Presented by :

Aaron Dhanukdharriesingh

Definition

Multiple endocrine neoplasia type 1 or MEN1 is part of
a group of disorders that affect the endocrine system.
It involves tumors in at least two endocrine glands.
Tumors can also develop in other organs and tissues.
These growths can be benign or malignant.

Tumours that are most frequent in MEN1-
o Tumors of the parathyroid gland
o Tumours of the pituitary gland
o Tumours of the pancreas



Epidemiology
Occurs in about 1 to 2 persons out of 100,000- Rare

M=F

The genetic abnormality of MEN1 is on the long arm of
chromosome 11

MEN1 is inherited in an autosomal dominant manner.

Approximately 10% of cases are caused by de novo mutations

Expression of the disease: <10 years

Syndrome presents: 20 - 40 years.

Cause
MEN1 is an autosomal dominant condition.
Associated gene- MEN1.
More than 90% of individuals who inherit the MEN1
mutation will develop one or more symptoms of
MEN1.

Signs and symptoms

Hyperparathyroidism is the most common sign of this
disorder.





Disrupts the normal
balance of calcium in
the blood
Loss of appetite
Osteoporosis
Kidney stones
Hypertension
Nausea
Weakness
Depression
Fatigue
Neoplasia in the pituitary gland can manifest
as prolactinomas.







Pituitary tumor in MEN1 can be large and cause signs
by compressing adjacent tissues.

Prolactin
Gonadotrophins
Sex hormones
-ve feedback

Pancreatic tumors usually form in the beta cells of the islets of Langerhans,
causing over-secretion of insulin, resulting in hypoglycemia.

However, many other tumors of the pancreatic Islets of Langerhans can occur
in MEN1.







Another is a tumor of the non-beta islet cells, known as a gastrinoma.





Zollinger-Ellison syndrome may include severe gastric ulcers, abdominal pain,
loss of appetite, chronic diarrhea, malnutrition, and subsequent weight loss.
Necrolytic migratory
erythema
Tumour involving
alpha cells
Glucagon
Hyperglycemia
Weight loss
Zollinger-Ellison
syndrome
Gastrinoma Gastrin
acid-production by
cells of the stomach
(parietal cells)
Diagnosis
Many people may also be diagnosed because of screening of first- and
second-degree relatives of patients with multiple endocrine neoplasia
type 1 (MEN1).

Diagnosis of MEN1 depends on having a high level of suspicion in
patients who present with multiple facial angiofibromas, collagenomas,
and lipomas, or other features such as hyperparathyroidism or
increased gastric acid secretion.

Investigations include hormone hypersecretion blood tests and
imaging studies to look for the presence of tumours.

DNA testing is available and identifies a mutation in about 80% of
patients with familial MEN1.
Prenatal diagnosis for pregnancies at increased risk is possible if the
disease-causing mutation in a family is known.


Assessment

Practice Guidelines for Surveillance of Multiple Endocrine Neoplasia Type 1 (MEN1)
















CT = computed tomography; MRI = magnetic resonance imaging; NETs = neuroendocrine tumors;
PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; US = ultrasound.
Biochemical Test or
Procedure
Condition
Screened For
Age Screening
Initiated (y)
Frequency
Serum prolactin and/or
insulin-like growth factor 1
Pituitary tumors 5 Every 1 y
Fasting total serum calcium
and/or ionized calcium and
PTH
Parathyroid tumors
and PHPT
8 Every 1 y
Fasting serum gastrin Duodenopancreatic
gastrinoma
20 Every 1 y
Chromogranin A, pancreatic
polypeptide, glucagon, and
vasointestinal polypeptide
Pancreatic NETs <10 Every 1 y
Fasting glucose and insulin Insulinoma 5 Every 1 y
Brain MRI Pituitary tumors 5 Every 35 y based
on biochemical
results
Abdominal CT or MRI Pancreatic NETs 20 Every 35 y based
on biochemical
results
Abdominal CT, MRI, or
endoscopic US
Pancreatic NETs <10 Every 1 y

Treatment

Pharmacological
Diazoxide can be used to inhibit release of insulin, especially in
tumours that are beyond surgery.

High-dose proton pump inhibitors are required for gastrin-secreting
tumours.

After surgery to the pituitary, hormone replacement may be required.


Surgical
Skin tumours may be removed because of cosmetic concerns.

The surgical approach to pancreatic endocrine tumours in multiple
endocrine neoplasia type 1 (MEN1) is is best achieved by removing the
pancreas and duodenum with adjacent lymph nodes.

Pituitary tumours: treatment is the same as for sporadic pituitary
tumours. This usually involves a transsphenoidal operation to remove
the tumour.

Parathyroidectomy, subtotal or complete, is practiced for MEN1 but
long-term follow-up reveals a high rate of recurrence in MEN1 despite
surgical intervention.

The treatment of metastatic disease is the same as in sporadic cases.

Complications of treatment

The most challenging treatment issues relate to
the pancreatic islet cell tumors. In addition to its role
in normal digestion, the pancreas regulates the level of
blood glucose through insulin production. Removal of
the pancreas will cause diabetes mellitus, which can
lead to significant health problems.


Prognosis

The average age of death -
o 55.4 years for men
o 46.8 years for women

Pancreatic endocrine tumours, particularly gastrinomas, become
malignant in about 50% of patients with MEN1. Untreated,
patients may die from peptic ulcer disease, metastatic endocrine
pancreatic carcinoma, or foregut carcinoid malignancy.

Pancreatic endocrine tumours associated with MEN1 are less
malignant than sporadic tumours and carry a better prognosis,
with a median survival of 15 years compared to 5 years for
patients with sporadic tumours. This may reflect less severity of
the disease or earlier diagnosis.


Glossary

Angiofibromas- small, reddish brown or even flesh-colored, smooth, shiny, 0.1- to 0.3 cm papules present over
the sides of the nose and the medial portions of the cheeks
Autosomal dominant- a trait or disorder in which the phenotype is expressed in those who have inherited
only one copy of a particular gene mutation (heterozygotes); specifically refers to a gene on one of the 22 pairs
of autosomes (non-sex chromosomes)
Benign tumour- a mass of cells that lacks the ability to invade neighboring tissue or metastasize.
Collagenoma - also known as a connective tissue nevus may be present at birth or appear within the first few
years, is elevated, soft to firm, varying from 0.5 to several centimeters in diameter, and may be grouped,
linear, or irregularly distributed.
Endocrine system- the body's network of hormone producing glands
Enucleation- the surgical removal of a mass without cutting into or dissecting it.
Germline mutations- alterations in the bodys egg or sperm cells that become incorporated into the DNA of
every cell in the body of the offspring
Gonadotropins- also known as glycoprotein hormones, are protein hormones secreted by gonadotrope
cells of the anterior pituitary. Hyperparathyroidism- Overactivity of the parathyroid gland.
hypoglycemia- condition resulting from low blood glucose levels.
Lipoma- a benign tumor composed of adipose tissue.
Malignant tumour- cancerous cells that have the ability to spread to other sites in the body (metastasize) or to
invade and destroy tissues. Malignant cells tend to have fast, uncontrolled growth due to changes in their
genetic makeup.
Necrolytic migratory erythema- a red, blistering rash that spreads across the skin, particularly the lower
abdomen, buttocks, perineum, and groin. It is strongly associated with glucagonoma, a glucagon-producing
tumor of the pancreas, but is also seen in a number of other conditions including liver disease and intestinal
malabsorption.
Neoplasia- formation of new tissue
Resection- a surgical procedure to remove part of an organ or gland
Syndrome- a group of symptoms that together are characteristic of a specific disorder
Zollinger-Ellison syndrome- caused by a nonbeta islet cell, gastrin-secreting tumor of the pancreas that
stimulates the acid-secreting cells of the stomach to maximal activity, with consequent gastrointestinal
mucosal ulceration.

References
Darling TN, Multiple Endocrine Neoplasia Type 1, Medscape, Mar
2012
National Cancer Institute www.cancer.gov
Association for Multiple Endocrine Neoplasia Disorders (AMEND)
www.amend.org.uk
Asgharian B, Turner ML, Gibril F, et al; Cutaneous tumors in
patients with multiple endocrine neoplasm type 1 (MEN1) and J
Clin Endocrinol Metab. 2004 Nov;89(11):5328-36.
Hausman MS Jr, Thompson NW, Gauger PG, et al; The surgical
management of MEN-1 pancreatoduodenal neuroendocrine
disease. Surgery. 2004 Dec;136(6):1205-11.
Marx SJ. Multiple endocrine neoplasia type 1. In: Metabolic Basis of
Inherited Diseases, 8th Ed. ed. Scriver CS, et al. McGraw Hill, NY,
2001.p943-966.