Cisplatin-induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) with life-threatening hyponatraemia

Abstract

We present a case of cisplatin-induced syndrome of inappropriate antidiuretic hormone (SIADH) in a patient with metastatic recurrent urothelial carcinoma. Cisplatin-induced SIADH is an uncommon but potentially life-threatening toxicity. Pharmacogenetic characteristics may result in different toxicity profiles in different populations. With such widespread use of cisplatin in a diverse range of cancers, prompt recognition is crucial to detect and prevent severe neurological sequelae.

Hyponatremia in the cancer patient

“…Antineoplastic drugs constitute a principal cause for SIAD. Some drugs such as vinca alkaloids (e.g., vincristine 66,67 and vinblastine 68,69 ), alkylating agents (e.g., cyclophosphamide 70 and ifosfamide [71][72][73], and platinum compounds (e.g., cisplatin [74][75][76] and carboplatin 77,78 ) have been shown to increase synthesis/release of vasopressin. Other antineoplastic agents such as cyclophosphamide also enhance the water permeability of the distal nephron in the absence of elevated vasopressin.…”

Severe Hyponatremia Due to Cisplatin-induced Syndrome of Inappropriate Secretion of Antidiuretic Hormone

“…In 1982, Levin et al first described the case of cisplatin-induced hyponatremia in a patient with malignant thymoma. Subsequently, it has been reported in patients with ovarian cancer, non-small cell lung cancer, esophageal cancer, cervical neuroendocrine tumor, squamous cell carcinoma, pediatric osteosarcoma, and urothelial carcinoma [3]. To the best of our knowledge, it is the first case of cisplatin-induced hyponatremia in a patient with squamous cell carcinoma of the base of the tongue.…”

“…Renal tubular necrosis and impaired sodium reabsorption have been proposed as the possible mechanisms of cisplatin-induced hyponatremia [4]. Neurotoxicity related to cisplatin can also be a contributing factor causing hyponatremia due to SIADH [3].…”

Anticancer Medications and Sodium Dysmetabolism

“…38 Acute life-threatening hyponatraemia with seizure and coma has also been reported with vincristine. 42 In a retrospective analysis, Asians were found [46][47][48] Antifungal azoles can inhibit metabolism and worsen hyponatraemia/neurotoxicity 44 Platinum compounds Hyponatraemia 1-2 days • SIADH -unclear mechanism [65][66][67][68] • RSWS -cisplatin-induced renal tubular necrosis [61][62][63][64] • Potent stimulation of ADH by therapy-induced nausea 35 • Overzealous administration of large volumes of hypotonic fluid 51,69 Overzealous co-administration of hypotonic fluid to be avoided Hypernatraemia -• Acquired NDI -reduced expression of AQP2 channels on apical membranes of renal tubules 45,52,70 • Cisplatin-induced hypokalaemia can cause reversible NDI by decreasing AQP2 expression;…”

“…Onset is early, occurring in the first 2 days after administration of cisplatin, and sodium levels normalise rapidly after removal of the offending drug. [65][66][67][68] Other causes…”