Multiple Endocrine Neoplasia Type 1 (MEN1) Clinical Presentation

Updated: Oct 31, 2017
  • Author: Catherine Anastasopoulou, MD, PhD, FACE; Chief Editor: George T Griffing, MD  more...
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Presentation

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:

  • Hyperparathyroidism is usually the initial clinical manifestation of MEN1
  • Some patients initially present with Zollinger-Ellison syndrome (ZES). [17] Gastrinoma symptoms caused by ZES include diarrhea and upper abdominal pain due to peptic ulcers and esophagitis; complications include ulcer perforation or bleeding.
  • 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. [18]
  • Glucagonoma syndrome consists of a rash (necrolytic migratory erythema), weight loss, anorexia, anemia, diarrhea, venous thrombosis, and stomatitis. The full syndrome is rarely expressed.
  • Carcinoid tumor presenting features can include flushing, diarrhea, and bronchospasm.
  • 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:

  • Prolactinomas may cause erectile dysfunction or decreased libido in men, while women may develop amenorrhea and galactorrhea.
  • 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.
  • 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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Causes

 

The putative gene for multiple endocrine neoplasia type 1 (MEN1) has been localized to band 11q13 and codes for the menin protein. Menin is involved with regulation of transcription and genome stability. Loss of heterozygosity for this region is associated with MEN1, suggesting that the gene has tumor suppression function. Patients inherit one mutated copy of the gene and require a somatic mutation of the second copy for tumor development. MEN1 is an autosomal dominant disorder, but sporadic mutations also occur.

 

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