Differential Diagnoses
(click links to learn more from eMedicine.com)
Carcinoid Tumor
Gastroesophageal Reflux
Hypercalcemia
Pheochromocytoma
VIPoma
Zollinger-Ellison Syndrome
Other Problems to Be Considered
Mastocytosis
Type 1 multiple endocrine neoplasia (MEN): Gastrinoma, adrenal adenoma, and glucagonomas
Type 2B MEN: Medullary carcinoma of the thyroid, mucosal neuromas, and ganglioneuromas
Other conditions associated with elevated gastrin levels
Massive small-bowel resection
Hypercalcemia
Treatment with histamine 2 (H2) blockers or proton-pump inhibitors (PPIs), such as omeprazole
Gastric-outlet obstruction
Workup
Laboratory StudiesLaboratory studies include investigations of the different tumor-expression patterns.
- Gastrinomas (ZES): Serum gastrin levels exceed 115 ng/mL and increase more than 200 ng/mL from baseline after secretin challenge (ie, intravenous injection of 2 U/kg of secretin). Approximately two-thirds of patients have basal gastrin levels of 150-1000 ng/mL.
- Insulinoma
- Results may reveal fasting hypoglycemia with inappropriately elevated serum insulin, C-peptide, or proinsulin concentrations.
- When the serum glucose level is less than 60 mg/dL, the serum insulin level should be less than 2 µU/mL. A serum insulin level of less than 2 µU/mL during hypoglycemia is consistent with hyperinsulinism.
- Additional diagnostic criteria include the following:
- Decreased fasting tolerance (defined during a controlled inpatient fast)
- Inappropriate glycemic response to glucagon challenge when the patient is hypoglycemic (ie, increase in serum glucose level by >30 mg/dL from a baseline of <60 mg/dL within 20 min after 1 mg of glucagon is intravenously or subcutaneously administered)
- Suppressed lipolysis (free fatty acid concentration <20 mM)
- Suppressed ketogenesis (undetectable plasma acetoacetate or beta-hydroxybutyrate) when the patient has hypoglycemia
- Acute insulin response to peripheral venous or intra-arterial calcium challenge (performed at centers including the University of Texas Health Science Center at San Antonio and the Children’s Hospital of Philadelphia)
- Glucagonoma: Findings are hyperglycemia with elevated serum glucagon levels.
- Watery diarrhea syndrome: Serum levels of vasoactive intestinal peptide are elevated. Serum K levels may be low.
- Carcinoids: levels of serotonin, urinary 5-hydroxyindoleacetic acid (5-HIAA), calcitonin, and 24-hour urinary free cortisol and corticotropin may be elevated.
- Pituitary tumors: Tests reveal persistent elevation of serum somatotropin (growth hormone [GH]) during oral glucose challenge; serum free or total insulinlike growth factor (IGF)-I level more than 2 standard deviations (for age, sex, and Tanner stage); or elevated serum prolactin levels.
- Type 2 multiple endocrine neoplasia
- MTC: Patients frequently have elevated calcitonin levels.
- Pheochromocytoma: Total urine catecholamine excretion exceeds 100-300 μg/d (over 24 h). Serum levels of more than 2000 μg/mL are pathognomonic. Measuring plasma free and urinary fractionated metanephrines with a 24-hour collection is best.
Imaging Studies
- Type 1 multiple endocrine neoplasia
- Gastrinomas: Somatostatin-receptor scintigraphy (SRS) has a sensitivity of 70-90%, which is more than that of any other imaging procedure. SRS depends on the SSR receptor profile (types 2 and 5, rarely type 3) and tumors size (exceeding 5 mm). Endoscopic ultrasonography can depict tumors in the pancreatic head but rarely in the duodenal wall.
- Insulinomas: Perform high-resolution CT scanning and MRI first. SRS findings are positive in about 50% of patients. Intraoperative ultrasonography of the pancreas is highly recommended to detect additional tumors.
- Pituitary tumors: Perform MRI, CT scanning, or both after biochemical evaluation.
- Pheochromocytoma: Radiologic imaging for pheochromocytomas includes CT scanning, MRI, metaiodobenzylguanidine (MIBG) scanning, OctreoScan imaging, and positive emission tomography (PET).
- Nonfunctioning pancreatic endocrine tumors: After type 1 multiple endocrine neoplasia (MEN) is confirmed, perform pancreatic endoscopic ultrasonography to monitor progression of nonfunctioning pancreatic endocrine tumors. Their incidence is high (54.9%), although their clinical significance remains uncertain. Follow-up of lesions discovered should be coordinated with experienced subspecialists.
Histologic Findings
- Parathyroid glands: The glands show hyperplasia and diffuse or nodular proliferations of chief cells, mixed with some oncocytic cells. All glands are involved.
- Pancreas: Numerous microadenomas (mostly in the pancreatic tail) are present. The tumors display a trabecular pattern. Immunohistochemically, tumor cells stain with antibodies directed to pancreatic polypeptide, glucagon, insulin, and gastrin.
- Duodenum: Duodenal tumors are most often gastrinomas in the first part of the duodenum. They stain positive for gastrin and may metastasize to regional lymph nodes.
- Stomach: In the stomach, diffuse hyperplasia of enterochromaffinlike (ECL) cells is found and is associated with tumors of considerable size but rarely of metastatic potential.
- Pituitary: Most tumors are single, are found in the anterior part of the gland, and produce prolactin and/or GH, and, occasionally, corticotropin.
Reprinted with permission from eMedicine.com, 2008.
Available at: http://emedicine.medscape.com/article/923269-diagnosis.
