Endocrine Abstracts

Introduction: Gonadotrophin-Releasing Hormone (GnRH) agonists are the mainstay of androgen deprivation therapy (ADT) in prostate cancer. They act through continuous stimulation of pituitary GnRH receptors, leading to receptor desensitisation, suppression of gonadotrophin release, and achievement of castrate testosterone levels. Persistent testosterone elevation during therapy is rare and may represent paradoxical pituitary stimulation rather than pharmacological ineffectiveness. Understanding such responses is crucial for accurate endocrine interpretation and oncological decision-making.

Case Presentation: A 70-year-old man with T3a Gleason 9 prostate adenocarcinoma commenced ADT with Decapeptyl (11.25 mg) in June and August 2023. Following the second dose, testosterone and FSH rose—peaking at 42.3 nmol/l and 18.7 U/l (NR 1–12) respectively—with a concurrent PSA increase. Other pituitary hormones were normal. MRI demonstrated a 21×19×18 mm pituitary macroadenoma. As gonadotrophins and testosterone remained elevated for several months, an FSH-secreting adenoma (FSHoma) was considered. Multidisciplinary endocrine review concluded that the biochemical profile was most consistent with paradoxical gonadotrophin stimulation secondary to GnRH agonist exposure rather than autonomous secretion. The GnRH agonist was discontinued after the second dose because of sustained hormonal elevation. Over 3–4 months, testosterone and FSH gradually normalised. The patient subsequently underwent radical radiotherapy for prostate cancer and was commenced on bicalutamide, a non-steroidal androgen receptor blocker. Follow-up pituitary MRI in 2024 showed adenoma reduction, with stability confirmed in 2025. Inoperable gastric cancer was diagnosed later in 2024.

Conclusion: This case highlights a rare but clinically significant paradoxical response to GnRH agonist therapy, where persistent gonadotrophin stimulation maintained testosterone production despite intended suppression. The mechanism likely reflects transient pituitary hypersensitivity rather than true androgen resistance. Recognition of this phenomenon is essential to prevent misinterpretation as treatment resistance, avoid inappropriate escalation, and guide timely endocrine evaluation and multidisciplinary management in patients with unexpected biochemical patterns.