Abstract 514 Poster Session II, Sunday, 5/2 (poster 208)

Salt-wasting CAH due to 21-hydroxylase deficiency is a disorder of cortisol and aldosterone biosynthesis. The diagnosis is easily made with an elevated serum 17-hydroxyprogesterone (17OHP). Serum cortisol and aldosterone are not usually measured as they are expected to be low or undetectable. A well virilized 15 day old boy presented in adrenal crisis with hyponatremia and hyperkalemia. CAH was diagnosed by elevated 17OHP (>1000 nmol/L). Additional pre-treatment blood work showed elevated serum cortisol (790 nmol/L; normal (nl) 77-634) and serum aldosterone (>3300 pmol/; nl 139-2500) causing the CAH diagnosis to be questioned. A retrospective chart review was used to identify all other infants with salt-wasting CAH seen over the past 25 years to determine the frequency of elevated serum cortisol and aldosterone prior to treatment. 27 patients with salt-wasting CAH (14 male) were identified. 12 patients (8 male) had cortisol and/or aldosterone measured pre-treatment. 10 of these infants including the index case presented in adrenal crisis with evidence of severe salt-wasting (hyponatremia and hyperkalemia)(8 male; age 17±10(x±SD) days). Each child had appropriately elevated 17OHP levels; clinical presentation and response to initial and maintenance therapy were consistent with classic salt-wasting CAH. 1 patient was challenged with Florinef withdrawal at age 4 years and clearly was salt-wasting; 8 other patients have shown persistent Florinef requirement based on intermittently elevated plasma renin. Contrary to the known pathophysiology of this disorder, all 10 infants in salt-wasting adrenal crisis had elevated serum cortisol (range: 790 to >1500 nmol/L; mean: 1251±275; n=9) and/or aldosterone levels (range: >3300-10580; mean: 5791±3249; n=7) before initiation of replacement hormone therapy (Hydrocortisone and Florinef). These cortisol and aldosterone levels are perplexing since these patients lack the adrenal P450c21 enzyme required for cortisol and aldosterone biosynthesis. Furthermore, these results are not consistent with the reported hormone levels in infants with salt-wasting CAH, although variable aldosterone production has been reported in young adults with this condition. Assay cross-reactivity is unlikely because similar results were found over 25 years despite varying assays, including the currently used highly specific assays. However, there exists the possibility of cross-reactivity with unidentified steroids. We postulate that adrenal crisis is associated with endogenous extra-adrenal cortisol and aldosterone production, due to extra-adrenal 21-hydroxylase activity distinct from P450c21. However, the high hormone levels had no clinical effect suggesting end-organ resistance due to competing steroids (eg 17OHP) or down-regulation at the receptor level. Awareness of this paradoxical elevation of serum cortisol and aldosterone in neonates with salt-wasting CAH is necessary to avoid misdiagnosis and incorrect treatment.