Determination of 17OHPreg and DHEAS by LCMSMS: Impact of Age, Sex, Pubertal Stage and BMI on the Δ5-steroid-pathway.

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Determination of 17OHPreg and DHEAS by LCMSMS: Impact of Age, Sex, Pubertal Stage and BMI on the Δ5-steroid-pathway.

J Clin Endocrinol Metab. 2016 Nov 3;:jc20162849

Authors: Kulle AE, Reinehr T, Simic-Schleicher G, Hornig NC, Holterhus PM

Abstract
BACKGROUND: Dehydroepiandrosterone-sulfate (DHEAS) and 17-hydroxypregnenolone (17OHPreg) are important for understanding the Δ5-pathway, e.g. in adrenarche and obesity. While mass spectrometry has become the state-of-the-art method for quantifying steroids, there are few comprehensive age-, sex- and pubertal stage-specific reference ranges for children.
AIMS: To develop a sensitive and reliable UPLC-MS/MS method for simultaneous quantification of DHEAS and 17OHPreg, and establish the entire age-, sex- and pubertal stage-specific reference ranges in children.
METHODS: 684 children, 453 with normal BMI (<90(th)) (243 f, 210 m) and 231 obese subjects (>97(th)) (132 f, 99 m), were categorized into eleven age groups and age- and Tanner stage (PH)-specific reference ranges were determined.
RESULTS: The method was linear up to 600 nmol/L (17OHPreg) and 6000 nmol/L (DHEAS) with limits of detection of 0.05 nmol/L and 0.5 nmol/L respectively. Both steroids declined after the neonatal period. Comparisons with RIA-assays (Siemens (DHEAS); in-house kit (17OHPreg) revealed 0.95 and 0.93 as coefficients of determination. While DHEAS - generally higher in boys - increased continuously starting at 3-6 years, 17OHPreg remained largely constant. In obese patient both were significantly elevated, also in part after alignment to Tanner stages (PH).
CONCLUSIONS: UPLC-MS/MS is sensitive and reliable for quantifying DHEAS and 17OHPreg. Our data support differential maturation of CYP17 during adrenarche with successively increasing 17/20 lyase activity but largely constant 17α-activity. Endocrine interpretation of 17OHPreg and DHEAS must consider differential patterns for age, gender, pubertal stage and BMI.

PMID: 27809697 [PubMed - as supplied by publisher]

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