Rare Case of Dual Paraneoplastic Endocrinopathies in Small Cell Lung Cancer: Triphasic Electrolyte Presentation

Introduction: Paraneoplastic endocrinopathies are well-recognized complications frequently observed in patients with neuroendocrine malignancies such as small cell lung carcinoma (SCLC). However, the concurrence of both the syndrome of inappropriate antidiuretic hormone (SIADH) and Cushing syndrome is rare, with <10 reported cases. This case is unique for its extreme hormonal imbalance and a triphasic pattern of electrolyte disturbances, highlighting diagnostic and management challenges. Case Description: An 81-year-old female, with history of localized squamous cell carcinoma of the right lower lung lobe, presented with confusion. Laboratory tests showed severe hyponatremia (110 mmol/L), suggestive of SIADH. Salt tablets were initiated with improvement in her [sodium] levels. CT scan revealed multiple lung and liver nodules, suggestive of disease recurrence. Instead, liver biopsy confirmed SCLC, for which chemo/immunotherapy was initiated. Nine months later, she presented with severe hypokalemia (2.3 mmol/L) and alkalosis (CO2 38 mmol/L) but was normonatremic (141) despite not taking her salt tablets. Urine studies revealed renal potassium wasting, and serum studies showed elevated AM cortisol (49.1 mcg/dL) and high ACTH (181 pg/mL). CT scan showed bilateral adrenal thickening. A high-dose dexamethasone suppression test confirmed ectopic Cushing syndrome, so she was started on metyrapone. Within 48 hours, her [sodium] declined from 138 to 130 mmol/L. Copeptin later came back at >5,000 pmol/L. Tolvaptan was considered, but fluid restriction, salt tablets, and urea normalized her [sodium]. Discussion: Hyponatremia resolving to hypokalemia/alkalosis and recurring to hyponatremia again should raise the suspicion for dual paraneoplastic syndrome in SCLC. Our patient exhibited a triphasic electrolyte evolution, highlighting an intricate hormonal interplay: hyponatremia due to SIADH, normalization during hypercortisolemia, and recurrent hyponatremia after cortisol reduction. The high cortisol's mineralocorticoid activity, overwhelming 11β-Hydroxysteroid dehydrogenase, likely masked hyponatremia, and then metyrapone-induced cortisol suppression may have unmasked persistent ADH-driven water retention. Anticipating this triphasic course is key to the diagnosis and treatment of a rare dual paraneoplastic syndrome in SCLC.