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SIADH for USMLE Step 2

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Syndrome of Inappropriate Antidiuretic Hormone (SIADH) for the USMLE Step 2 Exam
  • Pathophysiology
    • Excessive ADH Secretion: In SIADH, antidiuretic hormone (ADH) is secreted despite low plasma osmolality, leading to inappropriate water reabsorption by the kidneys.
SIADH pathophysiology
    • Water Retention: This results in dilutional hyponatremia and low plasma osmolality, while urine remains concentrated (high urine osmolality).
    • No Edema: Unlike hypervolemic states (e.g., heart failure), there is no peripheral edema because total body sodium is normal, and water retention occurs intracellularly.
  • Etiology
    • CNS Disorders: Conditions like head trauma, stroke, subarachnoid hemorrhage, and infections (e.g., meningitis, encephalitis) can trigger SIADH by disrupting ADH regulation.
    • Pulmonary Disorders: Pneumonia, tuberculosis, and COPD may cause SIADH through increased ADH release.
    • Malignancies: Ectopic production of ADH by tumors, especially small-cell lung carcinoma, can result in SIADH.
    • Medications: Drugs commonly associated with SIADH include:
    • SSRIs (e.g., sertraline, fluoxetine).
    • Antipsychotics (e.g., haloperidol).
    • Anticonvulsants (e.g., carbamazepine).
    • Chemotherapy Agents (e.g., vincristine, cyclophosphamide).
    • Surgery: Post-operative ADH release is a common cause of SIADH, particularly after major surgeries.
  • Clinical Features
    • Mild Hyponatremia (Na+ 130–135 mEq/L): Often asymptomatic or presents with nonspecific symptoms such as fatigue, headache, or nausea.
    • Moderate Hyponatremia (Na+ 120–129 mEq/L): May cause lethargy, confusion, dizziness, or muscle cramps.
    • Severe Hyponatremia (Na+ <120 mEq/L): Can result in seizures, altered mental status, or coma due to cerebral edema from intracellular fluid shifts.
  • Diagnosis
    • Hyponatremia with Low Plasma Osmolality: Serum sodium <135 mEq/L and plasma osmolality <275 mOsm/kg.
    • Inappropriately High Urine Osmolality: Urine osmolality >100 mOsm/kg, despite low plasma osmolality.
    • Urine Sodium >20–30 mEq/L: Indicates normal renal sodium handling and supports the diagnosis of SIADH.
    • Euvolemia: Physical exam should show no signs of dehydration or hypervolemia (e.g., edema).
    • Normal Thyroid, Adrenal, and Renal Function: Hypothyroidism, adrenal insufficiency, and renal disease must be ruled out as alternative causes of hyponatremia.
  • Management
    • Fluid Restriction:
    • First-line treatment for most cases. Limit daily water intake to 500–1,000 mL.
    • Hypertonic Saline (3%):
    • Used for severe hyponatremia (e.g., seizures, coma) to rapidly correct sodium levels. Serum sodium should be corrected by no more than 4–6 mEq/L in 24 hours to avoid osmotic demyelination syndrome (ODS).
    • Medications:
    • Vasopressin Receptor Antagonists (Vaptans): Drugs like tolvaptan or conivaptan block ADH at the V2 receptor, increasing free water excretion (aquaresis).
    • Demeclocycline: Induces nephrogenic diabetes insipidus and promotes free water excretion but may cause nephrotoxicity. Reserved for refractory cases.
    • Loop Diuretics: Furosemide may be used in conjunction with salt tablets to promote water excretion and prevent sodium loss.
  • Complications
    • Severe Hyponatremia: Can result in seizures, coma, and permanent brain damage if not promptly corrected.
    • Osmotic Demyelination Syndrome (ODS): Occurs with overly rapid correction of hyponatremia, leading to irreversible damage of brainstem neurons. Symptoms include dysarthria, dysphagia, and quadriplegia.
Key Points
  • Pathophysiology: SIADH results from inappropriate ADH secretion, leading to water retention, hyponatremia, and low plasma osmolality, but concentrated urine.
  • Etiology: Common causes include CNS disorders, pulmonary conditions, small-cell lung cancer, medications (e.g., SSRIs, anticonvulsants), and surgery.
  • Symptoms: Mild cases may be asymptomatic, while severe hyponatremia can cause seizures and coma.
  • Diagnosis: Characterized by hyponatremia, low plasma osmolality, high urine osmolality, and euvolemia.
  • Treatment: Fluid restriction is first-line; hypertonic saline for severe cases; and vaptans or demeclocycline for chronic or refractory cases.
  • Complications: Overly rapid correction of hyponatremia can lead to osmotic demyelination syndrome, a serious neurologic condition.

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