Congenital Adrenal Hyperplasia Causing Poor Response to Androgen Deprivation Therapy in Prostate Cancer

Mustafa Kinaan; Oksana Hamidi; Hanford Yau; Kevin D Courtney; Akin Eraslan; Kenneth Simon

doi:10.1210/jendso/bvaa158

Congenital Adrenal Hyperplasia Causing Poor Response to Androgen Deprivation Therapy in Prostate Cancer

J Endocr Soc. 2020 Oct 23;5(1):bvaa158. doi: 10.1210/jendso/bvaa158. eCollection 2021 Jan 1.

Authors

Mustafa Kinaan^{1

2}, Oksana Hamidi³, Hanford Yau^{1

2}, Kevin D Courtney⁴, Akin Eraslan^{1

2}, Kenneth Simon⁵

Affiliations

¹ Department of Internal Medicine, University of Central Florida College of Medicine, Orlando, Florida.
² Orlando VA Medical Center, Division of Endocrinology, Orlando, Florida.
³ Division of Endocrinology and Metabolism, UT Southwestern Medical Center, Dallas, Texas.
⁴ Simmons Comprehensive Cancer Center, Department of Internal Medicine, Division of Hematology-Oncology, University of Texas Southwestern Medical Center, Dallas, Texas.
⁵ Orlando VA Medical Center, Division of Oncology, Orlando, Florida.

Abstract

Androgen deprivation therapy (ADT) is recommended for the treatment of advanced prostate cancer. Inadequate suppression of testosterone while on ADT poses a clinical challenge and requires evaluation of multiple potential causes, including adrenal virilizing disorders. We present 2 cases of elderly patients with prostate cancer who had undiagnosed congenital adrenal hyperplasia (CAH) driving persistent testosterone elevation during ADT. The first patient is a 73-year-old man who underwent radical prostatectomy on initial diagnosis and was later started on ADT with leuprolide following tumor recurrence. He had a testosterone level of 294.4 ng/dL and prostate-specific antigen (PSA) level of 17.7 ng/mL despite leuprolide use. Additional workup revealed adrenal nodular hyperplasia, elevated 17-hydroxyprogesterone (19 910 ng/dL) and dehydroepiandrosterone sulfate (378 mcg/dL), and 2 mutations of the CYP21A2 gene consistent with simple virilizing CAH. The second patient is an 82-year-old man who received stereotactic radiation therapy at time of diagnosis. He had insufficient suppression of testosterone with evidence of metastatic disease despite treatment with leuprolide and subsequently degarelix. Laboratory workup revealed elevated 17-hydroxyprogesterone (4910 ng/dL) and dehydroepiandrosterone sulfate (312 mcg/dL). Based on clinical, radiographic and biochemical findings, the patient was diagnosed with nonclassic CAH. The first patient initiated glucocorticoid therapy, and the second patient was treated with the CYP17 inhibitor abiraterone in combination with glucocorticoids. Both patients experienced rapid decline in testosterone and PSA levels. Inadequate testosterone suppression during ADT should trigger evaluation for causes of persistent hyperandrogenemia. CAH can lead to hyperandrogenemia and pose challenges when treating patients with prostate cancer.

Keywords: adrenal androgens; androgen deprivation therapy; congenital adrenal hyperplasia; hyperandrogenemia; prostate cancer.

Publication types

Case Reports