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insulinoma
Epidemiology:
- 2nd most common endocrine tumor of the pancreas
Pathology:
1) rarely malignant [1]; 10% malignant [2]
2) single neoplasm, unless associated with MEN-1
Genetics:
- implicated genes: GNAL, CRTC2, INSM1
Clinical manifestations:
- Whipple's triad
a) fasting hypoglycemia
b) glucose < 50 mg/dL during symptoms
c) relief with oral or IV glucose
- weight gain
- symptoms of hypoglycemia
- cholinergic symptoms
- sweating
- adrenergic symptoms
- anxiety
- hunger
- diaphoresis
- tachycardia
- tremulousness
- PVC's
- irritability
- hyperthermia
- palpitations
- hypothermia
- neurologic symptoms
- headache
- behavioral changes (combativeness, agitation)
- cognitive change
- seizures
- coma
- hemiparesis
- aphasia
- visual changes
- Babinski's sign
Laboratory:
1) elevated plasma insulin
a) inappropriately high plasma insulin during hypoglycemia
b) plasma insulin > 6 mU/mL in association with plasma glucose < 50 mg/dL in males & < 40 mg/dL in females indicates hyperinsulinemia
2) decreased fasting serum glucose
3) elevated C-peptide (obtain when glucose is < 50 mg/dL)
- C-peptide > 0.2-0.4 nM suggests a beta-cell lesion
4) elevated pro-insulin > 20 pM
5) C-peptide suppression test
- elevated C-peptide after administration of insulin to induce hypoglycemia demonstrates autonomous production of endogenous insulin
6) glucagon tolerance panel, for insulinoma
7) insulin-induced C-peptide suppression panel
8) insulin:glucose ratio > 0.3 uU/mg
9) inhibited ketosis: plasma beta-hydroxybutyrate < 2.7 mM after a lengthy fast
10) transhepatic sampling of portal vein & pancreatic veins for insulin & C-peptide (requires special expertise)
11) see ARUP consult [4]
Special laboratory:
- endoscopic pancreatic ultrasonography (90% sensitivity) [3]
Radiology:
1) computed tomography of abdomen
a) 1st diagnostic test after biochemical diagnosis [3]
1] tumor is small
2] generally not visible with CT or US
3] lesions must be larger than 1.0-1.5 cm for visualization
2) magnetic resonance imaging (MRI)
- generally offers no benefit over CT
3) nuclear scanning with isotopically labeled somatostatin analogues not an effective diagnostic tool because insulinomas do not produce enough somatostatin receptors to render scintigraphy diagnostically useful [3]
4) imaging studies only after laboratory confirmation of hypoglycemia & hyperinsulinemia [3]
Differential diagnosis:
1) surreptitious use of sulfonylureas
2) insulin antibodies
Management:
1) surgical excision or distal pancreatectomy
2) diazoxide for persistent disease
a) inhibits insulin secretion
b) alternative agents:
1] phenytoin
2] propranolol
3] verapamil
4] octreotide
3) chemotherapy for maligant persistent or recurrent disease
a) sunitinib & everolimus are active [3]
b) capecitabine plus temozolomide is active [3]
c) older recommendationc
- streptozocin
- fluorouracil
Interactions
disease interactions
General
islet cell tumor; pancreatic neuroendocrine neoplasm; nesidioblastoma
References
- Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed)
Lippincott-Raven, Philadelphia, 1998, pg 267-68
- Harrison's Principles of Internal Medicine, 14th ed.
Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 585
- Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18.
American College of Physicians, Philadelphia 2009, 2012, 2015, 2018.
- ARUP Consult: Insulinoma
The Physician's Guide to Laboratory Test Selection & Interpretation
https://www.arupconsult.com/content/insulinoma
- Mathur A, Gorden P, Libutti SK.
Insulinoma.
Surg Clin North Am. 2009 Oct;89(5):1105-21
PMID: 19836487
- NEJM Knowledge+ Question of the Week. December 5, 2017
https://knowledgeplus.nejm.org/question-of-week/906/