How do you diagnose and manage Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

From the Guidelines

Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) should be diagnosed and managed promptly to prevent severe hyponatremia and its associated morbidity and mortality, with the most recent and highest quality study 1 guiding the approach to diagnosis and treatment.

Diagnosis of SIADH

Diagnosis of SIADH requires a combination of laboratory findings and clinical assessment, 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 thyroid and adrenal function
• Absence of diuretic use
• Euvolemic status clinically

Management of SIADH

Management of SIADH begins with identifying and treating the underlying cause, which may include malignancies, CNS disorders, pulmonary diseases, or medications.

• Fluid restriction to 800-1000 mL/day is the first-line treatment.
• For moderate hyponatremia, salt tablets (1-2 g three times daily) or oral urea (15-60 g/day) may be used.
• In severe or symptomatic cases (sodium < 120 mEq/L or neurological symptoms), hypertonic saline (3%) may be administered at 0.5-2 mL/kg/hour with careful monitoring to avoid rapid correction (limit to 6-8 mEq/L in 24 hours to prevent osmotic demyelination syndrome) 1.
• For chronic SIADH, vasopressin receptor antagonists like tolvaptan (starting at 15 mg daily, maximum 60 mg daily) can be effective but require careful monitoring for rapid sodium correction 1.
• Demeclocycline (300-600 mg twice daily) may be used as an alternative, though it has more side effects. Regular monitoring of serum sodium, fluid status, and neurological symptoms is essential throughout treatment to guide therapy adjustments and prevent complications. Key considerations in the management of SIADH include:
• Avoiding too rapid correction of severe hyponatremia to prevent osmotic demyelination syndrome
• Monitoring for hepatotoxicity with the use of tolvaptan
• Close monitoring in a hospital setting for patients with severe hyponatremia or those requiring hypertonic saline or vasopressin receptor antagonists.

From the FDA Drug Label

Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia (serum sodium <125 mEq/L or less marked hyponatremia that is symptomatic and has resisted correction with fluid restriction), including patients with heart failure and Syndrome of Inappropriate Antidiuretic Hormone (SIADH)

• Diagnosis of SIADH: The FDA drug label does not provide direct guidance on diagnosing SIADH.
• Management of SIADH: Tolvaptan tablets are indicated for the treatment of clinically significant hypervolemic and euvolemic hyponatremia, including patients with SIADH.
  • The usual starting dose for tolvaptan tablets is 15 mg administered once daily without regard to meals.
  • Increase the dose to 30 mg once daily, after at least 24 hours, to a maximum of 60 mg once daily, as needed to achieve the desired level of serum sodium.
  • Patients should be in a hospital for initiation and re-initiation of therapy to evaluate the therapeutic response and because too rapid correction of hyponatremia can cause osmotic demyelination resulting in serious neurologic sequelae 2

From the Research

Diagnosis of 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 3.
• SIADH should be suspected in any patient with hyponatremia, hyposmolarity, urine osmolality above 100 mosmol/hgH2O, urine sodium concentration usually above 40 mEq/L, and clinical euvolemia 4.
• Patients should be screened for thiazide use and adrenal or thyroid dysfunction should be ruled out before making a diagnosis of SIADH 5.
• Clinical mimics of SIADH like cerebral salt wasting and reset osmostat should be considered in some patients 5.

Management of SIADH

• The mainstay of treatment for SIADH is fluid restriction of 800-1200 mL/24 hours 6.
• Patients with severe hyponatraemia and symptoms of altered mental state or seizures should be admitted to hospital for monitoring of fluid restriction and consideration of hypertonic saline 6.
• Hypertonic (3%) saline should be used in patients with significant neurologic symptoms and maximal correction of serum Na level should be limited to <8 mEq over 24 hours to prevent osmotic demyelination syndrome (ODS) 5.
• Free water restriction combined with increased solute intake (e.g., urea) is the most effective therapy to treat patients with SIADH 5.
• Vasopressin receptor antagonists, called vaptans, have been introduced as specific and direct therapy of SIADH, but clinical experience with vaptans is limited 7.

Prevention of Osmotic Demyelination Syndrome (ODS)

• The rate of correction of hyponatremia is dependent upon the degree of hyponatremia and the presence or absence of symptoms 4.
• Excessively rapid correction of hyponatremia should be avoided because it can lead to the late onset of neurological complications from ODS 4.
• The increase in serum sodium should not exceed 10 mmol/L in 24 hours or 18 mmol/L in 48 hours 6.
• Simultaneous administration of parenteral desmopressin is one of the best ways to prevent overly rapid Na correction in high-risk patients 5.