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CAH: Newer Insights in Etiology and Management

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Prof (Dr) Richard Auchus, US    27 November 2019

  • 11-oxygenated 19-carbon (11oxC19) steroids are elevated in both men and women with classic 21-hydroxylase deficiency (21OHD). 11oxC19 steroids are specific biomarkers of adrenal-derived androgen excess (Turcu AF, et al. Eur J Endocrinol. 2016;174(5):601-9).
  • Potential therapies for management of congenital adrenal hyperplasia (CAH) – Modified-release hydrocortisone; Hydrocortisone subcutaneous infusion pump; Super-androgen receptor antagonists: P450 17A1 inhibitor – Abiraterone acetate, CRH receptor antagonist – NBI-77860, NBI-74788, SPR-001 = Tildacerfont and ACAT1 (SOAT1) inhibitor – ATR-101 (Nevanimibe).
  • Abiraterone for 21OHD – Abiraterone acetate is a potent P450 17A1 inhibitor that is FDA-approved for the treatment of prostate cancer with prednisone to prevent hypertension and hypokalemia. The concept is to add abiraterone acetate to replacement hydrocortisone to control androgen excess and mitigate the consequences of chronic supraphysiologic glucocorticoids.

Abiraterone acetate at 250 mg/day with hydrocortisone 20 mg/day for 1 week normalizes androgens in the majority of adult women with classic 21OHD, without causing hypertension or hypokalemia.

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