SUN-291 - A Case of Leydig Cell Tumor Causing Persistent Hyperandrogenism in a Patient on Androgen Deprivation Therapy

Introduction: Persistent or recurrent testosterone elevation during androgen-deprivation therapy (ADT) should prompt a thorough endocrine evaluation, including an assessment for endogenous androgen sources. We describe a rare case of Leydig cell tumor (LCT) identified after non-suppressed androgen levels on ADT during prostate cancer treatment.

Case description: A 51-year-old man with locally advanced prostate adenocarcinoma was referred to endocrinology for persistent hyperandrogenism during androgen-deprivation therapy (ADT). At prostate cancer diagnosis, prostate-specific antigen (PSA) was 54.687 ng/mL (0–4 ng/mL). CT abdomen/pelvis and bone scan showed no distant metastatic disease. He was started on leuprolide, abiraterone, and underwent radiation therapy. He initially responded to treatment with PSA declining to 1.14 ng/mL and testosterone suppressed to castrate levels ( < 50 ng/dL). During the second year of treatment, PSA rose to 1.24 ng/mL with testosterone reported up to 700-800 ng/dL range (250–1100 ng/dL), prompting transition to relugolix. Testosterone was again suppressed appropriately with PSA nadir 0.15 ng/mL. Approximately 4 years after diagnosis, testosterone again rose to 773 ng/dL with PSA increase from 0.15 to 1.24 ng/mL despite reported medication adherence and denial of exogenous androgen use. Repeat biochemical evaluation showed persistent testosterone elevation with total testosterone 881 ng/dL, free testosterone 140.1 pg/ml (35-129pg/ml), suppressed gonadotropins with FSH < 0.7 mIU/mL (1.4–12.8 mIU/mL) and LH < 0.2 mIU/mL (1.5–9.3 mIU/mL), and non-elevated adrenal androgen precursors, including 11-deoxycortisol 26 ng/dL ( < 42 ng/dL) and 17-hydroxyprogesterone 141 ng/dL (37–129 ng/dL). Additional testing showed estradiol 60 pg/mL ( < 33 pg/mL), PSA 1.51 ng/mL, and negative β-hCG. Scrotal ultrasonography identified a 2.2×1.5 cm vascular left intratesticular mass. Left orchiectomy was performed, and pathology confirmed a 2.1×1.7×1.7 cm Leydig cell tumor with negative margins. Testosterone was suppressed postoperatively.

Discussion: This case highlights the importance of endocrine evaluation in patients on ADT who develop persistent hyperandrogenism. While this patient initially responded appropriately to ADT therapy with suppressed testosterone and PSA, the subsequent rise in testosterone prompted further evaluation of the source of androgen production. LCT is a rare testicular sex cord-stromal tumor that may be incidental or present with symptoms related to hyperandrogenism. Rare case reports of LCT incidentally found during prostate cancer workup have been described in the literature. This case further contributes to the existing literature and highlights the importance of timely endocrine evaluation in patients with persistent hyperandrogenism while on ADT.

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