Insulinoma D13.7

Most frequent, mostly benign (>90%), predominantly solitary (in 10% of cases multiple adenomas) and sporadically occurring, size-limited (a size of 2 cm is usually not exceeded) endocrine pancreatic (B-cell) tumor. In 50% of cases insulinomas produce only insulin; otherwise production of other gastrointestinal hormones. 4% of insulinomas occur in the course of multiple endocrine neoplasia type I (MEN I).

1.0-2.0/100,000 persons

Unknown; for partial symptom of MEN 1 (mutation of the gene MEN1 - menin gene -, a tumor suppressor gene mapped on gene locus 11q13.

Insulinoma is characterized by recurrent hypoglycemiawith blood glucoselevels below 50 mg/dl. The classic clinical picture corresponds to the so-called Whipple triad:

1. Food deprivation induced spontaneous hypoglycemia (E16.2) <45mg/dl.
2. Autonomic symptoms: cravings, tremors, sweating, flushing, palpitations, tachycardia, nausea, dizziness.
3. Prompt improvement after oral or intravenous glucose administration.

In the case of a prolonged course of the disease, a marked increase in weight (anabolic effect of insulin) is also noticeable.

Localization diagnostics:

• Pre-operative: Uncertain in small tumours <1cm; endosonography, one-stop-shop MRI including MRCP and MRI angiography); PET-CT (Ga-DOTATOC-PET-CT). Exendin-4 SPECT/CT: highly sensitive method; the so-called "glucagon-like peptide-1 receptor" (GLP-1 receptor) is labelled with the aid of radioactive indium (111In-DTPA-exendin-4).
• Intraoperatively: Palpation, ultrasound and the possibility of an intraoperative histological freezing section should be available for a reliable intraoperative diagnosis of the insulinoma.

Hypoglycaemia factitia in diabetes mellitus and an overdose of insulin or sulphonylureas; hypoglycaemia(E16.2) of other etiology such as renal hypoglycaemia, hypoglycaemia in hepatocellular carcinoma, paraneoplastic secretion etc.)

In case of inoperability:

• palliative chemotherapy with streptozotocin 5FU.
• alternatively: sunitinib

Therapeutic guidelines are in accordance with these AWMF 2018 guidelines:

For (potentially benign) insulinomas, enucleation (laparoscopic or open) or limited pancreatic resection (laparoscopic or open) should be preferred to formal pancreatic resection.

In cases of suspected malignancy (<10%; large tumours and/or V.a. nodular involvement) without evidence of distant metastases, complete resection with formal pancreas resection and lymphadenectomy should be performed.

In the case of malignant insulinomas with resectable distant metastases, the complete removal of the primary tumour and metastases should be attempted. In the presence of liver metastases, hepatic (chemo)embolization.

In the case of malignant insulinomas with surgically incurable distant metastases, removal of the primary tumor and debulking of the distant metastases to improve hypoglycemia symptoms should be considered.

Blind resection of pancreatic tissue without intraoperative tumor detection should not be performed.

If the insulinoma is not found, the patient should be assigned to a specialized unit for further diagnosis and therapy.

Insulinomas are the most common tumors in ferrets. There they occur with a frequency of 10 to 20 %.

1. Perren A et al (2010): Classification and pathology of gastroenteropancreatic neuroendocrine tumors. Visceralmed 26: 234-240
2. Rinke A et al (2018) S2k guideline neuroendocrine tumors. Z Gastroenterol 56: 583-681
3. Ruszniewski P et al (2006) Well-differentiated gastric tumors/carcinomas. Neuroendocrinology 84:158-164
4. Scherübl H et al (2003) Neuroendocrine gastrointestinal tumors. Diagnosis and therapy. Dtsch Med Weekly 128: 81-83
5. Scherübl H et al (2011) Management of early gastrointestinal neuroendocrine neoplasms. World J Gastrointestinal test Endosc 3: 133-139