Endocrine · Topic 12 of 13

SIADH

Endocrine · water balance

SIADH

Euvolemic hypotonic hyponatremia with inappropriately concentrated urine: restrict fluid, treat the cause, and raise sodium no more than 8 mEq/L in 24 hours.

Key numbers

Euvolemic hypotonic hyponatremia with concentrated urineUosm > 100 · UNa > 30

Restrict fluid and treat the cause≤ 1 L/day

Raise sodium ≤ 8 mEq/L/day≤ 8 mEq/L / 24 h

Severe symptoms: 3% saline 100 mL bolus+4–6 mEq/L

01 · Defined byEuvolemic hypotonic hyponatremia with concentrated urine

SIADH = serum osmolality < 275 mOsm/kg with urine osmolality > 100 mOsm/kg and urine sodium > 30 mEq/L on normal salt intake, in a euvolemic patient off diuretics with normal thyroid and adrenal function.

02 · DoRestrict fluid and treat the cause

First-line therapy is fluid restriction (≤ 1 L/day, ideally about 500 mL/day below urine output; 250–500 mL/day in severe cases) plus treating the cause — stop the offending drug, treat the infection or tumor.

03 · The ruleRaise sodium ≤ 8 mEq/L/day

Chronic or unknown-duration hyponatremia: aim for a 4–8 mEq/L rise per 24 h (4–6 if osmotic demyelination risk is high) and do not exceed 8 mEq/L in the first 24 h.

Causes & risk factors

Why it happens

Causes: CNS disease, lung disease, small cell cancerCommon causes: CNS disorders (stroke, subarachnoid hemorrhage, head trauma, meningitis), pulmonary disease (pneumonia, TB, positive-pressure ventilation), and ectopic ADH from cancer — especially small cell lung carcinoma.

Drug causes: SSRIs, carbamazepine, opioids, cyclophosphamideThe drug classes most often implicated are antidepressants (SSRIs, venlafaxine), antiseizure drugs (carbamazepine), opioids and NSAIDs, antipsychotics, and cytotoxics (cyclophosphamide, vincristine).

Diagnosis & monitoring

Work-up

Low uric acid and normal BUN support SIADHSupporting labs: normal BUN and creatinine, low serum uric acid, urine sodium > 30 mEq/L and fractional excretion of sodium > 1%.

Do right now

In this order

First moves

Severe symptoms: 3% saline 100 mL bolus+4–6 mEq/L

→

Check TSH and cortisol before diagnosing SIADH

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Restrict fluid and treat the cause≤ 1 L/day

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Raise sodium ≤ 8 mEq/L/day≤ 8 mEq/L / 24 h

Why each step

Severe symptoms: 3% saline 100 mL bolusSeizures, coma or severe confusion: give 3% saline 100 mL IV over 10 minutes, repeated up to twice more, for a rapid 4–6 mEq/L rise — then slow so the 24-hour limit holds.

Check TSH and cortisol before diagnosing SIADHSIADH is a diagnosis of exclusion: order serum and urine osmolality and sodium, then test thyroid and adrenal function — hypothyroidism and glucocorticoid deficiency mimic it exactly.

Restrict fluid and treat the causeFirst-line therapy is fluid restriction (≤ 1 L/day, ideally about 500 mL/day below urine output; 250–500 mL/day in severe cases) plus treating the cause — stop the offending drug, treat the infection or tumor.

Raise sodium ≤ 8 mEq/L/dayChronic or unknown-duration hyponatremia: aim for a 4–8 mEq/L rise per 24 h (4–6 if osmotic demyelination risk is high) and do not exceed 8 mEq/L in the first 24 h.

Management

Orders

Tolvaptan: start 15 mg daily in hospitalTolvaptan (oral V2 antagonist) starts at 15 mg once daily in the hospital, titrated to 30–60 mg; do not fluid-restrict in the first 24 h, limit use to 30 days, and avoid in liver disease.

Chronic options: oral urea or salt tabletsWhen fluid restriction fails in chronic SIADH, add oral urea or sodium chloride tablets, sometimes with a loop diuretic; demeclocycline is rarely used because of nephrotoxicity.

Overcorrected? Re-lower with D5W and desmopressinIf sodium is rising too fast, stop hypertonic therapy and give hypotonic fluid (D5W or water) with or without desmopressin 2–4 mcg IV to halt the aquaresis and re-lower sodium.

Red flags & don'ts

Avoid harm

Overcorrection causes osmotic demyelination syndrome complicationToo-rapid correction causes osmotic demyelination days later: dysarthria, dysphagia, flaccid paralysis and possibly a locked-in state; damage is often permanent.

The rules

Know these

Predict fluid-restriction failure: Furst ratio > 1Fluid restriction tends to fail when urine osmolality > 500 mOsm/kg, urine Na + K exceeds serum Na (Furst ratio > 1), or sodium rises < 2 mEq/L/day on ≤ 1 L/day for 24–48 h.

SIADH or cerebral salt wasting?

Commonly confused

Volume status	Euvolemic
Urine sodium	> 30 mEq/L
Typical setting	CNS, lung disease, cancer, drugs
Response to 0.9% saline	No lasting correction
Treatment	Fluid restriction

More detail

Reference

Show 6 reference facts

Conivaptan (IV V2 antagonist) is for hospitalized euvolemic or hypervolemic hyponatremia: loading dose then infusion for up to 4 days; avoid with eGFR < 30 and with strong CYP3A inhibitors.

Tolvaptan boxed warning: a rise > 12 mEq/L/24 h can cause osmotic demyelination. Contraindicated in hypovolemic hyponatremia, anuria, inability to sense thirst and with strong CYP3A inhibitors; not for urgent correction.

Symptoms appear as effective osmolality falls below about 240 mOsm/kg: nausea, falls, confusion and lethargy; sodium < 115 mEq/L brings stupor, hyperreflexia, seizures and coma.

Look for the cause: chest radiograph for pneumonia or a lung mass in every patient; CNS imaging only when a brain disorder is suspected or no other cause is found.

Reset osmostat is a SIADH variant in which ADH is still suppressed, but at a lower serum osmolality, so sodium stays mildly low and stable.

A proactive "desmopressin clamp" (desmopressin 1–2 mcg every 8 h with 3% saline) prevents an unpredictable water diuresis and overshoot; stop it after 24 h of correction at the planned rate.

Pearl

In chronic hyponatremia, slow is safe: too fast a rise in sodium injures the pons days later.

Sources · Merck Manual Professional — Syndrome of Inappropriate ADH Secretion (SIADH) (full review Jun 2025) · Lawless SJ, Thompson C et al. The management of acute and chronic hyponatraemia. Ther Adv Endocrinol Metab 2022;13:20420188221097343 (summarizes the 2013 US expert panel and 2014 European guideline; PMC9109487) · Samsca (tolvaptan) prescribing information — DailyMed · Merck Manual Professional — Hyponatremia · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).