ESPEYB25 8. Adrenals Reviews (3 abstracts)
8.12. Development of 24-hour rhythms in cortisol secretion across infancy: a systematic review and meta-analysis of individual participant data
Kervezee L , Romijn M , van de Weijer KNG , Chen BSJ , Burchell GL , Tollenaar MS , Tamayo-Ortiz M , Philbrook LE , de Weerth C , Cao Y , Rotteveel J , Eiden RD , Azar R , Bush NR , Chis A , Kmita G , Clearfield MW , Beijers R , Gröschl M , Wudy SA , Kalsbeek A , Mörelius E & Finken MJJ
J Clin Endocrinol Metab. 2025; 110(2): e515-e524. PMID: 39207206 doi: 10.1210/clinem/dgae590. https://pubmed.ncbi.nlm.nih.gov/39207206/
Brief summary: This review investigated the development of 24-hour cortisol rhythmicity in infancy and demonstrated that a stable early-morning cortisol peak emerges by 6–9 months.
Comment: In adults, cortisol follows a daily rhythm, peaking in the early morning and dropping around midnight (1, 2). Hydrocortisone therapy for adrenal insufficiency aims to replicate this pattern. Incorrect dosing can lead to undertreatment, raising the risk of adrenal crises and, in patients with congenital adrenal hyperplasia, androgen excess or overtreatment, which increases the risk of obesity, high blood pressure, and insulin resistance (3). Inborn adrenal insufficiency typically presents shortly after birth, but infant dosing can be challenging due to uncertainty about when the normal cortisol rhythm is fully established.
These authors conducted an individual participant data meta-analysis of salivary cortisol concentrations in healthy infants to establish normative data and inform hydrocortisone dosing. By combining data from 15 cohorts, they found that a stable early-morning cortisol peak emerges by 6–9 months, supported by sensitivity analyses; cosinormodeling confirmed a clear 24-hour rhythm with a single morning peak in the second half of the first year.
The study enhances our understanding of hypothalamic-pituitary-adrenal (HPA) axis maturation. The authors recommend clinical trials to evaluate the long-term safety and efficacy of development-based hydrocortisone dosing before applying it in practice.
References: 1. Kalsbeek A, van der Spek R, Lei J, Endert E, Buijs RM, Fliers E. Circadian rhythms in the hypothalamo-pituitary-adrenal (HPA) axis. Mol Cell Endocrinol. 2012;349(1):20-29.2. Oster H, Challet E, Ott V, et al. The functional and clinical significance of the 24-hour rhythm of circulating glucocorticoids. Endocr Rev. 2017;38(1):3-45.3. Auer MK, Nordenstrom A, Lajic S, Reisch N. Congenital adrenal hyperplasia. Lancet 2023; 401: 227–244.
Volume 22
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ESPE Yearbook of Paediatric Endocrinology
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