SIADH

Risk factors

• Malignancy: small-cell lung cancer (classic), head and neck cancer, lymphoma, mesothelioma, pancreatic, prostate
• Pulmonary: pneumonia (bacterial, viral, fungal), TB, abscess, asthma, COPD exacerbation
• CNS: meningitis, encephalitis, brain abscess, TBI, stroke, subarachnoid hemorrhage, tumor
• Drugs: SSRIs, TCAs, MAOIs, carbamazepine, oxcarbazepine, valproate, cyclophosphamide, vincristine, vinblastine, MDMA, chlorpropamide, NSAIDs, antipsychotics, narcotics, desmopressin
• Surgery (postoperative period, especially pituitary surgery)
• HIV/AIDS, severe pain, nausea, prolonged exercise (marathon hyponatremia)

Pathophysiology

AVP is secreted despite normal or low plasma osmolality. ADH binds V2 receptors in collecting ducts, inserting aquaporin-2 channels and increasing water reabsorption. Free water retention dilutes plasma sodium. Volume expansion suppresses renin-angiotensin-aldosterone, increases ANP, and causes natriuresis — patient remains euvolemic, not edematous.

Clinical presentation

Differential diagnosis

• Hypovolemic hyponatremia — Volume depletion from diuretics, GI losses, third spacing; orthostatic, dry mucous membranes; urine Na <20 (extrarenal) or >20 (renal)
• Hypervolemic hyponatremia — CHF, cirrhosis, nephrotic syndrome; edema, ascites, JVD
• Adrenal insufficiency — Hypovolemia, hyperkalemia, hyperpigmentation; cosyntropin stim test
• Hypothyroidism (severe) — TSH elevated; rarely the sole cause of hyponatremia unless myxedema
• Primary polydipsia — Excess water intake; dilute urine appropriately; total water intake >10 L/day
• Beer potomania / tea-and-toast diet — Low solute intake limits water excretion; serum osm low; dilute urine; diet history
• Cerebral salt wasting — Hypovolemic hyponatremia in CNS injury; treat with NORMAL SALINE (opposite of SIADH); high urine Na
• Reset osmostat — Mild chronic hyponatremia, otherwise asymptomatic; pregnancy or chronic illness; normal handling of acute water load
• Pseudohyponatremia (hyperlipidemia, hyperproteinemia) — Sodium measured low on flame photometry but actually normal; check direct ion-selective electrode
• Hypertonic hyponatremia (hyperglycemia, mannitol) — Osmotically active solute draws water into vascular space; correct Na for glucose (1.6 mEq Na per 100 mg/dL glucose above 100)

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A["Hyponatremia<br/>(Na <135)"] --> B[Plasma osmolality]
  B --> C{"Osm low <275?"}
  C -->|"No (normal/high)"| D["Pseudo or hypertonic hyponatremia<br/>(glucose, mannitol, lipids)"]
  C -->|"Yes (hypotonic)"| E[Volume status assessment]
  E --> F{Hypovolemic?}
  F -->|Yes| G[GI losses / diuretics / Addison<br/>Treat with normal saline]
  F -->|Hypervolemic| H[CHF, cirrhosis, nephrotic<br/>Restrict water/Na, treat underlying]
  F -->|Euvolemic| I[Urine osm + urine Na + uric acid]
  I --> J{"Urine osm >100 + urine Na >30?"}
  J -->|Yes| K["Exclude hypothyroid + adrenal insufficiency<br/>→ SIADH"]
  J -->|"No (low urine osm)"| L[Primary polydipsia / beer potomania]
  K --> M["Treat: water restrict 800 mL/day<br/>+ salt/urea load; vaptan if refractory<br/>Acute severe: 3% saline; limit Na rise to ≤8-10 mEq/L per 24 h"]

Complications

• Acute: seizure, coma, brain herniation, death
• Chronic mild: falls, fractures, gait/cognitive impairment
• Osteoporosis (chronic hyponatremia increases osteoclast activity)
• Osmotic demyelination syndrome from over-rapid correction
• Underlying malignancy or CNS disease
• Tolvaptan-induced hepatotoxicity (limit duration ≤30 days)

PANCE pearls

• Always exclude HYPOTHYROIDISM and ADRENAL INSUFFICIENCY before diagnosing SIADH — these mimic and treat differently.
• Uric acid is HIGH in volume depletion and LOW in SIADH — useful adjunct.
• Cerebral salt wasting in the setting of CNS injury looks similar to SIADH but is HYPOVOLEMIC — treat with saline, NOT water restriction.
• Correct slowly: ≤8-10 mEq/L in 24 h (6 in high-risk) to prevent ODS.
• If you overshoot, re-lower with D5W ± DDAVP to bring sodium back to a safe trajectory.
• Beer potomania and 'tea and toast' diet cause hyponatremia from low solute intake — treat with normal saline and food (solute) restoration.

References

• European Society 2014 — Clinical Practice Guideline on Diagnosis and Treatment of Hyponatraemia (Spasovski et al., Eur J Endocrinol 2014 / Intensive Care Med 2014)
• U.S. Expert Panel 2013 — Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations (Verbalis et al., Am J Med 2013)
• Schwartz-Bartter 1957 — Original description of SIADH (Schwartz et al., Am J Med 1957)