Multiple endocrine neoplasia consists of benign, and
sometimes malignant, tumors (often multiple in a tissue) of the
parathyroids, enteropancreatic neuroendocrine system, anterior pituitary,
and other tissues. Skin angiofibromas and skin collagenomas are common.
Typically, tumors begin two decades earlier than sporadic tumors.
Multiple Endocrine Adenomatoses.
MEN Type I (Wermer Syndrome): Autosomal dominant disorder characterized by a high frequency of peptic
ulcer disease and primary endocrine abnormalities involving the pituitary,
parathyroid, and pancreas.
MEN Type II A (Sipple Syndrome): Autosomal dominant syndrome including medullary thyroid carcinoma,
pheochromocytoma, and parathyroid adenomas.
MEN Type IIB (Wagenmann-Froboese Syndrome; Mucosal Neuroma Syndrome): Characterized by multiple true nervous neuromas, pheochromocytoma, and
thyroid carcinoma without parathyroid adenomas. The thyroid cancer is a
medullary type, as in MEN IIA. Although the association of pheochromocytoma
with neurofibromatosis is well known, the nervous tumor reported in the MEN
IIB is a true neuroma, consisting only of nerve cells.
MEN type 1 was the first condition described. In 1954,
Wermer was instrumental in the presentation of this medical associative
condition as a distinct clinical entity.
MEN type I prevalence is estimated at 0.02-0.2:1000 persons; no
racial predilection; both sexes are affected equally. MEN type II has an overall
frequency of 1:30,000-50,000 persons in the United States. In both types,
data in children are not available.
In 1988, pedigree testing first linked the MEN
I gene to chromosome 11q13. MEN I is an autosomal dominant inherited disease
characterized by variable penetrance for tumors of the parathyroids,
enteropancreatic neuroendocrine system, and anterior pituitary and less
commonly by tumors in other tissues. The “multiple” designation refers
both to the occurrence of multiple tumors in the involved endocrine organ
(e.g., multiple pancreatic islet tumors) and to the occurrence of tumors in
multiple endocrine organs (e.g., parathyroid tumor plus pancreatic islet
Type I disease must be distinguished from type II disease, another autosomal
dominant inherited tumor syndrome. MEN II is characterized by bilateral medullary
carcinoma of the thyroid, pheochromocytomas (often bilateral), and, in the
most common variant, parathyroid tumors. All MEN II subtypes are inherited
in an autosomal dominant manner. The probability of a new gene mutation is
5% or less in index cases with MEN IIA and 50% in index cases with MEN
IIB. Offspring of affected individuals have a 50% chance of inheriting
the mutant gene. Prenatal testing is possible. DNA testing of the RET gene
(chromosomal locus 10q11) identifies disease-causing mutations in 95% of
individuals with MEN IIA and MEN IIB and in approximately 85% of families
with familial medullary thyroid carcinoma.
It has been suggested that MEN I, like many
hereditary cancer syndromes, is caused by a mutation in a tumor suppressor
gene that contributes to neoplasia when both gene copies in a tumor
precursor cell have been sequentially inactivated (“two-hit” oncogenesis
mechanism). Germline MEN I mutations were found ...