Wermer Syndrome (MEN Type 1) Clinical Presentation

  • Author: Irina Lendel, MD; Chief Editor: George T Griffing, MD   more...
 
Updated: Oct 8, 2010
 

History

  • Hyperparathyroidism: Although the initial clinical manifestation of MEN 1 usually is hyperparathyroidism, some patients may have ZES prior to primary hyperparathyroidism.[4]
  • Gastrinoma: The symptoms due to a gastrin-secreting tumor consist of abdominal pain and diarrhea or complications of peptic ulcer disease, such as ulcer perforation or bleeding.
  • Insulinomas also may be identified prior to hypercalcemia.
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Physical

The clinical picture depends on the endocrine organs involved and the hormones secreted. It varies from patient to patient.

  • Hyperparathyroidism
    • This usually presents with mild hypercalcemia, and patients rarely develop nephrolithiasis.
    • Other manifestations include bone abnormalities and musculoskeletal complaints, as seen in the images below. Anteroposterior radiographic view of the right hanAnteroposterior radiographic view of the right hand in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism. This image shows subperiosteal bone resorption along the radial aspects of the middle phalanges (arrows). Bilateral, anteroposterior radiographic views of tBilateral, anteroposterior radiographic views of the hands in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism. These images show subperiosteal bone resorption along the radial aspects of the middle phalanges.
    • In severe hypercalcemia, generalized weakness and alterations of mental status may develop.
    • These features are not different from those for other forms of hypercalcemia.
  • Gastrinoma: Symptoms caused by ZES include diarrhea and upper abdominal pain due to peptic ulcers and esophagitis.
  • Insulinoma: Fasting hypoglycemia is a frequent presenting symptom of this disorder.
  • Glucagonoma
    • The glucagonoma syndrome consists of a rash (necrolytic migratory erythema), anorexia, anemia, diarrhea, venous thrombosis, and glossitis.
    • The full syndrome is rarely expressed. However, most patients have some hyperglycemia.
  • Pituitary tumors
    • Symptoms including headache and visual-field defects may be due to local tumor growth.
    • Prolactinomas may cause erectile dysfunction or decreased libido in men, while women may develop amenorrhea and galactorrhea.
    • Growth hormone–secreting tumors may result in acromegaly. This is a slow process and is rarely clinically identifiable.
    • Cushing syndrome may also occur.
  • Carcinoid syndrome: Features include flushing, diarrhea, and bronchospasm. They are not common in MEN 1.
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Causes

The putative gene for MEN 1 has been localized to chromosome band 11q13 and codes for the menin protein. Loss of heterozygosity for this region is associated with MEN 1, suggesting that the gene has tumor suppression function. Patients inherit 1 mutated copy of the gene and require a somatic mutation of the second copy for tumor development.

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Contributor Information and Disclosures
Author

Irina Lendel, MD  Clinical Instructor in Endocrinology, Division of Endocrinology, Diabetes, and Metabolism, Milton S Hershey Medical Center

Disclosure: Nothing to disclose.

Coauthor(s)

James M Hammond, MD  Distinguished Professor of Medicine, Penn State University College of Medicine, Milton S Hershey Medical Center

James M Hammond, MD is a member of the following medical societies: Alpha Omega Alpha, American Diabetes Association, American Federation for Clinical Research, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Phi Beta Kappa, and Society for the Study of Reproduction

Disclosure: Nothing to disclose.

Klaus Radebold, MD, PhD  Research Associate, Department of Surgery, Yale University School of Medicine

Klaus Radebold, MD, PhD is a member of the following medical societies: American Gastroenterological Association and New York Academy of Sciences

Disclosure: Nothing to disclose.

Specialty Editor Board

Frederick H Ziel, MD  Associate Professor of Medicine, David Geffen School of Medicine at UCLA; Physician-In-Charge, Endocrinology/Diabetes Center, Director of Medical Education, Kaiser Permanente Woodland Hills; Chair of Endocrinology, Co-Chair of Diabetes Complete Care Program, Southern California Permanente Medical Group

Frederick H Ziel, MD is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Diabetes Association, American Federation for Medical Research, American Medical Association, American Society for Bone and Mineral Research, California Medical Association, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS  Professor of Medicine (Endocrinology, Adj), Johns Hopkins School of Medicine; Affiliate Research Professor, Bioinformatics and Computational Biology Program, School of Computational Sciences, George Mason University; Principal, C/A Informatics, LLC

Arthur B Chausmer, MD, PhD, FACP, FACE, FACN, CNS is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American College of Nutrition, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Informatics Association, American Society for Bone and Mineral Research, American Society of Law, Medicine & Ethics, Endocrine Society, and International Society for Clinical Densitometry

Disclosure: Nothing to disclose.

Mark Cooper, MBBS, PhD, FRACP  Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University

Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD  Professor of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

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Sagittal (left image) and coronal (right image), T1-weighted magnetic resonance images of the brain in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). These images show a pituitary macroadenoma (arrows).
Indium-111 (111In) octreotide scan in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). These nuclear images demonstrate abnormal activity in the pituitary macroadenoma (curved arrow), parathyroid adenoma (straight arrow), and gastrinoma metastases throughout the abdomen (arrowheads).
Technetium-99m sestamibi scan (99mTc MIBI) in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1). These images demonstrate persistent abnormal activity of the inferior right parathyroid gland that is consistent with an adenoma.
Computed tomography (CT) scan of the pancreas in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and a gastrinoma. This image 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.
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.)
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.)
Anteroposterior radiographic view of the right hand in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism. This image shows subperiosteal bone resorption along the radial aspects of the middle phalanges (arrows).
Bilateral, anteroposterior radiographic views of the hands in a patient with multiple endocrine neoplasia syndrome type 1 (MEN 1) and primary hyperparathyroidism. These images show subperiosteal bone resorption along the radial aspects of the middle phalanges.
 
 
 
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