Screening for Nonclassic Congenital Adrenal Hyperplasia in the Era of Liquid Chromatography-Tandem Mass Spectrometry

Alexander D Chesover; Heather Millar; Lusia Sepiashvili; Khosrow Adeli; Mark R Palmert; Jill Hamilton

doi:10.1210/jendso/bvz030

Screening for Nonclassic Congenital Adrenal Hyperplasia in the Era of Liquid Chromatography-Tandem Mass Spectrometry

J Endocr Soc. 2019 Dec 18;4(2):bvz030. doi: 10.1210/jendso/bvz030. eCollection 2020 Feb 1.

Authors

Alexander D Chesover¹, Heather Millar², Lusia Sepiashvili³, Khosrow Adeli³, Mark R Palmert^{1

4}, Jill Hamilton¹

Affiliations

¹ Division of Endocrinology, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto M5G 1H4, Canada.
² Section of Gynaecology, Division of Endocrinology, Department of Obstetrics and Gynaecology, The Hospital for Sick Children, University of Toronto M5G 1H4, Toronto, Canada.
³ Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto M5G 1H4, Canada.
⁴ Department of Physiology, University of Toronto, Toronto M5S 1A8, Canada.

Abstract

Context: Screening for and diagnosing non classic congenital adrenal hyperplasia (NCCAH) uses serum 17-hydroxyprogesterone (17OHP) thresholds established from immunoassay data; however, a new liquid-chromatography tandem mass spectrometry (LC-MS/MS) method results in lower 17OHP values. The evolution of immunoassays is also challenging our diagnostic cut-off for glucocorticoid insufficiency and few data re-evaluate the utility of testing for glucocorticoid insufficiency in NCCAH.

Objective: (1) Evaluate the 17OHP threshold that predicts NCCAH in children using LC-MS/MS, and (2) determine the prevalence of glucocorticoid insufficiency in NCCAH.

Methods: A retrospective chart review of pediatric patients who underwent ACTH stimulation tests with cortisol and 17OHP measurements from 2011 to 2018 for assessment of NCCAH. Other adrenal pathologies were excluded. A cortisol < 415 nmol/L defined glucocorticoid insufficiency. Published correlation data determined a 17OHP of 3.3 nmol/L by LC-MS/MS was equivalent to 6 nmol/L by immunoassay. Data analysis was by measures of diagnostic accuracy.

Results: Of 188 patients included, 23 (12%) had NCCAH (21/23 had genetic confirmation); the remaining 2 had peak 17OHP > 30 nmol/L. Baseline 17OHP ≥ 6 nmol/L most accurately screened for NCCAH-sensitivity and specificity 96%. Almost all genetically confirmed NCCAH (20/21) had peak 17OHP > 30 nmol/L; all subjects with other diagnoses peaked < 30 nmol/L. Glucocorticoid insufficiency was present in 55% with NCCAH.

Conclusions: Despite the increased specificity of LC-MS/MS, a baseline 17OHP ≥ 6 nmol/L most accurately screened for NCCAH; this supports current practice guidelines. This threshold identified all with glucocorticoid insufficiency, notably prevalent in our cohort and for whom glucocorticoid stress dosing should be considered.

Keywords: 17-hydroxyprogesterone; 21-hydroxylase; congenital adrenal hyperplasia; cortisol; mass spectrometry; pediatrics.