Clinical Background
Insulinomas are functional islet cell neoplasms which may be associated with Multiple Endocrine Neoplasias type 1 (MEN 1).
Epidemiology
- Incidence - 1-3/million yearly
- Age - median age of onset is 40-50 years
- Sex - slightly higher incidence in females
- Occurrence - sporadic most of the time
Risk Factors
- Genetic - around 10% associated with the MEN 1 Syndrome
Pathophysiology
- Insulinomas
- 5-10% are malignant - tend to be associated with familial disease
- Most common functioning endocrine tumor of the pancreas
- Second most common functioning pancreatic tumor in MEN 1 syndrome
- Diffuse islet cell hyperplasia, adenomas and carcinomas are typically present
- Islet cells can develop into macroadenomas, microadenomas or malignant adenocarcinomas
- Frequently multiple tumors are present
- Cause of symptoms is excess hormonal secretion of insulin
Clinical Presentation
- Hypoglycemia, confusion, headache, sweating, tremor
- Other manifestations associated with MEN 1 tumors may occur
- Pituitary, pancreatic and parathyroid tumors
See Also
Diagnosis
Diagnosis
- Laboratory testing
- Fasting blood sugar less than or equasl to45 mg/dL, serum insulin >6 µIU/mL and/or proinsulin levels greater than or equal to 5 pmol/L when glucose is less than or equasl to45 mg/dL, C-peptide levels greater than or equal to 0.6 ng/mL
- Urine/serum sulfonylurea screen to rule out factitious hypoglycemia
- Histological studies
- Final confirmation of tumor type - special stains may be required
- Imaging studies
Differential Diagnosis
- Diabetes mellitus
- Hypoglycemia from other causes including factitious
- Factitious use of sulfonylureas or insulin
- Nesidioblastoses
Tests generally appear in the order most useful for common clinical situations
| Test name: Glucose, Plasma or Serum
|
| ARUP #: 0020024 |
| Methodology: Enzymatic
|
| Use: Measure blood sugar levels |
| Limitations: |
| Follow-up:
|
| Test name: Insulin, Fasting
|
| ARUP #: 0070063 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Measure insulin levels |
| Limitations: |
| Follow-up:
|
| Test name: Proinsulin/Insulin Ratio
|
| ARUP #: 0070256 |
| Methodology: Refer to individual components
|
| Use: Measure insulin/proinsulin levels and ratio |
| Limitations: |
| Follow-up:
|
| Test name: C-Peptide, Serum or Plasma
|
| ARUP #: 0070103 |
| Methodology: Chemiluminescent Immunoassay
|
| Use: Measure C-Peptide |
| Limitations: |
| Follow-up:
|
| Test name: Sulfonylurea Hypoglycemics, Serum or Plasma
|
| ARUP #: 0090944 |
| Methodology: High Performance Liquid Chromatography/High Performance Liquid Chromatography
|
| Use: Differential diagnosis of hypoglycemia |
| Limitations: |
| Follow-up:
|
| Test name: Sulfonylurea Hypoglycemics, Urine
|
| ARUP #: 0091100 |
| Methodology: High Performance Liquid Chromatography/High Performance Liquid Chromatography
|
| Use: Differential diagnosis of hypoglycemia |
| Limitations: |
| Follow-up:
|
| Test name: Immunohistochemistry Stain Offering
|
| ARUP #: arup005 |
| Methodology: Immunohistochemistry
|
| Use: For fixed tissue samples, consultative services as well as immunohistochemical staining for insulin PGP9.5, synaptophysin and CAM5.2 (LMW) are available |
Additional Tests Available
| Test name: Insulin, Random
|
| ARUP #: 0070107 |
| Methodology: Chemiluminescent Immunoassay
|
| Comments: |
References
General References
de Herder WW, Niederle B, Scoazec JY, Pauwels S, Kloppel G, Falconi M, Kwekkeboom DJ, Oberg K, Eriksson B, Wiedenmann B, Rindi G, O'Toole D, Ferone D. Well-differentiated pancreatic tumor/carcinoma: insulinoma. Neuroendocrinology.
2006;
84(
3):
183-188.
de Herder WW. Biochemistry of neuroendocrine tumours. Best Pract Res Clin Endocrinol Metab.
2007;
21(
1):
33-41.
Doherty GM. Rare endocrine tumours of the GI tract. Best Pract Res Clin Gastroenterol.
2005;
19(
5):
807-817.
Goldin SB, Aston J, Wahi MM. Sporadically occurring functional pancreatic endocrine tumors: review of recent literature. Curr Opin Oncol.
2008;
20(
1):
25-33.
Grant CS. Insulinoma. Best Pract Res Clin Gastroenterol.
2005;
19(
5):
783-798.
Gutelius BJ, Korytkowski MT, Carty SE, Hamad GG. Diagnosis and minimally invasive resection of an insulinoma: report of an unusual case and review of the literature. Am Surg.
2007;
73(
5):
520-524.
Stephen AE, Hodin RA. Neuroendocrine tumors of the pancreas, excluding gastrinoma. Surg Oncol Clin N Am.
2006;
15(
3):
497-510.
Thompson GB. Diagnosis and management if insulinomas. Endocr Pract.
2002;
8(
5):
385-386.
Medical Reviewers
Lehman, Christopher M., M.D. Co-Medical Director, University Hospital Clinical Laboratory; Associate Professor, Clinical Pathology, University of Utah
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
Comprehensive Review: July 2008
Last Update: July 2008
