SIADH for ABIM

Already subscribed? Log in »

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) for the American Board of Internal Medicine Exam

Excessive ADH Secretion: ADH (antidiuretic hormone) promotes water reabsorption in the kidneys, concentrating the urine. In SIADH, excess ADH is secreted despite normal or low plasma osmolality, leading to impaired free water excretion.

Water Retention and Hyponatremia: The retention of free water without proportional retention of sodium leads to dilutional hyponatremia. Plasma osmolality decreases, while urine osmolality remains inappropriately high.
No Edema: Unlike other causes of hyponatremia, SIADH does not lead to peripheral edema because the water retention occurs intracellularly rather than in the extracellular space.

CNS Disorders: Head trauma, stroke, subarachnoid hemorrhage, meningitis, and encephalitis can disrupt the hypothalamic regulation of ADH.
Malignancies: Certain tumors, especially small-cell lung carcinoma, produce ectopic ADH. Other cancers (e.g., pancreatic or prostate cancer) can also cause SIADH.
Pulmonary Disorders: Pneumonia, tuberculosis, and lung abscesses can trigger SIADH. Mechanical ventilation may also stimulate ADH secretion.
Medications:
Antidepressants: SSRIs (e.g., fluoxetine) and tricyclics (e.g., amitriptyline).
Antipsychotics: Drugs like haloperidol.
Chemotherapy Agents: Vincristine and cyclophosphamide.
Other Medications: NSAIDs, opioids, and carbamazepine.
Post-Surgical State: SIADH can occur after major surgery due to stress-related ADH release.
Idiopathic: In some cases, no identifiable cause is found.

Symptoms of Hyponatremia:
Mild Hyponatremia (Na+ 130–135 mEq/L): May be asymptomatic or present with nonspecific symptoms like fatigue, headache, nausea, and vomiting.
Moderate Hyponatremia (Na+ 120–129 mEq/L): Can cause lethargy, confusion, dizziness, and muscle cramps.
Severe Hyponatremia (Na+ <120 mEq/L): Leads to neurologic symptoms such as seizures, altered mental status, and coma, due to cerebral edema from water shifts into brain cells.
Other Symptoms:
Weight Gain Without Edema: Water retention leads to weight gain, but without peripheral edema.
Decreased Urine Output: Concentrated urine despite low plasma osmolality.

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 hypotonic plasma.
Urine Sodium Concentration >20–30 mEq/L: Demonstrates renal sodium loss due to the kidneys' response to excess water.
Euvolemia: Clinical assessment should show no signs of volume depletion (e.g., dry mucous membranes, orthostatic hypotension) or hypervolemia (e.g., edema, ascites).
Normal Adrenal, Thyroid, and Renal Function: Rule out other causes of hyponatremia, such as adrenal insufficiency or hypothyroidism. Normal renal function excludes chronic kidney disease as the cause of water retention.

Other Causes of Hyponatremia:
Hypovolemic Hyponatremia: Occurs due to true volume depletion (e.g., vomiting, diarrhea, diuretics) with low urine sodium (<20 mEq/L).
Hypervolemic Hyponatremia: Caused by heart failure, cirrhosis, or nephrotic syndrome, with signs of fluid overload.
Adrenal Insufficiency: Can cause hyponatremia with low cortisol levels.
Hypothyroidism: Severe hypothyroidism can impair free water excretion.

Treatment of Underlying Cause: Address the primary cause of SIADH, such as removing an offending medication or treating a lung infection or tumor.

Fluid Restriction:
First-Line Therapy: Restrict free water intake to 500–1,000 mL/day to prevent further water retention.

Hypertonic Saline (3%):
Indicated for severe or symptomatic hyponatremia, especially when neurologic symptoms are present (e.g., seizures, coma).
Slow Correction: Increase serum sodium by no more than 4–6 mEq/L in the first 24 hours to avoid osmotic demyelination syndrome (ODS), a serious complication resulting from overly rapid correction.

Oral Salt Tablets or Loop Diuretics:
Used in moderate cases to increase solute intake or promote free water excretion.
Furosemide: Given to increase urinary water excretion while minimizing sodium loss.

Vasopressin Receptor Antagonists (Vaptans):
Tolvaptan and Conivaptan: Block ADH action at the V2 receptor, leading to increased free water excretion (aquaresis).
Indications: Considered for chronic, refractory SIADH in cases where fluid restriction alone is ineffective.

Demeclocycline:
An older tetracycline antibiotic that induces nephrogenic diabetes insipidus, thus promoting free water excretion.
Typically used in refractory cases but limited by potential nephrotoxicity.

Serum Sodium Monitoring: Frequent monitoring is required, especially during treatment, to prevent rapid changes in sodium levels.
Neurologic Monitoring: Close observation for signs of neurologic improvement or deterioration, particularly in severe hyponatremia.
Long-Term Management: In chronic SIADH, ongoing fluid restriction or medications (e.g., vaptans) may be necessary to maintain normal sodium levels.

Severe Hyponatremia: Can lead to seizures, coma, and potentially fatal complications if not treated.
Osmotic Demyelination Syndrome (ODS): Occurs with overly rapid correction of hyponatremia, causing demyelination of pontine neurons. Symptoms include quadriplegia, dysphagia, dysarthria, and altered consciousness, which may be irreversible.
Chronic Hyponatremia: Long-term effects may include cognitive dysfunction and gait disturbances, especially in elderly patients.

Key Points

Pathophysiology: SIADH results from excessive ADH secretion, leading to free water retention and dilutional hyponatremia.
Etiology: Causes include CNS disorders, malignancies (especially small-cell lung carcinoma), medications (SSRIs, antipsychotics), and pulmonary infections.
Clinical Features: Hyponatremia causes nonspecific symptoms like headache, nausea, and confusion, with severe cases resulting in seizures and coma.
Diagnosis: Based on hyponatremia with low plasma osmolality, high urine osmolality, and euvolemia, excluding other causes of hyponatremia.
Management: Includes fluid restriction, hypertonic saline for severe cases, and vasopressin receptor antagonists (vaptans) for chronic, refractory SIADH.
Complications: Rapid correction of hyponatremia can lead to osmotic demyelination syndrome, a potentially irreversible condition.