Syndrome of Inappropriate ADH (SIADH)

Snapshot

• A 44-year-old woman with a recent diagnosis of small cell lung cancer presents to the emergency room with her partner. She had reported some nausea and feelings of malaise yesterday. Today, she continued to feel unwell, and reported feeling lethargic and weak. She is oriented to person and place but not to time. On physical exam, she is noted to have normal skin turgor and no edema. Laboratory testing reveals hyponatremia and decreased serum osmolality.

Introduction

• Clinical definition
  • syndrome of inappropriate antidiuretic hormone (SIADH) is characterized by excessive free water retention and impaired water excretion, leading to dilutional hyponatremia
• Epidemiology
  • demographics
    • common in hospitalized patients, particularly those on mechanical ventilation
  • risk factors
    • older age
    • malignancy
    • pulmonary disease
      • pneumonia
      • tuberculosis
  • etiology
    • ectopic production
      • small cell carcinoma of the lung  
    • central nervous system disorders
      • infection
        • e.g., encephalitis and meningitis
      • malignancy
      • stroke
      • trauma
    • drugs
      • cyclophosphamide
      • nonsteroidal anti-inflammatory drugs
      • carbamazepine
      • selective serotonin reuptake inhibitors (SSRIs)
• Pathogenesis
  • impaired water excretion due to ↑ ADH
    • may be due to increased production of ADH
    • may be due to enhanced effects of ADH due to medications
• may be due to overdose of desmopressin

Presentation

• Symptoms 
  • depends on level of hyponatremia
  • mild symptoms (sodium usually 125-130 mEq/L)
    • nausea and malaise
  • moderate symptoms (115-125 mEq/L)
    • headaches
    • lethargy
    • weakness
  • severe symptoms (< 120 mEq/L)
    • seizures
    • coma
    • respiratory arrest
• Physical exam
  • euvolemic fluid status
    • absence of edema
• normal skin turgor 

Studies

• Serum labs 
  • ↓ serum osmolality (< 275 mOsm/kg)
  • ↓ serum sodium (< 135 mEq/L) 
  • ↓ serum uric acid (< 4 mg/dL)
  • adrenal and thyroid function are normal
• Urine studies 
  • urine osmolality > serum osmolality
  • ↑ urine osmolality (> 100 mOsm/kg) 
• ↑ urine sodium (40 mEq/L)

Differential

• Other causes of euvolemic hyponatremia
  • hypothyroidism
  • psychogenic polydipsia 
    • distinguishing factor
      • ↑ urine osmolality on water deprivation test
  • thiazide-diuretic use
  • certain diets
• e.g., “tea and toast” (low solute diet) and beer potomania

Treatment

• Management approach
  • sodium management is dependent on
    • symptom severity
    • duration of hyponatremia (acute vs chronic)
  • chronic hyponatremia must be corrected slowly to prevent osmotic demyelination syndrome (central pontine myelinolysis)
  • correct underlying cause when possible
• Medical
  • fluid restriction
    • indication
      • mild or moderate symptoms
      • asymptomatic cases
  • intravenous hypertonic (3%) saline
    • indication
      • chronic hyponatremia
        • severe symptoms
      • acute hyponatremia
        • all cases
  • salt tablets
    • indication
      • adjuvant therapy in patients who are asymptomatic
  • ADH receptor antagonists
    • indication
      • not routinely used
    • medications
      • demeclocycline 
• vaptans (tolvaptan or conivaptan)

Complications

• Osmotic demyelination syndrome (central pontine myelinolysis)
  • caused by rapid correction of chronic hyponatremia