Snapshot A 69-year-old man presents to his physician with complaint of malaise for the past 2 months. He also has a unrelenting cough that is bothersome to him and keeps him from sleeping well at night. In addition, he realized that he had unintentionally lost 18 pounds in the past months after weighing himself when his wife remarked that he looked thinner than usual. The patient has a 40 pack-year smoking history. Labs are drawn and he is found to have an elevated serum sodium level of 120 mEq/L. A chest radiograph is obtained and shown in the image. Introduction Overview paraneoplastic syndromes occur separately from the tumor itself, but result from substances produced by the tumor symptoms may affect various body systems (i.e., endocrine, hematologic, neuromuscular) Paraneoplastic SyndromesEndocrineSyndrome or Clinical ManifestationAssociated TumorsPotential Tumor ProductsHypercalcemiaSquamous cell carcinomas of the lung, head, and neck Renal carcinomasBladder carcinomasBreast carcinomasOvarian carcinomas PTHrP↑ 1,25-(OH)2 vitamin D3 (calcitriol)Cushing syndromeSmall cell lung cancer↑ ACTHHyponatremia (SIADH)Small cell lung cancer↑ ADHHematologicSyndrome or Clinical ManifestationAssociated TumorsPotential Tumor ProductsPolycythemiaRenal cell carcinomaPheochromocytomaHemangioblastomaLeiomyomaHepatocellular carcinoma↑ EPONeuromuscularLambert-Eaton myasthenic syndromeSmall cell lung cancerAntibodies against presynaptic Ca2+ channels at the neuromuscular junctionParaneoplastic encephalomyelitisSmall cell lung cancerAntibodies against Hu antigens in neuronsMyasthenia gravisThymomaAntibodies against postsynaptic ACh receptors at the neuromuscular junction