Wermer Syndrome (MEN Type 1) Workup

Updated: Feb 18, 2015
  • Author: Laura Williams, MD; Chief Editor: George T Griffing, MD  more...
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Workup

Laboratory Studies

Laboratory studies in patients known to have multiple endocrine neoplasia type 1 (MEN1) screen for different hormones associated with potential MEN1 tumors.

Gastrinomas

Gastrinomas can be confirmed by the presence of an elevated fasting gastrin level and increased basal gastric acid secretion. Gastric acid output is measured if gastrin is high (measured by pH probe). Screening should start by age 20 years. If serum gastrin is high (normal is < 115 ng/mL) and gastric acid output is high, then gastrin levels could be evaluated after secretin stimulation. An increase of gastrin level by more than 200 ng/mL after an intravenous injection of secretin at 2 IU/kg of body weight is abnormal. The secretin test is necessary to exclude other diseases associated with pathologically increased serum gastrin levels.

Insulinomas

A supervised 72-hour fast is used most often to confirm this diagnosis. Increased plasma insulin occurs with hypoglycemia. Elevated C-peptide and proinsulin levels occur. Screening should start by age 5 years. Exclude the presence of oral hypoglycemic agents.

Glucagonomas

Elevated serum glucagon levels and hyperglycemia are present. Diagnosis may occur incidentally with imaging studies. Screening should start in children younger than 10 years.

Vasoactive intestinal polypeptidomas (VIPomas)

Watery diarrhea with hypokalemia and achlorhydria can occur. Elevated serum levels of vasoactive intestinal polypeptide are present. Screening should start in children younger than 10 years.

Pancreatic polypeptidomas (PPomas)

PPomas are not associated with a clinical syndrome. Pancreatic polypeptide levels are elevated. Chromogranin A levels can be elevated in any pancreatic neuroendocrine tumor. Screening should begin by age 10 years.

Carcinoid tumors

Elevated levels of chromogranin A, calcitonin, corticotropin, or urinary 5-hydroxyindoleacetic acid (5-HIAA) can occur. However, screening is dependent on radiological imaging as no biochemical abnormality has been consistently observed. [1]

Pituitary tumors

Assess growth hormone levels (insulinlike growth factor-1 [IGF-1]) and prolactin. Screening should begin by age 5 years.

Hyperparathyroidism

Calcium is elevated with an inappropriately elevated parathyroid hormone level. Parathyroid hormone levels may be in the normal range, but they should be suppressed if hypercalcemia is present. Screening should start by age 8 years. Dual-energy x-ray absorptiometry (DEXA) can assess for structural bone abnormalities.

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Imaging Studies

Pituitary tumors

Magnetic resonance imaging (MRI), with attention to the sella turcica region (pancreatic protocol), is the screening test of choice. [14] Patients should also be screened every 3 years starting at age 5 years.

Gastrinomas

Biochemical evidence should be present in order to pursue radiological evaluation. Somatostatin-receptor scintigraphy is the imaging procedure of choice for gastrinomas. Its sensitivity range is 70-90%. Somatostatin-receptor scintigraphy findings can be enhanced by selective arterial secretagogue testing with secretin or calcium infusion. (In 10% of cases of gastrinomas, secretin is not diagnostically useful.) Endoscopic ultrasonography (EUS) helps detect tumors in the pancreatic head but rarely in the duodenal wall. It is more sensitive than CT scanning or transabdominal ultrasonography.

Insulinomas

Biochemical evidence should be present before pursuing radiological evaluation. CT scanning and MRI are recommended first. Somatostatin-receptor scintigraphy findings may be positive in up to 50% of patients with insulinomas. It is best used in conjunction with single-photon emission CT (SPECT) scanning. EUS (see image below) has a reported detection sensitivity of up to 94%. Selective arterial calcium stimulation with hepatic venous sampling is often required as patients with multiple endocrine neoplasia type 1 (MEN1) are likely to have multiple lesions. Intraoperative ultrasonography can be helpful.

Endoscopic ultrasonogram in a patient with an insu Endoscopic ultrasonogram in a patient with an insulinoma. The hypoechoic neoplasm (arrows) is seen in the body of the pancreas anterior to the splenic vein (SV). (From: Rosch T, Lightdale CJ, Botet JF, et al. Localization of pancreatic endocrine tumors by endoscopic ultrasonography. N Engl J Med. Jun 25 1992;326(26):1721-6.)

Parathyroid tumors

Parathyroid gland imaging with a sestamibi scanning is of limited benefit as all parathyroid glands may be affected and neck exploration is required regardless. An example of a positive scan is illustrated (see image below).

Technetium-99m sestamibi scan (99mTc MIBI) in a pa Technetium-99m sestamibi scan (99mTc MIBI) in a patient with multiple endocrine neoplasia syndrome type 1 (MEN1). These images demonstrate persistent abnormal activity of the inferior right parathyroid gland that is consistent with an adenoma.

Pancreatic neuroendocrine tumors

EUS can identify tumors in 55% of asymptomatic patients. Annual MRI, CT scanning, or EUS screening is recommended. Adrenal gland imaging should be undertaken at the same time. Radiological screening should start before age 10 years.

Thymic and bronchial carcinoid tumors

CT scanning or MRI of the chest is recommended every 1-2 years. Screening should begin by age 15 years.

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Other Tests

Genetic testing

Sequence analysis of the MEN gene for mutations provides the best evidence of gene carrier status. This genetic test is performed in several commercial laboratories. Testing should be done in an index case with 2 or more multiple endocrine neoplasia type 1 (MEN1)–associated endocrine tumors; asymptomatic first-degree relatives of a known MEN1 mutation carrier; first-degree relatives of a MEN1 mutation carrier with symptoms, signs, and biochemical or radiological evidence of MEN1 associated tumor(s); or in individuals with suspicion of MEN1 (parathyroid adenomas in an individual younger than 30 years or a history or gastrinoma or multiple pancreatic neuroendocrine tumors at any age). [1]

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Histologic Findings

Parathyroid glands show diffuse or nodular proliferations of chief cells, with some oncocytic cells. Usually, all 4 glands are involved and show signs of hyperplasia.

Neuroendocrine tumors of the pancreas manifest with numerous microadenomas, usually in the pancreatic tail. The tumors display a trabecular pattern and may show conspicuous connective-tissue stroma. Immunohistochemically, expression of multiple hormones is found. Pancreatic polypeptide and glucagon are expressed most often, followed by insulin and, rarely, gastrin. Nesidioblastosis and islet cell hyperplasia are not features of multiple endocrine neoplasia type 1 (MEN1), as previously thought.

Most duodenal tumors are located proximally. They stain for gastrin and can metastasize to regional lymph nodes.

The presence of diffuse hyperplasia of enterochromaffinlike (ECL) cells in the stomach is often associated with carcinoid tumors of considerable size (rarely metastases).

Pituitary tumors are found in the anterior part of the gland and are usually single. Most are macroadenomas, and one third show invasive features with infiltration of tumor cells through surrounding pituitary tissue.

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