ESPE Abstracts

Background: Basal 17OHP levels to indicate an ACTH-stimulation test and post-ACTH 17OHP cut-off levels diagnosing NC-CAH vary among different guidelines.

Objective: To establish the performance of basal and post-ACTH 17OHP concentrations for the NC-CAH diagnosis in children with precocious pubarche (PP).

Methods: Clinical, biochemical, and molecular analysis from 202 PP patients submitted to ACTH stimulation test (1997-2021). 17OHP was measured by RIA and CYP21A2 genotype was confirmed by allelic-specific PCR and direct sequencing. ROC curves were generated for basal 17OHP and post-ACTH 17OHP and sensitivity (S), specificity (E), and likelihood ratio (LH) levels were calculated to determine their performance in diagnosing NC-CAH.

Results: NC-CAH was confirmed in 35 patients while 167 were diagnosed with isolated PP and were considered as the control group. CYP21A2 analysis of was performed in 30 patients with NC-CAH, confirming the diagnosis in all, and in 22 controls, definitively excluding the disease. In this first tier of analysis, the only significant clinical difference was higher growth velocity in NC-CAH (33.3%) than in the controls (4.5%; P=0.02). Basal 17OHP concentration showed an area under the curve (AUC) of 0.94 (95% CI, 0.84-0.99) and the cut-off point with the best diagnostic combination was 170 ng/dL (S:97%, E:72%, LH+ 3.5). The post-ACTH 17OHP had an AUC of 1.0 (CI 95%) and a plasma concentration of 1,104 ng/dL and showed excellent diagnostic accuracy (S:100%, E: 100%). Adopting this post-ACTH 17OHP concentration as the cut-off point for diagnosing NC-CAH, a second tier of analysis was performed evaluating basal 17OHP in all patients with PP (202). The AUC was 0.97 (95% CI, 0.95-0.99), and the concentration of the basal 17OHP with the best diagnostic accuracy was confirmed to be 170 ng/dL (S:94%, E: 90 %, LH+ 9.9). Interestingly, all patients with basal 17OHP greater than 502 ng/dL had the diagnosis of NC-CAH confirmed (S:63%, E:100%), and would not require an ACTH-stimulation test. On the other hand, a basal 17OHP lower than 86 ng/dL excluded NC-CAH in all patients (S:100%, E: 70%).

Conclusion: In our cohort, basal and post-ACTH 17OHP levels presented an excellent diagnostic performance in patients with PP. A basal 17OHP concentration of 170 ng/dL and a post-ACTH level of 1,104 ng/dL represent the best cut-off values to, respectively, indicate the ACTH stimulation test and confirm the diagnosis of NC-CAH in these patients. Moreover, a basal 17OHP greater than 502 ng/dL confirmed NC-CAH.