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

Abstract

We report a rare case of severe hyponatremia due to cisplatin-induced syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in a 74-year-old male with a history of squamous cell carcinoma of the tongue who presented with a five days history of worsening confusion. He was found to have severe hyponatremia. His clinical and laboratory findings were consistent with hyponatremia due to SIADH. He was treated with fluid restriction and salt tablets after which his serum sodium markedly improved. Drugs including diuretics, antidepressants, antipsychotics are well known to cause hyponatremia. Cisplatin is a very common antineoplastic drug for solid tumors. Clinicians need to have prompt recognition of this rare side effect of cisplatin to prevent life-threatening hyponatremia.

Hyponatremia in the cancer patient

“…33 The use of hypertonic saline as a solvent vehicle for cisplatin is frequently employed to mitigate against the development of renal toxicity, including salt wasting resulting in hyponatremia. [34][35][36] Other conditions associated with reduced effective arterial blood volume. Decreased EABV-inducing vasopressin release can be observed in patients with cytokine release syndrome, a form of systemic inflammatory response due to rapid release of cytokines resulting in increase in capillary permeability associated with massive fluid leak and intravascular underfilling.…”

Cancer therapy-induced hyponatremia: A case-illustrated review

“…higher relative urine osmolality, and the absence of low urine sodium/fractional excretion of sodium). 12 The other cause of hyponatremia is RSWS, as described in the clinical case above. In this clinical scenario, platinum-chemotherapy related tubular necrosis results in renal sodium, magnesium, potassium, and calcium loss.…”

“…The more frequent of these etiologies is likely platinum-associated SIADH. 7,12 While the exact mechanism underlying SIADH in this setting has not been entirely elucidated, this presentation is distinct from RSWS in that hyponatremia develops within a few days of cisplatin administration, and resolves following chemotherapy cessation. Also, clinically these patients are euvolemic and have urinary findings in keeping with SIADH (e.g.…”

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…”