What are the recommendations for evaluating and managing Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH)?

SIADH Evaluation and Management

For SIADH evaluation, confirm the diagnosis with hyponatremia (serum sodium <134 mEq/L), plasma osmolality <275 mosm/kg, inappropriately high urine osmolality (>500 mosm/kg), and urine sodium >20 mEq/L, while excluding hypothyroidism, adrenal insufficiency, and volume depletion. 1

Diagnostic Criteria

Essential laboratory findings that must be present to diagnose SIADH include: 1

• Hyponatremia: Serum sodium <134 mEq/L 1
• Plasma hypoosmolality: <275 mosm/kg 1
• Inappropriately concentrated urine: Urine osmolality >500 mosm/kg 1
• Elevated urinary sodium: >20 mEq/L 1
• Euvolemic state: No clinical signs of hypovolemia (orthostatic hypotension, dry mucous membranes, decreased skin turgor) or hypervolemia (edema, ascites, jugular venous distention) 1, 2

Critical exclusions before confirming SIADH: 1

• Normal thyroid function (check TSH) 1, 2
• Normal adrenal function (exclude adrenal insufficiency) 1
• Absence of volume depletion 1
• Not taking diuretics 1

Volume Status Assessment

Distinguishing SIADH from cerebral salt wasting (CSW) is critical, particularly in neurosurgical patients, as they require opposite treatments. 1, 2

SIADH characteristics: 1, 2

• Euvolemic (normal ECF volume) 1
• Central venous pressure 6-10 cm H₂O 1
• No orthostatic hypotension 1
• Normal skin turgor and moist mucous membranes 1

Cerebral salt wasting characteristics: 1, 2

• Hypovolemic (ECF volume depletion) 1
• Central venous pressure <6 cm H₂O 1
• Orthostatic hypotension, tachycardia 1
• Dry mucous membranes, decreased skin turgor 1
• More common in poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 2

A serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH (though may include some CSW cases). 1, 2

Initial Workup

Complete the following laboratory evaluation: 1, 2

• Serum electrolytes (sodium, potassium, chloride) 1, 2
• Serum osmolality 1, 2
• Urine osmolality 1, 2
• Urine sodium concentration 1, 2
• Serum uric acid 1, 2
• Thyroid-stimulating hormone (TSH) 1, 2
• Serum creatinine and BUN 2
• Serum glucose (to exclude pseudohyponatremia) 2
• Morning cortisol if adrenal insufficiency suspected 2

Physical examination must assess: 1, 2

• Blood pressure (including orthostatic measurements) 1
• Volume status (skin turgor, mucous membranes, jugular venous pressure) 1
• Presence of edema, ascites 1
• Neurological status 1

Identifying Underlying Causes

Common etiologies to investigate: 1, 2, 3

Malignancies (particularly small cell lung cancer, which causes SIADH in 1-5% of cases): 1

• Chest imaging for lung cancer 1
• Consider CT chest/abdomen/pelvis if malignancy suspected 1

CNS disorders: 1, 3

• Meningitis, encephalitis 1
• Subarachnoid hemorrhage 1
• Head trauma 1
• Brain tumors 1

Pulmonary diseases: 1, 3

• Pneumonia 1
• Tuberculosis 1
• Positive pressure ventilation 1

Medications that commonly cause SIADH: 1, 3

• Antidepressants (SSRIs, tricyclics, trazodone) 1, 2
• Carbamazepine 1, 3
• Chemotherapy agents (cisplatin, vincristine, cyclophosphamide) 1, 3
• NSAIDs 1
• Opioids 1

Management Algorithm Based on Severity

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

This is a medical emergency requiring immediate ICU transfer and hypertonic saline, NOT fluid restriction. 1

Immediate treatment: 1

• Transfer to ICU for close monitoring 1
• Administer 3% hypertonic saline 1, 4
• Target correction: 6 mmol/L over first 6 hours OR until severe symptoms resolve 1
• Maximum correction: Never exceed 8 mmol/L in 24 hours 1, 4
• Monitor serum sodium every 2 hours initially 1

3% hypertonic saline administration: 2

• Give as 100 mL boluses over 10 minutes 2
• Can repeat up to 3 times at 10-minute intervals until symptoms improve 2

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

First-line treatment is fluid restriction: 1

• Restrict fluids to 1 L/day 1
• Avoid fluid restriction during first 24 hours if using tolvaptan 4
• If no response to fluid restriction, add oral sodium chloride 100 mEq three times daily 1, 2
• Monitor serum sodium every 24 hours initially 1

Second-line pharmacological options when fluid restriction fails: 1, 5, 6

Demeclocycline: 1, 3

• Induces nephrogenic diabetes insipidus 1
• Long history of use in persistent SIADH 1
• Typical dosing 600-1200 mg/day in divided doses 3

Urea: 1, 5, 6

• Considered very effective and safe 1, 6
• Dose: 30-60 g/day in divided doses 6
• May be more cost-effective than vaptans 5

Tolvaptan (vasopressin V2 receptor antagonist): 1, 4

• FDA-approved for clinically significant euvolemic/hypervolemic hyponatremia (sodium <125 mEq/L or symptomatic) 4
• Starting dose: 15 mg once daily 1, 4
• Can titrate to 30 mg after 24 hours, maximum 60 mg daily 1, 4
• Must initiate in hospital with close sodium monitoring 4
• Limit use to 30 days maximum to minimize liver injury risk 4
• Avoid fluid restriction during first 24 hours of therapy 4
• In clinical trials, 7% of patients with sodium <130 mEq/L had increases >8 mEq/L at 8 hours 4

Chronic Asymptomatic SIADH

Fluid restriction remains first-line: 1, 2

• Restrict to 1 L/day 1
• Average correction rate: 1.0 mEq/L/day 1
• Monitor compliance and sodium levels 1

If fluid restriction fails or poorly tolerated: 1, 5, 6

• Consider urea 30-60 g/day (very effective, safe, cost-effective) 1, 5, 6
• Consider demeclocycline 1
• Consider tolvaptan for short-term use (<30 days) 1, 4

Critical Safety Considerations

Osmotic demyelination syndrome prevention: 1, 4

• Never exceed 8 mmol/L correction in 24 hours 1, 4
• High-risk patients (advanced liver disease, alcoholism, malnutrition, prior encephalopathy) require even slower correction: 4-6 mmol/L per day 1, 4
• If overcorrection occurs, immediately give D5W or desmopressin to relower sodium 1, 2
• Watch for osmotic demyelination symptoms 2-7 days post-correction: dysarthria, dysphagia, oculomotor dysfunction, quadriparesis 1, 4

Special Populations

Neurosurgical patients with subarachnoid hemorrhage: 1, 2

• Avoid fluid restriction in patients at risk for vasospasm 1
• Consider fludrocortisone 0.1-0.2 mg daily 1, 2
• Consider hydrocortisone to prevent natriuresis 1, 2
• Distinguish carefully from cerebral salt wasting (requires volume replacement, not restriction) 1, 2

Small cell lung cancer patients: 1

• Treat underlying malignancy alongside hyponatremia management 1
• SIADH often improves with successful cancer treatment 1

Common Pitfalls to Avoid

Critical errors in SIADH management: 1, 2

• Using fluid restriction in cerebral salt wasting (worsens outcomes) 1
• Overly rapid correction leading to osmotic demyelination 1
• Inadequate monitoring during active correction 1
• Failing to identify and treat underlying cause 1
• Using fluid restriction in subarachnoid hemorrhage patients at risk for vasospasm 1
• Ignoring mild hyponatremia (increases fall risk 21% vs 5%, mortality risk) 2