Neoplastic disease, characterized by tumors or
hyperplasia of the parathyroid and pituitary glands and the islands of
Langerhans, with increased incidence of adrenocortical and thyroid disease.
Association with diffuse neuroendocrine tumors in the thymus, bronchi, and
Multiple Endocrine Neoplasia type I, MEN I.
Genetic disorder first reported by Paul Wermer, American
internist in 1954, and in 1955 by Robert Milton Zollinger and Edwin Homer
Ellison, American surgeons.
Both sexes equally affected. It is rare in childhood.
Prevalence in general population ranges between 1:20,000 and 1:40,000.
Autosomal dominant. More than 80% of cases caused by
inactivating mutations (including nonsense mutations, deletions and
insertions) of the MEN1 gene, MENIN; localized to chromosome 11q13.
Precise role of MENIN is unclear. It is likely to
be a tumor-suppressor gene. Mutations lead to hyperplasia of the endocrine
organs: pancreatic islet cell adenoma (40% of cases, most commonly
gastrinomas and insulinomas), parathyroid adenoma (95% of cases),
pituitary adenoma (30% of cases), adrenocortical adenoma, prolactinoma,
glucagonoma, insulinoma, and vasointestinal peptide tumor. Lesions of
nonendocrine organs may also be present: bronchial carcinoma and carcinoids,
thymomas and thymic carcinoid, duodenal carcinoid, malignant schwannoma,
ovarian tumors, and lipomas.
Clinical features and the results of biochemical tests according to the
presentation (hypoglycemia, hypercalcemia, hyperphosphatemia, anemia,
relevant endocrine abnormalities). Also, the addition of radiological information (delineation and
localization of peptic ulcers, pituitary tumor, renal stones, bronchial
tumors, etc.) is essential.
Symptoms and signs associated with the glands
involved and the function of adenomas; gastrinoma (intractable peptic ulcer,
high incidence of bleeding, perforation and obstruction, ectopic ulcers in
esophagus and small intestines, diarrhea, steatorrhea, weight loss);
pituitary adenoma (headache, visual field defects; acromegaly;
hyperthyroidism; amenorrhea); parathyroid adenoma (hypercalcemia and renal
stones); adrenal (Cushing syndrome); insulinoma (hypoglycemia); glucagonoma
(hyperglycemia, stomatitis, skin rash); islet cell tumors (can produce
glucagon, vasoactive inhibitory polypeptide, prostaglandins,
adrenocorticotropic hormone, parathyroid hormone, antidiuretic hormone,
serotonin); multiple lipomas; bronchial tumors (cough, hemoptysis,
Acid-base balance and electrolyte
disturbances must be corrected preoperatively to avoid arrhythmia,
hemodynamic instability, and potentiation of action of neuromuscular
Emergency surgery may be indicated for
complications of peptic ulcer disease. Presence of hypovolemia necessitates
perioperative fluid resuscitation, rapid sequence induction,
and pharmacological prophylaxis against gastric aspiration (e.g., sodium citrate). Invasive monitoring
may be indicated: close perioperative glucose monitoring for hypoglycemia,
anesthetic problems associated with acromegaly, Cushing syndrome, and
hyperthyroidism. Depending on size and site of bronchial tumor, expect
airway compression and ventilatory difficulties; superior vena cava
obstruction may impede venous return.
Renal dysfunction may affect
clearance of some drugs.
Brandi ML, Gagel RF, Angeli A, et al: Guidelines for diagnosis and
therapy of MEN type 1 and type 2. J Clin Endocrinol Metab
Thakker RV: Editorial: Multiple endocrine neoplasia—Syndromes of the
twentieth century. J Clin Endocrinol Metab 83;8:2617, 1998. ...