Syndrome of Inappropriate Antidiuretic Hormone Secretion and Thrombotic Microangiopathy as Paraneoplastic Syndromes Complicating BRCA2-Mutated Metastatic Prostate Cancer

Metastatic prostate cancer with a BRCA2 mutation is associated with aggressive clinical behavior and poor outcomes with standard systemic therapy. While the BRCA2 mutation predicts response to PARP inhibitors and platinum agents, its association with paraneoplastic syndromes is not well described. We report a 72-year-old male who presented with altered sensorium with severe hyponatremia who was diagnosed with syndrome of inappropriate antidiuretic hormone secretion (SIADH) in the context of newly diagnosed metastatic prostate adenocarcinoma. He was treated with free water restriction, hypertonic saline, and triplet systemic therapy (docetaxel, androgen deprivation, and darolutamide) and discharged in stable condition. After one year of disease remission, he relapsed with bone marrow metastases, confirming the BRCA2 mutation, and presented with thrombotic microangiopathy (TMA). The patient was managed with chemotherapy along with blood support, with clinical improvement; however, he succumbed to the disease within two months. While SIADH and TMA have been individually reported in prostate cancer, their sequential occurrence in a BRCA2-mutated setting is unique. Management of these complications requires addressing the underlying cancer with definitive treatment. The case highlights the vigilance for atypical paraneoplastic manifestations, the need for early genomic testing, and the exploration of novel therapeutic strategies in BRCA2-driven prostate cancer.