Does cancer cause electrolyte imbalance?

Abstract​

Patients with malignancies commonly experience abnormalities in serum electrolytes, including hyponatremia, hypokalemia, hyperkalemia, hypophosphatemia, and hypercalcemia. In many cases, the causes of these electolyte disturbances are due to common etiologies not unique to the underlying cancer. However, at other times, these electrolyte disorders signal the presence of paraneoplastic processes and portend a poor prognosis. Furthermore, the development of these electrolyte abnormalities may be associated with symptoms that can negatively affect quality of life and may prevent certain chemotherapeutic regimens. Thus, prompt recognition of these disorders and corrective therapy is critical in the care of the patient with cancer.

Key Words​

  1. Cancer
  2. Hyponatremia
  3. Hypokalemia
  4. Hypercalcemia
  5. Hypophosphatemia
 

Introduction​

Clinical Summary
•
Electrolyte disorders in patients with cancer are common and can be secondary to either the cancer or its therapy.
•
The most common electrolyte disorder seen in cancer patients is hyponatremia; this is most commonly due to the syndrome of inappropriate ADH secretion.
•
Electrolyte disorders in cancer patients are associated with a poor prognosis; appropriate treatment may improve short term outcomes and quality of life.
Electrolyte disorders are commonly encountered in the patient with cancer. In most cases, these disorders are associated with etiologies seen in all types of patients and are not specifically linked to the malignancy or its therapy (for example, diuretic-induced hyponatremia or hypokalemia). In other cases, electrolyte disorders are due to paraneoplastic syndromes or are specifically associated with chemotherapeutic regimens. When these malignancy-specific electrolyte disorders are manifest, they can lead to life-threatening complications that require emergent therapy. Thus, proper recognition and treatment of these disorders is important in the overall care of the patient with cancer. This review will discuss selected malignancy-associated electrolyte disorders.
 

Hyponatremia Associated With Cancer​

Hyponatremia is the most common electrolyte disorder encountered in patients with malignancies. Studies have reported a prevalence that ranges from approximately 4% to as high as 47%.1,2 Approximately 14% of hyponatremia encountered in medical inpatients is due to an underlying malignancy-related condition.3 It is important to note that nearly half of these cases represented hospital-acquired hyponatremia, suggesting that management of these patients (most likely with intravenous fluids) significantly contributes to the development of hyponatremia.
Hyponatremia is clearly associated with significant morbidity and mortality when it occurs in the patient with cancer. For instance, hospital length of stay is nearly doubled in patients with moderate to severe hyponatremia.1 The hazard ratio for death within 90 days after the diagnosis of hyponatremia was 4.74 in those patients with moderate hyponatremia and 3.46 in patients with more severe hyponatremia.1 Other studies have also demonstrated a marked association with hyponatremia and mortality in patients with non-Hodgkin’s lymphoma, renal cell carcinoma, gastric cancer, and small-cell lung cancer.4-6 Hyponatremia may affect patient response to therapy, as shown in non-Hodgkin’s lymphoma, in which patients with serum sodium less than 137 mEq/L had a lower rate and shorter duration of remission after chemotherapy as compared with patients with higher sodium levels.4 Likewise, hyponatremia may limit the use of chemotherapeutic options that require extensive hydration. Symptoms attributable to hyponatremia, such as confusion, lethargy, and headache, may also further compromise quality of life in this population. It is debatable whether hyponatremia independently contributes to these poor outcomes or is simply a marker of disease severity, progression, and overall debility. A recent study would argue that the latter is the case, although correction of hyponatremia before hospital discharge does seem to improve outcomes whereas persistent hyponatremia was associated with worse outcomes.7-10
 
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The differential diagnosis of hyponatremia in patients with cancer is extensive (Table 1) and requires a careful history, physical examination, and laboratory evaluation to elucidate the etiology. It should be emphasized that the symptoms related to hyponatremia may be nonspecific and attributable to the underlying disease and its therapy. Thus, clinicians should measure serum sodium values in patients with symptoms compatible with hyponatremia rather than assume that the etiology is due to the underlying disease. Understanding the etiology of hyponatremia is critical in allowing proper management. For example, intravenous 0.9% saline would be the appropriate therapy in a patient with hypovolemic hyponatremia due to vomiting but not for a patient with the syndrome of inappropriate ADH secretion (SIADH). In some cases of drug-associated hyponatremia, simply stopping the offending medication along with transient free water restriction will lead to correction of the hyponatremia.
a.
Syndrome of inappropriate antidiuretic hormone secretion
b.
Gastrointestinal fluid losses due to vomiting, diarrhea, enteric fistulas, and nasogastric suctioning
c.
Third-spacing (sequestration of fluid from the intravascular space) such as from ascites or anasarca
d.
Kidney failure
e.
Drugs: diuretics, cisplatin, carboplatin, selective serotonin reuptake inhibitors, nonsteroidal anti-inflammatory agents, steroid withdrawal, cyclophosphamide, vinca alkaloids, narcotics, haloperidol, carbamazepine
f.
Adrenal insufficiency
g.
Liver failure
h.
Heart failure (such as malignant pericardial disease)
i.
Central nervous system disorders (primary or metastatic disease)
j.
Hypothyroidism
k.
Primary polydipsia
l.
Cerebral salt-wasting
m.
Natriuretic-peptide-induced kidney salt-wasting
n.
Pain and emotional stress
o.
Nausea, vomiting
p.
Inappropriate intravenous fluids
 
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