Diagnostic Considerations
Hyperparathyroidism in multiple endocrine neoplasia type 1 (MEN1) must be separated from other familial forms of hypercalcemia, including familial parathyroid hyperplasia and familial adenomatous hyperparathyroidism. Familial hypocalciuric hypercalcemia may also have a similar presentation. These latter 2 syndromes have no pancreatic or pituitary manifestations.
Conditions other than Zollinger-Ellison syndrome (ZES) that are associated with elevated serum gastrin levels include the following:
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Retained gastric antrum
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Gastric outlet obstruction
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Hypercalcemia
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Massive small bowel resection
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Atrophic gastritis
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Proton pump inhibitor therapy
Patients with MEN1-associated ZES are on average 10 years younger than those with sporadic ZES at the time of diagnosis. ZES should be considered in MEN1 patients with new digestive symptoms, including loose stools, especially when diarrhea promptly disappears when using proton pump inhibitor (PPI) therapy, epigastric pain and signs of GERD without severe esophagitis or tiny duodenal erosions on gastroscopy.
Differential Diagnoses
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Neuroendocrine tumors
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Primary hyperparathyroidism
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Multiple endocrine neoplasia type 1 (MEN1). Sagittal (left image) and coronal (right image), T1-weighted magnetic resonance images of the brain in a patient with MEN1 show a pituitary macroadenoma (arrows).
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Multiple endocrine neoplasia type 1 (MEN1). Indium-111 (111In) octreotide scan in a patient with MEN1 demonstrates abnormal activity in the pituitary macroadenoma (curved arrow), parathyroid adenoma (straight arrow), and gastrinoma metastases throughout the abdomen (arrowheads).
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Multiple endocrine neoplasia type 1 (MEN1). Technetium-99m sestamibi scan (99mTc MIBI) in a patient with MEN1 demonstrates persistent abnormal activity of the inferior right parathyroid gland that is consistent with an adenoma.
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Multiple endocrine neoplasia type 1 (MEN1). Computed tomography (CT) scan of the pancreas in a patient with MEN1 and a gastrinoma shows a pancreatic head mass (large, white arrow), as well as a low-attenuating lesion in the liver (small, black arrowhead) that indicates metastases. Note the calcifications of the right renal medullary pyramids (medullary nephrocalcinosis; black arrows) in this nonenhanced CT scan.
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Multiple endocrine neoplasia type 1 (MEN1). 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.)
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Multiple endocrine neoplasia type 1 (MEN1). Computed tomography (CT) scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (From: Yeo CJ. Islet cell tumors of the pancreas. In: Niederhuber JE, ed. Current Therapy in Oncology. St. Louis, Mo: Mosby-Year Book; 1993: 272.)
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Multiple endocrine neoplasia type 1 (MEN1). Anteroposterior radiographic view of the right hand in a patient with MEN1 and primary hyperparathyroidism shows subperiosteal bone resorption along the radial aspects of the middle phalanges (arrows).
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Multiple endocrine neoplasia type 1 (MEN1). Bilateral, anteroposterior radiographic views of the hands in a patient with MEN1 and primary hyperparathyroidism show subperiosteal bone resorption along the radial aspects of the middle phalanges.
Tables
Tumor |
Age at which to begin screening (yr) |
Blood tests (annual) |
Imaging studies |
Insulinoma |
5 |
Fasting glucose, insulin |
– |
Anterior pituitary |
5 |
Prolactin, IGF-I |
MRI (every 3 yr) |
Parathyroid |
8 |
Calcium, PTH |
– |
Other pancreatic neuroendocrine tumors |
< 10 |
Chromogranin-A; pancreatic polypeptide, glucagon, VIP |
MRI, CT, or EUS (annually) |
Adrenal |
< 10 |
Only in patients with symptoms or signs of a functioning tumor and/or tumor >1 cm identified on an imaging study |
MRI or CT (annually with pancreatic imaging) |
Thymic and bronchial carcinoid |
15 |
None |
CT or MRI (every 1-2 yr) |
Gastrinoma |
20 |
Gastrin (± gastric pH) |
– |
CT = computed tomography; EUS = endoscopic ultrasound; IGF-1 = Insulin-like growth factor 1; ( MRI = magnetic resonance imaging; PTH = parathyroid hormone; VIP = vasoactive intestinal peptide Adapted from Thakker RV, et al. Clinical Practice Guidelines for Multiple Endocrine Neoplasia Type 1 (MEN1). J Clin Endocrinol Metab. 2012 Sep. 97(9):2990-3011. [1] |
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