Test with 5 mcg ACTH for Diagnosis of Non-classic Congenital AdrenalHyperplasia

Background: Short test with 250 mcg corticotropin (Tetracosactide acetate, a substance of first 24 amino acids from 39-acid chain of endogenous ACTH) is a diagnostic standard of non-classic form of congenital adrenal hyperplasia (CAH). However, it is well known that morning ACTH levels in healthy people fluctuate between 10 and 60 pg/ml, and peak cortisol levels can be achieved with 1-24 ACTH dose of 1 mcg or 5 mcg. Objective: To study the sensitivity and specificity of the test with 5 mcg ACTH to diagnose non-classic form of congenital adrenal hyperplasia (NCAN). Materials and Methods: During from 2006 to 2011, we screened 435 women aged from 16 to 35 (25 (21; 29) years) for CAH after exclusion of neoplastic hyperandrogenism. Protocol of low-dose (5 mcg) and standard (250 mcg) 1-24 ACTH tests: Blood sampling for basal 17-OHP and cortisol levels; blood sampling for 17-OHP and cortisol at 30 and 60 minutes after 5 mcg or 250 mcg 1-24 ACTH stimulation. Molecular genetic analysis for most prevalent CYP21 mutations was performed using allele specific polymerase chain reaction. Results: Diagnosis of non-classic CAH with 21-hydroxylase deficiency was proved in 5.3% (23/435) of patients. Conclusion: Low dose test with Tetracosactide 5 mcg can identify 21-hydroxylase deficiency in patients with stimulated 17-OHP concentrations over 14 ng/ml. Test with Tetracosactide 5 mcg had sensitivity of 72.7% and specificity of 100% with positive prognostic value (+PV) of 100%, and negative prognostic value (-PV) of 89.3%.