Insulinoma pathophysiology

Insulinoma Microchapters
Home
Patient Information
Overview
Historical Perspective
Classification
Pathophysiology
Causes
Differentiating Insulinoma from other Diseases
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications and Prognosis
Diagnosis
Staging
Diagnostic Criteria
History and Symptoms
Physical Examination
Laboratory Findings
X-ray
Ultrasound
CT
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Surgery
Primary Prevention
Secondary Prevention
Cost-Effectiveness of Therapy
Future or Investigational Therapies
Case Studies
Case #1
Insulinoma pathophysiology On the Web
Most recent articles
Most cited articles
Review articles
CME Programs
Powerpoint slides
Images
American Roentgen Ray Society Images of Insulinoma pathophysiology All Images X-rays Echo & Ultrasound CT Images MRI
Ongoing Trials at Clinical Trials.gov
US National Guidelines Clearinghouse
NICE Guidance
FDA on Insulinoma pathophysiology
CDC on Insulinoma pathophysiology
Insulinoma pathophysiology in the news
Blogs on Insulinoma pathophysiology
Directions to Hospitals Treating Insulinoma
Risk calculators and risk factors for Insulinoma pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Amandeep Singh M.D.[2]Parminder Dhingra, M.D. [3]

Overview

Insulinoma may occur as part of other genetic syndromes such as multiple endocrine neoplasia type 1 and von Hippel-Lindau syndrome. On microscopic histopathological analysis, solid or gyriform patterns, usually without glands are characteristic findings of insulinoma.

Genetics

• Insulinoma can occur in association with inherited syndromes, such as multiple endocrine neoplasia type 1, von Hippel-Lindau syndrome or sporadic.
• Multiple endocrine neoplasia type 1 is an autosomal dominant disorder caused by alterations of the MEN1 gene located at chromosomal region 11q13.

Microscopic Pathology

On microscopic histopathological analysis characteristic findings of insulinoma are:

• Solid or gyriform patterns, usually without glands

Overview

• The exact pathogenesis of [disease name] is not fully understood.

OR

• It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
• [Pathogen name] is usually transmitted via the [transmission route] route to the human host.
• Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
• [Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
• The progression to [disease name] usually involves the [molecular pathway].
• The pathophysiology of [disease/malignancy] depends on the histological subtype.

Pathophysiology

Pathogenesis

• Insulinoma is a rare benign pancreatic neuroendocrine tumor that arises from B islet cells, which are cells that are normally involved in the production of insulin. Few insulinomas can also produce other hormones such as Serotonin, gastrin, ACTH, glucagon, and somatostatin
• They are usually small(90%), sporadic(90%), solitary(90%) and benign(90%) tumors. Those associated with the MEN1 syndrome are usually malignant and higher recurrence rate(21% at 10 and 20 years) than in those without MEN I (5% at 10 and 7% at 20 years). . Although there is a case report of a large(9cm), pedunculated and weighing more than 100g.
• Almost all insulinomas are present throughout the pancreas and extrapancreatic ones causing hypoglycemia are rare(<2%)

• It is thought that insulinoma is mediated by mTOR/P70S6K signaling pathway.Inhibitors of mTOR(rapamycin) or dual PI3K/mTOR(NVP-BEZ2235) thus will be new drugs for treating insulinoma. The pathway will give more possibilities for medical treatment.

• The progression to hypoglycemia is actually because of decreased glucose synthesis rather than increased use due to the direct effect of insulin on the liver.

Genetics

• Insulinoma is transmitted in [mode of genetic transmission] pattern.
• Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
• The development of [disease name] is the result of multiple genetic mutations.

Associated Conditions

• Other pancreatic neuroendocrine tumors like gastrinoma, glucagonoma, VIPoma, somatostatinoma
• MEN 1
• von Hippel-Lindau
• Neurofibromatosis type 1

Gross Pathology

• On gross pathology insulinomas have a red brown appearance, are usually solitary, can be present anywhere in the pancreas(extrapancreatic are very rare).

Insulinoma- Red brown appearance. By Edward Alabraba et al. - Pancreatic insulinoma co-existing with gastric GIST in the absence of neurofibromatosis-1. World Journal of Surgical Oncology 2009, 7:18doi:10.1186/1477-7819-7-18, CC BY 2.0, https://commons.wikimedia.org/w/index.php?curid=6686376

Microscopic Pathology

• On microscopic histopathological analysis, [feature2], and [feature3] are characteristic findings of insulinoma.

• 
  Histopathology of pancreatic endocrine tumor (insulinoma). H&E stain
• 
  Histopathology of pancreatic endocrine tumor (insulinoma)
• 
  Histopathology of pancreatic endocrine tumor (insulinoma). Chromogranin A immunostain
• 
  Histopathology of pancreatic endocrine tumor (insulinoma). Insulin immunostain

References

Template:WikiDoc Sources