SIADH
Too much ADH, so water is retained and the sodium falls while the patient stays euvolemic. The whole diagnosis rests on paired osmolalities plus a volume assessment, and the whole danger is correcting too fast. Includes side-by-side comparisons with diabetes insipidus (the mirror image) and cerebral salt wasting (the look-alike with the opposite treatment).
💧 Overview
Diagnostic Criteria, ALL Must Be Present
- Serum Na⁺ < 135 mEq/L (hyponatremia)
- Serum osmolality < 275 mOsm/kg (truly hypo-osmolar, which excludes pseudohyponatremia and hyperglycemia)
- Urine osmolality > 100 mOsm/kg (inappropriately concentrated: in a hypo-osmolar state the kidney should be making maximally dilute urine)
- Urine sodium > 40 mEq/L on a normal salt intake (the kidney is not volume-depleted, so it is not avidly retaining sodium)
- Clinically euvolemic (no edema, no orthostasis, no JVD)
- Normal thyroid and adrenal function, and no recent diuretic
SIADH is a diagnosis of exclusion. Check TSH and an AM cortisol before you commit to it. Hypothyroidism and adrenal insufficiency both produce euvolemic hyponatremia with concentrated urine, both are treatable with specific therapy, and both are missed if you anchor on SIADH early. Thiazides are the other great mimic: they cause hyponatremia with a high urine sodium and can look identical.
Why the Sodium Falls
SIADH is a water problem, not a salt problem. ADH acts on V2 receptors in the collecting duct, inserting aquaporin-2 channels and retaining free water. The retained water dilutes the sodium. Volume expansion is only transient, because the kidney escapes by excreting sodium (pressure natriuresis plus natriuretic peptides), which is why the patient ends up euvolemic with a high urine sodium rather than edematous. That is also why giving isotonic saline can make things worse: if urine osmolality exceeds the osmolality of the fluid you infuse, the kidney excretes the salt and keeps the water. This is the desalination phenomenon.
Causes, Grouped the Way You Should Search for Them
| Category | Specifics | Clinical clue |
|---|---|---|
| Drugs the first thing to review | SSRIs (most common drug cause), carbamazepine and oxcarbazepine, cyclophosphamide, vincristine, NSAIDs, antipsychotics, MDMA, desmopressin, thiazides (a mimic rather than true SIADH) | Onset typically 2 to 4 weeks after starting the drug, and the elderly are most at risk. Check a sodium at that interval after starting an SSRI. |
| CNS disease | Stroke, subarachnoid hemorrhage, head trauma, meningitis, encephalitis, brain tumor, and post-neurosurgical states | In a hyponatremic SAH patient you must separate SIADH from cerebral salt wasting before restricting fluids. See the comparison tab. |
| Pulmonary disease | Pneumonia, tuberculosis, lung abscess, empyema, and positive-pressure ventilation | Often resolves as the lung process resolves; no specific therapy is needed beyond treating the pneumonia. |
| Malignancy | Small cell lung cancer is the classic ectopic ADH producer, then head and neck cancers | Unexplained SIADH in a smoker warrants chest imaging. Hyponatremia may be the presenting sign of SCLC. |
| Pain, nausea, post-op | Any severe pain or nausea is a potent physiologic ADH stimulus | Frequently overlooked. Treating the pain and nausea treats the hyponatremia, so do that before reaching for tolvaptan. |
🧪 Workup
The Three Tests That Make the Diagnosis
Send a serum osmolality, a urine osmolality and a urine sodium at the same time, before you give any fluid. Paired samples are the entire workup. A urine osmolality drawn after a saline bolus is uninterpretable, and this is the single most common way the diagnosis gets muddied.
| Step | Test | How to read it |
|---|---|---|
| 1. Is it truly hypo-osmolar? | Serum osmolality | < 275 confirms true hyponatremia. If normal or high, you have pseudohyponatremia (severe hyperlipidemia or paraproteinemia) or a second osmole such as glucose, mannitol or ethanol. Correct sodium for glucose before going further. |
| 2. Is ADH acting? | Urine osmolality | > 100 means ADH is on when it should be off. A urine osmolality < 100 points instead to primary polydipsia, beer potomania or low solute intake, where the kidney is diluting appropriately and the problem is intake. |
| 3. What is the volume state? | Urine sodium plus the bedside exam | > 40 with clinical euvolemia supports SIADH. < 20 means an avidly sodium-retaining kidney, so think hypovolemia or a low effective circulating volume state (heart failure, cirrhosis). |
Before You Commit to the Diagnosis
- TSH and AM cortisol on every patient, because hypothyroidism and adrenal insufficiency mimic SIADH exactly and are treatable
- Review the medication list with SSRIs, carbamazepine and thiazides specifically in mind
- Serum uric acid is low (< 4 mg/dL). Urate is reabsorbed in the proximal tubule coupled to sodium. SIADH retains water, which mildly expands the effective circulating volume, and that expansion switches off proximal sodium reabsorption. Urate is lost along with it. It does not distinguish SIADH from cerebral salt wasting, where it is also low
- BUN is low or low-normal from dilution; a raised BUN should make you reconsider hypovolemia
- Chest imaging if the cause is not obvious, particularly in a smoker, to look for small cell lung cancer
- Document the acuity. Hyponatremia known to be under 48 hours old can be corrected faster; anything undocumented is treated as chronic, which is the safe assumption
⚡ Management
Treatment by Severity
| Scenario | Treatment | Correction target and cautions |
|---|---|---|
| Symptomatic (seizure, coma, severe altered mental status) | 3% hypertonic saline 100 to 150 mL IV bolus over 10 to 20 min. May repeat up to twice if symptoms persist. ICU admission and frequent sodium checks. | Immediate goal is to raise the sodium by 4 to 6 mEq/L in the first 6 hours, which is enough to stop seizures and reduce cerebral edema. Then hold at ≤ 8 mEq/L total in 24 hours. You are treating the brain, not the number. |
| Asymptomatic or chronic (Na 120 to 134) | Fluid restriction 800 to 1000 mL/day, stop the offending drug, and treat the underlying cause. Add salt tablets or oral urea 15 to 30 g daily if restriction alone fails. | ≤ 8 mEq/L per 24 hours. The brain has adapted by extruding osmolytes, so a fast correction is what injures it. Fluid restriction is slow and often unpopular with patients, so set expectations. |
| Refractory | Tolvaptan 15 mg PO daily, a V2 receptor antagonist producing a free water aquaresis. SALT-1 and SALT-2, 2006 | Start inpatient only and check sodium at 4 to 6 h, 8 to 12 h and 24 h. Do not combine with hypertonic saline or fluid restriction during initiation, since the combination overcorrects. Hepatotoxicity limits use to 30 days. |
Predicting who will fail fluid restriction. Restriction is unlikely to work if the urine osmolality is above 500, or if the urine sodium plus urine potassium exceeds the serum sodium (the patient is generating negative free water clearance and would need an impractically tight restriction). Those patients need salt plus a loop diuretic, urea, or tolvaptan rather than a doomed trial of restriction.
Verbalis Expert Panel, 2013 Osmotic demyelination syndrome. Correcting faster than 8 mEq/L in 24 hours destroys myelin in the central pons, producing dysarthria, dysphagia, quadriparesis and a locked-in syndrome. It appears 2 to 6 days later and is irreversible. Highest risk: chronic hyponatremia, Na < 105, alcohol use disorder, malnutrition, hypokalemia and liver disease, where the ceiling drops to 6 mEq/L per 24 h. If you are overcorrecting, act immediately: D5W plus DDAVP 2 mcg IV q8h to re-lower the sodium onto a safe trajectory.
⚖️ SIADH vs DI & CSW
SIADH vs Diabetes Insipidus, the Mirror Image
Same hormone, opposite ends. SIADH is too much ADH so water is retained and the sodium falls. DI is too little ADH, or a kidney that cannot respond to it, so free water is lost and the sodium rises. Both are diagnosed with paired serum and urine osmolalities.
| Feature | SIADH | Diabetes Insipidus |
|---|---|---|
| ADH | Excess (or ectopic) | Deficient (central) or ineffective (nephrogenic) |
| Serum sodium | Low, often 120s | High, if the patient cannot reach water |
| Serum osmolality | < 275 | > 290 |
| Urine osmolality | > 100, inappropriately concentrated | < 300, inappropriately dilute |
| Urine output | Normal or low | Polyuria > 3 L/day |
| Volume status | Euvolemic | Euvolemic to hypovolemic |
| Treatment | Restrict water. Salt, urea or tolvaptan if refractory | Give water. DDAVP for central; remove the cause plus thiazide for nephrogenic |
They can occur in the same patient, in sequence. After pituitary surgery about a quarter of patients show the triphasic response: DI for a few days, then a SIADH phase around days 5 to 10 as stored ADH is released from the dying posterior pituitary, then permanent DI. Continuing DDAVP into the SIADH phase causes fatal hyponatremia, so when the urine output falls and the sodium starts dropping, stop the DDAVP.
SIADH vs Cerebral Salt Wasting, the Dangerous Look-Alike
The labs are nearly identical and the treatments are opposite. Both give hyponatremia, urine osmolality above 100, urine sodium above 40, and a low uric acid, usually in a patient with intracranial pathology. Volume status is the discriminator. Fluid-restricting a cerebral salt wasting patient with subarachnoid hemorrhage worsens volume depletion and drives delayed cerebral ischemia and vasospasm.
| Feature | SIADH | Cerebral salt wasting |
|---|---|---|
| Primary defect | ADH excess, so water is retained | Renal sodium wasting, so water follows the salt out |
| Volume status the discriminator | Euvolemic | Hypovolemic: dry mucous membranes, orthostasis, flat neck veins |
| Urine output | Normal or low | High, often frankly polyuric |
| BUN / creatinine | Low-normal, dilutional | Raised, prerenal pattern |
| Hematocrit, albumin | Normal or low | Raised, hemoconcentrated |
| CVP, weight | Normal; weight stable or up | Low; weight down |
| Serum uric acid | Low | Low. Does not distinguish them, which is the classic trap |
| Fractional excretion of urate | Elevated in both while hyponatremic, so it is useless on first encounter. After the sodium is corrected it normalizes to < 11% in SIADH but stays > 11% in cerebral salt wasting, which is the most reliable discriminator described. | |
| Response to saline | No change, or the sodium falls further through desalination | Improves |
| Treatment | Fluid restriction | Isotonic saline and salt repletion. Fludrocortisone 0.1 to 0.2 mg daily reduces the natriuresis. Never fluid restrict. |
Practical approach at the bedside: assess volume properly with strict intake and output, daily weights, orthostatics and a CVP if a line is already in, then consider a trial of isotonic saline, since cerebral salt wasting improves and SIADH does not. Note that the existence of cerebral salt wasting is contested, with many arguing most labeled cases are really SIADH, but in the neurosurgical population the distinction still changes what you do.
💊 Medications
Key Medications in SIADH
| Drug | Dose | Role | Watch for |
|---|---|---|---|
| Hypertonic saline 3% | 100 to 150 mL IV bolus over 10 to 20 min, repeat up to twice | Symptomatic hyponatremia only (seizure, coma, severe altered mental status) | Aim for a 4 to 6 mEq/L rise in 6 h, then stop. Recheck sodium 2 h after each bolus. Peripheral administration of small boluses is acceptable. |
| Sodium chloride tablets | 1 g PO TID, titrated | Add-on when fluid restriction alone is not enough | Often paired with a loop diuretic when urine osmolality is high, since the loop lowers urinary concentrating ability. |
| Urea (oral) | 15 to 30 g daily | Induces an osmotic diuresis of free water; useful for chronic SIADH | Poor palatability is the main limit. Cheaper than tolvaptan and no hepatotoxicity ceiling. |
| Tolvaptan (Samsca) | 15 mg PO daily, titrate to 30 to 60 mg | V2 receptor antagonist producing free water aquaresis without sodium loss | Inpatient initiation only. Sodium at 4 to 6 h, 8 to 12 h and 24 h. Do not combine with hypertonic saline or fluid restriction at initiation. Hepatotoxicity limits use to 30 days. |
| Desmopressin (DDAVP) | 2 mcg IV q8h for rescue; 1 to 2 mcg IV/SC q12h for central DI | Two opposite roles: ODS rescue in overcorrected hyponatremia, and replacement in central DI | In rescue, pair with D5W to re-lower the sodium. Know which indication you are treating before you order it. |
| Fludrocortisone | 0.1 to 0.2 mg PO daily | Cerebral salt wasting, to reduce renal sodium wasting | Watch for volume overload, hypokalemia and hypertension. Not a treatment for SIADH. |
The commonest medication error here is treating the number instead of the patient. A sodium of 118 that is chronic and asymptomatic needs fluid restriction and patience. A sodium of 124 with a seizure needs hypertonic saline now. Symptoms, not the absolute value, decide how aggressive you are.
📋 On Rounds
A patient's Na corrected from 112 to 124 in 18 hours. What do you do?
That's a 12 mEq/L correction in 18h, too fast. The safe limit is ≤ 8 mEq/L in 24h. Immediate steps: (1) D5W infusion (free water to re-lower Na), (2) DDAVP 2 mcg IV q8h (replaces ADH so the kidneys retain free water and Na drops back), (3) target Na no more than 8 mEq/L above the starting value for the 24h period. The goal is to "re-lower" the sodium onto a safe correction trajectory.
Hyponatremia in a patient 5 days after subarachnoid hemorrhage. Why is fluid restriction the wrong reflex?
Because it may be cerebral salt wasting, not SIADH. The labs look identical (low Na, urine osm > 100, urine Na > 40, low uric acid) but CSW patients are hypovolemic. Restricting fluid deepens the volume depletion and increases delayed cerebral ischemia and vasospasm. Assess volume status, and if uncertain give isotonic saline: CSW improves, SIADH does not.
Why do thiazides paradoxically help nephrogenic DI?
Counterintuitive but elegant: thiazides block NaCl reabsorption in the distal convoluted tubule causing mild sodium and volume depletion, so the body compensates by increasing proximal tubule reabsorption of sodium and water. Less water reaches the ADH-insensitive collecting duct, so less dilute urine is produced and urine volume falls, by roughly 30 to 50%.
How does tolvaptan work and why must you start it inpatient?
Tolvaptan is a V2 receptor antagonist that blocks ADH at the collecting duct, inducing a free water diuresis (aquaresis) without sodium loss, so the urine concentrates and the plasma dilutes and sodium rises. It must be started inpatient because the correction can be rapid and unpredictable, risking overcorrection and osmotic demyelination. Check sodium at 4 to 6h, 8 to 12h and 24h after the first dose.
What are the criteria for diagnosing SIADH?
All must be met: (1) serum osm < 275 (hypo-osmolar), (2) urine osm > 100 (inappropriately concentrated, since the kidney should be making dilute urine in a hypo-osmolar state), (3) euvolemic (no edema, no JVD, no orthostasis), (4) urine Na > 40, (5) normal thyroid and adrenal function with no recent diuretic.
A patient with Na 118 and seizures. What do you give and how fast do you correct?
3% hypertonic saline 100 to 150 mL bolus over 10 to 20 min, repeatable up to twice. Target a 4 to 6 mEq/L rise in the first 6h to stop the seizure. Do not exceed 8 mEq/24h (6 if high-risk). Overcorrection causes osmotic demyelination syndrome.
What is the most dangerous time for osmotic demyelination syndrome?
ODS presents 2 to 6 days after overcorrection with dysarthria, dysphagia, quadriparesis and locked-in syndrome. Risk factors: chronic hyponatremia over 48h, alcohol use disorder, malnutrition, liver disease and hypokalemia.
Why must you check TSH and cortisol before diagnosing SIADH?
Both hypothyroidism and adrenal insufficiency cause hyponatremia and mimic SIADH exactly (euvolemic, concentrated urine). Both are treatable with specific therapy and both are missed if you anchor early. SIADH is a diagnosis of exclusion.
Clinical Examples
📋 Case 1, SSRI-Induced SIADH
Patient: 72-year-old woman started on escitalopram 3 weeks ago for depression. Presents with fatigue, nausea, mild confusion. Na 118, serum osm 248, urine osm 520, UNa 58. Euvolemic. TSH and AM cortisol normal.
Key findings: Classic SSRI-induced SIADH. All diagnostic criteria met: hypo-osmolar, inappropriately concentrated urine, euvolemic, UNa > 40, normal thyroid and adrenal function.
Management:
- Hold escitalopram (offending agent)
- Fluid restriction < 1 L/day
- Na q4-6h (symptomatic with confusion)
- If Na not improving: salt tabs 1g TID
- Correction rate ≤ 8 mEq/L per 24h (high risk: elderly)
Teaching point: SSRIs are the most common drug cause of SIADH. Always check a sodium 2 to 4 weeks after starting an SSRI in an elderly patient. Leth-Moller et al., 2016
📋 Case 2, Post-Neurosurgical Central DI
Patient: 38-year-old man, POD 1 from transsphenoidal pituitary adenoma resection. UOP 650 mL/hr x 4 hours. Clear, dilute urine. Na 151 (was 140 pre-op), serum osm 308, urine osm 78.
Key findings: Post-surgical central DI. Massive polyuria with inappropriately dilute urine and a rising sodium. Watch for the triphasic response.
Management:
- DDAVP 1 mcg IV q12h
- D5W to replace the free water deficit and match ongoing losses
- Na q4h, strict I&Os, hourly UOP
- If UOP drops and Na falls on days 5-10: STOP DDAVP immediately (SIADH phase)
Teaching point: The triphasic response (DI, then SIADH, then permanent DI) occurs in roughly 25% of pituitary surgery patients. Continuing DDAVP into the SIADH phase causes fatal hyponatremia.
📋 Case 3, Overcorrection Rescue
Patient: 65-year-old man with chronic hyponatremia (Na 108) from SCLC-associated SIADH. After 18 hours of 3% saline and fluid restriction, Na corrected to 122, a 14 mEq/L rise.
Key findings: Overcorrection. 14 mEq/L in 18h exceeds the safe limit of 8 mEq/L per 24h. High risk for ODS: chronic, severe hyponatremia and malignancy.
Management:
- STOP hypertonic saline immediately
- DDAVP 2 mcg IV q8h to re-lower Na
- D5W infusion to bring Na back down
- Target: Na no more than 8 mEq/L above the starting value for the 24h period (goal Na ≤ 116)
- Na q2h until trending downward
Teaching point: ODS rescue (DDAVP plus D5W) should start the moment overcorrection is detected. ODS presents 2 to 6 days later and is irreversible. Verbalis Expert Panel, 2013
📣 Sample Presentation
One-Liner
"Mr. Foster is a 68-year-old started on sertraline 3 weeks ago presenting with Na⁺ 122, serum osm 258, urine osm 480, UNa 52, euvolemic. TSH and cortisol normal. SIADH from SSRI."
Key Points to Cover on Rounds
SIADH, euvolemic hypo-osmolar hyponatremia with inappropriately concentrated urine and a high urine sodium. Cause: sertraline, since SSRIs are the most common drug cause. Asymptomatic, no seizure or altered mental status. Treatment: fluid restriction under 1 L/day started, sertraline held, alternative antidepressant to be discussed with psychiatry. Na trending 122 to 124 to 126 over 36h, a rate of 3 mEq/24h which is safe against a ceiling of 8. Plan: if refractory to restriction, salt tabs 1g TID; if still refractory, tolvaptan inpatient with Na checks at 4 to 6h, 8 to 12h and 24h. ODS rescue protocol available if overcorrected (D5W plus DDAVP).
Monitoring in SIADH
| Parameter | Frequency | Target / Action |
|---|---|---|
| Serum sodium | q2h while on hypertonic saline, q4-6h if symptomatic, q12-24h once stable | Ceiling ≤ 8 mEq/L per 24 h, or ≤ 6 if high-risk for ODS. The single most important number on this page. |
| Urine output and fluid balance | Strict, hourly if on hypertonic saline | A sudden water diuresis means the ADH stimulus has switched off and the sodium is about to rise fast. Anticipate overcorrection and consider pre-emptive DDAVP. |
| Urine osmolality | At diagnosis, then if not responding | Above 500 predicts failure of fluid restriction. Falling values mean ADH is switching off. |
| Potassium | Daily | Hypokalemia raises ODS risk, and repleting it also raises the sodium, so count it in your 24h correction budget. |
| Neurologic exam | Each assessment | Improving mental status guides how aggressive to be. New dysarthria, dysphagia or weakness 2 to 6 days after correction suggests ODS. |
⚡ Summary
Summary
The Diagnosis Rests on Paired Osmolalities Plus Volume
Hypotonic hyponatremia with a low serum osmolality, inappropriately concentrated urine (osmolality above 100), a urine sodium above 30 to 40 on a normal salt intake, and clinical euvolemia, with normal thyroid and adrenal function and no diuretics. All of these must be present: SIADH is a diagnosis of exclusion, not a label for any hyponatremia.
Assess Volume Status First
Hypovolemic hyponatremia and SIADH have overlapping labs and completely opposite treatments. Giving saline to true SIADH can lower the sodium further, because the salt is excreted while the water is retained. A cautious saline challenge helps: hypovolemia improves, SIADH does not or worsens.
Search the Causes in Four Groups
CNS disease (stroke, hemorrhage, infection, trauma), pulmonary disease (pneumonia, tuberculosis, positive pressure ventilation), malignancy (small cell lung cancer above all), and drugs (SSRIs, carbamazepine, cyclophosphamide, antipsychotics, NSAIDs, MDMA). Pain, nausea and the postoperative state are potent and reversible stimuli that are frequently overlooked.
Uric Acid Points Toward It
Serum uric acid is low, below about 4 mg/dL. Urate is reabsorbed in the proximal tubule coupled to sodium; the mild volume expansion of SIADH switches off proximal sodium reabsorption and urate is lost with it. It does not distinguish SIADH from cerebral salt wasting, where it is also low.
Correct Slowly: 8 mEq/L in 24 Hours
Do not exceed 8 mEq/L in 24 h, or 6 in high-risk patients (alcohol use disorder, malnutrition, hypokalemia, advanced liver disease, chronic hyponatremia). Overcorrection causes osmotic demyelination syndrome, which is devastating and irreversible. Check sodium every 2 to 4 h during active correction, and be prepared to relower with D5W and desmopressin if you overshoot.
Severe Symptoms Override the Slow Rule
Seizures, coma or severe confusion mean 3% hypertonic saline, 100 to 150 mL boluses, aiming for a rapid 4 to 6 mEq/L rise to stop the symptoms. Then stop and revert to the slow limit: the initial bolus buys brain safety, it is not the start of a fast correction.
Match the Chronic Treatment to Severity
Fluid restriction first line for mild to moderate disease, though it works poorly when the urine osmolality is very high. Salt tablets with a loop diuretic, or urea, for inadequate response. Tolvaptan for refractory cases, in hospital with close monitoring, since it causes rapid free water diuresis and overcorrection. Above all, treat the cause, which is what actually resolves it.
Know the Two Look-Alikes
Cerebral salt wasting is hypovolemic, with a high urine output and a genuine negative sodium balance, and it is treated with salt and volume, the opposite of fluid restriction; volume status is the discriminator. Diabetes insipidus is the mirror image: too little ADH or resistance to it, with a high sodium, high output and dilute urine, treated with desmopressin or by removing the renal cause.
Related Topics
HyponatremiaHypernatremiaElectrolyte ReplacementAdrenal CrisisHypercalcemiaIntracerebral Hemorrhage