SIADH for USMLE Step 3

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Syndrome of Inappropriate Antidiuretic Hormone (SIADH) for the USMLE Step 3 Exam

Increased ADH Secretion: In SIADH, antidiuretic hormone (ADH) is secreted inappropriately, leading to water reabsorption by the kidneys even when plasma osmolality is low.

Hyponatremia and Low Plasma Osmolality: Retained free water dilutes the plasma, resulting in hyponatremia and low plasma osmolality. However, urine remains inappropriately concentrated due to continued ADH action.
No Edema: Despite water retention, there is no edema or hypervolemia because sodium levels remain normal, preventing extracellular fluid overload.

CNS Disorders: Stroke, head trauma, meningitis, encephalitis, and subarachnoid hemorrhage can cause SIADH by disrupting hypothalamic regulation of ADH.
Pulmonary Disorders: Conditions like pneumonia, tuberculosis, and chronic obstructive pulmonary disease (COPD) can stimulate ADH release.
Malignancies: The most notable cause is small-cell lung carcinoma, which can produce ectopic ADH. Other cancers such as pancreatic or prostate cancer can also trigger SIADH.
Medications:
SSRIs (e.g., sertraline, fluoxetine), tricyclic antidepressants (e.g., amitriptyline).
Anticonvulsants (e.g., carbamazepine), antipsychotics (e.g., haloperidol).
Chemotherapy Agents (e.g., vincristine, cyclophosphamide).
Surgery: SIADH can occur after major surgeries, often due to stress-induced ADH release.

Mild Hyponatremia (Na+ 130–135 mEq/L): Patients may be asymptomatic or experience nonspecific symptoms like fatigue, headache, or nausea.
Moderate Hyponatremia (Na+ 120–129 mEq/L): Symptoms may include confusion, lethargy, muscle cramps, and irritability.
Severe Hyponatremia (Na+ <120 mEq/L): Neurological symptoms such as seizures, altered mental status, and coma due to cerebral edema from fluid shifts.

Serum Sodium <135 mEq/L: Hyponatremia is the hallmark of SIADH.
Low Plasma Osmolality (<275 mOsm/kg): Indicates free water retention and dilution of serum solutes.
High Urine Osmolality (>100 mOsm/kg): Despite hyponatremia and low plasma osmolality, urine remains concentrated due to ADH action.
Elevated Urine Sodium (>20–30 mEq/L): Reflects ongoing renal sodium excretion despite hyponatremia.
Normal Thyroid, Adrenal, and Renal Function: These must be normal to rule out other causes of hyponatremia (e.g., hypothyroidism, adrenal insufficiency).

Fluid Restriction:
First-line treatment for most cases, restricting fluid intake to 500–1,000 mL/day to reduce water retention.
Hypertonic Saline (3%):
Used for severe or symptomatic hyponatremia (e.g., seizures, coma). Sodium correction should be slow (no more than 4–6 mEq/L in 24 hours) to avoid osmotic demyelination syndrome (ODS).
Medications:
Vasopressin Receptor Antagonists (Vaptans): Tolvaptan or conivaptan blocks ADH at the V2 receptor, leading to increased free water excretion.
Demeclocycline: Causes nephrogenic diabetes insipidus, reducing water reabsorption, but is typically reserved for chronic cases due to potential nephrotoxicity.
Loop Diuretics: Furosemide can be used to increase free water excretion while minimizing sodium loss, especially in conjunction with oral salt supplementation.

Severe Hyponatremia: Can result in seizures, coma, and even death if untreated.
Osmotic Demyelination Syndrome (ODS): Rapid correction of sodium levels can cause demyelination in the brainstem, leading to irreversible neurological damage, including quadriplegia, dysphagia, and altered consciousness.

Key Points

Pathophysiology: SIADH is characterized by excessive ADH secretion, leading to free water retention, dilutional hyponatremia, and concentrated urine.
Causes: Common triggers include CNS disorders, lung diseases, small-cell lung cancer, medications (e.g., SSRIs, anticonvulsants), and postoperative states.
Symptoms: Mild cases may be asymptomatic, while severe hyponatremia can cause confusion, seizures, or coma.
Diagnosis: Identified by hyponatremia, low plasma osmolality, high urine osmolality, and normal thyroid, adrenal, and renal function.
Treatment: Fluid restriction is the cornerstone of therapy; hypertonic saline for severe cases; and vasopressin antagonists or demeclocycline for chronic SIADH.
Complications: Rapid correction of hyponatremia can lead to osmotic demyelination syndrome, causing permanent neurological damage.