Hyponatremia is a disorder defined by a low concentration of sodium in the blood, an electrolyte imbalance that can significantly impact body function. Cancer can definitively cause this condition. This decrease in sodium is frequently linked to a paraneoplastic syndrome, which is a condition caused by the tumor’s effect on the body rather than its physical presence. A malignancy can disrupt the delicate mechanisms that regulate fluid and sodium balance, leading to this common complication for many cancer patients.
Understanding Hyponatremia: Definition and Symptoms
Hyponatremia is medically defined as a serum sodium concentration that falls below 135 milliequivalents per liter (mEq/L). Sodium is an electrolyte that plays a fundamental role in regulating water balance in and around the body’s cells, and supporting nerve and muscle function. When the sodium level drops, the body’s water levels rise, causing cells to swell.
The severity is categorized by the serum sodium level, with mild hyponatremia occurring between 130 and 134 mEq/L, and severe cases falling below 125 mEq/L. Mild symptoms can include non-specific issues such as headache, nausea, and general malaise. These signs may be subtle and easily mistaken for other conditions or side effects of cancer treatment.
When the sodium level drops rapidly or becomes profoundly low, symptoms escalate due to swelling within the brain. Severe hyponatremia can manifest as neurological dysfunction, including confusion, lethargy, muscle cramps, and loss of energy. This electrolyte imbalance can lead to seizures, coma, and death.
How Cancer Leads to Low Sodium Levels
The primary mechanism linking cancer to low sodium is often the Syndrome of Inappropriate Antidiuretic Hormone (SIADH). This condition involves the body retaining too much water, which effectively dilutes the sodium concentration in the bloodstream. Certain tumors produce and release Arginine Vasopressin (AVP), also known as Antidiuretic Hormone (ADH), a substance normally produced by the brain to regulate water reabsorption in the kidneys.
When ADH is released inappropriately by the tumor cells, the kidneys are signaled to hold onto water even when the body does not need it. This excess water retention increases the total body fluid volume, but the amount of sodium remains unchanged, resulting in a dilution effect. Because this hormone production is independent of the body’s actual need for water conservation, the condition is deemed “inappropriate.”
Other mechanisms related to malignancy can also reduce blood sodium. Some chemotherapy agents, such as Vincristine and Cyclophosphamide, are known to stimulate the release of ADH, leading to drug-induced SIADH. The use of Cisplatin, a common chemotherapy drug, can sometimes cause direct damage to the renal tubules, leading to excessive sodium loss in the urine.
Cancer and its treatments can also lead to significant fluid and sodium losses through the gastrointestinal tract. Severe vomiting or diarrhea can cause hypovolemic hyponatremia, a state where the body loses more sodium than water. In patients with brain tumors or metastases, cerebral salt wasting (CSW) can occur, causing the kidneys to excrete excessive amounts of sodium.
Specific Cancers That Affect Sodium Balance
The ability of a tumor to produce hormone-like substances is most commonly observed with Small Cell Lung Cancer (SCLC). Approximately 10 to 15% of SCLC patients present with hyponatremia at the time of diagnosis. SCLC cells are neuroendocrine in origin, explaining their capacity to synthesize and secrete ADH.
While SCLC is the most frequent cause, other malignancies can also lead to sodium imbalance through ectopic hormone production. Tumors of the head and neck, as well as Non-Small Cell Lung Cancer (NSCLC), have been implicated in SIADH. Mesothelioma, a cancer arising from the thin layer of tissue covering organs, is another malignancy associated with this paraneoplastic effect.
Neuroendocrine tumors, regardless of location, have an inherent capacity to secrete various hormones, including ADH, which results in hyponatremia. Cancers like pancreatic cancer and certain hematological malignancies have also been linked to sodium-regulating disturbances. For these tumors, the development of hyponatremia often signals a more advanced stage of disease and a poorer overall prognosis.
Treating Low Sodium When Caused by Cancer
Treatment for cancer-related hyponatremia must address both the immediate electrolyte imbalance and the underlying malignancy. For patients experiencing severe, acute symptoms like seizures or significant confusion, the medical team may administer hypertonic saline, a highly concentrated salt solution. This is given intravenously to quickly raise the blood sodium concentration and prevent brain swelling.
For patients with less severe or chronic hyponatremia, the first step is often fluid restriction, which limits water intake to allow the kidneys to excrete excess fluid and concentrate the sodium. If fluid restriction is insufficient, specialized medications such as vasopressin receptor antagonists, like tolvaptan, may be used. These drugs block the effect of ADH on the kidneys, promoting the excretion of water without sodium loss, a process known as aquaresis.
Correction of sodium levels must be done slowly and incrementally to avoid osmotic demyelination syndrome. This severe neurological complication involves damage to the protective layer of nerve cells and occurs if the brain is exposed to a rapidly rising sodium concentration. Ultimately, the most definitive long-term solution for cancer-induced SIADH is treating the tumor itself, as successful therapy eliminates the source of inappropriate ADH production.