Neuroendocrine GEP-Tumors (GEP-NET)


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- 2nd frequent NET of pancreas with inadaequate insulin-(proinsulin) secretion
- first described as Langerhans - adenoma: Nichols 1902 (J Med Res) + Warren 1926 (Am J Pathol) : ass "Insulinoma": Wilder et al 1927 (JAMA)
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1 - 4 per 1 Mill. / year
more frequent in women > men / median age > 50 years

Pathology - Pathophysiology

Insulin secretion: inadaequately elevated during hypoglycemia ( < 40 mg/dl) as a cause of predominantly neuroglycopenic (neurological) symptoms due to a shortage of glucose supply in the brain, in addition a variety of unspecific adrenergical warning symptoms through activation of the sympathetic adrenergic nervous system (epinephrine)

- mostly small and benign tumors (1-2 cm), evenly distributed over the entire pancreatic organ (extrapancreatic localization an absolute rarity - tumors may protrude from the pancreas), often localized in the processus uncinatus
- malignant tumors often identified only on the basis of metastases, more frequent larger tumors (but also < 1 cm ! ), metastases in local lymph nodes and liver, suspicverdächtig bei jahrelanger Anamnese, Tendenz steigend (10 - < 20 %)



typical clinical syndrome

1. Whipple Trias

- biochemical hypoglycemia (blood glucose <50 mg/dl)
- simultaneous compatible adrenergic and/or neurological symptoms
- amelioration of symptoms after carbohydrate intake

2. adrenergic unspecific symptoms and / or

3. neurological (=neuroglucopenic) symptoms

frequent-symptoms: dizziness, disturbance or loss of consciousness, weight gain, sweating, seizures





Test: standardized fasting test, start in the morning, preferentially after oral intake of 100 g of gluocse.

! Interpretation of fasting tests requires knowledge of normal limits pointing towards or against an insulinoma diagnosis (not to be confused with "normal values for insulin" - these require a simultaneous normal blood glucose level)

Laboratory: insufficiently suppressed insulin secretion at reproducible ( ! ) biochemical hypoglycemia ( < 40 mg/dl ) - laboratory method ! no"test strip" !
  • blood glucose
  • C-Peptide
  • < 40 mg/dl
    > 6 µU/ml or > 36 pmol/l
    > 10 pmol/l
  • > 0.6 ng/ml or > 200 pmol/l

!! beware of "specific" insulin assays: these might miss frequently or singularly elevated proinsulin concentrations !!


always surgical resection (also in case of rare "malignant" insulinoma if possible), danger of malignant transformation if usual benign tumors are left, no safe symptomatic therapy available

Symptoms : Glucose or rapidly absorbed carbohydrates intravenously or orally

Somatostatin subcutaneously: frequently unsuccessful - many insulinomas do not express the necessary somatostatin receptors in contrast to other GEP-NETs, paradox aggravation of hypoglycemia possible due to inhibiton of glucagon

Diazoxide: due to severe side effects no alternative treatment for longer periods



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