Urinary steroid metabolome testing aids CAH growth optimisation

medwireNews: Researchers have defined urinary steroid metabolite levels that indicate inadequate and excessive adrenal suppression for children with congenital adrenal hyperplasia (CAH) undergoing glucocorticoid treatment.

As growth velocity is the “clinical gold standard of patient care” for CAH, these reference values mean “evidence based biochemical monitoring of such children is now possible”, say Stefan Wudy (Justus Liebig University, Giessen, Germany) and co-investigators.

The team collated information on 24-hour gas chromatography–mass spectrometry (GC-MS) urinary steroid metabolome analysis and 1-year height velocity (HV) standard deviation scores (SDSs) for 63 prepubertal patients, aged an average of 7.2 years, who had 21-hydroxylase deficiency CAH. The patients were receiving treatment with hydrocortisone and fludrocortisone.

The SDS of the sum of eight urinary androgen metabolites, including androsterone and etiocholanolone, was a highly significant and positive biomarker for HV, so that a 1 SD increase was associated with a 0.97 SDS increase in HV in multivariate analysis.

By contrast, levels of the cortisol metabolite tetrahydrocortisol had a significant and negative relationship with HV, so that each body surface area-corrected logarithmic unit was associated with a 1.75 SDS decrease in HV.

However, there was no significant correlation between HV and concentrations of the other six major urinary cortisol metabolites tested, nor with the sum of total cortisol metabolites.

HV was also independent of urinary excretion of three major metabolites of 17α-hydroxyprogesterone and their summed excretion, and of oral hydrocortisone replacement dosage, the team says.

Using data from 35 undertreated children and 39 children with normal growth, the researchers determined that adrenal androgen excess – defined as a HV SDS above 1.5 – was best predicted by a urinary androgen metabolites SDS of +0.512, with 66.2% accuracy, 57.1% sensitivity and 74.4% specificity.

Similarly, analysis of data from 15 slow-growing children showed that overtreatment – defined as having a HV SDS below –1.5 – was best predicted by a tetrahydrocortisol excretion level above 1480 µg/m2 body surface area per day in combination with a suppressed urinary androgen metabolites SDS of less than 0.163. When used together, these thresholds were 79.6% accurate for overtreatment, with 40.0% sensitivity and 94.9% specificity.

“GC-MS urinary steroid metabolome analysis is suitable to distinguish children with an adequate adrenal suppression from those who were over-treated or reached an insufficient adrenal suppression”, Wudy and co-authors summarise in The Journal of Clinical Endocrinology & Metabolism.

By Lynda Williams

medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group

J Clin Endocrinol Metab 2019; DOI:10.1210/jc.2019-00438
Martin Savage
Programme Director

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