Hypertension and Hirsutism in a Young Female: A Rare Form of Congenital Adrenal Hyperplasia?

Background: Rare forms of congenital adrenal hyperplasia (CAH) especially can be a diagnostic and management challenge. We present a case of hypertension and hirsutism with elevated mineralocorticoid and sex steroid precursors concerning for non-classic rare form of CAH. Clinical Case: A 22 y/o female was evaluated in our endocrinology clinic for primary hypertension and hirsutism (modified Ferriman-Gallwey score of 12) but without menstrual irregularity, clitoromegaly or deepening of voice. Family history was significant for hypertension and hirsutism in her mother. Renal and pelvic ultrasonographies were normal. CT abdomen showed thickened bilateral adrenal glands. Case detection testing was positive with PAC/PRA of 19.4/0.4 however intravenous saline suppression test suppressed aldosterone to 5 ng/dL, hence ruled out primary aldosteronism. Cortisol suppressed to 0.6 mcg/dL after 1 mg overnight Dexamethasone, hence ruled out Cushing’s syndrome; prolactin and TSH were normal, serum HCG was undetectable. This prompted work up for other endocrine causes of hypertension and hirsutism which revealed follicular phase elevated dehydroepiandrosterone-sulfate of 772 mcg/dL (35–430), pregnenolone of 603 ng/dL (15–132), 17-hydroxypregnenolone of 1516 ng/dL (<226), 11-deoxycortisol of 39.4 ng/dL (<32); but normal 17-hydroxyprogesterone of 36.8 ng/dL (15–70), androstenedione of 1.12 ng/mL (0.26–2.14) and free testosterone of 26 ng/dL (9–44). 250-mcg ACTH administration stimulated cortisol to 24.6 mcg/dL, pregnenolone to 1478 ng/dL, 17-hydroxypregnenolone to 1716, 11-deoxycortisol to 64.2 ng/dL but 17-hydroxyprogesterone only stimulated to 59.9 ng/dL. We initiated spironolactone at 12.5 mg increased to 25 mg daily, which normalized her blood pressure. She was counseled regarding its teratogenicity but is she declined birth control, as she was not engaging in heterosexual intercourse. Urinary steroid analysis and genetic testing were pending. Conclusions: Hypertension and hirsutism accompanied by elevated pregnenolone, 17-hydroxypregnenolone, 11-deoxycortisol and dehydroepiandrosterone-sulfate, however, normal baseline as well as stimulated 17-hydroxyprogesterone, raise concern for co-occurrence of partial 3-betahydroxysteroid dehydrogenase deficiency in addition to non-classic 11-betahydroxylase deficiency. Management with mineralocorticoid receptor antagonist helped control hypertension.