An Uncommon Link: Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) in the Setting of Myeloproliferative Neoplasms

Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a well-known cause of hyponatremia, frequently associated with small-cell lung carcinoma. Its association with myeloproliferative neoplasms (MPNs), however, is rare and underreported. We describe the case of an 81-year-old female with a history of chronic hyponatremia attributed to SIADH, requiring multiple hospitalizations. During her hospitalizations, she would be on fluid restriction and urea tablets. Her medical history included paroxysmal atrial fibrillation, a stable pulmonary nodule, and seropositive rheumatoid arthritis. Initial hematologic evaluations for cytopenias were unremarkable. Nearly a decade later, she developed pancytosis, and subsequent testing revealed a JAK2 V617F mutation with a 40.1% clone size. A bone marrow biopsy confirmed a diagnosis of polycythemia vera, an MPN. Treatment with intermittent phlebotomy and ruxolitinib led to hematologic improvement and complete normalization of serum sodium levels without the need for continued SIADH-specific therapy. This case highlights a rare but significant association between MPNs and SIADH. Proposed mechanisms include ectopic antidiuretic hormone (ADH) production by malignant cells and microvascular changes promoting ADH release. The resolution of hyponatremia with MPN-directed therapy suggests a causal relationship. Clinicians should consider MPNs in the differential diagnosis of unexplained SIADH. Further research is warranted to elucidate the underlying pathophysiological link.