Asymptomatic fasting-associated ketosis with high-anion-gap metabolic acidosis during phentermine-assisted weight loss: a case report

Introduction Starvation ketoacidosis is an underrecognized cause of high-anion-gap metabolic acidosis that results from prolonged fasting or severe caloric restriction. It is characterized by elevated ketone bodies (especially β-hydroxybutyrate) and euglycemia or hypoglycemia. We report a case of asymptomatic fasting-associated ketosis with high-anion-gap metabolic acidosis, compatible with probable starvation ketoacidosis, discovered in a 59-year-old man undergoing pharmacologically assisted weight loss with phentermine and intermittent fasting. Despite metabolic abnormalities including hyperkalemia (serum potassium of 6.6 mmol/L), high-anion-gap acidosis (anion gap 22 mEq/L), and elevated β-hydroxybutyrate level (3.8 mmol/L), the patient remained clinically well. Sustained caloric and carbohydrate restriction appear to be the primary drivers of the metabolic disturbance, with phentermine as a possible contributing factor through appetite suppression and increased lipolytic substrate availability. A venous blood gas was not obtained, precluding confirmation of acidemia or respiratory compensation; the low bicarbonate value reflects serum total CO₂ from a chemistry panel rather than direct blood gas measurement, and the elevated β-hydroxybutyrate level establishes significant ketogenesis but does not by itself establish ketoacidosis, since ketone concentrations may rise substantially during fasting or carbohydrate restriction. Follow-up biochemical data were also unavailable. The case is therefore best characterized as fasting-associated ketosis with high-anion-gap metabolic acidosis and low serum total CO₂, compatible with probable starvation ketoacidosis. Case presentation A 59-year-old man without a diagnosis of diabetes presented for a routine evaluation while undergoing a medically supervised weight loss regimen including phentermine and intermittent fasting. Despite being clinically asymptomatic, laboratory findings revealed hyperkalemia with serum potassium of 6.6 mmol/L, high-anion-gap metabolic acidosis with an anion gap of 22 mEq/L, and significantly elevated β-hydroxybutyrate level of 3.8 mmol/L. Blood glucose remained within normal limits. The patient was considered to have fasting-associated ketosis with high-anion-gap metabolic acidosis, compatible with probable starvation ketoacidosis, in the setting of aggressive caloric restriction and marked weight loss, with phentermine as a possible amplifying factor. He remained asymptomatic. His hyperkalemia was initially treated with sodium zirconium cyclosilicate and the patient continued phentermine until his subsequent nephrology evaluation, at which time phentermine was discontinued and caloric intake liberalized. Conclusions This case highlights the potential for sympathomimetic weight-loss agents to exacerbate metabolic derangements. It underscores the importance of monitoring acid-base status in patients on phentermine, even in the absence of clinical symptoms. Clinicians should maintain a high index of suspicion for starvation ketoacidosis in patients using weight-loss pharmacotherapy to prevent progression to symptomatic metabolic acidosis. Clinical trial number Not applicable.