Researchers found that when conventional biomarkers were inconclusive, 11-oxyandrogens were useful for the management of congenital adrenal hyperplasia (CAH). These findings were published in the Journal of the Endocrine Society.
Data from adults (n=142) and children (n=208) with classic 21-hydroxylase-deficiency collected at the National Institutes of Health Clinical Center between 2006 and 2019 were retrospectively reviewed. Early morning blood samples were obtained during multiple visits and were assessed for hormones and biomarkers of CAH.
A total of 2738 laboratory assessments were performed, in which 17% indicated discrepant 17-hydroxyprogesterone (17OHP) and androstenedione (A4) results. Among children, 92% had elevated 17OHP and in-range A4, and 8% had elevated A4 with in-range 17OHP. Among adults, elevated 17OH with in-range A4 was less common (69%; P <.001) and elevated A4 with in-range 17OHP was more common (31%; P <.001).
Stratified by elevated biomarker, 51% of those with elevated 17OHP were women or girls, 66% were children, and 68% were in good clinical control. Of those with elevated A4, 40% were women or girls, 20% were children, and 40% were in good clinical control.
Stratified by clinical control, those with good or poor control differed significantly by 11-ketoandrostenedione elevation (median fold elevation, 1.76 vs 3.57; P =.047) and 11-hydroxytestosterone elevation (median fold elevation, 0.91 vs 2.82; P =.003), respectively.
Among adults, those in good clinical condition had significantly lower-fold elevation of 11-hydroxytestosterone (0.91 vs 5.76; P =.009), which was similar to that seen among children (0.99 vs 1.97; P =.036) and men and boys (0.72 vs 4.06; P =.002).
A model using 11-hydroxytestosterone fit clinical control well (Receiver Operating Characteristic [ROC] area, 0.78; 95% CI, 0.62-0.93). The best cut-off was a 3.48-fold elevation of 11-hydroxytestosterone (sensitivity, 97%; specificity, 47%). This model improved when stratified by age (adults: ROC area, 0.95; 95% CI, 0.83-1.00; children: ROC area, 0.69; 95% CI, 0.47-0.90).
This study may have been limited by using clinical control as a stratification method because clinical interventions may take up to 12 months to improve clinical characteristics.
The study authors concluded 11-hydroxytestosterone may be an important biomarker for patients with CAH when making clinical decisions, especially when discordant results are observed for conventional biomarkers.
Disclosure: One author has a relationship with the pharmaceutical industry unrelated to this study. See the original article for more detail.
Jha S, Turcu AF, Sinaii N, Brookner B, Auchus RJ, Merke DP. 11-oxygenated androgens useful in the setting of discrepant conventional biomarkers in 21-hydroxylase deficiency. J Endocr Soc. 2020;5(2)bvaa192. doi: 10.1210/jendso/bvaa192