Endocrinology: Sodium and Water disorders (Complete)

• Basics: Sodium and Water Balance
• Low sodium: Hyponatraemia: Approach | Severe Hyponatraemia: Treatment | SIADH | Other Causes of Hyponatraemia | Osmotic Demyelination
• High sodium and polyuria: Hypernatraemia | Polyuria: Diagnostic Approach | AVP Deficiency (Cranial DI) | AVP Resistance (Nephrogenic DI)
• Revision: Drug Reference Table | Spot the Diagnosis | Exam-style Scenarios | Key Points | Guidelines and Further Reading

💧 Sodium and water disorders are among the commonest problems in hospital medicine. The plasma sodium mostly reflects water balance, controlled by thirst and arginine vasopressin (AVP). This chapter covers hyponatraemia, SIADH, hypernatraemia and the polyuric states AVP deficiency and AVP resistance.
Your four questions for every patient: How unwell is the patient, and how fast did this happen? Is the patient dry, normal or overloaded? What do the plasma and urine osmolality and urine sodium show? How fast is it safe to correct?

Sodium and Water Balance

The key idea: The plasma sodium concentration mostly reflects water balance, not sodium balance. A low sodium usually means too much water relative to sodium; a high sodium usually means too little water.

• Water balance is controlled by:
  • Thirst.
  • Arginine vasopressin (AVP, also called antidiuretic hormone, ADH). Made in the hypothalamus and released from the posterior pituitary when plasma osmolality rises (or blood volume falls). It inserts water channels (aquaporin-2) into the collecting duct, so the kidney retains water and the urine is concentrated.
• Sodium (volume) balance is controlled by the renin–angiotensin–aldosterone system and natriuretic peptides. It determines whether the patient is dry, normal or overloaded.
• Plasma osmolality (normal about 275–295 mOsm/kg) is roughly 2 × Na + glucose + urea.
• Big volume loss overrides osmolality: Severe volume depletion triggers AVP release even when sodium is low. This is why vomiting, heart failure and cirrhosis cause hyponatraemia.

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Hyponatraemia: Approach

Definition: Sodium below 135 mmol/L. Mild: 130–134. Moderate: 125–129. Profound: below 125.

It is the commonest electrolyte disorder in hospital, especially in older people.

Step 1 - Is it urgent? Look at the symptoms, not just the number:

• Severe symptoms - emergency treatment:
  • Vomiting. Seizures. Reduced consciousness (GCS 8 or below).
  • Cardiorespiratory distress.
• Moderate symptoms: Nausea, confusion, headache.
• Chronic, mild: Unsteadiness, falls, poor concentration. Even mild chronic hyponatraemia increases falls and fractures.
• Speed of onset: Acute (under 48 hours - e.g. post-op, marathon runners, MDMA) is more dangerous to the brain, but safer to correct quickly.

Step 2 - Check plasma osmolality to confirm true (hypotonic) hyponatraemia:

• Normal osmolality - pseudohyponatraemia: Very high lipids or protein (e.g. myeloma).
• High osmolality: Very high glucose (or mannitol) pulls water out of cells and dilutes sodium.

Step 3 - Urine osmolality: Below 100 mOsm/kg: The kidney is correctly making dilute urine, so the problem is too much water intake - primary polydipsia, "tea and toast", beer potomania.

Step 4 - Urine sodium and volume status (urine sodium is unhelpful on diuretics):

• Urine sodium below 30 mmol/L - kidneys holding on to sodium:
  • Hypovolaemic: Vomiting, diarrhoea, burns, poor intake.
  • Hypervolaemic: Heart failure, cirrhosis, nephrotic syndrome.
• Urine sodium above 30 mmol/L:
  • Hypovolaemic: Diuretics (especially thiazides), adrenal insufficiency (mineralocorticoid deficiency), salt-wasting kidney disease, cerebral salt wasting.
  • Euvolaemic: SIADH, hypothyroidism (severe), glucocorticoid deficiency.

Baseline tests:

• Plasma and urine osmolality.
• Urine sodium - taken before giving fluids.
• U&E, glucose, lipids. TSH.
• 9 am cortisol (or a short Synacthen test).
• Medication review.

💡 Clinical Pearl: Always exclude adrenal insufficiency before diagnosing SIADH. Missed Addison's or hypopituitarism can kill, and its biochemistry can look exactly like SIADH.

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Severe Hyponatraemia: Treatment

Severe symptoms (seizures, reduced consciousness, vomiting, cardiorespiratory distress) - Society for Endocrinology emergency guidance:

• Hypertonic saline: 150 mL of 2.7% or 3% sodium chloride IV over 15–20 minutes.
• Check sodium at 20 minutes, and repeat the bolus (up to 3 boluses in total) until symptoms improve or sodium has risen by 5 mmol/L.
• Manage in HDU or ICU, with senior input.
• Correction limit: No more than 10 mmol/L in the first 24 hours, and 8 mmol/L in each 24 hours after that.
• High risk of osmotic demyelination - aim for about 4–6 mmol/L a day and no more than 8 mmol/L in 24 hours. High-risk patients have: Alcohol misuse. Malnutrition. Hypokalaemia. Liver disease. Sodium below 120 mmol/L.
• Monitoring: Check sodium every 4–6 hours, and more often initially. Keep a fluid balance chart and measure urine output.

Overcorrection: Watch for a sudden high urine output (water diuresis) once the cause is removed - e.g. stopping a thiazide, or giving fluids to someone who was dry. If sodium rises too fast:

• Stop the hypertonic or isotonic fluids. Give 5% glucose.
• Consider IV desmopressin (e.g. 1–2 micrograms), with specialist advice, to bring sodium back down.

Moderate or chronic hyponatraemia: Treat the cause and correct slowly.

• Hypovolaemic: 0.9% saline.
• Hypervolaemic: Fluid restriction, and optimise heart, liver or kidney treatment.
• SIADH: Fluid restriction.
• Stop offending drugs.

⚠️ Safety Pearl: The danger in chronic hyponatraemia is usually the treatment, not the sodium. Over-rapid correction can cause osmotic demyelination, which is often irreversible.

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SIADH

Mechanism: Syndrome of inappropriate antidiuresis - AVP is released (or acts) despite low osmolality. The kidney keeps water, so sodium is diluted. Sodium excretion carries on normally, so the patient is euvolaemic.

Diagnostic criteria:

• Plasma osmolality below 275 mOsm/kg.
• Urine osmolality above 100 mOsm/kg - inappropriately concentrated.
• Urine sodium above 30 mmol/L on a normal salt and water intake.
• Clinically euvolaemic. No recent diuretics.
• Normal thyroid and adrenal function.

Causes:

• Drugs - the commonest cause in practice:
  • SSRIs, SNRIs, tricyclics. Carbamazepine, oxcarbazepine, sodium valproate.
  • Antipsychotics. PPIs. Opioids. Cyclophosphamide, vincristine, cisplatin. MDMA.
• Lung: Pneumonia, TB, abscess, positive pressure ventilation.
• Brain: Meningitis, encephalitis, subarachnoid haemorrhage, head injury, stroke, tumours.
• Cancer: Small cell lung cancer (ectopic AVP), head and neck, pancreatic and others.
• Other: Post-operative state, pain, nausea, HIV, acute porphyria. Idiopathic in older people - a diagnosis of exclusion; consider imaging for occult malignancy.

Management:

• Treat the cause and stop offending drugs.
• Fluid restriction - typically 500–1,000 mL a day. Less likely to work if urine osmolality is above about 500 mOsm/kg, or if urine Na + K is greater than plasma Na.
• If fluid restriction fails or is impractical:
  • Oral urea (e.g. 15–30 g daily), which causes an osmotic water loss.
  • Tolvaptan (a vasopressin V2 receptor antagonist, specialist). Start in hospital at a low dose (7.5–15 mg), with frequent sodium checks because of the risk of overcorrection. Avoid in liver disease (hepatotoxicity).
• Severe symptoms: Hypertonic saline, as for severe hyponatraemia.

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Other Causes of Hyponatraemia

• Thiazide diuretics: A very common cause, especially in older women. Can develop at any time, but often within weeks of starting. Stop the drug. Do not rechallenge if it was severe. Correct cautiously - sodium may rise rapidly once the thiazide is stopped and the patient is rehydrated.
• Hypovolaemia (vomiting, diarrhoea, poor intake): Dry patient, low urine sodium (unless renal or adrenal loss). Give 0.9% saline. Watch for rapid correction once volume is restored, because AVP is then switched off.
• Heart failure, cirrhosis, nephrotic syndrome: Overloaded, with low effective circulating volume. Fluid restriction; optimise disease treatment; review diuretics. Hyponatraemia here is a marker of poor prognosis.
• Adrenal insufficiency:
  • Primary (Addison's): Low aldosterone causes salt wasting, hypovolaemia and often high potassium.
  • Secondary (pituitary): Cortisol deficiency causes an SIADH-like picture.
  • Hydrocortisone corrects it - sometimes rapidly.
• Severe hypothyroidism: A rare cause, usually only in myxoedema.
• Low solute intake ("tea and toast", beer potomania): Not enough solute to excrete water, so urine osmolality is low. Correction can be very rapid once eating starts.
• Primary polydipsia: Psychiatric illness, very high water intake. Urine osmolality below 100 mOsm/kg.
• Exercise-associated: Endurance athletes drinking too much water.
• Cerebral salt wasting: After subarachnoid haemorrhage or neurosurgery. The patient is volume-depleted (unlike SIADH). Treat with saline (and fludrocortisone) - not fluid restriction.

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Osmotic Demyelination

• Mechanism: In chronic hyponatraemia, brain cells adapt by losing solutes. Correcting sodium too quickly draws water out of the cells, damaging myelin - classically in the pons (central pontine myelinolysis), and sometimes elsewhere.
• Clinical pattern:
  • Often a delay of 2–6 days after correction.
  • Dysarthria and dysphagia. Spastic quadriparesis.
  • Behavioural change. Reduced consciousness. "Locked-in syndrome".
• Diagnosis: MRI may lag behind symptoms by up to 2 weeks.
• Prevention: Respect the correction limits (10 mmol/L in 24 hours, or 8 if high risk). Monitor sodium closely. Re-lower sodium early if overcorrected.
• Outcome: Treatment is supportive. Some recover, but many are left with permanent disability.

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Hypernatraemia

Mechanism: Sodium above 145 mmol/L, almost always because the patient has lost water (or not drunk enough) and cannot respond to thirst. The usual patients are older, frail or confused people, ICU patients, and infants.

Causes:

• Poor water intake: Dementia, stroke, sedation, no access to water.
• Water loss: Fever. Diarrhoea and vomiting. Burns. Osmotic diuresis - hyperglycaemia, urea after relief of obstruction or high-protein feeds.
• AVP deficiency or resistance (diabetes insipidus).

Clinical pattern:

• Thirst - if able to feel it. Lethargy, confusion, weakness.
• Seizures and coma when severe. Rapid rises can tear cerebral veins, causing haemorrhage.

Management:

• Replace water: Orally or by NG tube where possible, otherwise IV 5% glucose.
• If hypovolaemic or shocked: 0.9% saline first to restore circulation.
• Lower sodium slowly in chronic hypernatraemia: No more than about 10 mmol/L in 24 hours (about 0.5 mmol/L per hour). Faster correction risks cerebral oedema.
• Check sodium every 4–6 hours. Treat the cause.
• Consider AVP deficiency if urine is dilute despite high sodium.

💡 Clinical Pearl: Hypernatraemia in a hospital patient is usually a sign of poor access to water. Making sure frail patients can reach and drink water is basic but vital care.

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Polyuria: Diagnostic Approach

Definition: Urine output above about 3 L a day in adults. First exclude:

• Diabetes mellitus - glucose. Hypercalcaemia. Hypokalaemia.
• Diuretics. Recovery from AKI or obstruction.

The three main causes of dilute (hypotonic) polyuria:

• AVP deficiency (formerly cranial diabetes insipidus) - not enough AVP.
• AVP resistance (formerly nephrogenic diabetes insipidus) - the kidney does not respond.
• Primary polydipsia - drinking too much, so AVP is appropriately switched off.

The old terms were renamed in 2022 to avoid confusion with diabetes mellitus.

Clues:

• High-normal or high sodium: Favours AVP deficiency or resistance.
• Low-normal sodium: Favours primary polydipsia.
• Sudden onset and nocturia (or a cold water preference): Suggests AVP deficiency.

Tests (specialist):

• Water deprivation test - no fluids for up to 8 hours, monitoring weight, sodium and osmolality, then desmopressin:
  • Urine concentrates normally (above about 600–750 mOsm/kg) with deprivation: Primary polydipsia.
  • Urine stays dilute, then concentrates after desmopressin: AVP deficiency.
  • Urine stays dilute even after desmopressin: AVP resistance.
  Stop the test if the patient loses more than 3% of body weight or sodium rises above 145–150 mmol/L.
• Copeptin (a stable marker of AVP release) is increasingly used:
  • A high baseline copeptin (above about 21 pmol/L) indicates AVP resistance.
  • Hypertonic saline- or arginine-stimulated copeptin tests separate AVP deficiency from primary polydipsia more accurately than water deprivation.
• If AVP deficiency is confirmed: Pituitary MRI and anterior pituitary function tests.

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AVP Deficiency (Cranial DI)

Causes:

• Pituitary or hypothalamic surgery - often transient. A "triphasic" pattern may occur: polyuria, then SIADH, then permanent polyuria.
• Head injury, subarachnoid haemorrhage.
• Tumours - craniopharyngioma, germinoma, metastases (breast, lung). Pituitary adenomas rarely cause it before surgery.
• Infiltration - Langerhans cell histiocytosis, sarcoidosis, hypophysitis, IgG4 disease.
• Infection - meningitis.
• Genetic - familial; Wolfram syndrome (DIDMOAD): diabetes insipidus, diabetes mellitus, optic atrophy, deafness.
• Idiopathic - possibly autoimmune.

Treatment: Desmopressin (a synthetic AVP analogue, DDAVP):

• Doses: Oral 100–200 micrograms two to three times daily (the range varies widely), sublingual, intranasal, or 1–2 micrograms SC or IV.
• Main risk: Hyponatraemia from water overload. Patients should drink only to thirst. A weekly delayed dose allows a "breakthrough" diuresis.
• Monitoring: Check sodium regularly.
• Adipsic AVP deficiency (no thirst): Very difficult. Patients need fixed fluid intake and daily weighing.

⚠️ Safety Pearl: Never omit desmopressin in a patient with AVP deficiency, especially if they are nil by mouth or unable to drink. Missed doses have caused severe hypernatraemia and death (NHS patient safety alert). Give it by another route and monitor sodium and fluid balance.

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AVP Resistance (Nephrogenic DI)

• Mechanism: The kidney fails to respond to AVP.
• Causes:
  • Lithium - the commonest acquired cause. It can persist after stopping.
  • Hypercalcaemia. Hypokalaemia. Demeclocycline.
  • Relief of urinary obstruction. CKD, sickle cell disease.
  • Inherited: X-linked AVPR2 receptor mutations (boys) or aquaporin-2 mutations.
• Tests: Urine stays dilute despite desmopressin; copeptin is high.
• Management:
  • Correct calcium or potassium. Review lithium (with psychiatry).
  • Adequate water intake.
  • Low salt and low protein diet.
  • Thiazide diuretics - these paradoxically reduce urine volume, by causing mild volume depletion and increasing water reabsorption earlier in the nephron.
  • NSAIDs (e.g. indometacin) in some cases.
  • Amiloride for lithium-induced AVP resistance.

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Drug Reference Table

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Spot the Diagnosis

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Exam-style Scenarios

1. An 80-year-old woman on indapamide is confused. Sodium is 114 mmol/L; she has vomited and had a seizure.
Answer: Severe symptomatic hyponatraemia.

• 150 mL of 3% saline over 15–20 minutes, recheck, and repeat up to 3 times until a 5 mmol/L rise.
• HDU care.
• Stop the thiazide.
• She is at high risk of osmotic demyelination and of rapid self-correction after the thiazide is stopped - limit the rise to 8 mmol/L in 24 hours and monitor urine output.

2. A 66-year-old smoker has sodium 124 mmol/L, is clinically euvolaemic, plasma osmolality 258, urine osmolality 520, urine sodium 55.
Answer: Picture of SIADH.

• Check TSH and cortisol before confirming it.
• Review drugs.
• Chest X-ray (small cell lung cancer).
• Fluid restriction; oral urea or tolvaptan if it fails.

3. A man is nil by mouth after a hip fracture. He has AVP deficiency after craniopharyngioma surgery, and his sodium has risen to 156.
Answer: Missed desmopressin.

• Give desmopressin by an alternative route (SC or IV).
• IV 5% glucose, lowering sodium by no more than about 10 mmol/L in 24 hours.
• Strict fluid balance, and endocrinology input.

4. A 40-year-old woman passes 6 L of urine a day. Sodium is 136 and urine is dilute. Glucose and calcium are normal.
Answer: Hypotonic polyuria - distinguish AVP deficiency, AVP resistance and primary polydipsia.

• Low-normal sodium favours primary polydipsia.
• Water deprivation test or stimulated copeptin test.
• Pituitary MRI if AVP deficiency is confirmed.

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Key Points

• Plasma sodium mostly reflects water balance, not total body sodium.
• Hyponatraemia: assess symptoms first. Severe symptoms need 3% saline.
• Never correct faster than 10 mmol/L in 24 hours (8 if high risk). Watch for a water diuresis.
• Confirm true hyponatraemia with plasma osmolality; use urine osmolality and sodium (taken before fluids) and volume status to find the cause.
• Exclude adrenal insufficiency and hypothyroidism before diagnosing SIADH.
• Drugs (thiazides, SSRIs, carbamazepine, PPIs) are the commonest reversible causes.
• Hypernatraemia usually means lack of access to water. Lower it slowly.
• Never omit desmopressin in AVP deficiency.

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Guidelines and Further Reading

• Society for Endocrinology: Emergency endocrine guidance - acute hyponatraemia; AVP deficiency (cranial diabetes insipidus)
• European Clinical Practice Guideline on diagnosis and treatment of hyponatraemia (ESE/ESICM/ERBP)
• NHS patient safety alert: risk of severe harm and death from withholding or missing desmopressin in cranial diabetes insipidus
• Name change: "Changing the name of diabetes insipidus" - joint international statement (2022)
• BNF / BNFc - for current doses

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