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I am Jim Smirniotopoulos, M.D.
Today we're going to talk about multiple endocrine neoplasia syndromes part 1
we have no conflicts nor significant financial disclosures to report
multiple endocrinopathies or multiple endocrine neoplasia syndromes
are autosomal dominantly inherited disorders that involve
inactivation of regulatory genes. These affected patients develop multiple
neuroendocrine tumors, hyperplasia or adenopathies, including: anterior pituitary
(both micro- and macro-adenoma); almost 100% have parathyroid adenomas
or hyperplasia Mitchell a retiree cancer
time making bronchial carcinoid tumors, pancreatic or gastroduodenal
neuroendocrine tumors (NETs);
adrenal cortical and medullary neoplasms;
and, neck, thoracic, and abdominal paragangliomas.
These MEN syndromes
include up to 8, or nine, or ten different disorders (depending on classification)
But, we're going to focus on a few
instead of doing the entire alphabet soup of all of them.
MEN1, MEN2a, MEN2b, and familial medullary thyroid cancer.
MEN2b was originally, and may still be
called MEN3
These diseases also have eponyms - they're all named after physicians - mostly deceased physicians.
MEN1 is Wermer syndrome, MEN2a is Sipple
syndrome, and two beers wagon min for both to use
How can we remember these different multiple endocrine neoplasia
syndromes? Well, if we think first about MEN1 - these patients develop a pituitary lesions
and an almost all of them (~100%) will have
parathyroid hyperplasia and/or parathyroid adenomas. One-half to one-third
have pancreatic or gastroduodenal carcinoid tumors.
Notice that all of these start with the letter "P" so ...
MEN1 is sometimes called the "3p syndrome" in addition to being called
Wermer syndrome. When we think about the 3 P's we want to remember P - pituitary
P - parathyroid
and P - pancreatic islet cell tumors (these tumors may also occur in the wall
of the stomach or duodenum).
We also see cutaneous lesions including angiofibromas,
and collagenomas.
Adrenal cortical masses (hyperplasia/adenoma)
that may be the result of ACTH secretion by pituitary adenoma
or maybe autonomous adrenal cortical adenomas,
carcinoid tumors, and other CNS tumors including meningioma
and ependymoma. MEN1 is an autosomal dominant disorder with a prevalence of
two to three per hundred thousand - about the same as von Hippel-Lindau disease.
The gene has been mapped out to 11q13.
The penetrance is about a hundred percent by age 50, with most of the
patients having parathyroid adenoma or hyperplasia.
10 to 70 percent will have a pituitary adenoma,
which are usually prolactin secreting tumors - although they may produce growth
hormone or ACTH - occasionally LH/FSH
About 30 to 75 % of the patients have pancreatic or gastroduodenal
neuroendocrine tumors; and, the most significant of these - in terms of
morbidity and symptomatology -
are gastrin secreting tumors or gastronomas. About eighty-five percent
will also have facial angiofibromas
which, while very similar to those that occur in tuberous
sclerosis (TS)
are usually far less numerous than in that other disorder.
The diagnostic criteria for MEN1 include major lesions such as pituitary adenoma, parathyroid
disease, pancreatic or gastroduodenal endocrine tumors (islet cell, carcinoid)
and two of these three are required. Familial MEN and requires that you have
one of the major disease
features and a first-degree relative who is also affected.
Switching to the MEN 2 diseases,
they are primarily diseases of the medulla op the thyroid and the medulla
of the adrenal gland. By that we mean that
these patients develop medullary thyroid cancer
and pheochromocytoma - usually from the medulla of the adrenal gland.
So, to me, MEN2 is a "medullary" disease.
MEN2b is very similar to MEN2a - but adds
the presence cutaneous neuromas on the lips, tongue, or other mucous membranes
and a "Marfanoid" body habitus or shape.
So MEN2b is medullary PLUS cutaneous and/or body morphology disease
MEN2b patients may also have ganglioneuromatosis of the
the intestines. The diagnostic criteria for MEN2
include having medullary carcinoma the thyroid (MTC),
adrenal medullary or other location pheochromocytoma,
In some series, these patients may also have parathyroid abnormalities ...
which is a little bit confusing because it crosses into the realm with MEN1
There is a third disorder related related to MEN2 - which is familial inheritance
of medullary carcinoma of the thyroid - but without
any the other conditions that we have just described.
Simply, this is called "Familial MTC".
MEN2a and 2b are both autosomal dominant. MEN21 is far more common with
a prevalence of approximately one in thirty thousand.
its due to a germline mutation in the RET gene 10q11.2,
and an incredibly high risk for medullary thyroid cancer.
about half the patients will have pheochromocytoma.
About eighty percent of all the MEN2 patients are type 2a
and about 5 percent have MEN2b - so it is far less common.
and about 15 percent at the patients with this RET 10q11 mutation
will only have medullary thyroid cancer (familial MTC - NOT, MEN2a nor MEN2b)
Sipple disease is the eponym for MEN2a
and Wagenmann--Froboese is the eponym for MEN2b
and again in MEN2b - or "MEN 3", the choice is yours -
these patients have mucosal neuromas
unusual faces with a high arched palate and a Marfanoid habitus,
and they may also have gastrointestinal ganglioneuromas.
The treatment for the patients with any of the mutations causeing MTC
is a prophylactic thyroidectomy, typically performed in childhood,
under the age of five. So should we call it MEN3 - or should we call it MEN2b.
MEN2b or NOT 2b
To Be ... or NOT to Be,
that is the question but perhaps again
the ganglioneuromas are the answer. Which raises an interesting question.
Many authors have suggested that Abraham Lincoln actually had MEN2b.
He had a somewhat tall and thin Marfanoid habitus; and, he also had lesions on his
lips
that appear in these old photographs to be mucosal neuromas.
I'll leave that discussion to you and your consultant Dr. Google
I'm James Smirniotopoulos, and I want to thank-you for your attention.
I hope everyone has a very joyous holiday season!