Paraneoplastic Syndromes in Lung Cancer: SIADH

The work-up of hyponatremia can be broken down into 3 main categories based the patient’s volume status: hypovolemia, euvolemia, and hypervolemia. Causes of hypovolemic hyponatremia include renal or gastrointestinal losses, while cirrhosis and congestive heart failure can lead to hypervolemic hyponatremia. Euvolemic hyponatremia can be caused by SIADH, uncontrolled pain, hypothyroidism, and certain types of brain damage. Euvolemia is supported by a lack of orthostatic changes on physical exam, blood urea nitrogen less than 10 mg/dL, and uric acid less than 4 mg/dL.

The underlying pathophysiology of paraneoplastic SIADH involves the uncontrolled secretion of antidiuretic hormone (ADH) and atrial natriuretic peptide (ANP) by cancer cells. These hormones lead to an overall increase in free water absorption, which when uncontrolled can dilute the patient’s serum and cause hyponatremia.

When attempting to treat a patient’s paraneoplastic SIADH, the degree of sodium correction and the time it takes to do so must be closely monitored, as overcorrection can lead to serious side effects. In more acute situations where the patient’s sodium drops over 48 hours, a patient’s sodium should not be corrected more than 8 to 10 mmol/L during the first 24 hours of treatment to avoid central pontine myelinolysis, which can have devastating central nervous system effects. Patients with chronic hyponatremia should be corrected at a slower rate initially, with a goal of 0.5 to 1.0 mmol/L/hour.

SIADH can be difficult to treat as a paraneoplastic syndrome, especially if the patient has concurrent gastrointestinal and renal losses. With chemotherapy directed at the underlying malignancy, the sodium will typically normalize within several weeks. If these patients do not respond to chemotherapy, or if a more aggressive correction is required, additional treatment options to consider include a fluid restricted diet, demeclocycline, and vasopressin receptor antagonists. It is important to safely normalize the patient’s sodium level, as a failure to do so can result in a shorter survival. 

References

1. Kanaji N, Watanabe N, Kita N et al. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 2014;5(3):197-223.
2. Spiro SG, Gould MK, Colice GL; American College of Chest Physicians. Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes: ACCP evidenced-based clinical practice guidelines (2nd edition). Chest. 2007;132(3 Suppl):149S-160S.
3. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85(9):838-54.
4. Hansen O, Sorensen P, Hansen KH. The occurrence of hyponatremia in SCLC and the influence on prognosis: a retrospective study of 453 patients treated in a single institution in a 10-year period. Lung Cancer. 2010;68(1):111-4.