What are the diagnostic criteria and treatment for SIADH (Syndrome of Inappropriate Antidiuretic Hormone Secretion)?

From the Guidelines

The diagnosis of SIADH requires a combination of clinical and laboratory findings, including hyponatremia (serum sodium <135 mEq/L), decreased serum osmolality (<275 mOsm/kg), inappropriately concentrated urine (urine osmolality >100 mOsm/kg), elevated urine sodium (>20 mEq/L), normal volume status (no edema or dehydration), and normal thyroid, adrenal, and kidney function. The diagnostic criteria for SIADH include:

• Hyponatremia (serum sodium <135 mEq/L) 1
• Decreased serum osmolality (<275 mOsm/kg)
• Inappropriately concentrated urine (urine osmolality >100 mOsm/kg)
• Elevated urine sodium (>20 mEq/L)
• Normal volume status (no edema or dehydration)
• Normal thyroid, adrenal, and kidney function

Treatment of SIADH depends on the severity and symptoms of the condition. For mild asymptomatic SIADH, fluid restriction to 800-1000 mL/day is the first-line approach. Salt tablets (1-2 g three times daily) may be added to increase sodium intake. For moderate to severe symptomatic hyponatremia, pharmacological options include loop diuretics like furosemide (20-40 mg daily) combined with salt tablets, urea (15-60 g/day), or vasopressin receptor antagonists such as tolvaptan (starting at 15 mg daily, may increase to 30-60 mg) 1.

It is essential to address the underlying cause of SIADH, such as malignancy, medications, or CNS disorders, simultaneously with the treatment of hyponatremia. Sodium correction should not exceed 8 mEq/L in 24 hours to prevent neurological complications. Regular monitoring of serum sodium, fluid status, and neurological symptoms is crucial during treatment.

In severe symptomatic hyponatremia (serum sodium <120 mEq/L with neurological symptoms), hypertonic saline (3%) should be administered at 1-2 mL/kg/hour with careful monitoring to raise sodium by 4-6 mEq/L in the first 24 hours to prevent osmotic demyelination syndrome. The use of vaptans, such as tolvaptan, has been shown to be effective in improving serum sodium concentration in patients with SIADH, but their safety has only been established for short-term treatments lasting from one week to one month 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Diagnostic Criteria for SIADH

• The diagnosis of SIADH is confirmed by demonstration of a high urine osmolality with a low plasma osmolality, in the absence of diuretic use 2.
• It is essential to ascertain the euvolemic state of extracellular fluid volume, both clinically and by laboratory measurements 3.
• Laboratory tests are necessary for the diagnosis of SIADH, but in severe, symptomatic cases of hyponatremia, patients need treatment before the results of laboratory tests can be obtained 4.

Treatment Options for SIADH

• Immediate treatment of the symptomatic patient with SIADH includes intravenous furosemide and 3% sodium chloride injection to produce a negative free-water balance 2.
• The cornerstone of treatment for SIADH is fluid restriction 5.
• Demeclocycline can be used to induce a negative free-water balance if fluid restriction is not tolerated by the patient 2.
• Vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH, and appear to be advantageous for patients as they do not require fluid restriction and can achieve correction of hyponatremia comfortably and within a short time 3.
• Tolvaptan, a vaptan, might be an attractive treatment option for correction of hyponatremia due to SIADH, especially in pediatric patients or refractory cases 6.

Considerations for Treatment

• It is crucial to limit the daily increase of serum sodium to less than 8-10 mmol/liter to prevent osmotic demyelination 3.
• The serum sodium should be measured after 0,6,24, and 48 hours of treatment with vaptans to prevent overly rapid correction of hyponatremia 3.
• Discontinuation of any vaptan therapy for longer than 5 or 6 days should be monitored to prevent hyponatremic relapse 3.
• Treatment decisions should be individualized based on a patient's needs and priorities, considering factors such as signs and symptoms, risks and benefits of different treatments, psychosocial factors, and the patient's wishes 4.