Pituitary apoplexy induced by gonadotropin-releasing hormone (GnRH) agonist administration for treatment of prostate cancer: a systematic review

Abstract

Objective We aimed to review of literature on the clinical presentation, management and outcomes of pituitary apoplexy following gonadotrophic release hormone (GnRH) agonist administration for the treatment of prostate cancer. Methods We used PRISMA guidelines for our systematic review and included all English language original articles on pituitary apoplexy following GnRH agonist administration among prostate cancer patients from Jan 1, 1995 to Dec 31, 2020. Data on patient demographics, prostate cancer type, Gleason score at diagnosis, history of pituitary adenoma, clinical presentation, GnRH agonist, interval to pituitary apoplexy, laboratory evaluation at admission, radiologic findings, treatment of pituitary apoplexy, time to surgery if performed, pathology findings, and clinical/hormonal outcomes were collected and analyzed. Results Twenty-one patients with pituitary apoplexy met our inclusion criteria. The mean age of patients was 70 (60–83) years. Leuprolide was the most common used GnRH agonist, used in 61.9% of patients. Median duration to symptom onset was 5 h (few minutes to 6 months). Headache was reported by all patients followed by ophthalmoplegia (85.7%) and nausea/vomiting (71.4%). Three patients had blindness at presentation. Only 8 cases reported complete anterior pituitary hormone evaluation on presentation and the most common endocrine abnormality was FSH elevation. Tumor size was described only in 15 cases and the mean tumor size was 26.26 mm (18–48 mm). Suprasellar extension was the most common imaging finding seen in 7 patients. 71.4% of patients underwent pituitary surgery, while 23.8% were managed conservatively. Interval between symptoms onset to pituitary surgery was 7 days (1–90 days). Gonadotroph adenoma was most common histopathologic finding. Clinical resolution was comparable, while endocrine outcomes were variable among patients with conservative vs surgical management. Conclusion Although the use of GnRH agonists is relatively safe, it can rarely lead to pituitary apoplexy especially in patients with pre-existing pituitary adenoma. Physicians should be aware of this complication as it can be life threatening. A multidisciplinary team approach is recommended in treating individuals with pituitary apoplexy.

Late onset of pituitary apoplexy following gonadotropin-releasing hormone agonist for prostate cancer treatment

“…GnRH agonists are commonly used in the management of patients with PCa and can rarely lead to PA 6 11. In a systematic review by Raj et al , authors reported 21 such cases between 1990 and 2020 with only three cases happening in previously known pituitary adenoma 6. In this case, the patient did not have any known pituitary adenoma as suggested by previously normal pituitary imaging and was only found to have abnormal imaging at the diagnosis of PA.…”

“…Although PA commonly happen in setting of known pituitary tumours, in over 60% of cases, the underlying lesion can be diagnosed at the time of apoplectic event 10. GnRH agonists are commonly used in the management of patients with PCa and can rarely lead to PA 6 11. In a systematic review by Raj et al , authors reported 21 such cases between 1990 and 2020 with only three cases happening in previously known pituitary adenoma 6.…”

“…Although the exact mechanism of PA following GnRH agonists remain unclear, several mechanisms have been suggested and include: increased tumour vascularity,6 blood supply mismatch,12 increased tumour size resulting in compression of surrounding structure13 14 and cytoskeletal structure changes in gonadotroph cells 15. Majority (up to 62%) of the patients with PA presents within 24 hours of GnRH agonists administration, few cases has been described with presentations up to 6 months after receiving GnRH agonist 6 11. Our patient presented with PA approximately 12 months after receiving leuprolide none the less, he started having symptoms of pituitary hormone deficiency at least 6 months prior to his presentation.…”

“…GnRH agonists (leuprolide, goserelin and triptorelin) are systemic therapy used in the treatment of advanced prostate cancer (PCa), suppresses luteinising hormone (LH) production and, therefore, the synthesis of testicular androgens. Very few cases of PA have been reported among patients receiving GnRH agonists for the treatment of PCa 5 6. Although previously PA was considered a neurosurgical emergency,7 recent evidence has suggested spontaneous clinical recovery with a conservative approach 8 9.…”

“…Although previously PA was considered a neurosurgical emergency,7 recent evidence has suggested spontaneous clinical recovery with a conservative approach 8 9. Additionally, in the absence of classical sign and symptoms of PA, its diagnosis can get delayed and hence it is crucial that clinicians keep a very high index of suspicion for PA for the patients on GnRH agonists therapy for PCa treatment 3 5 6…”