What is the treatment for severe hyponatremia in a patient with ascites and metastatic papillary thyroid cancer (PTC) with lung metastases?

From the Guidelines

The treatment of hyponatremia (sodium 121 mEq/L) in a patient with ascites and metastatic papillary thyroid cancer requires careful fluid restriction and potentially pharmacologic therapy, with tolvaptan being a suitable option, starting at 15 mg once daily, as recommended by the most recent guidelines 1. The patient's condition, with a sodium level of 121 mEq/L, indicates severe hyponatremia, which requires prompt attention to prevent further complications.

• Initially, restrict fluid intake to 800-1000 mL/day to prevent further dilution of serum sodium, as suggested by the guidelines 1.
• For this patient, tolvaptan would be appropriate as it antagonizes vasopressin receptors in the kidneys, promoting free water excretion without affecting sodium balance, with a recommended starting dose of 15 mg once daily, potentially increasing to 30-60 mg daily if needed 1.
• Alternatively, consider hypertonic (3%) saline for severe symptoms at 1-2 mL/kg/hr with frequent monitoring, although this should be reserved for short-term treatment of patients with symptomatic or severe hyponatremia 1.
• Avoid rapid correction exceeding 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome, as emphasized by the guidelines 1. The underlying mechanism is likely a combination of dilutional hyponatremia from ascites-related portal hypertension causing increased antidiuretic hormone (ADH) secretion, and possibly syndrome of inappropriate ADH secretion (SIADH) from the metastatic thyroid cancer.
• Diuretics like furosemide (20-40 mg IV/oral) may help manage ascites while addressing hyponatremia, but use cautiously to avoid worsening electrolyte imbalances.
• Monitor serum sodium every 4-6 hours initially, then daily until stable, while also addressing the underlying cancer with appropriate oncologic therapy.

From the FDA Drug Label

In two double-blind, placebo-controlled, multi-center studies (SALT-1 and SALT-2), a total of 424 patients with euvolemic or hypervolemic hyponatremia (serum sodium <135 mEq/L) resulting from a variety of underlying causes (heart failure, liver cirrhosis, syndrome of inappropriate antidiuretic hormone [SIADH] and others) were treated for 30 days with tolvaptan or placebo, then followed for an additional 7 days after withdrawal.

The mean serum sodium concentration at study entry was 129 mEq/L

For patients with a serum sodium of <130 mEq/L or <125 mEq/L, the effects at Day 4 and Day 30 remained significant

Treatment of Hyponatremia with sodium 121 in a patient with ascites and known papillary thyroid cancer with lung metastases can be managed with Tolvaptan.

• The patient's serum sodium level is 121 mEq/L, which is less than 130 mEq/L.
• Tolvaptan has been shown to be effective in increasing serum sodium levels in patients with hyponatremia, including those with serum sodium levels less than 130 mEq/L.
• The recommended initial dose of Tolvaptan is 15 mg once daily, which can be increased to 30 mg once daily, and then to 60 mg once daily, as needed to raise serum sodium levels.
• Patients should be monitored for signs and symptoms of hypovolemia and dehydration, and fluid restriction should be avoided during the first 24 hours of therapy to prevent overly rapid correction of serum sodium levels 2.

From the Research

Treatment of Hyponatremia

• The treatment of hyponatremia in a patient with ascites and known papillary thyroid cancer with lung metastases depends on several factors, including symptom severity, onset timing, and extracellular volume status 3.
• When hyponatremia is caused by the syndrome of inappropriate antidiuretic hormone (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 3, 4.
• Pharmacological therapy, such as the orally active, selective AVP receptor 2 (V(2))-receptor antagonist tolvaptan, may be necessary when fluid restriction is insufficient 3.
• It is essential to consider other potential causes of hyponatremia, such as secondary adrenal insufficiency due to pituitary metastatic tumors, which can mask central diabetes insipidus 5.
• The management of hyponatremia in lung cancer patients should be personalized based on severity and duration of sodium serum reduction, extracellular fluid volume, and etiology 6.

Considerations in Papillary Thyroid Cancer

• Lung metastases from papillary thyroid cancer with persistently negative thyroglobulin and elevated thyroglobulin antibody levels have an excellent prognosis and survival rate during radioactive iodine treatment and follow-up 7.
• The timing of diagnosis of lung metastases, maximal size of lung metastases, and radioactive iodine avidity are significantly associated with progression-free survival rate 7.
• The loss of radioactive iodine avidity remains the strongest independent predictor of a poor prognosis and survival in these patients 7.

Clinical Implications

• Hyponatremia is a common electrolyte disorder in lung cancer patients and can be related to many causes, including incidental medications, concurrent diseases, and side effects of antineoplastic treatments or the disease itself 6.
• Early correction of serum concentration levels is crucial to prevent prolonged hospitalization, delays in scheduled chemotherapy, worsening of patient performance status and quality of life, and negative effects on treatment response and survival 6.