ESPE Yearbook of Paediatric Endocrinology

Brief summary: In this Minireview, one pediatric and one adult case with 21-hydroxylase deficiency (21OHD) are discussed with respect to different clinical questions and steroid biomarkers reflecting their diagnosis, treatment and disease control. Basics of the disease mechanisms with different aspects throughout life (childhood, adulthood, sex, fertility and pregnancy) are discussed to lay grounds for the interpretation and use of laboratory data, including the newer 11-oxygenated androgens, for clinical decision making of optimal treatment.

Congenital adrenal hyperplasia due to 21OHD caused by CYP21A2 variants is a fairly common genetic disorder that requires personalized care throughout life. The diagnosis is made ideally by genetic analysis, or by biochemical investigations of a panel of steroids (mostly immunoassays) or a steroid profile (LC–MSMS) under basal and/or ACTH stimulated conditions. By contrast, optimal treatment of CAH by hormonal replacement of glucocorticoids (GC) and mineralocorticoids remains a major challenge but is crucial to avoid severe short- and long-term adverse effects of undertreatment and overtreatment. The many challenges faced in clinical care for CAH patients are comprehensively explained in this Minireview that provides the underlying evidence and highlights our current gaps in knowledge and needs for improvement.

However, the Minireview also highlights the recent advances in steroid profiling that have and will bring newer disease biomarkers into play, the adrenal derived 11-oxy androgens. Although promising, much remains to be evaluated on their performance in different clinical scenario of the disease. In addition, current monitoring of GC treatment is mostly done by a single measurement of adrenal biomarkers reflecting disease control at one specific time point and does not reflect complete information of disease control and androgen exposure overall. But large diurnal variability exists in both the underlying biological system as well as the GC therapy currently provided in most cases by hydrocortisone which has a short half-life, and requires individualized decisions on dose, timing and interval.

There is hope that newer monitoring options (e.g. daily profiling of a biomarker as in diabetes) or novel drugs might give us better tools at hand to optimize treatment for our patients with CAH and improve their long-term outcome in the near future.

A similar review on the same topic, including steroid disorders beyond 21-hydroxalyse deficiency, was published in April 2023 (1).

Reference: 1. The clinical and biochemical significance of 11-oxygenated androgens in human health and disease. Karl-Heinz Storbeck and Michael W. O’Reilly. Eur J Endocr. 2023 Apr 5;188(4):R98–R109. DOI: 10.1093/ejendo/lvad047.