Diagnosis and Management of Hyponatremia in Cancer Patients

Hyponatremia, a common electrolyte abnormality in oncology practice, may be a negative prognostic factor in cancer patients based on a systematic analysis of published studies. The largest body of evidence comes from small-cell lung cancer (SCLC), for which hyponatremia was identified as an independent risk factor for poor outcome in six of 13 studies. Hyponatremia in the cancer patient is usually caused by the syndrome of inappropriate antidiuretic hormone (SIADH), which develops more frequently with SCLC than with other malignancies. SIADH may be driven by ectopic production of arginine vasopressin (AVP) by tumors or by effects of anticancer and palliative medications on AVP production or action. Other factors may cause hypovolemic hyponatremia, including diarrhea and vomiting caused by cancer therapy. Hyponatremia may be detected on routine laboratory testing before or during cancer treatment or may be suggested by the presence of mostly neurological symptoms. Treatment depends on several factors, including symptom severity, onset timing, and extracellular volume status. Appropriate diagnosis is important because treatment differs by etiology, and choosing the wrong approach can worsen the electrolyte abnormality. When hyponatremia is caused by SIADH, hypertonic saline is indicated for acute, symptomatic cases, whereas fluid restriction is recommended to achieve a slower rate of correction for chronic asymptomatic hyponatremia. Pharmacological therapy may be necessary when fluid restriction is insufficient. The orally active, selective AVP receptor 2 (V2)-receptor antagonist tolvaptan provides a mechanism-based option for correcting hyponatremia caused by SIADH or other conditions with inappropriate AVP elevations. By blocking AVP effects in the renal collecting duct, tolvaptan promotes aquaresis, leading to a controlled increase in serum sodium levels. The Oncologist 2012;17:756–765 INTRODUCTION Hyponatremia is an electrolyte abnormality commonly encountered in oncology practice and is usually defined by a serum sodium level 135 mEq/L [1, 2]. Although many cases are asymptomatic, hyponatremia may cause neurological symptoms, particularly when serum sodium declines rapidly or by a substantial extent [3]. The incidence and prevalence of hyponatremia vary greatly, depending on the cancer type, clinical setting, and serum sodium cutoff point. Among cancer patients, hyponatremia occurs most frequently with small cell lung cancer (SCLC). In an analysis of nine consecutive clinical trials conducted jointly at four hospitals in Denmark and Sweden, a serum sodium level 136 mEq/L was identified in 415 of 1,684 SCLC patients (24.6%) [4]. Rates of 25%–44% were reported in smaller SCLC cohorts when a similar serum sodium cutoff was used [5–7], whereas rates of 15% were found when a serum sodium level 130 mEq/L was used as