Neonatal reference intervals for serum steroid hormone concentrations measured by LC-MS/MS

Anouk Olthof; Naafs Jolanda C; Nitash Zwaveling-Soonawala; Heinen Charlotte A; Hannema Sabine E; Hillebrand acquelien J; Anita Boelen; Paul AS; van Trotsenburg; Annemieke C Heijboer

doi:10.1530/ey.22.14.15

14.15

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 14.15 | DOI: 10.1530/ey.22.14.15

ESPEYB25 14. The Year in Science and Medicine Metabolomics, Steroidomics (5 abstracts)

14.15. Neonatal reference intervals for serum steroid hormone concentrations measured by LC-MS/MS

Anouk Olthof , Jolanda C Naafs , Nitash Zwaveling-Soonawala , Charlotte A Heinen , Sabine E Hannema , Jacquelien J Hillebrand , Anita Boelen , Paul AS , van Trotsenburg & Annemieke C Heijboer

Clin Chem Lab Med. 2025;63(4):805-11. doi: 10.1515/cclm-2024-0393

Brief Summary: In this study, serum steroids of healthy term neonates were measured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) at two timepoints (130 samples at day 3–8 (T1) and 126 samples at day 13–15 (T2)) to establish reference intervals (RIs) for serum cortisol, cortisone, corticosterone, 11-deoxycortisol, 21-deoxycortisol, 11-deoxycorticosterone, testosterone, androstenedione, and 17-hydroxyprogesterone. These RIs are intended to improve the diagnostic accuracy of conditions like congenital adrenal hyperplasia (CAH) and differences of sex development (DSD) in neonates.

Age- and sex-specific neonatal RIs for steroid hormones are essential for accurate interpretation of diagnostic results during the neonatal period. Although chromatographic-mass-spectrometric methods are considered the gold standard for measuring steroid hormones, RIs for these hormones in serum have been lacking so far for neonates, particularly during the first two weeks of life, when abnormal screening results require reliable laboratory diagnostics. Establishing these RIs is crucial to support the transition from immunoassay-based to LC-MS/MS-based diagnostics, which offer superior specificity and accuracy.

The study was ‘only’ able to establish RIs for 9 serum steroids as for some hormones (e.g., 21-deoxycortisol, 11-deoxycorticosterone) concentrations were below the lower limit of quantification (LLOQ).

Further studies are needed to establish RIs in preterm and low-birth-weight neonates. Expansion to include additional steroid hormones could improve diagnostic coverage for rarer endocrine disorders. In addition, longitudinal data beyond the first two weeks of life would help understand hormone dynamics during early infancy and provide RIs for controlling treatment success in infants with disorders of steroid biosynthesis.