Pancreatic endocrine tumors arise from hormone-secreting cells and are capable of secreting virtually any type of hormone: at least nine different clinical syndromes have been described to date. The hormones responsible for the syndromes are:
- insulin (insulinoma)
- Gastrin (gastrinoma or Zollinger-Ellison syndrome)
- VIP or vasoactive intestinal peptide (WDHA syndrome)
- Glucagon (glucagonoma)
- ACTH (ectopic ACTH syndrome)
- MSH (hyperpigmentation)
- PTH (ectopic hyperparathyroidism)
- 5-hydroxytryptamine (carcinoid syndrome)
- Somatostatin (somatostatinoma)
INSULINOMA
It is one of the most frequent pancreatic endocrine tumors; it can occur at any age and has no gender preference. In most cases, it is unique and benign (85%). It originates from islet beta cells and produces insulin regardless of blood sugar levels.
Symptoms
The most common manifestations of insulinoma include a set of non-specific and non-diagnostic symptoms, all identifiable as "minor symptoms," which are: marked muscle weakness, fainting spells, headaches, tingling, fine tremors in the extremities, dizziness, pain-type cramps, and excessive hunger.
Among the "major" manifestations, we find emotional instability, generalized seizures, and movement disorders of one or more parts of the body. These manifestations appear on an empty stomach or after intense physical exertion and, in general, when hypoglycemia occurs, which can give rise, especially at night, to a hypoglycemic coma (which is easily resolved with the administration of fast-acting sugars). absorption).
Diagnosis
Evidence of low serum glucose levels in multiple blood samples (glucose < 50 mg/dL), associated with hyperinsulinemia, is in itself diagnostic. When insulin levels are especially high, a malignant neoplasm should be suspected, with possible metastatic locations to the liver that, invading it, prevent it from demolishing the excess insulin present in the circulation. When the proinsulin dose reaches 50–75% of total circulating insulin levels, the diagnosis is virtually certain.
Radiological confirmation of the presence of insulinoma is essential but often difficult; in about 10% of cases, the tumor is so small that it cannot be detected even by intraoperative ultrasound. Selective preoperative arteriography visualizes about 50% of insulinomas, but false positives are common; CT also offers poor results. A recent diagnostic approach involves transhepatic percutaneous venous catheterization, which determines insulin levels at various levels of the venous system.
Treatment
Since repeated hypoglycemic episodes can cause permanent brain damage over time, and given the possibility of malignant transformation of the neoplasm, surgical removal should be considered as soon as possible. This can be implemented by performing an enucleation (if the diameter of the lesion does not exceed 2-3 cm), a partial resection of the pancreas, through a duodenocephalopancreatectomy (if it is located in the head of the pancreas), or a caudal resection. In the rare cases in which no sign of neoplasia is found intraoperatively, insulin concentrations are measured at the level of the splenic and portal veins.
When surgical intervention is not possible, medical treatment with somatostatin or streptozotocin relieves symptoms in a high percentage of cases.
GASTRINOMA
It is the most common of all pancreatic endocrine tumors, affecting 1 person in 500,000. It originates from pancreatic and duodenal G cells, which secrete gastrin, which stimulates an increase in the number and secretory activity of gastric cells responsible for acid production. The resulting symptoms are called "Zollinger-Ellison syndrome".
Gastrinomas can be located in the pancreas (70–90% of cases), in the duodenal wall (15–20%), or in extraintestinal sites (5–15%), such as lymphatic tissue or the liver. Tumor growth is usually slow.
Gastrinomas in patients with MEN I syndrome are associated with parathyroid hyperplasia and pituitary prolactinoma; they are rarely malignant but are almost always multifocal.
Symptoms
The disease usually presents with symptoms related to gastric hyperacidity, e.g., dyspeptic disorders and bleeding, diarrhea due to reduced absorbent mucosal surface area, and greasy stools. Esophagitis, heartburn, and dysphagia may also occur in a smaller number of patients, leading to weight loss and malnutrition over time.
Treatment
The treatment mainly uses the blockade of gastric secretion, by means of anti-H2 drugs (cimetidine, ranitidine) or proton pump inhibitors (omeprazole), which are much more powerful. The use of chemotherapy (streptozotocin) may have some efficacy, especially in the case of malignancy.
Surgical therapy, which should be performed whenever possible, should aim at complete removal of the tumor, if this is technically feasible; In the much more frequent cases in which the tumor is inoperable, a total gastrectomy is performed. The frequent involvement of gastrinoma in MEN I syndrome or the presence of liver metastases can make any therapeutic strategy complex.
Diagnosis
In the presence of multiple erosions and ulcers involving the digestive tract (particularly the stomach and duodenum), refractory to standard medical therapy, ultrasonography, esophago-gastro-duodenoscopy (EGDS), and an X-ray of the digestive tract with baryta contrast. These reveal a thickening of the gastric wall and the presence of excessive gastric secretion. A CT scan and/or abdominal MRI are also performed.
Diagnostic certainty is obtained by measuring gastrinemia, performed on blood samples taken at different times of the day, since gastrin secretion is fluctuating. Various stimulation tests can also be used, such as the secretin test, which causes a diagnostic increase in blood gastrin. Other dynamic tests make use of the evaluation of gastrinemia after ingestion of food.
In case of diagnostic doubt, selective arteriography allows serial measurements of gastrinemia.
Treatment
The therapy mainly uses the blockade of gastric secretion using anti-H2 drugs (cimetidine, ranitidine) or proton pump inhibitors (omeprazole), which are much more powerful. The use of chemotherapy (streptozotocin) may have some efficacy, especially in the case of malignancy.
Surgical therapy, which must be carried out in any case, must aim at complete removal of the tumor, if this is technically possible; In the much more frequent cases in which the tumor is inoperable, a total gastrectomy is performed. The frequent involvement of gastrinoma in MEN I syndrome or the presence of liver metastases can make any therapeutic strategy complex.
VIPOMA
It is a pancreatic endocrine tumor, originated from non-beta islet cells, which secrete VIP (Vasoactive Intestinal Polypeptide). It is more common in women and between the ages of 30 and 40; in 80–85% of cases, it is single, often located in the tail of the pancreas; 50–60% of neoplasms are malignant, and in these cases, at the time of diagnosis, they have often already given rise to metastases.
Symptoms
VIP-oma is manifested by hypersecretion of water and electrolytes in the intestine, with watery diarrhea (up to 5–10 liters during acute attacks), marked dehydration, malabsorption, partial or total deficiency of gastric acid secretion, and vasodilatation with flushing of the face and skin. Potassium deficiency caused by its loss through the feces can cause cardiac arrhythmias, generalized muscle cramps, asthenia, generalized abdominal pain, and kidney damage.
Metabolic acidosis due to bicarbonate loss is common. Other electrolyte disturbances may also be associated, such as hypophosphatemia, hypomagnesemia, and hypercalcemia.
Diagnosis
Preoperative diagnosis, in the presence of the characteristic clinical presentation, is achieved by selective angiography with injection of contrast medium. The prognosis, in the case of surgical abstention, does not exceed one year of life.
Treatment
Whenever possible, surgical removal (according to the same methods described for insulinoma) is the treatment of choice. If it is not possible to identify the exact location of the neoplasm, it is still possible to proceed with a resection of the gland.
As for insulinoma, drug therapy uses somatostatin and streptozotocin.
GLUCAGONOMA
It is a very rare tumor that originates from alpha islet cells and presents malignant characteristics in 75% of cases. It is located mainly in the body and tail of the pancreas.
Symptoms
Glucagonoma presents with a wide variety of non-specific symptoms, such as diabetes mellitus (usually mild, weakness, malnutrition, depressive syndrome, diarrhea with malabsorption, thrombosis of the lower limbs, appearance of "cutaneous-mucosal syndrome" in corners and nostrils, and nail dystrophies. Migratory necrotic erythema is characteristic, that is, the appearance of macules and papules, which transform into bubbles and then undergo lysis, especially at the level of the perineal skin, the back, and the roots of the lower limbs, which produce characteristic scars, of course. serpiginous
Diagnosis
The finding of elevated serum glucagon levels and their correlation with clinical symptoms are almost always diagnostic. Radiological confirmation is achieved by selective pancreatic arteriography or abdominal CT. In 2/3 of cases, at the time of diagnosis, metastases were already present in the liver, lymph nodes, adrenal glands, or vertebrae.
Treatment
If technically possible, the tumor is removed, even when it is not possible to remove it completely. The chemotherapy of choice, in cases of inoperable lesions, is streptozotocin and dicarbazide. As in almost all pancreatic endocrine neoplasias, somatostatin reduces symptoms and sometimes leads to a reduction in the size of the lesion.
SOMATOSTATINOMA
Somatostatinoma is a rare pancreatic endocrine tumor that is malignant in most cases. It originates from the delta islet cells, which produce somatostatin.
Symptoms
The symptomatic range of somatostatinoma is nonspecific and includes moderate diabetes mellitus, diarrhea with malabsorption, dilation of the bile duct, and the presence of stones in the gallbladder and/or bile ducts.
Diagnosis
In the presence of the clinical picture, the diagnosis is possible by finding elevated serum levels of somatostatin. However, the exact diagnosis is usually made only after a histological examination of the neoformation.
Treatment
Surgical therapy is indicated when the disease is localized. However, in most cases, liver metastases are already present at the time of diagnosis, so chemotherapy with streptozotocin and dicarbazide is usually the treatment of choice.