Syndrome Inappropriate ADH Secretion

Aka: Syndrome Inappropriate ADH Secretion, Syndrome of Inappropriate Antidiuretic Hormone, Inappropriate ADH Syndrome, SIADH, Medication Causes of SIADH

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II. Causes: General

  1. Malignancy
    1. Small Cell Lung Cancer (most common ectopic ADH source)
    2. Duodenal Cancer
    3. Pancreatic Cancer
    4. Head and neck cancers
  2. Lung disease
    1. Bacterial Pneumonia
    2. Empyema
    3. Legionella pneumonia
    4. Pulmonary Tuberculosis
    5. Acute Respiratory Distress Syndrome (ARDS) or other Acute Respiratory Failure
  3. Neurologic disorders
    1. Brain Abscess
    2. Brain Tumor
    3. Bacterial Meningitis
    4. Subarachnoid Hemorrhage
    5. Subdural Hematoma
    6. Cerebrovascular Accident
    7. Head Injury
    8. Multiple Sclerosis
    9. Guillain-Barre Syndrome
  4. Miscellaneous causes
    1. Psychiatric illness
    2. Rocky Mountain Spotted Fever
      1. Hyponatremia is common in this uncommon Tick Borne Illness
    3. Post-operative period
      1. Young women have postoperative ADH levels 40x higher than postmenopausal women
      2. Young women are at higher risk of postoperative hyponatremic encephalopathy

III. Causes: Medications

  1. Cardiovascular agents
    1. Amiodarone
    2. Clofibrate
    3. Thiazide Diuretics (e.g. Hydrochlorothiazide)
  2. Neuropsychiatric agents
    1. Amitriptyline (Elavil)
    2. Barbiturates
    3. Carbamazepine (Tegretol)
    4. Chlorpromazine (Thorazine)
    5. Haloperidol
    6. Selective Serotonin Reuptake Inhibitors
    7. Thiothixene
    8. Thioridazine
  3. Analgesics
    1. Morphine Sulfate and other Opioids
    2. NSAIDs
  4. Chemotherapeutic agents
    1. Vinca alkaloids (e.g. Vincristine)
    2. Platinum Chemotherapy (e.g. Cisplatin)
    3. Other Alkylating Agents (e.g. Cyclophosphamide)
  5. Miscellaneous agents
    1. Nicotine
    2. Theophylline
  6. Sulfonylureas
    1. Chlorpropamide
    2. Tolbutamide

IV. Differential Diagnosis

  1. SIADH is a diagnosis of exclusion
  2. Isovolemic Hypoosmolar Hyponatremia
  3. Non-osmotic causes for ADH secretion
    1. Hypovolemic Hypoosmolar Hyponatremia
  4. Causes of Decreased urine diluting capacity

V. Symptoms

  1. Nausea or Vomiting
  2. Constipation
  3. Muscle Weakness

VI. Labs

  1. Hyponatremia
    1. See Isovolemic Hypoosmolar Hyponatremia
  2. Urine Osmolality > 100 mOsm/kg water
    1. Dilution not maximized despite serum hypoosmolality
  3. Urine Sodium > 20-30 mEq/L
  4. Serum Osmolality decreased <280 mOsm
  5. Hypouricemia (Serum Uric Acid <4 mg/dl)
  6. Antidiuretic Hormone (ADH) elevated

VII. Management

  1. Treating underlying cause is key in SIADH
    1. Example: Treat underlying Bronchogenic Carcinoma
    2. Relevant Consultation (e.g. oncology, nephrology)
  2. Overall strategy
    1. See Isovolemic Hypoosmolar Hyponatremia
    2. Fluid restriction (<1000 to 1500 ml/day)
    3. Diuretics
      1. Furosemide (Lasix)
      2. Potassium-Sparing Diuretics
    4. Slow Serum Sodium correction
      1. See Hyponatremia Management
      2. Do not correct more quickly than 12 mEq/L in 24 hours or 18 mEq/L in 48 hours
    5. Avoid Normal Saline infusion
      1. May worsen Hyponatremia with Fluid Shifts intravascularly
  3. SIADH refractory to above measures
    1. Induce Nephrogenic Diabetes Insipidus
    2. Demeclocycline (600-1200 mg/day)
    3. Lithium Carbonate 300 mg PO tid
    4. Tolvaptan (Samsca)
      1. Selective Vasopressin (V2) receptor Antagonist
      2. Increases free water excretion
      3. Adverse effects: Hepatotoxin

VIII. References

  1. Le and Drogell (2015) Crit Dec Emerg Med 29(11): 13-19
  2. Kone in Tisher (1993) Nephrology, p. 87-100
  3. Levinsky in Wilson (1991) Harrison's IM, p. 281-84
  4. Preston (2011) Acid-Base, Fluids and Electrolytes, Medmaster, Miami
  5. Rose (1989) Acid-Base and Electrolytes, p. 601-38
  6. Goh (2004) Am Fam Physician 69:2387-94 [PubMed]
  7. Higdon (2018) Am Fam Physician 97(11):741-8 [PubMed]
  8. Braun (2015) Am Fam Physician 91(5): 299-307 [PubMed]

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