Multiple Endocrine Neoplasias (MEN)

MEN Type 1

•     Characterized by
  • Parathyroid Hyperplasia
  • Pancreatic/Duodenal Neuroendocrine Tumors
  • Pituitary (Anterior) Adenomas
• Genetics
  • Mapped to chromosome 11q13
  • "Double-Hit" model of oncogenesis
  • MEN 1 tumor suppressor gene encodes for an amino acid called "menin"
  • Menin involved in regulation of cell growth
  • Diverse array of mutations
    • Missense: point mutations in which a DNA base pair change results in the substitution of an erroneous amino acid
    • Nonsense: base pair changes that result in a codon that does not specify an amino acid leading to premature termination of translation
    • Frame Shift: changes the reading frame and usually causes premature termination of translation
  • Autosomal dominant inheritane with ~100% penetrane but variable expressivity
• Clinical Findings
  • usually expressed in 3-4th decade of life, rare in those <10yo, males=females
  • abnormality distribution:
    • Parathyroid hyperplasia:    ~95%
    • Pancreatic tumors:            ~30-80%
    • Pituitary tumors:                ~15-50%
  • Parathyroid
    • generalized chief cell hyperplasia
    • hypercalcemia usually first abnormality detected
    • MEN1 HPT usually occurs earlier and more mild then sporadic form
    • Dx by measuring serum calcium & parathyroid hormone (PTH) levels
    • surgical procedure is a 31/2 gland resection or 4 gland resection with autotransplantation into forearm with a transcervical partial thymectomy
    • imaging studies generally NOT needed since must identify all 4 glands anyway
    • sestamibi scan or U/S may be useful for localization before reoperative surgery
  • Pancreatic/Duodenum
    • tumors cause symptoms either via hormone over secretion or mass effect
    • highly malignant potential
    • non-functioning tumors most common
    • functioning tumors:
      • Gastrinoma most common -> hypergastrinemia (ZE syndrome)
        • epigastric pain
        • reflux esophagitis
        • secretory diarrhea
        • wt loss
        • active PUD in 70-80% patients
        • Dx by documented acid hypersecretion & associated elevated fasting levels of serum gastrin
        • Secretin test can be used to confirm
          • give iv secretin & look for rise in serum gastrin level
        • usually malignant
        • maybe hard to find on CT, endoscopic U/S maybe helpful
        • wide local resection to control tumor and prevent malignant dissemination maybe indicated
        • total gastrectomy NOT needed for PUD since medical Rx works so well
        • Pts with HPT should get parathyroidectomy because it improves the ZES
      • Insulinoma -> second most common
        • usually small, evenly distributed throughout pancreas
        • symptoms of neuroglycopenia: sweating, dizziness, confusion, syncope
        • Dx by documenting hypoglycemia with inappropriately high insulin & C-Peptide levels
        • r/o factitous hypoglycemia
        • Rx is surgical resection (can be hard to localize)
          • mobilize panc, intraop U/S maybe helpful
          • maybe enucleated or require partial pancreatectomy
          • blind subtotal pancreatectomy is NOT recommended
        • 10% are malignant & disseminated disease maybe Rx'd with Streptozotocin
  • Pituitary
    • most are prolactin secreting adenomas
      • lead to amenorrhea/galactorrhea in females or hypogonadism in males
    • Bromocriptine maybe used to treat prolactinomas
    • may also get acromegaly if growth hormone secreted or Cushing's disease if corticotropin produced

MEN Type 2

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