What is the diagnosis and treatment for Insulinoma (Islet cell tumor)?

From the Guidelines

Surgical removal of the tumor is the primary treatment for insulinoma, which is curative in about 90% of cases. The management of insulinoma involves a multidisciplinary approach, including medical management, surgical intervention, and monitoring for recurrence. Before surgery, patients should manage symptoms by eating small, frequent meals high in complex carbohydrates and avoiding fasting. Medical management includes diazoxide (starting at 50-100mg three times daily and titrating up to 300-600mg daily) to inhibit insulin release, as recommended by the National Comprehensive Cancer Network 1.

For severe hypoglycemic episodes, immediate treatment with oral glucose (15-20g) or intravenous dextrose is necessary, followed by glucagon (1mg intramuscularly or subcutaneously) if unresponsive. Most insulinomas are benign (90%), but all require treatment due to the dangerous hypoglycemia they cause. Diagnosis typically involves documenting Whipple's triad (low blood glucose, hypoglycemic symptoms, and symptom relief with glucose administration) and confirming inappropriate insulin secretion through specialized testing, such as serum insulin, proinsulin, and C peptide levels 1.

Localization of the tumor using CT, MRI, endoscopic ultrasound, or selective arterial calcium stimulation is essential before surgical intervention. The surgical management of insulinomas involves enucleation, which can be performed laparoscopically for localized solitary tumors within the body and tail of the pancreas, as reported in a study published in the Journal of the National Comprehensive Cancer Network 1. Regular follow-up is important to monitor for recurrence, especially in cases of malignant insulinoma. Preoperative management includes stabilizing glucose levels with diet and/or diazoxide, and everolimus can also be considered in this scenario, as recommended by the National Comprehensive Cancer Network 1.

Some key points to consider in the management of insulinoma include:

• The use of octreotide or lanreotide should be avoided in patients with insulinoma, as they can precipitously worsen hypoglycemia, unless somatostatin scintigraphy is positive 1.
• Patients who might require splenectomy should receive preoperative trivalent vaccine (ie, pneumococcus, haemophilus influenzae b, meningococcus group c) 1.
• The diagnosis of insulinoma can be challenging, and a 48- to 72-hour observed or inpatient observed fast may be helpful in confirming the diagnosis, as reported in a study published in the Journal of the National Comprehensive Cancer Network 1.

From the FDA Drug Label

In patients with insulinoma, administration may produce an initial increase in blood glucose; however, Glucagon for Injection may stimulate exaggerated insulin release from an insulinoma and cause hypoglycemia. Insulinoma ( 4)

• Insulinoma is a contraindication for the use of Glucagon for Injection.
• The use of Glucagon for Injection in patients with insulinoma may stimulate exaggerated insulin release, leading to hypoglycemia.
• If a patient develops symptoms of hypoglycemia after a dose of Glucagon for Injection, give glucose orally or intravenously 2.

From the Research

Definition and Symptoms of Insulinoma

• Insulinoma is a rare neuroendocrine tumor that causes oversecretion of insulin, leading to symptoms of hypoglycemia 3.
• Common autonomic symptoms of insulinoma include diaphoresis, tremor, and palpitations, whereas neuroglycopenenic symptoms include confusion, behavioral changes, personality changes, visual disturbances, seizure, and coma 4.

Diagnosis of Insulinoma

• Diagnosis of suspected cases is based on standard endocrine tests, especially the prolonged fasting test 4.
• Non-invasive imaging procedures, such as computed tomography and magnetic resonance imaging, are used when a diagnosis of insulinoma has been made to localize the source of pathological insulin secretion 4.
• Invasive modalities, such as endoscopic ultrasonography and arterial stimulation venous sampling, are highly accurate in the preoperative localization of insulinomas and have frequently been shown to be superior to non-invasive localization techniques 4.

Management and Treatment of Insulinoma

• A high proportion of patients with insulinomas can be cured with surgery 4.
• In patients with malignant insulinomas, an aggressive medical approach, including extended pancreatic resection, liver resection, liver transplantation, chemoembolization, or radiofrequency ablation, is recommended to improve both survival and quality of life 4.
• Management includes conservative treatment with drugs targeting insulin-induced hypoglycemia, non-operative invasive procedures, as well as curative open or laparoscopic tumor resection 5.
• The use of a factory-calibrated continuous glucose monitoring system is useful for evaluating the course of medical treatment, monitoring hypoglycemic episodes during the diagnostic period, detecting unconscious hypoglycemia, monitoring the response to medical treatment, and treating insulinoma after surgery 6.

Treatment Options for Hypoglycemia

• Pharmacological management including diazoxide, somatostatin receptor antagonists (SSAs), everolimus and glucocorticoids, in addition to other therapeutic interventions such as peptide receptor radionuclide therapy (PRRT) and endoscopic ablation 7.
• Nutritional management of hypoglycemia, including the use of cornstarch products and artificial nutrition 7.