When Less is More: A Physiology-Driven Approach to a 17-Hydroxylase Deficiency Case Series

17-hydroxylase deficiency (17OHD) is a very rare form of congenital adrenal hyperplasia (CAH) caused by autosomal recessive mutations in the cytochrome P450 family (CYP17A1). Despite low cortisol, adrenal insufficiency does not typically manifest because elevated corticosterone, a weaker glucocorticoid (GC), exerts GC effects. Exogenous GC are the foundation of treatment but can be associated with significant side effects. Published literature regarding management strategies is limited.

We describe three female adolescents treated for 17OHD with different GC regimens. All patients presented at age 14 with delayed puberty, hypertension, and primary ovarian insufficiency. Patient 1 was initially treated with physiological hydrocortisone divided three times daily (10 mg/m2/d) and spironolactone 100 mg/d, separately and combined, which did not lower her blood pressure (BP). Eventually, a combination of physiological hydrocortisone once daily (8.8 mg/m2/d) and gradual titration to a higher spironolactone dose (100 mg bid) normalized her BP (115/75 mmHg) with no side effects. Patient 2 was treated with dexamethasone 0.25 mg daily for 10 years with poor follow-up and developed multiple complications related to supraphysiological GC use. She was transitioned and successfully treated with hydrocortisone 10 mg every morning and 5 mg every afternoon with a normal BP and potassium for over a year. Patient 3 was treated with cortisone acetate for 2.6 years and then with dexamethasone for about 10 months before discontinuation of GC and transition to spironolactone monotherapy. Her potassium and BP remained normal.

In conclusion, 17OHD is a rare form of CAH, with about 500 published cases and limited established management guidance. Our cases highlight the importance of considering the pathophysiology of 17OHD when developing a management plan; a supraphysiological GC therapy may not be necessary to manage the hypertension and hypokalemia. Physiological hydrocortisone dosing lowers but does not normalize DOC production allowing DOC to exert GC effects. Physiological hydrocortisone and/or monotherapy with mineralocorticoid receptor antagonists both mitigate GC-related side effects, avoid adrenal suppression, and minimize risk for adrenal crisis in patients with 17OHD.