Ann Behan, Amar Agha and Mark Sherlock contributed equally to this work. 1 Department of Endocrinology, Tallaght University Hospital, Dublin, Ireland 2 Academic Department of Endocrinology, Beaumont Hospital and Royal College of Surgeons in Ireland, Dublin, Ireland Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a li
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