History and Physical Examination
The presentation in multiple endocrine neoplasia type 1 (MEN1) varies from patient to patient. Patients may be asymptomatic, or may present with signs and symptoms related to the endocrine organs involved and the hormones secreted, as follows:
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Hyperparathyroidism is usually the initial clinical manifestation of MEN1
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Some patients initially present with Zollinger-Ellison syndrome (ZES). [20] Gastrinoma symptoms caused by ZES include diarrhea and upper abdominal pain due to peptic ulcers and esophagitis; complications include ulcer perforation or bleeding.
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Insulinomas also may be identified prior to primary hyperparathyroidism-associated hypercalcemia. Hypoglycemia after a fast or exertion, with improvement in symptoms after sugar intake, is the classic presentation. [21]
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Glucagonoma syndrome consists of a rash (necrolytic migratory erythema), weight loss, anorexia, anemia, diarrhea, venous thrombosis, and stomatitis. The full syndrome is rarely expressed.
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Carcinoid tumor presenting features can include flushing, diarrhea, and bronchospasm.
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Anterior pituitary tumors may produce signs and symptoms from hormonal secretion and/or mass effect.
MEN1 patients with hyperparathyroidism usually present with mild hypercalcemia, and rarely develop nephrolithiasis. Other manifestations include bone abnormalities and musculoskeletal complaints. Patients may report increased thirst and urination and/or constipation. In more severe hypercalcemia, generalized weakness and alterations of mental status may develop. These features are similar to presentations of other forms of hypercalcemia.
Clinical manifestations of anterior pituitary tumors are similar to those of sporadic pituitary adenomas and depend on hormone secretion and tumor size. Mass effects from tumor growth include headache and visual-field defects. Hormonal effects may include the following:
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Prolactinomas may cause erectile dysfunction or decreased libido in men, while women may develop amenorrhea and galactorrhea.
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Growth hormone–secreting tumors can cause acromegaly and result in enlargement of the hands, feet, and jaw; this last can manifest with increased drooling and larger spaces between teeth.
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Corticotropin-producing tumors cause excess cortisol secretion; patients can present with large, purplish abdominal stretch marks; increased bruising; and proximal muscle weakness.
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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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