Insulinoma is the most common functional pNEN (pancreatic neuroendocrine neoplasm) and is slightly more prevalent in women than in men. Most cases are benign and solitary, with 80% of insulinomas measuring less than 2 cm in diameter.
Clinical Manifestations
The clinical manifestations of insulinomas are complex and varied, often leading to misdiagnoses. Hypoglycemia is the initial symptom and frequently occurs in the early morning or after physical activity. Neurological symptoms caused by hypoglycemia include headache, blurred vision, memory loss, seizures, and even coma. Additionally, excessive release of catecholamines due to hypoglycemia can result in profuse sweating, fatigue, palpitations, tremors, and pallor. Eating snacks can alleviate hypoglycemic symptoms, and patients often eat frequently to manage their symptoms, leading to weight gain.
Diagnosis
Qualitative Diagnosis
Whipple's triad is the hallmark clinical presentation of insulinoma and includes the following: hypoglycemic symptoms occurring during fasting or after exercise; blood glucose levels below 2.8 mmol/L during symptom episodes; and rapid symptom relief after food intake or intravenous glucose administration. If hypoglycemic symptoms do not occur spontaneously, a 72-hour fasting test may be performed. A diagnosis can be confirmed if the patient develops hypoglycemic symptoms during fasting and meets the following six criteria:
- Blood glucose level ≤ 2.22 mmol/L (≤ 40 mg/dL).
- Insulin level ≥ 6 μU/mL (≥ 36 pmol/L).
- C-peptide level ≥ 200 pmol/L.
- Proinsulin level ≥ 5 pmol/L.
- β-hydroxybutyrate ≤ 2.7 mmol/L.
- Absence of sulfonylurea drug metabolites in blood and urine.
Localizing Diagnosis
Identification of tumor location, number, and the presence of metastases is essential.
Conventional Imaging Methods
Surface ultrasonography or standard CT scanning has limited utility in localizing insulinomas. Thin-slice contrast-enhanced CT with three-dimensional reconstruction is effective for accurately localizing most insulinomas and can also involve pancreatic perfusion scans to improve diagnostic sensitivity. Enhanced MRI of the pancreas is another option, offering high detection rates for liver metastases. If CT or MRI fails to accurately localize the tumor, endoscopic ultrasound (EUS) can be considered, with EUS-guided fine-needle aspiration biopsy performed if necessary.
Surgical Exploration
Surgical exploration combined with intraoperative ultrasound achieves localization accuracy rates of 95%–100%. Intraoperative ultrasound is particularly advantageous for identifying multiple or occult tumors and for assessing the relationship between the tumor and the main pancreatic duct.
Treatment
To minimize hypoglycemic episodes, strict adherence to scheduled meals is recommended.
The definitive treatment for insulinoma is surgical tumor resection, with the surgical approach determined by the tumor's location and its relationship with the pancreatic duct. Some tumors can be cured with local resection or enucleation. For insulinomas unsuitable for local resection or enucleation, more extensive pancreatic resections, such as distal pancreatectomy or pancreaticoduodenectomy, may be performed.
For patients who are not candidates for surgery, a multidisciplinary treatment approach can be adopted. Treatment options include somatostatin analogs, hepatic arterial embolization chemotherapy, and chemotherapeutic agents such as streptozotocin, temozolomide, or platinum-based drugs. Peptide receptor radionuclide therapy (PRRT) has shown potential in improving the prognosis of select patients with advanced pNENs and has promising application prospects.