SIADH for USMLE Step 1

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Syndrome of Inappropriate Antidiuretic Hormone (SIADH) for the USMLE Step 1 Exam

Excess ADH Secretion: In SIADH, antidiuretic hormone (ADH) is secreted inappropriately, leading to excessive water reabsorption in the kidneys. This results in water retention and dilutional hyponatremia.

Hyponatremia with Low Plasma Osmolality: Despite low plasma osmolality, the kidney continues to reabsorb water, concentrating the urine (high urine osmolality). However, total body sodium remains normal or slightly increased.
No Edema: Unlike hypervolemic conditions (e.g., heart failure), SIADH causes intracellular fluid retention without peripheral edema due to normal total body sodium.

Central Nervous System (CNS) Disorders: Conditions such as stroke, head trauma, meningitis, or encephalitis can disrupt ADH regulation by affecting the hypothalamus or pituitary gland.
Pulmonary Diseases: Pneumonia, tuberculosis, or chronic obstructive pulmonary disease (COPD) can trigger SIADH due to increased ADH release.
Malignancies: Small-cell lung carcinoma is a common malignancy associated with ectopic ADH production. Other cancers like pancreatic or prostate cancers may also cause SIADH.
Medications: Common drugs include:
Selective Serotonin Reuptake Inhibitors (SSRIs): Fluoxetine, sertraline.
Antipsychotics: Haloperidol.
Anticonvulsants: Carbamazepine.
Chemotherapy: Cyclophosphamide and vincristine.
Surgery: Post-operative ADH release is often seen after major surgeries.

Mild Hyponatremia (Na+ 130–135 mEq/L): Often asymptomatic or presents with nausea, headache, or mild lethargy.
Moderate Hyponatremia (Na+ 120–129 mEq/L): Symptoms may include confusion, dizziness, muscle cramps, and difficulty concentrating.
Severe Hyponatremia (Na+ <120 mEq/L): Neurological symptoms like seizures, altered mental status, and even coma due to cerebral edema from fluid shifts into brain cells.

Hyponatremia with Low Plasma Osmolality: Serum sodium <135 mEq/L with plasma osmolality <275 mOsm/kg.
Inappropriately High Urine Osmolality: Urine osmolality >100 mOsm/kg, despite low plasma osmolality.
Elevated Urine Sodium (>20–30 mEq/L): Demonstrates inappropriate sodium retention in the context of hyponatremia.
Euvolemia: Clinical evaluation should show no signs of hypovolemia (e.g., dehydration, orthostatic hypotension) or hypervolemia (e.g., edema, ascites).
Normal Adrenal, Thyroid, and Renal Function: Other causes of hyponatremia (e.g., adrenal insufficiency, hypothyroidism) must be excluded.

Fluid Restriction: Primary treatment for mild to moderate SIADH is limiting free water intake to 500–1,000 mL/day.
Hypertonic Saline (3%): Used for severe hyponatremia with neurologic symptoms, such as seizures or coma. Correct serum sodium slowly (increase 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 block ADH action at the renal V2 receptor, increasing free water excretion.
Demeclocycline: An antibiotic that induces nephrogenic diabetes insipidus and is used in refractory cases.
Oral Salt Tablets or Loop Diuretics: These may be used in chronic SIADH to promote water excretion while maintaining sodium balance.

Severe Hyponatremia: Can cause seizures, coma, and permanent neurologic damage if not corrected promptly.
Osmotic Demyelination Syndrome (ODS): Overly rapid correction of hyponatremia may lead to irreversible demyelination of neurons, causing quadriplegia, dysphagia, and other neurological deficits.

Key Points

Pathophysiology: SIADH results in excessive ADH secretion, leading to water retention, dilutional hyponatremia, and high urine osmolality without edema.
Causes: Common causes include CNS disorders, pulmonary diseases, malignancies (especially small-cell lung cancer), medications (SSRIs, anticonvulsants), and post-surgery states.
Symptoms: Mild hyponatremia may be asymptomatic, while severe hyponatremia can cause seizures, confusion, and coma.
Diagnosis: Based on hyponatremia, low plasma osmolality, high urine osmolality, and euvolemia.
Management: Treatment includes fluid restriction, hypertonic saline for severe cases, and vasopressin receptor antagonists. Avoid rapid correction to prevent osmotic demyelination syndrome.