Adrenomedullary Function in 21-Hydroxilase Deficiency. Is There an Association with adrenal Crises?

Background: Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is characterized by impairment in normal steroid production. Patients with the most severe forms also have decreased adrenomedullary function. However, the clinical implications of epinephrine deficiency are not clear. Objective: Evaluate the adrenomedullary function in children with salt-wasting congenital adrenal hyperplasia (SW CAH) and assess its relationship to the number of hospitalizations due to adrenal crises. We compare the clinical, analytical and genotypic characteristics and the therapeutic needs of patients with and without adrenomedullary disfunction. Methods: We measured 24-hours urine catecholamine levels (epinephrine, norepinephrine, and dopamine) and 21-hydroxylase genotype in 21 SW CAH. Results: 11 SW CAH had adrenomedullary disfunction characterized by undetectable urine epinephrine, and interestingly, had >8 adrenal crises during infanthood. Other 10 SW CAH had normal values of urine epinephrine and had less than 4 adrenal crises during infanthood. There were no significant differences in hydrocortisone (16.08 ± 3.4 mg/m2/day vs 16.98 ± 5.01 mg/m2/day) and 9fluorohydroxortisone (0.072 ± 0.06 mg/m2/day vs 0,101 ± 0.12 mg/m2 /day) doses, although the mean value of 17-OHP (0.04 ng/ml (0.1-1.3) vs 26.7 ng/ml (0.1-79)); ATCH (45pg/ml (30.9-122)vs 71 pg/ml (34-271)), aldosterone (50 pg/ml (50-50) vs 50 pg/ml (50-244)), and androstenedione(0 ng/ml (0-0,4) vs 2,6 ng/ml (0-5.3)) was lower in patients with undetectable urine epinephrine. 11 SW CAH with urinary epinephrine deficiency had most severe genotype. Conclusion: SW CAH with undetectable epinephrine in urine had several crises during infanthood. The measurement of urine epinephrine is well correlated with the clinical severity of the disease and the expected activity of 21-hydroxilase.