Endocrine tumours of the pancreas

The islet of Langerhans contain three types of cells: alpha  beta and gama and of these the beta-cell is most prevalent. Tumours of these endocrine cells comprise 1 per cent of all pancreatic tumours.

Pathology

The actual islet cell lesion may be one of the following: (1) generalised hyperplasia; (2) discrete adenoma; (3) generalised adenomatosis; and (4) carcinoma. In about one-third of cases they are multiple and in one-third they are malignant. As part of the multiple endocrine neoplasia syndrome they may be associated with tumours in other endocrine glands, especially the anterior pituitary, the parathyroids and the adrenal cortex. The neuroendocrine tumours may secrete hormones which give rise to the following conditions: insulinoma (insulin), gas­trinoma (gastrin), watery diarrhoea hypokalaemia achlorhydria syndrome (WDHA) (vasoactive intestinal peptide), glucagonoma (glucagon), somatostatinoma (somatostatin), CCKoma (CCK), ectopic adrenocorticotrophic hormone syndrome (ACTH), hyperpigmentation syndrome (melanocyte­stimulating hormone), ectopic hyperparathyroidism (para­thyroid hormone-related protein), carcinoid syndrome (5-hydroxytryptamine), pancreatic polypeptidoma (PPoma) (pancreatic polypeptide) and growth hormone secreting factor tumour. The commonest of these is the insulinoma.

Hyperinsulinism

Clinical features

The symptoms are many and varied, but the attacks are always associated with hypoglycaemia and occur at irregular intervals, often with progressively increasing frequency and severity. The symptoms include epigastric discomfort, nervousness, ‘feeling unwell’, trembling, sweating, dizziness, episodes of inarticulate speech and uncoordinated movements and, in extreme cases, fits indistinguishable from epilepsy. The age of the patient is variable.

Diagnosis

Diagnosis is made by the three criteria described by Whipple which consists of the signs and symptoms of hypoglycaemia, serum levels of less than 2.8 mmol/litre and the prompt relief of symptoms by the administration of glucose. The hypoglycaemia should be documented and associated with inappropriate levels of serum insulin (greater than 6 l. micro units/dl) and elevated C-peptide levels. Once the diagnosis has been made, the next step is to localise the tumour. The prime investigation is that of a high-quality CT scan of the pancreas with rapid injection (5—7 ml/second) of intravenous contrast (Fig. 55.12). The diagnosis of the characteristic ‘blush’ noted at the site of the tumour can be confirmed by endoscopic ultrasound. Angiography and selective sampling is no longer indicated. Further information is not required.

Treatment

The only curative treatment is extirpation of the tumour. Appropriate intravenous therapy with glucose and insulin is started preoperatively to maintain the blood sugar between 5 and 8 mmol/litre. The tumour is located usually with ease. Occasionally, the tumour cannot be palpated and then intraoperative ultrasound will invariably localise the tumour if present. Enucleation is the procedure of choice. Resection is rarely necessary unless the tumour is adjacent to the main duct in the head of the pancreas or there are multiple tumours in close proximity. The operative mortality rate is 1 per cent and the symptoms should be relieved in more than 95 per cent of patients.

Zollinger—Ellison syndrome

Diagnosis

The diagnosis should be suspected when peptic ulcer disease occurs at a very young age, there is virulent peptic ulcer disease, peptic ulcer disease occurs in unusual sites such as the jejunum, there is a marginal ulcer, unexplained diarrhoea, coexistent parathyroid disease or a family history of endocrinopathy.

The diagnosis of Zollinger—Ellison syndrome is confirmed by the demonstration of hypergastrinaemia and concurrent gastric hyperacidity. If there is doubt about the diagnosis a confirmatory secretin or calcium infusion test should be performed.

Location and localisation

In 1984 Stabile et a!. described the ‘gastrinoma triangle’ (confluence of the cystic duct and common bile duct superiorly, junction of the second and third parts of the duodenum inferiorly, and the junction of the neck and body of the pancreas medially) and suggested that 80—90 per cent of gastrinomas would be found within this triangle. This is, indeed, the case. A high percentage of tumours will he found in the duodenal wall and these are often quite small (4—6 mm). As 50—60 per cent of patients with the Zollinger—Ellison syndrome have malignant tumours careful investigation should be performed preoperatively to exclude metastatic disease. If there is no metastatic disease exploration should be undertaken.

Treatment

If the tumour is localised then resection of the tumour should be undertaken. Unfortunately, the surgical cure rate is only 30 per cent. Nevertheless, if a single tumour is found and excised the patient is cured. If other problems coexist, the patient can be managed medically with omeprazole and octreotide. Total gastrectomy is advised only if medical therapy fails.