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A missense mutation at codon 618 of the RET proto-oncogene is a rather unusual cause of multiple endocrine neoplasia 2A. We report the phenotypic expression of this specific RET mutation in a large Swedish family. The family was mapped back to the 18th century. Since 1971 the family has been included in a biochemical screening program, and since 1994 has undergone genetic screening. Twenty-seven individuals were found to have medullary thyroid carcinoma (MTC). Eighteen were detected by screening. The incidence of pheochromocytoma (4%) and hyperparathyroidism (7%) was low. Five individuals died of MTC, but of these none had been included in the screening program. One patient underwent prophylactic thyroidectomy after positive genetic screening. MTC tumor aggressivity differed markedly between gene carriers. The screening program shows that the clinical aggressivity of MTC can be mitigated by early and adequate surgical intervention.

Measurement of gastrin in serum or plasma in patients with gastrinoma may be complicated by the presence of circulating biosynthetic intermediates which may not be detected by commonly available immunoassays. In contrast, the "processing-independent analysis" of gastrins developed by professor Jens Rehfeld et al in Copenhagen detects gastrin forms irrespective of their size. The authors review gastrinoma pathophysiology, the biochemistry of gastrin and other biomarkers of gastrinoma, the differential diagnosis of hypergastrinemia as well as other methods currently employed in the workup of gastrinoma patients, and illustrate with a clinical case.

Adult hyperinsulinaemia is usually caused by benign insulinomas. These tumours are often small, and are associated with excellent outcome of surgical removal. In cases of negative outcome of surgical exploration, or of persistent hyperinsulinaemic hypoglycaemia, the possibility must be considered of some rare condition such as the presence of metastatic insulinoma, B-cell hyperplasia, multiple micro- or macro-adenomas, hyperinsulinaemia factitia, or nesidiodysplasia. The latter is the most common cause of hyperinsulinaemia in children but is rare in adults. It is defined as a maldistributed islet cell mass within the normal exocrine pancreas, with disturbed control of hormone synthesis/secretion resulting in hormone overproduction, usually hyperinsulinaemia. In persistent hyperinsulinaemic hypoglycaemia of infancy, inactivating mutations of the sulphonylurea receptor gene is one possible cause of nesidiodysplasia. Adult nesidiodysplasia is discussed in the article, and illustrated by the case of a patient undergoing distal pancreatectomy for hyperinsulinaemia, the diagnosis being subsequently established histologically. Following spleen- and duodenum-preserving subtotal (95%) pancreatectomy, the patient was symptom-free.

Several neuroendocrine tumours, such as carcinoids and pancreatic endocrine tumours, may manifest relatively slow tumour growth. The patients may suffer from severe hormonal symptoms, largely due to liver metastases which sometimes are amenable to cytoreductive surgery. If residual tumour after primary tumour resection is multilobar, liver transplantation may be one way to treat hormonal symptoms and possibly prolonging survival. Early long-term outcome of liver transplantation in patients with neuroendocrine tumours suggests prognosis to be more favourable for carcinoids than for endocrine pancreatic tumours. It is suggested that liver transplantation may be appropriate for patients with isolated hepatic tumour disease in the following situations: 1, tumour recurrence after liver surgery for cure; 2, non-resectable liver disease, especially in cases of severe hormonal symptoms; and 3, disease progression after hepatic arterial embolisation and medical therapy. These indications are discussed in the light of three case reports.

Verification of the presence of somatostatin receptors on neuroendocrine tumour cells opened up unique diagnostic and therapeutic possibilities. Long-acting somatostatin analogues are currently used to alleviate symptoms of excessive hormone synthesis in patients with such tumours. Radiolabelled somatostatin analogues can be used both for high specificity and high sensitivity scintigraphic localisation of such tumours and for intraoperative scintillation detection. Detailed studies in patients and in tumour cells in vitro have shown 111In-octreotide uptake to be high and retention times long in tumour tissue, and have yielded evidence of intracellular localisation of the radionuclide. These findings thus showed somatostatin receptor-mediated radiotherapy to be a possible treatment alternative after close characterisation of the individual tumour. In the future, it may be possible to use other peptide receptors (e g, growth factor receptors) according to the same principles as applied in the case of somatostatin receptors.

Glucagon-producing neoplasms are rare pancreatic tumours that may give rise to a characteristic syndrome including, diabetes and typical skin manifestations (necrolytic migrating erythema). Dermatological problems are often the first signs of the disease and the diagnosis is easily overlooked. In most series reported to date, glucagonomas had already metastasized at diagnosis, which means that curative surgery was possible to perform in less than half of the patients. To increase awareness of glucagonoma symptomatology a review of the syndrome is presented together with the clinical histories of three patients, recently treated. These cases illustrate aspects of modern diagnosis and treatment.