Clinical challenges of paraneoplastic endocrine metabolic syndromes: An illustrative example

Paraneoplastic endocrine metabolic syndromes are rare, but clinically significant manifestations of underlying malignancies, often complicating clinical course and impacting treatment outcomes. Four different paraneoplastic syndromes manifested in an 81-year-old female with metastatic carcinoma rectum, presenting with generalized weakness, inability to walk, severe pain, and low-grade fever. 1. Paraneoplastic Hyponatremia: Hyponatremia (127, 129), with elevated urine sodium, suggestive of inappropriate antidiuretic hormone (ADH) secretion, was treated with fluid restriction, liberal salt intake, 3% intravenous saline, oral sodium bicarbonate and tolvaptan and tapentadol. 2. Paraneoplastic Leukemoid Reaction: Progressively severe leukocytosis [29960, 36670, 44130, 58450 cells/mm3; with neutrophilia and absence of evidence for infectious/ leukemic etiology; procalcitonin= 0.083 ng/mL (<0.1)], was attributed to granulocyte macrophage colony-stimulating factor (GM-CSF) secretion from neoplasm, and empirical antibiotic coverage was provided. 3. Paraneoplastic Hypokalemia: Hypokalemia (2.9, 3.0), likely due to intracellular potassium uptake (in vivo/ in vitro) by rapidly proliferating leukocytes and primary/ metastatic neoplastic cells (ectopic ACTH secretion ruled out) was treated with intravenous/ oral potassium supplementation. 4. Paraneoplastic Fever: Cytokine release from tumor cells or infiltrating immune cells was implicated in the development of fever. Endocrine metabolic paraneoplastic syndromes can impact prognosis and even be confused as metastatic spread or another “non-existent” clinical entity. They can precede, occur concomitantly or present at later stage of tumour development. Recognition of these diverse clinical manifestations improves clinical outcomes (earlier cancer diagnosis, better quality of life, optimal tumour-directed therapy or decision towards non-aggressive focussed palliative care). Teaching Points • Paraneoplastic endocrine metabolic syndromes complicate clinical course/ therapy • They include hyponatremia, hypokalemia, leukemoid reaction and fever • High index of suspicion and prompt recognition foster optimal outcomes/ better care Clinical Relevance: • Endocrine metabolic paraneoplastic syndromes can impact prognosis and even be confused as metastatic spread or another “non-existent” clinical entity. They can precede, occur concomitantly or present at later tumour development stage. Recognition of these diverse clinical manifestations improves clinical outcomes (earlier cancer diagnosis, better quality of life, optimal tumour-directed therapy).