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Q1: What other conditions besides Zollinger-Ellison syndrome could cause a raised gastrin level?
Causes of hypergastrinaemia are given in box 1.
Q2: Why does hypercalcaemia sometime present with abdominal pain?
There are various clinical manifestations of hypercalcaemia (see box 2). Abdominal pain associated with hypercalcaemia could be due to the manifestations of renal calculi, constipation, peptic ulcer disease (also associated with multiple endocrine neoplasia type 1 (MEN1) in patients with Zollinger-Ellison syndrome), pancreatitis, and enlargement of spleen in haematological malignancies.
Box 1: Causes of hypergastrinaemia
H2 receptor antagonist.
Proton pump inhibitors.
Gastric surgery (antrum retained).
Box 2: Clinical manifestations of hypercalcaemia
Neurological—lethargy, confusion, irritability, stupor.
Gastrointestinal—anorexia, nausea, vomiting, pancreatitis.
Cardiovascular system—short QT interval, increase myocardial activity.
Renal—nephrolithiasis, nephrogenic diabetes insipidus.
Q3: How would you proceed to investigate whether the adrenal mass is functioning or just an incidental finding?
Adrenal tumours are common in MEN1 syndrome and have been reported in up to 36% of these patients.1 They are usually benign non-functioning adenomas and occur in association with pancreatic tumours.
Adrenal incidental mass is defined as an adrenal mass discovered by non-invasive abdominal imaging technique (computed tomography, magnetic resonance imaging, or ultrasound) performed for reasons other than suspected adrenal disease.2 The majority of adrenal incidental masses are benign non-secretory adenomas.
A cost effective approach should be followed to decide whether the adrenal mass is secretory, and whether it is benign or malignant. Hormonal screening should include urinary catecholamines or metanephrines, urinary free cortisol and, in hypertensive patients, plasma renin activity and aldosterone level.2
Primary adrenal carcinoma is rare, whereas metastasis from pancreatic tumours to the adrenal is common. The relative frequency of primary adrenal carcinoma in adrenal incidental masses varies from 4% to 25% according to two different series. Features that suggest malignancy include tumour diameter of more than 6 cm, haemorrhage, calcification, and necrosis.
Adrenal metastases vary in size, and tend to be smaller than the lesion of primary adrenal carcinoma and larger than those of adenoma. They are often bilateral.
Imaging techniques, scintigraphy, and fine needle aspiration biopsy are useful diagnostic tools in the evaluation of adrenal masses. Regular clinical and radiological follow up is needed to monitor the progress of adrenal masses not needing immediate action. Causes of incidental adrenal masses are given in box 3.
Box 3: Causes of incidental adrenal masses
Adrenal cortex—adenoma, nodular hyperplasia, carcinoma.
Adrenal medulla—phaeochromocytoma, ganglioneuroma, neuroblastoma.
Other adrenal masses—lipoma, neurofibroma.
Pseudoadrenal masses—from kidney, spleen, or liver.
Q4: Why did this man develop diabetes mellitus?
The likely cause of diabetes in this patient is pancreatic insufficiency after surgery, although the time lapse between his surgery and development of diabetes is rather long. However, he was noted to have had impaired glucose tolerance five years after surgery. Autoimmune diabetes should also be considered, and can be screened for by checking anti-islet autoantibodies including glutamic acid decarboxylase antibodies.
MEN1 syndrome is associated with multiple pancreatic tumours, some of which are associated with diabetes mellitus, like glucagonomas and somatostatinomas. Our patient screened negative for pancreatic endocrine tumours other than gastrinoma.
Somatostatin analogues (for example, octreotide) are used for symptomatic relief in patients with pancreatic endocrine tumours. Octreotide inhibits insulin release, and sometimes impairs postprandial glucose tolerance. In rare instances with chronic adminstration, a state of persistent hyperglycaemia may be induced.3
Q5: Why is it important to screen his family?
This patient has the features of MEN1 syndrome, which is an autosomal dominant condition. Attempts to screen for the development of MEN1 tumours in asymptomatic relatives depend largely on measuring serum calcium, prolactin, and gastrointestinal hormones. Recent cloning of the MEN1 gene will enable earlier diagnosis and will possibly be used as a screening process for family members.4 Annual screening has been suggested from the age of 5 until the eighth decade in first and second degree relatives. Screening history and physical examination should be directed towards eliciting the symptoms and signs of hypercalcaemia, renal calculi disease, peptic ulcer disease, neuroglycopenia, galactorrhoea, amenorrhoea, Cushing's syndrome, visual field loss, and the presence of subcutaneous lipomas.
Q6: Why did he develop a distal oesophageal stricture?
Gastrin causes contraction of the lower oesophogeal sphincter/cardia, which is why oesophagitis and stricture formation is uncommon in Zollinger-Ellison syndrome. The presence of the nasogastric tube, after his initial surgery, coupled with his recumbent posture during recovery probably allowed reflux.
Multiple endocrine neoplasia type 1 (MEN1) syndrome with primary adrenal carcinoma.
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