eMedicine Specialties > Oncology > Carcinomas of Endocrine Organs

Insulinoma

Author: Zonera Ashraf Ali, MD, Consulting Staff, Main Line Oncology Hematology Associates, Lankenau Cancer Center
Coauthor(s): Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Contributor Information and Disclosures

Updated: Dec 29, 2008

Introduction

Background

Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism.

In a large single-center series of 125 patients with neuroendocrine tumors, insulinomas constituted the majority of cases (55%), followed by gastrinomas (36%), VIPomas (vasoactive intestinal polypeptide tumor) (5%), and glucagonomas (3%).

In 1927, Wilder established the association between hyperinsulinism and a functional islet cell tumor. In 1929, Graham achieved the first surgical cure of an islet cell adenoma. Insulinomas can be difficult to diagnose. It was not uncommon for patients to have been misdiagnosed with psychiatric illnesses or seizure disorders before insulinoma was recognized.

Pathophysiology

An insulinoma is a neuroendocrine tumor deriving mainly from pancreatic islet cells that produce excessive amounts of insulin. About 90% of insulinomas are benign. In healthy individuals, insulin and C-peptide are secreted in equimolar quantities because they derive from the same inactive precursor, proinsulin. Normally, less than 20% of proinsulin is released directly into the circulation.

Some insulinomas secrete additional hormones, such as gastrin, 5-hydroxyindolic acid, adrenocorticotropic hormone (ACTH), glucagon, human chorionic gonadotropin, and somatostatin. The tumor may secrete insulin in short bursts, causing wide fluctuations in blood levels.

Approximately 10% of insulinomas are malignant (metastases are present), and 10% are multiple, particularly in patients with multiple endocrine neoplasia type 1 (MEN 1). Of patients with multiple insulinomas, 50% have MEN 1. Insulinomas are associated with MEN 1 in 5% of patients. On the other hand, 21% of patients with MEN 1 develop insulinomas. Since about 5% of insulinomas are associated with the MEN 1 syndrome consideration should be given to screening patient's family members for this disorder.

Frequency

United States

Insulinomas are the most common pancreatic endocrine tumors. The incidence is 3-10 cases per million people per year. These make up 55% of neuroendocrine tumors, as stated in Background.

International

Exact data for international incidence of insulinomas are not available. One source from Northern Ireland reported an annual incidence of 1 case per million persons. A study from Iran found 68 cases in a time span of 20 years in a university in Tehran.1 Another study from Spain looked at surgical means of treating 49 patients in a period of 10 years. These reports may be an underestimate.

Mortality/Morbidity

  • The postoperative morbidity rate in a recently published series was 14%, mainly due to local complications, such as fistula formation after pancreatic resections. The postoperative mortality rate in another series of 117 insulinoma patients was 7.7%.
  • The median survival in metastatic disease to the liver ranges from 16-26 months.

Race

Insulinomas have been reported in persons of all races. No racial predilection appears to exist.

Sex

The male-to-female ratio for insulinomas is 2:3.

Age

  • The median age at diagnosis is about 47 years, except in insulinoma patients with MEN 1, in whom the median age is the mid 20s.
  • In one series, patients with benign disease were younger (mean age of 38 y) than those with metastases (mean age of 52 y). The age range for peak incidence of insulinoma is between 30 and 60 years.

Clinical

History

  • Symptoms caused by effects of local tumor mass are very rare for insulinoma.
  • About 85% of patients present with symptoms of hypoglycemia with diplopia, blurred vision, palpitations, or weakness.
  • Other symptoms include confusion, abnormal behavior, unconsciousness, or amnesia.
  • About 12% of patients have grand mal seizures.
  • Adrenergic symptoms (hypoglycemia causes adrenalin release) include weakness, sweating, tachycardia, palpitations, and hunger.
  • Symptoms may be present from 1 week to as long as several decades prior to the diagnosis (1 mo to 30 y, median 24 mo, as found in a large series of 59 patients). Symptoms may occur most frequently at night or in the early morning hours.
  • Hypoglycemia usually occurs several hours after a meal.
  • In severe cases, symptoms may develop in the postprandial period. Symptoms can be aggravated by exercise, alcohol, hypocaloric diet, and treatment with sulfonylureas.
  • Weight gain occurs in 20-40% of patients. Because of hyperinsulinism, many patients may be overweight.
  • A case report of a patient with type 2 diabetes who developed recurrent hypoglycemia was published from France.2

Physical

Insulinomas are characterized clinically by the Whipple triad (which occurred in 75% of 67 insulinoma patients as reported recently).

  • Episodic hypoglycemia
  • Central nervous system (CNS) dysfunction temporally related to hypoglycemia (confusion, anxiety, stupor, convulsions, coma)
  • Dramatic reversal of CNS abnormalities by glucose administration

Most of the patients have normal physical examination findings.

Causes

The genetic changes in neuroendocrine tumors are under investigation.3

  • The gene of MEN, an autosomal dominant disease, is called MEN1 and maps to band 11q13. MEN1 is thought to function as a tumor suppressor gene.
  • New data suggest that the MEN1 gene also is involved in the pathogenesis of at least one third of sporadic neuroendocrine tumors.
  • Researchers were able to detect loss of heterozygosity in band 11q13 in DNA samples from resected insulinoma tissue by using fluorescent microsatellite analysis.

One study showed k -ras mutation to be present in 23% of insulinomas.

More on Insulinoma

Overview: Insulinoma
Differential Diagnoses & Workup: Insulinoma
Treatment & Medication: Insulinoma
Follow-up: Insulinoma
References
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References

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Further Reading

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Keywords

insulinoma, hyperinsulinism, endogenous hyperinsulinism, islet cell adenoma, pancreatic islet cell, neuroendocrine tumor, hypoglycemia, B-cell tumor of the pancreas, adenoma of the islets of Langerhans

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Contributor Information and Disclosures

Author

Zonera Ashraf Ali, MD, Consulting Staff, Main Line Oncology Hematology Associates, Lankenau Cancer Center
Zonera Ashraf Ali, MD is a member of the following medical societies: American Society of Clinical Oncology and American Society of Hematology
Disclosure: Nothing to disclose.

Coauthor(s)

Klaus Radebold, MD, PhD, Research Associate, Department of Surgery, Yale University School of Medicine
Klaus Radebold, MD, PhD is a member of the following medical societies: American Gastroenterological Association and New York Academy of Sciences
Disclosure: Nothing to disclose.

Medical Editor

Pradyumna D Phatak, MBBS, MD, Chair, Associate Professor, Department of Internal Medicine, Division of Hematology and Medical Oncology, Rochester General Hospital
Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

CME Editor

Rajalaxmi McKenna, MD, FACP, Consulting Staff, Department of Medicine, Southwest Medical Consultants, SC, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting

 
 
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