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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- SIADH = hypotonic hyponatremia with euvolemia, inappropriately concentrated urine, and elevated urine sodium
- Diagnostic pattern: low serum osmolality, urine osmolality >100 mOsm/kg, urine sodium >30 mEq/L, normal adrenal/thyroid/renal function
- Common causes: CNS disease, pulmonary disease, malignancy (small cell lung cancer), pain/nausea, postoperative state, SSRIs, carbamazepine, cyclophosphamide
- Severe symptomatic hyponatremia: 3% hypertonic saline bolus with close monitoring
- Avoid overly rapid correction: osmotic demyelination risk, especially chronic hyponatremia, alcoholism, malnutrition, liver disease, hypokalemia
Overview
Syndrome of inappropriate antidiuresis is caused by persistent ADH effect despite low plasma osmolality, leading to free-water retention, dilutional hyponatremia, and concentrated urine. Patients are clinically euvolemic because mild volume expansion triggers natriuresis. SIADH is a diagnosis of exclusion: adrenal insufficiency, hypothyroidism, kidney failure, diuretics, hyperglycemia, and pseudohyponatremia must be considered.
Epidemiology
SIADH is one of the most common causes of hyponatremia in hospitalized patients. Etiologies include pulmonary disease such as pneumonia or tuberculosis, CNS pathology such as stroke, hemorrhage, trauma, infection, or psychosis, malignancy especially small cell lung carcinoma, medications such as SSRIs, SNRIs, carbamazepine, oxcarbazepine, cyclophosphamide, vincristine, MDMA, and postoperative pain/nausea. Older adults and patients on multiple medications are at higher risk.
Clinical Features
Symptoms
Often asymptomatic if mild or chronic
Nausea, headache, malaise, gait instability
Confusion, agitation, delirium from cerebral edema
Seizures, coma, respiratory arrest in severe acute hyponatremia
Symptoms of underlying cause: cough, pneumonia, malignancy, CNS event
Signs
Clinically euvolemic: no edema, no orthostasis, no signs of dehydration
Neurologic findings proportional to sodium level and rapidity of fall
Normal skin turgor and mucous membranes
Absence of heart failure, cirrhosis, nephrotic syndrome, or diuretic-driven volume depletion
Seizure or severe altered mental status is an emergency
Investigations
First-line
Serum sodium and serum osmolalityConfirm hypotonic hyponatremia; exclude hyperglycemia-related translocational hyponatremia and pseudohyponatremia
Urine osmolalityInappropriately >100 mOsm/kg in SIADH; maximally dilute urine suggests primary polydipsia or low-solute intake
Urine sodiumUsually >30 mEq/L in SIADH with normal salt intake
Glucose, creatinine, TSH, morning cortisolExclude hyperglycemia, renal failure, hypothyroidism, and adrenal insufficiency
Second-line
Medication reviewSSRIs, carbamazepine, antipsychotics, chemotherapy, opioids, NSAIDs, MDMA
Chest X-rayEvaluate pneumonia, tuberculosis, or lung malignancy when no obvious cause
Head CT/MRIIf neurologic symptoms, trauma, seizure, or suspected CNS pathology
Specialist
Frequent sodium monitoringEvery 2-4 hours during hypertonic saline or high-risk correction
Malignancy evaluationIf persistent unexplained SIADH, smoking history, weight loss, or pulmonary symptoms
1
Severe symptomatic hyponatremia
- 3% hypertonic saline bolus with goal initial sodium rise of 4-6 mEq/L to stop seizures or severe cerebral edema symptoms
- Avoid complete normalization acutely
- Monitor sodium closely and use desmopressin/free water if overcorrection occurs
2
Chronic or mild/moderate SIADH
- Fluid restriction, often 800-1000 mL/day, is first-line
- Increase solute intake with salt tablets or urea when appropriate
- Loop diuretics with salt may be used to increase free-water clearance in selected cases
3
Treat underlying cause
- Stop offending medications when possible
- Treat pulmonary/CNS disease, pain, nausea, or malignancy
4
Vaptans and refractory cases
- Vasopressin receptor antagonists may be used in selected hospitalized patients but require careful monitoring
- Avoid vaptans in severe symptomatic hyponatremia needing immediate hypertonic saline and in patients unable to respond to thirst
5
Safe correction limits
- For chronic hyponatremia, generally avoid correction >8-10 mEq/L in 24 hours; use lower limits in high-risk patients
- High-risk osmotic demyelination: alcoholism, malnutrition, liver disease, hypokalemia, very low sodium
Complications
- Cerebral edema: Acute severe hyponatremia causes headache, vomiting, seizures, coma
- Osmotic demyelination syndrome: Overly rapid correction of chronic hyponatremia causes dysarthria, dysphagia, quadriparesis, locked-in syndrome
- Falls and fractures: Even mild chronic hyponatremia impairs gait and attention
- Medication recurrence: Hyponatremia may recur if offending drug restarted
- Missed adrenal insufficiency: Can mimic SIADH and be fatal if untreated
USMLE Step 2 CK Exam Tips
- 1SIADH labs: low serum osmolality, urine osmolality >100, urine sodium >30, euvolemia
- 2Adrenal insufficiency and hypothyroidism must be excluded before calling it SIADH
- 3Small cell lung cancer is the classic malignancy associated with SIADH
- 4Seizure from hyponatremia = hypertonic saline, not normal saline or fluid restriction alone
- 5Do not correct chronic hyponatremia too quickly — osmotic demyelination is the feared complication
- 6Primary polydipsia has very dilute urine; SIADH does not
- 7Normal saline can fail or worsen SIADH because sodium is excreted while water is retained
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