SAT-468 - Treat the Patient and Not the ACTH: Balancing Hormonal Control and Clinical Outcomes in Classic Congenital Adrenal Hyperplasia

Classic congenital adrenal hyperplasia (CAH) due to 21 hydroxylase deficiency is an autosomal recessive disorder of adrenal steroidogenesis, requiring lifetime glucocorticoid and mineralocorticoid replacement. Dose titration is based upon key laboratories markers like androstenedione (A4), 17-hydroxyprogesterone (17OHP), and plasma renin activity (PRA), manifestations of androgen and/or glucocorticoid excess, and presence of adrenal rest tumors

A 23-year-old male with simple virilizing CAH returned to the NIH endocrine clinic after being lost to follow up. He was diagnosed at 8 years with precocious puberty and advanced bone age and originally treated with glucocorticoids and fludrocortisone. During the interval he had received outside care, ACTH levels were persistently found to be elevated. Focus was shifted to pituitary evaluation to work up elevated ACTH in the setting of maternal history of pituitary disease. Fludrocortisone had been discontinued, and glucocorticoid regimen had been decreased. As a result, patient developed symptoms of adrenal insufficiency (low blood pressure, dizziness, salt cravings, fatigue) and continued headaches and anxiety from psychological distress. His symptoms were attributed to lifestyle rather than deficiency of steroid hormones. Pituitary magnetic resonance imaging (MRI) was unremarkable, but the patient lost confidence in his medical care and was confused about his management. Upon returning to our institute, fludrocortisone was resumed, daily glucocorticoid dosage was up titrated and switched to prednisone, Crenessity was initiated with the goal of tapering glucocorticoid regimen in the future, and he was educated on importance of following sick day rules to prevent adrenal crisis. His symptoms resolved and he had an overall improved sense of well-being.

We highlight the importance following the appropriate disease markers, including renin. Acceptable management allows for 17OHP and A4 levels in the upper normal to mildly elevated range, with aim for normal PRA. We emphasize treatment with fludrocortisone and following PRA, as salt wasting and volume depletion is a direct stimulus for ACTH production via indirect stimulation of vasopressin. Vasopressin synergistically acts with CRF to augment ACTH production. ACTH does not serve as a therapeutic target in classic CAH. Attempts to suppress ACTH may lead to glucocorticoid overtreatment, unnecessary diagnostic testing, and patient distress as in this case. In the management of classic CAH, we reinforce that medication should be titrated by assessing the entire clinical picture and all patients with classic CAH may require fludrocortisone therapy.

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