Endocrine Abstracts

Cosyntropin stimulation test is the gold diagnostic standard used to test for NCAH. Genetic testing is not currently considered to be the primary diagnostic tool for NCAH. Still, it may be helpful in establishing a diagnosis if other results are unequivocal or for genetic counselling purposes. The study aimed at verifying the currently accepted threshold of 17-hydroxyprogesterone (17OHP) level (³ 2.0 ng/ml) at which a cosyntropin stimulation test should be performed.

Material and methods

The retrospective study included 343 patients referred for a cosyntropin stimulation test due to suspected NCAH. Serum 17-OHP was measured with ELISA assay using Ledect96 Microplate Reader before, 30 minutes and 60 minutes after a 250 µg of cosyntropin intravenous injection. CYP21A2 gene sequencing by the Sanger method was performed in 30 patients of the group. NCCAH diagnosis was made if cosyntropin-stimulated 17OHP level exceeded 10.0 ng/ml. Detection of a pathogenic variant was considered a positive result of the genetic test. The ROC curve was determined, and the cut-off point with the highest sensitivity and specificity was established in both groups. The study was approved by the Ethics Board of JUMC. Results. A total of 79 patients were diagnosed with NCCAH based on cosyntropin stimulation test results (22 patients in the genetically screened group). The baseline 17OHP cut-off value that qualified patients best for testing was 2.79 ng/ml in the whole group, with sensitivity and specificity of 77.2% and 91.3%, respectively. The sensitivity and specificity for a guideline-recommended cut-off point (17OHP ³ 2.0 ng/ml) was 86.1% and 76%, respectively. Pathogenic variants of the CYP21A2 gene were found in 9 patients. If a pathogenic variant was found, baseline 17OHP cut-off which qualified subjects best for testing was 2, 88 ng/ml with 77.8% sensitivity and 47.6 % specificity. However, for 17-OHP cut-off ³ 2.0 ng/ml, these values were 77.8 and 35.7%, respectively. Conclusions. Our results suggest considering an upward shift in the 17OHP threshold at which patients suspected for NCAH should be referred for further evaluation. This may reduce the number of unnecessary cosyntropin stimulation tests, particularly since patients with a mild phenotype (or asymptomatic) frequently may not require any treatment.