Unilateral Autonomous Testicular Testosterone Production Mimicking Androgen Independent Prostate Cancer

0022-5347/02/1683-1098/0 THE JOURNAL OF UROLOGY® Copyright © 2002 by AMERICAN UROLOGICAL ASSOCIATION, INC.®

Vol. 168, 1098 –1099, September 2002 Printed in U.S.A.

DOI: 10.1097/01.ju.0000024763.12869.48

UNILATERAL AUTONOMOUS TESTICULAR TESTOSTERONE PRODUCTION MIMICKING ANDROGEN INDEPENDENT PROSTATE CANCER MICHAEL LAVELLE, KATHRYN G. SCHUFF,* FREDERICK S. KELLER, CHRISTOPH A. BINKERT, MICHAEL O’HARA, CYNTHIA A. FAIRFAX AND TOMASZ M. BEER† From the Divisions of Urology, Endocrinology, Diabetes and Clinical Nutrition, and Hematology and Medical Oncology, and Dotter Intervention Institute, Oregon Health and Science University, Portland, Oregon, and Urologists, P. A., Boise, Idaho KEY WORDS: testosterone, adenocarcinoma, prostatic neoplasms

Reduction in circulating testosterone levels is the mainstay of treatment for advanced prostate cancer. Failure to achieve castrate testosterone levels (less than 30 ng./dl.) with gonadotropin-releasing hormone (Gn-RH) agonist therapy is rare.1–3 To our knowledge we report the first case in which selective venous sampling revealed an autonomous unilateral testicular source of testosterone presenting as suspected androgen independent prostate cancer. CASE REPORT

A 64-year-old man with persistently elevated prostate specific antigen (PSA) after radical retropubic prostatectomy and bilateral pelvic lymphadenectomy for stage pT3bN0M0, Gleason score 9, PSA 7.0 ng./ml. adenocarcinoma presented with an increasing PSA 12 months after surgery. Bone scan and computerized tomography of the abdomen and pelvis were negative. 111Indium capromab pendetide scan (ProstaScint, Cytogen Corp., Princeton, New Jersey) showed bilateral pelvic lymph node uptake, and anastomotic biopsies demonstrated no malignant tissue. When PSA reached 5.7 ng./ml., therapy with leuprolide was initiated, which subsequently produced a nadir PSA of 0.4 ng./ml. During the ensuing 24 months PSA control was maintained with a variety of hormonal therapies, including leuprolide with and without bicalutamide, bicalutamide alone, bicalutamide plus finasteride, goserelin plus nilutamide and goserelin alone. With goserelin PSA began to increase, reaching 45 ng./ml. Serum total testosterone levels were 493 ng./dl. and 551 ng./dl. on goserelin therapy. Gonadotropin suppression was examined by measurement of luteinizing hormone, which was 1.35 mIU/ml. (normal 0.9 to 5.6), and follicle-stimulating hormone, which was 0.5 mIU/ml. (normal 1.6 to 8.0). Tumor related human chorionic gonadotropin was undetectable. Computerized tomography of the abdomen and pelvis revealed a new finding of mild thickening of the anterior limb of the left adrenal gland. Simultaneous adrenal and testicular vein sampling before and after intravenous administration of 250 ␮g. corticotropin showed a significantly higher testosterone level in the right testicular vein (11,707 ng./dl.) compared to the left testicular vein (601 ng./dl.) and both adrenal veins (382 and 393 ng./dl.) (fig. 1). Simultaneous measurement of cortisol before and after administration of corticotropin confirmed appropriate catheter position in the adrenal veins. The patient underwent bilateral orchiectomy. Testosterone levels decreased to within the castrate range and a greater than 75% reduction in PSA was observed (fig. 2). Detailed

FIG. 1. Cannulation of both gonadal veins under fluoroscopy

pathological examination of the testes, including slicing at 2 mm. intervals, revealed only mild atrophy.

DISCUSSION

To our knowledge this is only the fifth reported case demonstrating a normal testosterone level despite Gn-RH agonist therapy, and the first case involving selective venous sampling to locate the source of testosterone production. Ectopic and/or autonomic sources of testosterone are rare. A luteinizing hormone secreting adenoma proved to be the source of Gn-RH agonist resistance in 2 reported cases of prostate cancer. Ectopic testosterone production has been reported in testicular tumors, adrenal cortical tumors, congenital adrenal hyperplasia and hepatocellular carcinoma, although none of these conditions has been reported to coexist with prostate

Accepted for publication April 19, 2002. * Financial interest and/or other relationship with Abbott Laboratories. † Financial interest and/or other relationship with Aventis Pharmaceutical, D-Novo Therapeutics, Immunex Pharmaceuticals, Bristol-Myers Squibb, Pharmacia, Novartis Oncology, Dendreon Corp., Praecis Pharmaceuticals, AVI Biopharma and Roche Pharmaceuticals. 1098

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This case reinforces the importance of considering inadequate testosterone suppression when confronted with suspected androgen independent prostate cancer. Recognition of this syndrome is essential so that adequate testosterone suppression can be achieved before more toxic therapies for androgen independent prostate cancer are offered. REFERENCES

FIG. 2. Effect of orchiectomy on serum PSA and testosterone. Orchiectomy was performed on day 0.

cancer. While selective venous sampling allowed us to identify a single testicle as the source of testosterone production, no pathological abnormality was found.

1. Oefelein, M. G. and Cornum, R.: Failure to achieve castrate levels of testosterone during luteinizing hormone releasing hormone agonist therapy: the case for monitoring serum testosterone and a treatment decision algorithm. J Urol, 164: 726, 2000 2. Smith, M. R. and McGovern, F. J.: Gonadotropin-releasing hormone agonist failure in a man with prostate cancer. J Urol, 166: 211, 2001 3. Ogan, K., Berger, M. and Ball, R.: Gonadotropin releasing hormone analogue antiandrogen failure secondary to a pituitary adenoma. J Urol, 160: 497, 1998