12 APUDomas: acute complications and their medical management J. PHILIPPE
APUD (amine precursor uptake and decarboxylation) cells constitute a family of endocrine cells distributed throughout the body and characterized by the ability to take up and decarboxylate amino acid precursors of biogenic amines. This property results in the synthesis of bioactive amines or polypeptide hormones. APUD cells are found in organs as diverse as the pituitary gland, peripheral autonomic ganglia, adrenal medulla, gastrointestinal tract, pancreas, lung, gonads and thymus. Endocrine tumours originating from cells characterized by the APUD properties have been referred to as APUDomas. The initial clinical manifestations of most of these tumours can be attributed to the overproduction of biogenic amines or hormones. Although many endocrine tumours can be classified as APUDomas, only those whose clinical manifestations may require emergency management are considered here, excluding insulinomas and tumours originating from the autonomic ganglia or adrenal medulla (see Chapters 2 and 7). ZOLLINGER-ELLISON SYNDROME Definition The Zollinger-Ellison syndrome (ZES) is usually the first manifestation of gastrin-producing tumours (gastrinomas) and is secondary to an increased gastrin production. ZES is characterized by severe gastric acid hypersecretion, which causes peptic ulceration and diarrhoea. The most serious acute complications are bleeding and bowel perforation. Gastrinomas occur rarely, the incidence being one new case/million/year. In two-thirds of the patients gastrinoma occur sporadically while the other cases are associated with other endocrine tumours, such as pituitary and parathyroid tumours in the context of the multiple endocrine neoplasia syndrome type I (MEN-l). In MEN-1 patients, hypercalcaemia due to hyperparathyroidism may aggravate the severity of gastric acid hypersecretion. Most gastrinomas are located in the pancreas or within the duodenal wall and are frequently multiple, particularly in MEN-1 patients. Only a minority of patients with gastrinomas (20-40%) may be cured by surgery as tumours 13ailli~re's Clinical Endocrinology and Metabolism-217 Vol. 6, No. 1, January 1992 Copyright © 1992, by Bailli~re Tindall ISBN 0-7020-1485-0 All rights of reproduction in any form reserved
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are either not found by imaging studies or not entirely removed at surgery or have already metastatisized. Indeed, at the time of diagnosis, about 50% of the patients have metastasis to the lymph nodes, liver or bones (for review see Maton et al, 1989a). Recently, visualization of enteropancreatic tumours in vivo after intravenous administration of a labelled somatostatin analogue has been reported (Lamberts et al, 1990). This new imaging technique which relies on the presence of somatostatin receptors on most of these tumours may become useful in localizing primary tumours and detecting metastases.
Clinical manifestations Most if not all of the symptoms due to localized gastrinomas are secondary to gastric acid hypersecretion. Indeed, increased gastrin production and hypergastrinaemia are responsible for thickening of the gastric mucosa, augmented parietal cell number and high gastric acid output. Both basal (normal
APUD (amine precursor uptake and decarboxylation) cells constitute a family of endocrine cells distributed throughout the body and characterized by the ability to take up and decarboxylate amino acid precursors of biogenic amines. This property results in the synthesis of bioactive amines or polypeptide hormones. APUD cells are found in organs as diverse as the pituitary gland, peripheral autonomic ganglia, adrenal medulla, gastrointestinal tract, pancreas, lung, gonads and thymus. Endocrine tumours originating from cells characterized by the APUD properties have been referred to as APUDomas. The initial clinical manifestations of most of these tumours can be attributed to the overproduction of biogenic amines or hormones. Although many endocrine tumours can be classified as APUDomas, only those whose clinical manifestations may require emergency management are considered here, excluding insulinomas and tumours originating from the autonomic ganglia or adrenal medulla (see Chapters 2 and 7). ZOLLINGER-ELLISON SYNDROME Definition The Zollinger-Ellison syndrome (ZES) is usually the first manifestation of gastrin-producing tumours (gastrinomas) and is secondary to an increased gastrin production. ZES is characterized by severe gastric acid hypersecretion, which causes peptic ulceration and diarrhoea. The most serious acute complications are bleeding and bowel perforation. Gastrinomas occur rarely, the incidence being one new case/million/year. In two-thirds of the patients gastrinoma occur sporadically while the other cases are associated with other endocrine tumours, such as pituitary and parathyroid tumours in the context of the multiple endocrine neoplasia syndrome type I (MEN-l). In MEN-1 patients, hypercalcaemia due to hyperparathyroidism may aggravate the severity of gastric acid hypersecretion. Most gastrinomas are located in the pancreas or within the duodenal wall and are frequently multiple, particularly in MEN-1 patients. Only a minority of patients with gastrinomas (20-40%) may be cured by surgery as tumours 13ailli~re's Clinical Endocrinology and Metabolism-217 Vol. 6, No. 1, January 1992 Copyright © 1992, by Bailli~re Tindall ISBN 0-7020-1485-0 All rights of reproduction in any form reserved
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are either not found by imaging studies or not entirely removed at surgery or have already metastatisized. Indeed, at the time of diagnosis, about 50% of the patients have metastasis to the lymph nodes, liver or bones (for review see Maton et al, 1989a). Recently, visualization of enteropancreatic tumours in vivo after intravenous administration of a labelled somatostatin analogue has been reported (Lamberts et al, 1990). This new imaging technique which relies on the presence of somatostatin receptors on most of these tumours may become useful in localizing primary tumours and detecting metastases.
Clinical manifestations Most if not all of the symptoms due to localized gastrinomas are secondary to gastric acid hypersecretion. Indeed, increased gastrin production and hypergastrinaemia are responsible for thickening of the gastric mucosa, augmented parietal cell number and high gastric acid output. Both basal (normal
