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Abstract: SA-PO470

SIADH Escape or Tolvaptan Resistance in Progressive Small Cell Lung Cancer

Session Information

Category: Fluid‚ Electrolyte‚ and Acid-Base Disorders

  • 1002 Fluid‚ Electrolyte‚ and Acid-Base Disorders: Clinical


  • Mandal, Sunny, University of Pikeville Kentucky College of Osteopathic Medicine, Pikeville, Kentucky, United States
  • Kannan, Lakshmi, Pikeville Medical Center, Pikeville, Kentucky, United States

Syndrome of inappropriate antidiuretic hormone(SIADH) occurs in 11-15% of patients with small-cell lung cancer. The pathophysiology is through direct tumor secretion, enhanced secretion of ADH from adrenal metastases, chemotherapy, opioids, NSAIDs, or side effects of treatment like nausea, vomiting, stress, and pain. We report a patient with small-cell lung cancer initially managed with tolvaptan but developed resistance to the aquaretic effects of the drug.

Case Description

A 61-year-old male with small cell lung cancer and chronic hyponatremia on tolvaptan presented with unsteady gait and weakness. Workup showed serum sodium of 111 mEq/L(baseline-122-125 mEq/L), serum osmolality of 236 mOsm/ Kg H2O, urine osmolality of 589 mOsm/Kg H2O, and urine sodium of 62 mEq/L. The patient was admitted for 3% hypertonic saline for SIADH. His sodium improved to 120 mEq/L with the resolution of symptoms. Reviewing his records, the patient was diagnosed with T3N3 IIIC small cell lung cancer 11 months prior to this admission. He underwent two cycles of cisplatin and etoposide. In a span of 3 months, the patient had four hospitalizations for acute on chronic hyponatremia despite being on tolvaptan as his surveillance CT abdomen/pelvis revealed multiple new liver metastases. The timeline of events is shown in Figure 2.


Syndrome of inappropriate antidiuretic hormone is characterized by euvolemic hypotonic hyponatremia where tolvaptan has been used since 2009. The first two cases of resistance to tolvaptan therapy were described in 2018 in patients with small-cell lung cancer and this is the third report of SIADH escape to tolvaptan. The possible cause of resistance to the aquaretic effects of the drug is due to extraordinarily high ADH levels from the progression of lung cancer. In these cases, successful treatment of the malignancy will eliminate or reduce the inappropriate ADH secretion. One key factor to consider is the search for new metastasis when patients present with recurrent acute or acute on chronic hyponatremia.