Diagnosis

Insulinoma

Etiology

Cause [b9s]

• Most cases are sporadic (30% of these with mutations in the YY1 and Kras genes)

• Some are linked to multiple endocrine neoplasia type 1 (MEN1) syndrome

Pathophysiology [b9s]

1. Normal physiology: Declining blood glucose suppress insulin secretion to prevent hypoglycemia

2. An insulin-secreting neuroendocrine tumor, deriving mainly from pancreatic islet cells

3. Some insulinomas also secrete other hormones: gastrin, 5-hydroxyindolic acid, adrenocorticotropic hormone, glucagon, human chorionic gonadotropin, and somatostatin

4. Genetic mutations/dysregulations in signaling pathways that govern cell proliferation and hormone secretion

5. Pathophysiology: Loss of feedback inhibition --> Autonomous and unregulated secretion of insulin --> hyperinsulinemia --> hypoglycemia --> catecholamine release

Epidemiology

Incidence per 100.000 [1ad][tru][b9s]

Approach

• Blood test: [1ad][b9s]

  • Fasting plasma glucose level < 3 mmol/L

  • Insulin level > 18 pmol/L

  • C-peptide > 0.2 nmol/L (>1.7ng/mL)

  • Proinsulin > 5 pmol/L (>25%)

• CT pancreas

• MRI pancreas

• Ga-DOTATATE PET-CT [tru]

• Endoscopic ultrasound

• Explorative laparoscopy/laparotomy

Treatment

1. Dietary modifications [1ad]

2. Medication to avoid hypoglycemia: Diazoxide, octreotide, pasireotide

3. Surgical resection with intraoperative ultrasound [b9s]

   • Enucleation: small (<2 cm) benign tumors

   • Distal pancreatectomy

   • Central pancreatectomy

   • Pancreaticoduodenectomy

4. Malignant insulinoma:

   • Surgery: complete oncological resection and regional lymph nodes dissection

   • 80% of the patients have liver metastasis:

     • Hepatic resection

     • Hepatic artery embolization combined with doxorubicin or streptozotocin

     • Liver transplantation [hqr]

     • Unresectable/metastatic:

       • Everolimus/sunitinib (antiproliferative effect)

       • Chemotherapy (streptozotocin, doxorubicin, 5-FU, cisplatin, etoposide)

       • Somatostatin positive tumor: radionuclide therapy (yttrium/lutetium)

Differential diagnoses

Adrenal insufficiency, Glucagonoma, Munchausen syndrome, Wermer syndrome