What is the diagnosis and treatment of insulinoma (insulin-producing tumor)?

From the Guidelines

Surgical removal of the tumor is the primary treatment for insulinoma, which is curative in most cases, and before surgery, symptoms can be managed with frequent small meals, avoiding fasting, and medications like diazoxide to inhibit insulin release. Insulinoma is a rare pancreatic tumor that secretes excessive insulin, causing hypoglycemia (low blood sugar) 1. These tumors are typically small, benign, and occur as single growths in the pancreas. Patients experience symptoms of hypoglycemia including confusion, dizziness, sweating, shakiness, and in severe cases, seizures or loss of consciousness.

Diagnosis and Treatment

Diagnosis involves documenting hypoglycemia with inappropriately high insulin levels during a supervised 72-hour fast, followed by imaging studies like CT, MRI, or endoscopic ultrasound to locate the tumor 1. Treatment primarily involves surgical removal of the tumor, which is curative in most cases. The primary treatment for exophytic or peripheral insulinomas is enucleation, which can be performed laparoscopically for localized solitary tumors within the body and tail of the pancreas 1.

Management of Symptoms

Before surgery, symptoms can be managed with frequent small meals, avoiding fasting, and medications like diazoxide to inhibit insulin release 1. Diazoxide has been shown to be effective in controlling hypoglycemic symptoms in patients with insulinoma, with common side effects including fluid retention and hirsutism 1. In cases where surgery isn't possible, medications or targeted therapies may be used for long-term management.

Prognosis

Early diagnosis and treatment are important as these tumors can cause serious neurological damage if hypoglycemic episodes are frequent or severe. Most patients have an excellent prognosis after successful tumor removal, though follow-up is necessary to monitor for recurrence 1.

From the FDA Drug Label

Diazoxide Oral Suspension is indicated for the management of hypoglycemia due to hyperinsulinism associated with the following conditions: Adults: Inoperable islet cell adenoma or carcinoma, or extrapancreatic malignancy.

Infants and Children: Leucine sensitivity, islet cell hyperplasia, nesidioblastosis, extrapancreatic malignancy, islet cell adenoma, or adenomatosis

Insulinoma treatment may involve the use of diazoxide, as it is indicated for the management of hypoglycemia due to hyperinsulinism associated with inoperable islet cell adenoma or carcinoma.

• The drug can be used preoperatively as a temporary measure and postoperatively if hypoglycemia persists.
• Treatment with diazoxide should be considered when other specific medical therapy or surgical management has been unsuccessful or is not feasible 2.

From the Research

Definition and Diagnosis of Insulinoma

• Insulinoma is a rare tumor of the Langerhans islets of the pancreas that produces insulin and causes severe hypoglycemia with neuroglycopenic symptoms 3.
• The diagnosis is based on the presence of Whipple's triad and the result of a fasting test 4, 3.
• Whipple's triad includes symptoms of hypoglycemia, glucose level below 50 mgs/dl, and relief of symptoms by the administration of glucose 4.

Treatment Options for Insulinoma

• Surgery is the ideal treatment of insulinoma and can cure over 90% of benign and single tumors by simple excision 5, 4, 3.
• Systemic therapy may be required to prevent severe preoperative hypoglycaemia, when surgery is contraindicated, delayed, or refused, and in case of unresectable metastatic disease 5.
• Diazoxide is commonly used but is not always effective and can cause serious side effects, while somatostatin analogues (octreotide and lanreotide) may be an alternative option 5, 6.
• Octreotide has been successfully used to treat insulinoma in elderly patients who are unsuitable for surgery, with a single daily dose being effective in some cases 6.

Surgical Management of Insulinoma

• The surgical management of insulinoma involves the diagnosis, localization of the tumor, and treatment, with enucleation being the most frequent type of surgery 4, 3.
• Depending on the location, insulinomas can be enucleated, might require partial or distal pancreatectomy, or pancreaticoduodenectomy 4.
• Complications such as abscesses and pancreatic fistula can occur, with a frequency of 18% in some studies 3.

Medical Management of Insulinoma

• Conservative treatment with drugs targeting insulin-induced hypoglycemia is an option for patients who are not suitable for surgery or have unresectable metastatic disease 7.
• Somatostatin analogues have been shown to be effective in controlling hypoglycemia in patients with insulinoma, with lanreotide being a safe and well-tolerated option in some cases 5.