Endocrine Abstracts

Background: Androgen-deprivation therapy (ADT) is commonly used in the management of advanced prostate cancer. ADT can be achieved through bilateral orchidectomy, by administration of GnRH receptor agonists, or by using by the newer GnRH receptor antagonist Degarelix. The classical desired biochemical goal is to achieve a serum testosterone of <1.7 nmol/l.

Case Presentation: A man with metastatic prostate cancer on androgen deprivation therapy and serum total testosterone above the therapeutic goal (3.7 nmol/l), was referred to the Endocrine clinic. He had a previous medical history of hyperprolactinaemia and hypogonadism diagnosed 17 years prior to his presentation. In the past he had been treated with Caberogline followed by testosterone replacement therapy with parenteral testosterone undecanoate. Previous MRI head scanning was normal. The last testosterone undecanoate injection was 13 months prior to his referral to the Endocrine clinic. Androgen deprivation consisted initially of Goserelin for four months, followed by Leuprorelin acetate for three months and subsequently Degarelix for another three months. During the time of treatment with the GnRH agonists (Goserelin followed by Leuprorelin) and the GnRH antagonist Degarelix, serum testosterone had shown little variation and was always above the therapeutic threshold. He was additionally on the androgen receptor inhibitor Enzalutamide, PSA was declining and the disease was clinically stable. Investigations showed a raised extracted testosterone with MS/LC-MS, undetectable gonadotropins, normoprolactinaemia and no rise in other serum androgens. Urine steroid biochemistry showed low androgen metabolites making an adrenal source for the measured testosterone unlikely, and measured testosterone did not change following a low dose dexamethasone suppression test. Review of available cross-sectional imaging showed unilateral adrenal nodularity that was unchanged in repeated scanning. In the subsequent months, total testosterone started to decline with a lowest achieved level of 1.8 nmol/l.

Discussion: Evidence suggests that a testosterone level below the classical therapeutic target in advanced prostate cancer is associated with improved outcomes and lower progression toward castration-resistant prostate cancer. In this context serum testosterone is together with PSA an important biochemical target. Because of its mechanism of action, the GnRH antagonist Degarelix prevents testosterone microsurges that have been observed immediately following GnRH agonists administration, with potential clinical implications. We speculate that the persistently detectable testosterone levels here are likely to arise from insufficient response to treatment with GnRH agonists, with eventual decline on prolonged treatment with Degarelix. A less likely explanation is the presence of residual testosterone undecanoate depot.