Insulinoma
Section snippets
Historical background
Paul Langerhans, while a medical student, first described pancreatic islet cells in 1869.2 Several decades later, in 1922, Banting and Best isolated insulin, or “isletin,” as they called it, from a solution extract of a dog's pancreas. One year later, in 1923, Harris suggested a clinical possibility of hyperinsulinism and contrasted it with the hypoinsulinism of diabetes.2 His suspicion was confirmed the following year, when several case reports of patients with symptomatic hyperinsulinism were
Sporadic versus multiple endocrine neoplasia type 1
Insulinoma can occur sporadically, or it can be associated with multiple endocrine neoplasia type 1 (MEN-1). MEN-1 syndrome is an autosomal dominant condition that occurs as a result of inactivating mutations of the MEN1 gene located on chromosome 11.4 This syndrome is characterized by primary hyperparathyroidism, anterior pituitary adenomas, and tumors of the endocrine pancreas and duodenum. The most common functioning islet cell tumors in MEN-1 are gastrinomas and insulinomas.4
Insulinoma
Diagnosis
As described by “Whipple's triad,” hypoglycemia and neuroglycopenic symptoms that are corrected by the administration of carbohydrate are the hallmarks of the diagnosis of insulinoma. Inappropriately elevated insulin levels cause hypoglycemic episodes characterized by neuroglycopenic symptoms and sympathetic overdrive (Table 1). These symptoms are typically precipitated by fasting or exercise, but can also occur postprandially, or have no relationship to eating.7
Neuroglycopenic symptoms vary in
Localization
After establishing a diagnosis of insulinoma, a variety of imaging modalities with different sensitivities can localize the tumor. The role of preoperative imaging is 2-fold. First, imaging is used to evaluate for evidence of metastatic disease; second, localization can better facilitate discussions with the patient with regard to extent and type of operation. Because virtually all sporadic insulinomas are small and intrapancreatic, preoperative localization fails 10% to 27% of the time.13 The
Medical Management
For patients who are not surgical candidates or those who are waiting for an operation, several measures can be taken to manage the symptoms, including dietary modification and pharmacologic agents. Dietary modification includes consumption of frequent, small meals throughout the day and middle of the night to avoid symptomatic hypoglycemia. The initial drug of choice, and the most well studied, is diazoxide, a benzothiadiazide. Diazoxide directly inhibits insulin release from β cells via
Metastatic disease
The documentation of metastatic disease, either at the time of surgery or by imaging studies, is the only accurate means of diagnosing a malignant insulinoma. Metastases predominantly present in the liver or lymph nodes but can also be found in the bone and peritoneal tissue, resulting in uncontrolled insulin secretion.33, 34 Life-threatening and debilitating hypoglycemia can occur from these hormone active lesions.33, 35, 36 Achievement of glycemic control becomes critical and pharmacologic
Summary
Insulinoma is a rare, usually benign, pancreatic islet cell tumor. A patient with a suspected insulinoma should undergo a monitored 48-hour fast with appropriate confirmatory laboratory values to establish the diagnosis. Next, a CT scan is carried out evaluate for metastatic disease as well as to localize the lesion within the pancreas. If CT is unable to localize the lesion, intra-arterial calcium stimulation to regionalize the tumor is recommended.
The patient is then taken to the operating
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