MON-362 Undiagnosed Non-classic Congenital Adrenal Hyperplasia as a Driving Force for Persistent Hyperandrogenemia in Prostate Cancer

Abstract

Background Non-classic congenital adrenal hyperplasia (CAH) is a common condition and can lead to adrenal hyperandrogenemia. Clinical case We present a case of an 82-year-old man with prostate adenocarcinoma (Gleason 4+3=7) diagnosed 5 years prior to presentation. During surveillance, he was found to have lymphadenopathy, extra-capsular extension, and rising prostate specific antigen (PSA) (from 4.5 to 14.2 ng/ml, n< 4). Stereotactic radiation therapy and androgen deprivation therapy (ADT) with Gonadotropin-releasing hormone (GnRH) analog leuprolide (22.5 mg every 3 months) were initiated. Post-treatment labs showed inadequate testosterone suppression (total testosterone [TT], 87 ng/dl; target,<5.0). Therefore, bicalutamide (50 mg daily), an androgen receptor inhibitor, was added. Subsequently, PSA declined to 0.29 ng/ml and TT remained at 88.4 ng/dl. Prostate cancer remained stable and Leuprolide was discontinued. Three months prior to presentation, F18-Fluciclovine PET/CT revealed skeletal metastases and incidental bilateral adrenal enlargement. PSA increased to 10.86 ng/dl and TT to 218 ng/dl. ADT was resumed with the GnRH analog degarelix (240 mg monthly). Subsequently, PSA remained elevated (10.6 ng/dl) with TT only partly suppressed (90 ng/dl). Further work-up revealed 17-hydroxyprogesterone 4910 ng/dl (n<220), DHEAS 312 mcg/dl (n<166), corticotropic hormone 39 pg/mL (n,7.2-63), cortisol 5.6 mcg/dl (n,5-23), plasma normetanephrine 1.1 nmol/l (n<0.9), plasma metanephrine 0.39 nmol/l (n<0.5), aldosterone 4.0 ng/dl (n<21), and TT 119 ng/dl. An adrenal CT showed diffuse bilateral adrenal hyperplasia, with a 5.6-cm right adrenal gland and 6.7-cm left adrenal gland. The patient shared that he underwent precocious puberty, was shorter than predicted based on the sex adjusted mid-parental height, and never fathered children. In light of his history, he was diagnosed with non-classic CAH due to partial 21-hydroxylase deficiency (21-OHD), causing inadequate testosterone suppression and progression of prostate cancer despite ADT and androgen receptor blocker. Following the diagnosis, the patient was treated with abiraterone (1000 mg daily), a CYP17A1 inhibitor, and prednisone (2.5 mg twice daily), to suppress adrenal androgen production. TT became undetectable (< 5 ng/dl) and PSA declined from 12.93 to 1.27 ng/ml. Conclusion: Non-classic CAH is a common autosomal recessive disorder and presents in late childhood as premature pubarche and accelerated bone age. The prevalence of non-classic CAH is 0.1%-1% among Caucasians and even higher among Ashkenazi Jews and Hispanics. Treatment in men is generally not required unless there is oligospermia in those desiring fertility. Adrenal hyperandrogenemia can be treated with systemic steroids. Non-classic 21-OHD CAH should be considered in men with prostate cancer with inadequate testosterone suppression after ADT.