Carcinoid tumor accounts for 75% of GI endocrine tumors; incidence is about 15 cases per million population. Ninety percent originate in Kulchitsky cells of the GI tract, most commonly the appendix, ileum, and rectum. Carcinoid tumors of the small bowel and bronchus have a more malignant course than tumors of other sites. About 5% of pts with carcinoid tumors develop symptoms of the carcinoid syndrome, the classic triad being cutaneous flushing, diarrhea, and valvular heart disease. For tumors of GI tract origin, symptoms imply metastases to liver.
Diagnosis can be made by detecting the site of tumor or documenting production of >15 mg/d of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the urine. Octreotide scintigraphy identifies sites of primary and metastatic tumor in about two-thirds of cases.
Surgical resection where feasible. Symptoms may be controlled with histamine blockers, serotonin receptor antagonists, and octreotide, 150–1500 mg/d in three doses or the sustained release formulation octreotide-LAN 10–30 mg IM monthly. Hepatic artery embolization and chemotherapy (5FU plus streptozocin or doxorubicin) have been used for metastatic disease. IFN-α at 3–10 million units SC three times a week may relieve symptoms. Everolimus, an mTOR inhibitor, and sunitinib, a kinase inhibitor, have antitumor effects. Radiolabeled octreotide congeners are also effective. Prognosis ranges from 95% 5-year survival for localized disease to 20% 5-year survival for those with liver metastases. Median survival of pts with carcinoid syndrome is 2.5 years from the first episode of flushing.
Gastrinoma, insulinoma, VIPoma, glucagonoma, and somatostatinoma account for the vast majority of pancreatic islet-cell tumors; their characteristics are shown in Table 72-3. The tumors are named for the dominant hormone they produce. They are generally slow-growing and produce symptoms related to hormone production. Gastrinomas and peptic ulcer disease constitute the Zollinger-Ellison syndrome. Gastrinomas are rare (4 cases per 10 million population), and in 25–50%, the tumor is a component of a multiple endocrine neoplasia type 1 (MEN 1) syndrome.
|SYNDROME||CELL TYPE||CLINICAL FEATURES||PERCENTAGE MALIGNANT||MAJOR PRODUCTS|
|Carcinoid syndrome||Entero-chromaffin, enterochro-maffin-like||Flushing, diarrhea, wheezing, hypotension||∼100||Serotonin, histamine, miscellaneous peptides|
|Zollinger-Ellison, gastrinoma||Non-β islet cell, duodenal G cell||Peptic ulcers, diarrhea||∼70||Gastrin|
|Insulinoma||Islet β cell||Hypoglycemia||∼10||Insulin|
|VIPoma (Verner-Morrison, WDHA)||Islet D1 cell||Diarrhea, hypokalemia, hypochlorhydria||∼60||Vasoactive intestinal peptide|
|Glucagonoma||Islet A cell||Mild diabetes mellitus, erythema necrolytica migrans, glossitis||>75||Glucagon|
|Somato-statinoma||Islet D cell||Diabetes mellitus, diarrhea, steatorrhea, gallstones||∼70||Somatostatin|
Insulinoma may present with Whipple’s triad: fasting hypoglycemia, symptoms of hypoglycemia, and relief after IV glucose. Normal or elevated serum insulin levels in the presence of fasting hypoglycemia are diagnostic. Insulinomas may also be associated with MEN 1.
Verner and Morrison described a syndrome of watery diarrhea, hypokalemia, achlorhydria, and renal failure associated with pancreatic islet tumors that produce vasoactive intestinal polypeptide (VIP). VIPomas are rare (1 case per 10 million) but often grow to a large size before producing symptoms.
Glucagonoma is associated with diabetes mellitus and necrolytic migratory erythema, a characteristic red, raised, scaly rash usually located on the face, abdomen, perineum, and distal extremities. Glucagon levels >1000 ng/L not suppressed by glucose are diagnostic.
The classic triad of somatostatinoma is diabetes mellitus, steatorrhea, and cholelithiasis.
Provocative tests may facilitate diagnosis of functional endocrine tumors: tolbutamide enhances somatostatin secretion by somatostatinomas; pentagastrin enhances calcitonin secretion from medullary thyroid (C cell) tumors; secretin enhances gastrin secretion from gastrinomas. If imaging techniques fail to detect tumor masses, angiography or selective venous sampling for hormone determination may reveal the site of tumor. Metastases to nodes and liver should be sought by CT or MRI.
Tumor is surgically removed, if possible. Everolimus 10 mg PO qd or sunitinib 37.5 mg PO qd may produce meaningful delay (∼12 months) in progressive disease and prolong survival in pts with metastatic disease. Octreotide inhibits hormone secretion in the majority of cases. Radiolabeled octreotide agents have antitumor effects and can induce long-term stable disease. IFN-α may reduce symptoms. Streptozotocin plus doxorubicin combination chemotherapy may produce responses in 60–90% of cases. Embolization or chemoembolization of hepatic metastases may be palliative.