Seizure in a woman on a thiazide with a sodium of 112
A 72-year-old woman is brought in after a generalised seizure. Three weeks earlier her GP started hydrochlorothiazide 25 mg daily for hypertension; she also takes fluoxetine 20 mg daily and has been drinking more water because of a dry mouth. She is confused but rousable and afebrile. Blood pressure 118/70 mmHg, pulse 84, no postural drop, JVP not raised, mucous membranes moist, no oedema, weight unchanged. Serum sodium 112 mmol/L, potassium 3.4, chloride 78, bicarbonate 24, urea 3.2 mmol/L, creatinine 68 micromol/L, glucose 6.1 mmol/L, serum osmolality 240 mOsm/kg. Urine osmolality 486 mOsm/kg, urine sodium 62 mmol/L. She takes no other diuretic.
1. Interpret these results and state what else you must exclude before accepting a diagnosis of thiazide-induced SIADH.
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These results describe hypotonic hyponatraemia: serum osmolality 240 mOsm/kg, urine osmolality 486 mOsm/kg (inappropriately concentrated), urine sodium 62 mmol/L, and a clinically euvolemic patient with low urea and normal creatinine. That pattern fits SIADH, and the thiazide started three weeks earlier is the likely trigger, with fluoxetine and increased water intake as contributors.
Before accepting that, exclude:
- Hypothyroidism (TSH, free T4) and adrenal insufficiency (9 am cortisol; synacthen if borderline) - both impair free-water clearance.
- Diuretic effect: urine sodium can be high with a thiazide, but the low urea and absence of postural signs argue against true volume depletion. A urine sodium below 30 mmol/L would push towards hypovolaemia.
- Pseudohyponatraemia if lipids or total protein are very high; check them.
- Hyperglycaemia and mannitol as osmotically active causes.
- Renal salt wasting and cerebral salt wasting - unlikely without brain injury or polyuria.
Note that the seizure makes this symptomatic hyponatraemia regardless of the underlying cause. She is not oedematous and has no JVP elevation, so heart failure and cirrhosis are unlikely. The combination of thiazide, SSRI and polydipsia is a classic triad; the pitfall is attributing the urine sodium to SIADH when the thiazide itself is the cause.
2. Outline your immediate and 48-hour management, including the target rate of correction and exactly what you would do if the sodium rose by 12 mmol/L in the first 12 hours.
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Immediate (0–6 hours): This is a medical emergency with seizure. Give 3% hypertonic saline 100–150 mL as an intravenous bolus over 10–20 minutes, aiming for a 4–6 mmol/L rise in serum sodium; repeat once or twice until the seizure stops or sodium reaches about 120 mmol/L. Do not aim for a normal sodium in the first hours.
Then: Stop hydrochlorothiazide and fluoxetine. Fluid-restrict to 800–1000 mL/day once the acute phase is over. Check sodium every 4–6 hours initially, then 12-hourly.
Correction limits: Because the hyponatraemia is chronic (at least three weeks), aim for no more than 8 mmol/L in 24 hours and 16 mmol/L in 48 hours. She has several osmotic demyelination risk factors: age, hypokalaemia and possibly poor nutrition.
If it overcorrects: If sodium rises by 12 mmol/L in the first 12 hours, act immediately: give 5% dextrose with or without desmopressin 1–2 micrograms to re-lower the sodium to the planned trajectory, and involve critical care and nephrology. Do not simply observe.
Other points: Correct potassium cautiously - raising potassium also raises sodium. Avoid vasopressin antagonists in the acute seizure setting. Look for another cause of the seizure if sodium correction does not explain it. The common errors are continuing 3% saline after symptoms resolve, and using normal saline, which can worsen hyponatraemia in SIADH by desalination.