Modelling adrenal steroid profiles to inform monitoring guidance in congenital adrenal hyperplasia
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Background
There is no consensus on how to monitor adrenal androgens in Congenital Adrenal Hyperplasia (CAH).
Methods
Modelling of serum and salivary steroid profiles in healthy participants and patients with CAH randomised to either standard treatment or modified-release hydrocortisone hard capsules (MRHC).
Findings
Changes in serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) paralleled each other in healthy participants (n = 19) and patients with CAH (n = 122). However, healthy participants had similar absolute levels of 17OHP and A4 whereas patients with CAH had proportionally higher levels of 17OHP. Cross-correlation showed no lag between serum 17OHP and A4. In CAH, Bayesian multiple change point analysis converged on a 17OHP of 4.5 nmol/l below which in proportion to 17OHP the A4 is lower. Patients on standard treatment had a morning peak in 17OHP and A4 whereas patients on MRHC had relatively flat profiles. Salivary androgens including 11-ketotestosterone correlated with serum 17OHP and A4 in female patients (r = 0.7 to 0.9).
Interpretation
In CAH, elevated 17OHP drives the production of A4. High A4 reflects poor control, but low A4 does not indicate overtreatment. Accepting 17OHP is higher than A4, both measurements give similar reflection of control, and a 17OHP <38 nmol/l (1250 ng/dl) was associated with an A4 in the normal range <5 nmol/l (143 ng/dl) in 95% of patients and in clinical trials was used to define good control. On MRHC, which controls androgen levels over 24 h, a single sample of 17OHP and/or A4 can be used to monitor control. Salivary measurements reflect similar results to serum.
Funding
Diurnal; MRC; NIH; NIHR.
There is no consensus on how to monitor adrenal androgens in Congenital Adrenal Hyperplasia (CAH).
Methods
Modelling of serum and salivary steroid profiles in healthy participants and patients with CAH randomised to either standard treatment or modified-release hydrocortisone hard capsules (MRHC).
Findings
Changes in serum 17-hydroxyprogesterone (17OHP) and androstenedione (A4) paralleled each other in healthy participants (n = 19) and patients with CAH (n = 122). However, healthy participants had similar absolute levels of 17OHP and A4 whereas patients with CAH had proportionally higher levels of 17OHP. Cross-correlation showed no lag between serum 17OHP and A4. In CAH, Bayesian multiple change point analysis converged on a 17OHP of 4.5 nmol/l below which in proportion to 17OHP the A4 is lower. Patients on standard treatment had a morning peak in 17OHP and A4 whereas patients on MRHC had relatively flat profiles. Salivary androgens including 11-ketotestosterone correlated with serum 17OHP and A4 in female patients (r = 0.7 to 0.9).
Interpretation
In CAH, elevated 17OHP drives the production of A4. High A4 reflects poor control, but low A4 does not indicate overtreatment. Accepting 17OHP is higher than A4, both measurements give similar reflection of control, and a 17OHP <38 nmol/l (1250 ng/dl) was associated with an A4 in the normal range <5 nmol/l (143 ng/dl) in 95% of patients and in clinical trials was used to define good control. On MRHC, which controls androgen levels over 24 h, a single sample of 17OHP and/or A4 can be used to monitor control. Salivary measurements reflect similar results to serum.
Funding
Diurnal; MRC; NIH; NIHR.
Date Issued
2025-06-01
Date Acceptance
2025-04-25
Citation
EBioMedicine, 2025, 116
ISSN
2352-3964
Publisher
Elsevier
Journal / Book Title
EBioMedicine
Volume
116
Copyright Statement
© 2025 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40398353
PII: S2352-3964(25)00193-8
Subjects
21-Hydroxylase deficiency
Adrenal insufficiency
COHORT
Congenital adrenal hyperplasia
General & Internal Medicine
Glucocorticoid
Hydrocortisone
HYDROCORTISONE
Life Sciences & Biomedicine
Medicine, General & Internal
Medicine, Research & Experimental
Modified release hydrocortisone
MODIFIED-RELEASE
Monitoring
Research & Experimental Medicine
Science & Technology
Publication Status
Published
Coverage Spatial
Netherlands
Article Number
105749
Date Publish Online
2025-05-20