Modelling adrenal steroid profiles to inform monitoring guidance in congenital adrenal hyperplasia
Bibliographic record
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.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.013 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".