How should SIADH be diagnosed and managed in an adult patient presenting with euvolemic hyponatremia?

SIADH: Diagnosis and Management

Diagnostic Criteria

SIADH requires five cardinal features to be present simultaneously: hypotonic hyponatremia (serum sodium <135 mEq/L with plasma osmolality <275 mOsm/kg), inappropriately concentrated urine (urine osmolality >500 mOsm/kg despite low plasma osmolality), elevated urinary sodium (>20-40 mEq/L), clinical euvolemia (absence of edema, orthostatic hypotension, dry mucous membranes, jugular venous distention, or ascites), and normal thyroid, adrenal, and renal function. 1, 2, 3

Essential Laboratory Workup

• Serum osmolality to confirm hypotonic hyponatremia and exclude pseudohyponatremia from hyperglycemia or hyperlipidemia 1
• Urine osmolality and urine sodium measured simultaneously with serum tests 1
• Thyroid-stimulating hormone (TSH) to exclude hypothyroidism 1
• Serum cortisol (morning cortisol) to rule out adrenal insufficiency 1
• Serum creatinine and electrolytes (including potassium, calcium, magnesium) to assess renal function 1
• Serum uric acid <4 mg/dL has a 73-100% positive predictive value for SIADH 4, 1

Volume Status Assessment

Clinical euvolemia is the hallmark of SIADH and distinguishes it from hypovolemic causes (cerebral salt wasting) and hypervolemic causes (heart failure, cirrhosis). 1 Physical examination alone is unreliable for determining volume status, with a sensitivity of only 41.1% and specificity of 80%, so clinical assessment must be combined with laboratory data. 4, 1

Euvolemic patients (SIADH) present with normal skin turgor, moist mucous membranes, no orthostatic hypotension, no edema, and no jugular venous distention. 1 In neurosurgical patients, distinguishing SIADH from cerebral salt wasting is critical because they require opposite treatments—SIADH requires fluid restriction while cerebral salt wasting requires volume and sodium replacement. 4, 1, 5

Management Algorithm

Severe Symptomatic Hyponatremia (Seizures, Coma, Altered Mental Status)

For severe symptomatic hyponatremia, immediately transfer to ICU and administer 3% hypertonic saline with a goal to correct 6 mmol/L over 6 hours or until severe symptoms resolve. 4, 5 Monitor serum sodium every 2 hours initially. 4, 5 The total correction must not exceed 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome. 4, 5

Mild Symptomatic or Asymptomatic Hyponatremia (Sodium <120 mEq/L)

Fluid restriction to 1 L/day is the cornerstone of first-line treatment for chronic SIADH. 4, 5, 6 This approach allows the kidneys to gradually correct dilutional hyponatremia over time, with a correction rate averaging 1.0 mEq/L/day. 5

If fluid restriction fails after 24-48 hours, add oral sodium chloride 100 mEq three times daily (approximately 7 grams of sodium per day). 4

Second-Line Pharmacological Options

Demeclocycline can be considered as second-line treatment for chronic SIADH when fluid restriction is ineffective or poorly tolerated. 5, 6 Demeclocycline induces nephrogenic diabetes insipidus and reduces the kidney's response to ADH. 5

Vasopressin receptor antagonists (tolvaptan) are FDA-approved for clinically significant euvolemic hyponatremia. 5, 7 Starting dose is 15 mg once daily, which can be titrated to 30 mg after 24 hours, with a maximum of 60 mg daily as needed. 5 Tolvaptan produces correction at approximately 3.0 mEq/L/day. 5

Other second-line therapies include urea, lithium, and loop diuretics, although these are less commonly used. 5, 6 Urea is considered very effective and safe in recent literature. 5

Correction Rate Guidelines

Standard correction rate: 4-8 mEq/L per day, not exceeding 10-12 mEq/L in 24 hours. 4 For high-risk patients (advanced liver disease, alcoholism, malnutrition, or prior encephalopathy), limit correction to 4-6 mEq/L per day, with an absolute maximum of 8 mEq/L in 24 hours. 4, 5

If overcorrection occurs, immediately discontinue hypertonic saline and administer 5% dextrose in water (D5W) or desmopressin to lower the sodium level. 4

Common Etiologies to Address

• Malignancy: Particularly small cell lung cancer (affects 1-5% of patients) 1, 5
• Medications: SSRIs, SNRIs, carbamazepine, oxcarbazepine, chemotherapeutic agents (cisplatin, vinca alkaloids), NSAIDs, tramadol, opioids 1, 5
• CNS disorders: Infections, tumors, malformations, subarachnoid hemorrhage 1, 7
• Pulmonary diseases: Pneumonia, other lung pathology 1, 7
• Postoperative state: Inappropriate infusion of hypotonic fluids 2

Discontinuing offending medications is essential in treating the underlying cause of SIADH. 5 Treatment of the underlying malignancy is important alongside hyponatremia management in cancer patients. 5

Critical Pitfalls to Avoid

• Never correct chronic hyponatremia faster than 8 mmol/L in 24 hours—this causes osmotic demyelination syndrome characterized by dysarthria, dysphagia, ocular motor deficits, and quadriparesis 2-7 days after overcorrection 4, 3
• Never use fluid restriction in cerebral salt wasting—this worsens outcomes and can precipitate cerebral ischemia 4, 5
• Never use fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm—consider fludrocortisone instead 4, 5
• Never ignore mild hyponatremia (130-135 mmol/L)—this increases fall risk and mortality 1
• Never rely solely on physical examination for volume status assessment—combine with laboratory data 1