Beyond the Liver: Diuretic-Induced Hyperammonemia in Patients Without Cirrhosis: A Case Series
DOI:
https://doi.org/10.68163/ptr.2026.73Keywords:
Diuretics, hepatic encephalopathy, Hyperammonemia, non-cirrhoticAbstract
Background and Objective: Hyperammonemic encephalopathy is conventionally attributed to hepatic failure, inherited urea-cycle defects, or portosystemic shunting. Diuretic therapy, widely used for hypertension, heart failure and fluid overload, is a less recognized trigger that can increase serum ammonia levels through mechanisms unrelated to the severity of underlying liver disease. We describe three such cases and examine their implications for clinical recognition.
Materials and Methods: We conducted a retrospective review of three patients who developed hyperammonemia temporally associated with diuretic therapy, identified through pharmacovigilance reporting and clinical evaluation.
Results: We report three elderly women, aged 68-72 years, with hypertension and cardiometabolic comorbidities but no documented chronic liver disease, who developed hyperammonemia temporally associated with diuretic use. The implicated regimens included a combination of hydrochlorothiazide, torsemide and spironolactone; spironolactone monotherapy and torsemide monotherapy. Clinical presentations varied widely, ranging from altered sensorium accompanied by diarrhea and generalized weakness, to progressive breathlessness with pedal edema, to sudden eyelid myoclonus with high-grade fever, none of which was initially suggestive of hyperammonemia. Serum ammonia concentrations ranged from 110 to 153 mcg/dL. Two patients recovered following diuretic withdrawal, whereas the third did not survive despite similar management.
Conclusion: Diuretic-induced hyperammonemia is not restricted to loop or thiazide diuretics and can occur with potassium-sparing therapy alone. A low threshold for ammonia testing may therefore be warranted in diuretic-treated patients presenting with unexplained neurological, respiratory, or systemic symptoms, irrespective of hepatic status.
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Data Availability Statement
The datasets analyzed during the current study are available from the corresponding author on reasonable request.
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Copyright (c) 2026 Ashish D. Rajput, Priyanka R. Diwan , Sapna D. Gupta , Supriya D. Malhotra
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This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
