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.