How is the syndrome of inappropriate antidiuretic hormone (ADH) secretion managed?

Management of Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Secretion

The first-line treatment for SIADH is fluid restriction (1-1.5 L/day), followed by pharmacological interventions such as vaptans for refractory cases when fluid restriction is ineffective or poorly tolerated.

Diagnosis of SIADH

Before initiating treatment, confirm the diagnosis with these criteria:

• Hyponatremia (serum sodium < 134 mEq/L)
• Hypoosmolality (plasma osmolality < 275 mosm/kg)
• Inappropriately high urine osmolality (> 500 mosm/kg)
• Inappropriately high urinary sodium concentration (> 20 mEq/L)
• Absence of hypothyroidism, adrenal insufficiency, or volume depletion 1

Management Algorithm

Step 1: Initial Measures

• Discontinue contributing medications if possible, including:
  • Chemotherapeutic agents (platinum-based, vinca alkaloids)
  • Opioids
  • NSAIDs
  • Anticonvulsants
  • Antidepressants 1
• Fluid restriction (1-1.5 L/day) - first-line treatment for asymptomatic mild SIADH 1
• Ensure adequate oral salt intake 1

Step 2: For Symptomatic or Severe Hyponatremia

• Hypertonic 3% saline IV for life-threatening or acute symptomatic severe hyponatremia (< 120 mEq/L) 1
  • Caution: Avoid correction > 8-9 mmol/L per day to prevent central pontine myelinolysis 1
  • Initial rapid correction aimed at attenuating clinical symptoms (5 mmol/L in first hour) for severe symptoms 1

Step 3: For Refractory Cases

• Vaptans (vasopressin-2 receptor antagonists):
  • Tolvaptan (oral): Starting dose 15 mg/day, can be titrated to 30 mg and then 60 mg if needed 1, 2
  • Conivaptan (IV): For short-term (2-4 days) treatment 1
  • Indicated for clinically significant hyponatremia (serum sodium <125 mEq/L or symptomatic hyponatremia resistant to fluid restriction) 2
• Demeclocycline may be considered as an alternative 1

Special Considerations

Etiology-Based Approach

• Malignancy-related SIADH (especially small cell lung cancer):
  • Treat the underlying malignancy when possible 1
  • SIADH occurs in approximately 10-45% of SCLC cases but is symptomatic in only 1-5% 1

Monitoring

• Monitor serum sodium levels frequently during correction
• For vaptans, initiate treatment in hospital with close monitoring 1
• Target rate of sodium correction: < 8-9 mmol/L/day 1

Cautions and Pitfalls

1. Avoid overcorrection of serum sodium, which can lead to osmotic demyelination syndrome
2. Hypertonic saline should be used cautiously as it can worsen edema and ascites in patients with volume overload 1
3. Vaptans should not be given to patients with altered mental state who cannot drink appropriate amounts of fluid due to risk of dehydration 1
4. Drug interactions with vaptans: Avoid strong CYP3A inhibitors (ketoconazole, grapefruit juice, clarithromycin) which can increase vaptan effects 1
5. Fluid restriction may not be appropriate for patients with short prognosis if not aligned with their goals of care 1

Efficacy of Different Treatments

• Hypertonic saline and tolvaptan produce the greatest mean rate of sodium change (approximately 3.0 mEq/L/day)
• Isotonic saline produces moderate change (approximately 1.5 mEq/L/day)
• Fluid restriction produces the slowest change (approximately 1.0 mEq/L/day) 3

Despite available treatments, many patients are discharged from hospitals still hyponatremic, highlighting the importance of appropriate diagnosis and treatment selection 3.