From the Guidelines
Insulinoma is diagnosed using the Whipple triad, which consists of three criteria: documented hypoglycemia, symptoms of hypoglycemia during hypoglycemic episodes, and relief of symptoms after glucose administration, as supported by the most recent guidelines 1. The diagnostic criteria for insulinoma include:
- Documented hypoglycemia (blood glucose <50 mg/dL)
- Symptoms of hypoglycemia during hypoglycemic episodes
- Relief of symptoms after glucose administration To confirm the diagnosis, a 72-hour supervised fast is the gold standard test, during which blood samples are collected to measure glucose, insulin, C-peptide, and proinsulin levels when symptoms occur or glucose drops below 45 mg/dL, as recommended by recent studies 1. Inappropriately elevated insulin (≥3 μU/mL) and C-peptide (≥0.6 ng/mL) levels during hypoglycemia strongly suggest insulinoma. Management primarily involves surgical resection of the tumor, which is curative in about 90% of cases, with enucleation being the primary treatment for exophytic or peripheral insulinomas, and pancreatoduodenectomy or distal pancreatectomy being considered for tumors in the head or body/tail of the pancreas, respectively 1. Preoperative localization using CT, MRI, endoscopic ultrasound, or selective arterial calcium stimulation testing helps guide surgical approach. For patients who are not surgical candidates or with metastatic disease, medical management includes diazoxide (200-600 mg/day in divided doses) to inhibit insulin release, frequent small meals, and avoiding fasting, as well as somatostatin analogs (octreotide 50-200 μg subcutaneously three times daily), glucocorticoids, and in malignant cases, chemotherapy with streptozocin and doxorubicin 1. Patients should be educated about hypoglycemia symptoms and carry glucose tablets or glucagon for emergency use. Some key points to consider in the management of insulinoma include:
- The use of somatostatin analogs should be done with caution in patients with insulinoma, as they may transiently worsen hypoglycemia 1
- Everolimus and sunitinib may be considered for the treatment of advanced or metastatic disease 1
- Hepatic regional therapy, such as arterial embolization or chemoembolization, may be considered for patients with liver metastases 1
From the Research
Diagnostic Criteria for Insulinoma using Whipple Triad
- The Whipple triad is a diagnostic criterion for insulinoma, consisting of:
- Biochemical diagnosis of insulinoma can be made by demonstrating hyperinsulinism during a spontaneous hypoglycemic episode or during a supervised fast, which may be prolonged up to 72 hours 6
- A 72-hour fasting test can be used to investigate potential endogenous causes of excessive insulin production, and laboratory results can indicate a notable rise in C peptide and insulin levels, alongside beta hydroxybutyrate suppression, which fulfills the diagnostic criteria for insulinoma 5
Management of Insulinoma
- Supportive measures and somatostatin receptor ligands can be used to control hypoglycemia 2
- For single solitary insulinomas, curative surgical excision remains the treatment of choice 2, 3, 4
- In aggressive malignant cases, debulking procedures, somatostatin receptor ligands, peptide receptor radionuclide therapy, everolimus, sunitinib, and cytotoxic chemotherapy can be valuable options 2
- Medical management with diazoxide and octreotide can be considered for recurrent hypoglycemia in the preoperative period and in patients with unresectable or metastatic tumors 5
- Localization of the insulinoma and exclusion or confirmation of metastatic disease can be done using computed tomography, endoscopic ultrasound, or magnetic resonance imaging, and glucagon-like peptide 1 receptor positron emission tomography/computed tomography or positron emission tomography/magnetic resonance imaging can be used for seemingly occult, indolent, localized insulinomas 2, 6