Insulinoma

The main clinical manifestation of an insulinoma is fasting hypoglycemia. Symptoms are insidious and can mimick various central nervous system disorders, like epilepsy and psychiatric disorders [6]. The presentation is characterized by the Whipple triad in many patients which includes:

• Presence of symptoms and signs of hypoglycemia.
• Concomitant low blood sugar. 
• Reversibility of symptoms by glucose administration.

Adrenergic symptoms resulting from the catecholaminergic response include weakness, anxiety, nausea, hunger, sweating, tremor, tachycardia, and palpitations. Neuroglycopenic symtoms oberserved in patients are headache, confusion, lethargy, diplopia, blurred vision, amnesia, seizures and in more severe cases unconsciousness. The symptoms can be aggravated by alcohol intake, exercise, and certain medications.

Physiologically, the blood glucose level is maintained by a negative feedback mechanism. Decrease in blood glucose levels reduces insulin secretion. Inappropriately elevated levels of insulin in the presence of hypoglycemia and serum insulin to plasma glucose ratio > 0.3 (μU/mL)/(mg/dL) are diagnostic of insulinoma. Prolonged (ie, 48 or 72 h) supervised fast in hospitalized patients is the main test in diagnosing the condition. When symptoms of hypoglycemia appear, blood should be sampled and the biochemical diagnosis can be made, if the following parameters are found [7]:

• Blood glucose less than 40 mg/dL 
• C-peptide exceeding 2.5 ng/mL
• Absence of plasma sulfonylurea
• Increased serum insulin level of 10 µU/mL or more
• Increased proinsulin level of ≥25% or ≥22 pmol

After the biochemical diagnosis has been established, imaging studies are used to localize the tumor which is necessary to plan the surgical approach. Helical or multislice CT scan has 82-94% sensitivity, magnetic resonance imaging (MRI) 40-70%. Transabdominal ultrasonography, 111-In-pentetreotide imaging, and fluorine-18-L-dihydroxyphenylalanine positron emission tomography (18F-DOPA PET) are other noninvasive tests. Invasive modalities help to localize the tumor when non-invasive techniques are not sufficient. Endoscopic ultrasonography has up to 90% sensitivity [8], the accuracy of selective arteriography is 82%.

Medical therapy is indicated in patients with malignant insulinomas and in those who are not surgical candidates. Diazoxide, octreotide and lanreotide (somatostatin analogues), verapamil [9] and phenytoin [10] and everolimus are used to treat insulinoma. Experiences with radiotherapy and chemotherapy are limited. Surgical excision of the insulinoma is the definitive treatment and currently the therapy of choice. Enucleation is the treatment option for all benign insulinomas, when technically feasible. For tumors that are anatomically unsuitable for enucleation or multiple tumors, a larger segmental resection of the pancreas, distal pancreatectomy or pancreaticoduodenectomy is performed.

The long-term survival rate of patients with benign insulinoma is normal. In patients with malignant insulinomas, survival is significantly worse. After surgical removal, the long-term risk of recurrence is high in patients with MEN-1 syndrome [4].

Insulinomas can occur sporadically or in association with multiple endocrine neoplasia (MEN)-1 syndrome. MEN-1 syndrome is an autosomal dominant disorder characterized by development of tumors in pituitary, parathyroid gland, pancreas, and the skin. It is associated with mutations in the MEN1 gene mapped to chromosome 11q13 [2] [3] and loss of heterozygosity. Sporadic insulinomas are typically less than 2 cm in diameter and solitary. Insulinomas associated with MEN-1 syndrome develop earlier, are frequently multiple and tend to recur.

The incidence is 3 to 10 cases per 1,000,000, but was reported to be higher in autopsy studies. The median age at diagnosis is approximately 47 years, with a mild female preponderance [4]. 5 to 10% are malignant and 16% of cases are associated with MEN-1 syndrome [5]. The median age at diagnosis of insulinomas in conjunction with MEN-1 syndrome is the mid 20s and malignant insulinomas are seen more frequently in this patient group. Insulinomas have been reported in all ethnic groups.

An insulinoma is a rare pancreatic endocrine tumor, deriving mainly from islet cells, that hypersecretes insulin. Rarely other hormones such as adrenocorticotropic hormone (ACTH), glucagon, gastrin, human chorionic gonadotropin, and somatostatin are produced by the tumor. Malignant tumors are usually larger in size and liver and regional lymph nodes are the most common sites of metastatic spread.

There are no guidelines for the prevention of insulinoma.

An insulinoma is a rare pancreatic endocrine tumor, deriving mainly from islet cells, that produces excessive amounts of insulin. 90-95% of insulinomas are benign. The incidence is 3 to 10 cases per 1,000,000 [1] and the majority of patients are between 30 and 60 years of age. The presentation is characterized by the Whipple triad in many patients which includes:

• Presence of symptoms and signs of hypoglycemia.
• Concomitant low blood sugar. 
• Reversibility of symptoms by glucose administration.

Surgical removal of the tumor is currently the treatment of choice and is curative in most cases. Medical therapy is indicated in patients with malignant insulinomas and in those who are not surgical candidates.

An insulinoma is a rare tumor in the pancreas that secretes insulin. In the majority of cases, the tumor is not cancerous (benign). Insulinomas are rare and tend to affect women more than men. They most frequently are diagnosed in people who are between ages 30 and 60.

The pancreas is an organ located behind the stomach which produces several important hormones, including insulin, glucagon, and somatostatin that control the level of sugar in the blood. When an insulinoma developed in the pancreas, it continues to secrete insulin, even when the blood sugar is too low, a condition called hypoglycemia. Symptoms include double vision, blurred vision, headache, lethargy, confusion, weakness, sweating, hunger, tremors, tremulousness, anxiety, rapid heart rate and in severe cases, seizures and coma.

To make the diagnosis, the doctor will perform a blood test to check blood sugar, insulin levels and several other values. To determine the location and size of the insulinoma, imaging studies will be made. The most common treatment for an insulinoma is surgical removal of the tumor and there are various types of surgery available to remove the insulinoma. If surgery is not possible, medical treatment is necessary.

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