Endocrine Abstracts

Introduction: Although the first-line treatment of insulinoma remains to be surgical resection, medical therapy is necessary for non-localizable or non-resectable tumors, poor surgical candidates, or when surgery is declined. We present an interesting case of a patient with well-controlled insulinoma on diazoxide for 5 years who presented acutely with diabetic ketoacidosis (DKA).

Case presentation: A 85-year-old female presented to the Emergency Department with 2 days of severe vomiting associated with poor oral intake, generalized weakness, polydipsia and polyuria. For the last 5 years, she was compliant with low dose diazoxide with generally good control of her insulinoma. There was no fever, diarrhea, or abdominal discomfort. She reported unintentional weight loss over 4–5 months as well as polyuria for about 2–3 weeks. On examination, she was hypotensive and tachypneic but afebrile. With a plasma glucose of 57.9 mmol/l, high anion gap metabolic acidosis (pH 7.17, bicarbonate 9 mmol/l), ketonuria and ketonemia, and a calculated effective serum osmolality of 304 mOsm/kg, she had diabetic ketoacidosis with hypovolemic shock and severe acute kidney impairment (Creatinine 399 umol/l). She was treated with fluids, intravenous insulin, and cessation of diazoxide, leading to resolution of DKA within 2 days, and normalisation of renal impairment after 5 days. There were no clinical evidence of any acute precipitating factors apart from diazoxide use. Further history revealed that she had a recent admission 3 weeks ago for a rare event of symptomatic hypoglycemia despite compliance to diazoxide. Her diazoxide dose was increased from 100 mg to 300 mg, which precipitated hyperglycemia and acute kidney injury. There were no clinical evidence to suggest a metachronus change in the insulinoma to glucagonoma. There was no necrolytic migratory rash, and serum glucagon concentration was appropriately suppressed during hyperglycemia. MRI of the pancreas also showed that the insulinoma was stable in size at 6 mm without new nodules in the pancreas or liver. Her diazoxide dose was reduced to her usual dose and she did not have further recurrence of hyperglycemia at 1 year of review. In view of her old age and comorbidities, she declined surgical intervention for insulinoma

Conclusion: Diazoxide is a non-diuretic renally-cleared benzothiadiazine derivative that binds to ATP-dependent potassium channel on the beta-cell, hence inhibiting calcium influx and exocytosis of insulin. Patients on diazoxide are at risk of DKA and care should be taken to avoid diazoxide toxicity, especially in the elderly.