EP1848 - LBA_ECE_1170 - Dual-mechanism life-threatening hyponatraemia: NSAID-induced hyporeninemic hypoaldosteronism unmasking Sheehan's syndrome latent for four decades

Abstract Introduction Severe hyponatraemia refractory to saline resuscitation typically prompts investigation of a single cause. We report the first characterisation of concurrent NSAID-induced hyporeninemic hypoaldosteronism and panhypopituitarism from Sheehan's syndrome, two pathologies that synergised to produce refractory salt-wasting hyponatraemia through dual peripheral and central mechanisms, identifiable through parallel mineralocorticoid and pituitary axis evaluation. Given widespread NSAID use and increasing migrant populations with undiagnosed peripartum pituitary injury across Europe, this combination may be under-recognised. Case Description A 64-year-old woman presented with bilateral lower limb pain, proximal myopathy, weight loss (>7 kg), fatigue and polyuria after three months of NSAID use and recent radiocontrast exposure. She had a prior episode of severe hyponatraemia (Na 112 mmol/L) four years earlier without aetiological workup. Sodium was 121 mmol/L on admission, dropping to 110.8 mmol/L despite 0.9% normal saline 1 litre TDS–QDS and repeated 2.7% hypertonic saline boluses throughout a 32-day admission with 30 days in ICU. Urinary sodium was 160 mmol/L with output peaking at 7185 mL/24 h, representing daily renal sodium losses exceeding 500 mmol. Serum osmolality was 231 mOsmol/kg against inappropriately concentrated urine (656 mOsm/kg) with flat IVC on ultrasound. A desmopressin challenge worsened hyponatraemia (133-123 mmol/L), excluding SIADH and confirming salt-wasting physiology. Results Parallel axis evaluation identified two mechanistically distinct pathologies. Mineralocorticoid axis: aldosterone 39 pg/mL (ref 68-249), renin 3.4 pg/mL (suppressed), ARR 11.47, with hypokalaemia and low bicarbonate at normal anion gap, confirming hyporeninemic hypoaldosteronism. Pituitary axis: fasting cortisol 96 nmol/L, ACTH 12.4 pg/mL (inappropriately low, confirming central aetiology), FT4 4.1 pmol/L (ref 9.8-23), FT3 2.1 pmol/L (ref 4.7-7.2), TSH 0.38 mIU/L (inappropriately low), prolactin 64 mIU/L (low), IGF-1 12 µg/L (ref 36-244). MRI revealed empty sella with tiny residual pituitary. Autoimmune screen was negative. Collateral history uncovered prolonged labour, lactation failure and premature menopause, consistent with Sheehan's syndrome undiagnosed for four decades. This coexistence has not been previously described. Conclusions Fludrocortisone, hydrocortisone and levothyroxine normalised sodium to 136-140 mmol/L. At three-month follow-up, aldosterone normalised (39-158 pg/mL) and fludrocortisone was discontinued, establishing the NSAID-induced component as transient, while permanent pituitary deficiency required ongoing replacement, with complete resolution of myopathy confirming the diagnosis. This case establishes that refractory salt-wasting hyponatraemia can arise from simultaneous peripheral and central endocrine failure, distinguishable only through systematic parallel evaluation of mineralocorticoid and pituitary axis. We propose this approach for any patient with NSAID exposure presenting with unexplained, refractory or recurrent hyponatraemia.