- Author: Praveen K Roy, MD, AGAF; Chief Editor: Julian Katz, MD more...
Somatostatinomas are rare neuroendocrine tumors that arise from the pancreas or the gastrointestinal tract and are characterized by excessive secretion of somatostatin hormone by tumor cells of D-cell origin. They are frequently associated with a classic clinical pentad of diabetes mellitus, cholelithiasis, weight loss, steatorrhea and diarrhea, and hypochlorhydria and achlorhydria.[1, 2, 3, 4, 5, 6]
In 1977, Larsson et al and Ganda et al independently reported the first 2 cases of somatostatinoma. A full description of somatostatinoma syndrome followed in 1979 when Krejs and colleagues described the morphologic and biochemical properties of a tumor of the ampulla of Vater in a 52-year-old man with distinct clinical symptoms and excessive somatostatin levels.
In an unusual case reported by Colovic et al, a 57-year-old woman was found to have 2 synchronous nonfunctioning somatostatinomas: one solid duodenal lesion and one cystic lesion in the pancreatic head. The patient had no secondary lesions in the liver or in the removed lymph nodes. Both tumors were successfully resected with a pylorus-preserving Whipple procedure, and the patient remained well and symptom free 18 months postoperatively.
Somatostatinomas very rarely arise in other locations (eg, lungs, liver, kidneys). Larger tumors are usually found in the pancreas (5 cm vs 2.5 cm in the duodenum), although malignancy is of equal incidence for primary tumors of the pancreas and duodenum (65%). Metastases are present in most patients at the time of clinical presentation.[3, 4, 5] Pancreatic and duodenal somatostatinomas can sometimes be distinguished by their clinical presentations.
Somatostatin is a cyclic peptide present in both 14-amino acid and 28-amino acid forms. It acts in both an endocrine and a paracrine manner to inhibit the secretion of many hormones, including insulin, glucagon, growth hormone, gastrin, cholecystokinin (CCK), secretin, and vasoactive intestinal peptide (VIP). This inhibitory action is thought to be responsible for the clinical manifestations that mark the disease. The generalized inhibition of gastrointestinal hormones results in restriction of gallbladder contractility, pancreatic exocrine function, and intestinal secretion and motility.
Somatostatin's reduction of insulin secretion results in diminished glucose use and hepatic glucose overproduction. Thus, the associated inhibitory syndrome leads to development of diabetes mellitus in 95% of patients. The clinical severity of diabetes can range from mild glucose intolerance to frank ketoacidosis. Cholelithiasis and biliary tract disease occur in 25-68% of patients with somatostatinoma; the conditions are secondary to suppression of CCK, inhibition of biliary motility, and altered fat metabolism. Diarrhea and steatorrhea are common symptoms of pancreatic somatostatin tumors and contribute to weight loss. In most patients, hypochlorhydria or achlorhydria occurs because of inhibited gastric acid secretion.
Somatostatinomas often simultaneously produce other hormone products, including insulin, gastrin, VIP, glucagon, corticotropin (previously adrenocorticotropic hormone [ACTH]), calcitonin, pancreatic polypeptide, and others. If these products are secreted into the bloodstream in significant quantities, they affect the clinical presentation and diagnosis.
Duodenal somatostatinomas may be associated with neurofibromatosis, which is an autosomal dominant disorder characterized by abnormalities of growth and differentiation of the nervous system. Features of neurofibromatosis include multiple café-au-lait spots, neurofibromas, and congenital abnormalities (eg, abnormal bone and joint formation, mental retardation). Malignant tumors such as pheochromocytoma, Wilms tumor, and sarcoma may also occur in association with this syndrome.
A case of somatostatinoma of the duodenal papilla (minor ampulla) in a patient with neurofibromatosis 1 has been reported. The lesion was removed via uncomplicated open local excision.
Somatostatinomas occur with an annual incidence of 1 case per 40 million population. Somatostatinomas occur sporadically in 93% of cases, and 7% of cases are seen in conjunction with multiple endocrine neoplasia type 1 (MEN 1) syndrome. MEN 1 involves parathyroid, pancreatic, and pituitary neoplasms. Neurofibromatosis and pheochromocytoma are associated with the duodenal form of somatostatinoma.
Race-, sex-, and age-related demographics
No racial predilection has been identified, and males and females are equally affected.
Most patients are in their fourth, fifth, or sixth decade of life.
Prognosis primarily depends on the presence or absence of metastatic disease at the time of presentation and initial treatment. Most somatostatinomas (84%) are metastatic at the time of presentation, but a number of 5-year survivors following combination surgery and chemotherapy have been reported among patients with metastatic disease. If treated with appropriate resection, virtually all patients with nonmetastatic somatostatinoma enjoy a cure.
Postoperative 5-year survival rates of patients with metastatic somatostatinoma is 30-60%, but patients without metastases have a 5-year survival rate approaching 100%. Tanaka and associates reviewed 32 cases of duodenal somatostatinomas and found that primary tumors of patients with metastases were significantly larger (>2 cm) than tumors of patients without metastases. Extremely elevated somatostatin levels that persist suggest large malignant tumors with metastases. Some of the clinical symptoms of unresectable metastatic somatostatinoma can be controlled medically.
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