🧠 Key approach: first confirm this is true hypotonic hyponatraemia. Then classify by volume status: hypovolaemic, euvolaemic or hypervolaemic. Always review drugs — thiazides, SSRIs/SNRIs, antiepileptics, antipsychotics, NSAIDs and desmopressin are common culprits.

Category	Mechanism	Common Causes	Drug Causes	Clinical Notes
🧪 Pseudohyponatraemia	Lab artefact: sodium appears low but plasma water sodium is normal	Severe hyperlipidaemia Severe hyperproteinaemia, e.g. myeloma	IV immunoglobulin can contribute via high protein load	Serum osmolality is usually normal. Confirm with direct ion-selective electrode / blood gas sodium if suspected.
🍬 Hypertonic / translocational hyponatraemia	Osmotically active solute pulls water out of cells, diluting serum sodium	Hyperglycaemia Mannitol exposure Radiocontrast exposure	Mannitol Hypertonic glucose infusions SGLT2 inhibitor-related severe hyperglycaemia/DKA context, rarely contributory	Serum osmolality is high. Correct sodium for glucose before treating as true hypotonic hyponatraemia.
💧 Hypovolaemic hypotonic hyponatraemia	Salt and water loss, with relatively more sodium loss; ADH rises because circulating volume is low	Vomiting Diarrhoea GI fistula or stoma losses Burns Pancreatitis Third spacing Adrenal insufficiency Renal salt wasting	Thiazides: bendroflumethiazide, indapamide, hydrochlorothiazide Loop diuretics: furosemide, bumetanide Mineralocorticoid antagonists: spironolactone, eplerenone SGLT2 inhibitors, if dehydrated or unwell Cisplatin Co-trimoxazole / trimethoprim	Thiazides are a classic and common cause, especially in older adults. Check lying/standing BP, U&Es, urine sodium and medication history.
🧠 Euvolaemic hypotonic hyponatraemia — SIADH	Excess ADH causes water retention without obvious oedema	Pneumonia TB Lung cancer, especially small cell CNS infection, stroke, SAH, head injury Postoperative state Pain and nausea HIV	SSRIs: sertraline, citalopram, fluoxetine SNRIs: venlafaxine, duloxetine Tricyclics: amitriptyline Antipsychotics: haloperidol, risperidone, olanzapine, quetiapine Carbamazepine Oxcarbazepine Sodium valproate Lamotrigine, rarely Opioids, especially tramadol NSAIDs PPIs, especially omeprazole/lansoprazole Vincristine Cyclophosphamide MDMA/ecstasy	Diagnose SIADH only after excluding adrenal insufficiency, hypothyroidism, renal failure and diuretic effect. Psychotropic drugs and antiepileptics are well-recognised SIADH causes. :contentReference[oaicite:1]{index=1}
🌊 Euvolaemic hypotonic hyponatraemia — excess water intake	Water intake exceeds renal free-water excretion	Primary polydipsia Psychogenic polydipsia Low solute intake: “tea and toast” diet Beer potomania Excess hypotonic fluid intake	MDMA/ecstasy: ADH release + excess water intake Desmopressin with excess fluid intake Excess IV dextrose or hypotonic fluids	Urine osmolality is often very low in primary polydipsia or low-solute states, unless ADH is also stimulated.
🧬 Euvolaemic hypotonic hyponatraemia — endocrine	Hormone deficiency impairs free-water clearance or reduces effective circulating volume	Adrenal insufficiency Hypopituitarism / ACTH deficiency Severe hypothyroidism	Glucocorticoid withdrawal Ketoconazole, etomidate or immune checkpoint inhibitors causing adrenal insufficiency Amiodarone or lithium causing thyroid disease	Always consider cortisol deficiency in unexplained hyponatraemia. Missing adrenal insufficiency can be dangerous.
🫀 Hypervolaemic hypotonic hyponatraemia	Low effective arterial volume triggers ADH despite total body fluid excess	Heart failure Cirrhosis Nephrotic syndrome Advanced CKD	Overuse of hypotonic IV fluids Diuretics may contribute or complicate interpretation NSAIDs worsen renal water handling	Look for oedema, ascites, raised JVP or pulmonary congestion. Treatment differs from SIADH or dehydration.
🏥 Hospital-acquired / postoperative hyponatraemia	High ADH state plus excess free water	Postoperative pain Nausea Stress response Sepsis Hypotonic fluid administration	IV 5% dextrose Hypotonic maintenance fluids Desmopressin Opioids Antiemetics may contribute indirectly via nausea/ADH context	Common inpatient problem. Check fluid chart carefully before diagnosing SIADH.
👶 Neonatal / paediatric causes	Water excess, renal immaturity, endocrine or congenital disease	Excess hypotonic fluids Gastroenteritis Congenital adrenal hyperplasia Renal tubular disorders SIADH after CNS/pulmonary disease	Hypotonic IV fluids Desmopressin Diuretics	Children are vulnerable to cerebral oedema. Severe or symptomatic hyponatraemia needs urgent senior review.

💊 High-Yield Drug Causes of Hyponatraemia

Drug Group	Examples	Typical Mechanism	Notes
💧 Thiazide / thiazide-like diuretics	Bendroflumethiazide, indapamide, hydrochlorothiazide, chlortalidone	Renal sodium loss + impaired urinary dilution	One of the commonest drug causes; often severe in older adults. Risk is high soon after initiation but can occur later with illness or low intake. :contentReference[oaicite:2]{index=2}
🚽 Loop diuretics	Furosemide, bumetanide	Salt and water loss	Less classic than thiazides but important in frailty, dehydration, HF or over-diuresis.
🧠 Antidepressants	SSRIs, SNRIs, TCAs, mirtazapine	Usually SIADH	SSRIs/SNRIs are common culprits, especially in older adults and soon after starting. Venlafaxine is well recognised.
⚡ Antiepileptics	Carbamazepine, oxcarbazepine, valproate, lamotrigine	SIADH-like effect or increased renal sensitivity to ADH	Oxcarbazepine and carbamazepine are classic causes. Oxcarbazepine often carries higher risk.
🧠 Antipsychotics	Haloperidol, risperidone, olanzapine, quetiapine	SIADH; sometimes polydipsia contributes	Check whether urine is concentrated or very dilute to distinguish SIADH from primary polydipsia.
💊 NSAIDs	Ibuprofen, naproxen, diclofenac	Potentiate renal ADH effect by reducing prostaglandins	Often a contributor, especially with diuretics, CKD, heart failure or frailty.
🌊 Desmopressin	Desmopressin for nocturia, diabetes insipidus, bleeding disorders	Direct ADH analogue → water retention	Can cause profound dilutional hyponatraemia if fluid intake is not restricted.
🩹 Opioids	Morphine, oxycodone, tramadol	ADH stimulation; nausea/pain-related ADH	Tramadol is particularly associated. Postoperative pain and nausea add to risk.
🧪 Chemotherapy	Vincristine, cyclophosphamide, cisplatin	SIADH or renal salt wasting	Cisplatin may cause renal salt wasting; vincristine/cyclophosphamide more classically SIADH.
🧫 Antibiotics / antimicrobials	Co-trimoxazole, trimethoprim, ciprofloxacin, linezolid	Variable: renal salt wasting or SIADH-like effect	Trimethoprim can behave like amiloride, causing natriuresis, hyperkalaemia and hyponatraemia.
🧪 PPIs	Omeprazole, lansoprazole, pantoprazole	Possible SIADH / idiosyncratic	Uncommon but worth considering in unexplained recurrent hyponatraemia in older adults.
🧴 Recreational drugs	MDMA/ecstasy	ADH release + excess water intake	Can cause acute severe hyponatraemia, seizures and cerebral oedema.
💉 IV fluids	5% dextrose, hypotonic maintenance fluids, excess free water	Dilutional hyponatraemia	Important hospital-acquired cause, especially postoperative or high-ADH states.

🚩 Red Flags in Hyponatraemia

🧠 Confusion, seizures, reduced GCS or coma
📉 Sodium <120 mmol/L, or rapid fall in sodium
🤢 Severe nausea, vomiting, headache or agitation
🧬 Suspected adrenal crisis
🏥 Postoperative, paediatric, pregnant or frail older patient
⚠️ Risk of over-correction: alcoholism, malnutrition, liver disease or very low sodium

🎓 Exam Tips

💧 Thiazides are the classic drug cause in older adults.
🧠 SSRIs/SNRIs cause SIADH, especially soon after starting.
⚡ Carbamazepine and oxcarbazepine are classic SIADH-like causes.
🌊 Desmopressin causes water retention and can produce dangerous dilutional hyponatraemia.
🍺 Beer potomania / low solute intake causes impaired free-water excretion despite low ADH.
🧬 Always exclude adrenal insufficiency before confidently diagnosing SIADH.

The content on this website is provided for educational and informational purposes only to support exam preparation (e.g., MLA, MRCP, USMLE) and learning. This is NOT medical advice, diagnosis, treatment, or professional guidance. It does not replace consultation with a qualified healthcare professional, official guidelines (e.g., NICE, GMC, BNF), or supervised clinical practice. Always verify information with current, authoritative sources. Makindo and its contributors accept no liability for any reliance on this content, including errors, omissions, or any resulting harm, loss, or consequences. By using this site, you agree to these terms.

Hyponatraemia ✅

🧂 Causes of Hyponatraemia

💊 High-Yield Drug Causes of Hyponatraemia

🚩 Red Flags in Hyponatraemia

🎓 Exam Tips

Categories