SAT-LB303 Severe Refractory Volume Overload With Diazoxide in the Treatment of Insulinoma

Background: Insulinoma is the most common neuroendocrine tumor (NET), occurring in 1-4 people per million. Surgical resection remains standard of care for symptomatic control and long-term remission. Where surgery is not feasible medical therapy with diazoxide and somatostatin analogues is used as supportive management. Case: A 88-year-old male with background hypertension, remote myocardial infarct and chronic kidney disease (CKD) (Cr 130-150 umol/L; N 60-115) was diagnosed with insulinoma following a presentation for confusion and CBG of 0.9 mmol/L. Diagnosis was confirmed by 72 hour fast with inappropriate insulin (85 pmol/L; N&lt95) and elevated c-peptide (1875 pmol/L; N 325-1090) with documented hypoglycemia (2.8 mmol/L). CT abdomen localized a 1.2 cm exophytic lesion in the pancreatic tail suggestive of insulinoma. Normal morning cortisol (547 nmol/L) excluded adrenal insufficiency. Initial management included resuscitation with dextrose infusions. Due to advanced age and high cardiac risk profile, the patient was not a candidate for surgical resection of the NET. Endoscopic ultrasound (EUS) ablation was deferred at time of initial hospitalization due to stabilization of hypoglycemia with high glycemic diet. An episode of nocturnal hypoglycemia prompted initiation of diazoxide 100 mg as an outpatient. Subsequent dyspnea (NYHA IV) developed and acute on chronic kidney injury (peak Cr 416 umol/L) with evidence of anasarca secondary to diazoxide use prompted readmission to hospital. With conversion to octreotide, discontinuation of diazoxide and treatment with multiple diuretics, volume overload did not improve. The patient was deemed not a candidate for intermittent hemodialysis and the decision was made to change goals of care. The patient died of complications of volume overload from cardiorenal syndrome 21 days after the initiation of diazoxide. Conclusion: Volume overload has been documented as a complication of diazoxide use in both hypoglycemia and hypertension, occurring in up to 50% of cases, however mortality is not common with supportive management.(1, 2) Risk factors for refractory volume overload appear to include reduced ejection fraction, extremes of age and history of CKD(3). Possible mechanisms for acute decompensation in CKD include increased unbound diazoxide levels, prerenal effect from hypotension and sodium retention(4,5). This case highlights the need for close monitoring with diazoxide use in high risk patients. Clinicians should consider echocardiogram, close monitoring of clinical volume status and renal parameters. References: 1) Goode PN. (1986). World J Surg 10: 586. 2) Komatsu Y. (2016) Endocr J. 63(3): 311. 3) Tarçin O. (2018). Endocrine Abstracts56 EP4. 4) Pearson RM. (1977) Clinical Pharmacokinetics vol 2: 198. 5) Allen WR. (1983). Pharmacology 27: 336.