MEN 1 Syndrome Diagnosis

MEN 1 Syndrome can be diagnosed based on its characteristic that can be found trough
anamnesis, physical examination, laboratory test and imaging. MEN1 syndrome is characterized
by the occurrence of primary tumors involving two or more endocrine tissues within a single
patient. It encompasses tumors of the parathyroid (95% of cases), pancreatic islets (from 30 to
80% of cases) and anterior pituitary (from 15 to 90% of cases).
[1,2]
Other endocrine and non-
endocrine lesions, such as adrenal cortical tumors, carcinoids of the bronchi, gastrointestinal
tract and thymus, lipomas, angiofibromas and collagenases have been described, but with a lower
frequency.
[1,2]

In the anamnesis we can ask the patient based on the characteristic of MEN 1 Syndrome, usual
symptoms that can be found in patient with MEN 1 syndrome can be seen on Table 1. MEN 1 is
an autosomal dominant disease, so in the anamnesis we must ask the patient about its family
history is there anyone in the family suffer from MEN 1 Syndrome because people with MEN 1
Syndrome have 50% of probability of transmitting the gene defect to the progeny, independently
by sex.
[1]

Table 1. Sign and Symptoms of MEN 1 Syndrome
[1,2]

Characteristic of MEN 1 Sign and Symptoms
Parathyroid tumors
(affecting more than 95% of all MEN1 patients)

central nervous system: altered mental status,
including lethargy, depression, decreased alertness
and confusion;
gastrointestinal tract: anorexia, constipation, nausea
and vomiting:
Kidneys: polyuria, nycturia, polydipsia, impaired
concentrating ability, dehydration, hypercalciuria
and increased risk for kidney stones;
Skeleton: increased fracture risk, osteoporosis
cardiovascular system hypertension, shortened
QT interval
Pancreatic tumors
(occur in about 3080% of MEN1 patients)
Gastrinomas: upper abdominal pain, diarrhoea,
oesophageal reflux, vomiting and acid-peptic or
duodenal ulcers and, more rarely, heart-burn and
weight loss
Insulinomas: hypoglycaemia, Whipples triad
VIPoma: Watery Diarrhoea, Hypokalaemia and
Achlorhydria
Anterior pituitary tumors
(varies from 15 to 90%)
Mass effects include visual field defects, headaches
and blurred vision
Prolactinoma: galactorrhoea, amenorrhoea and
infertility in women, and hypogonadism, sexual
dysfunction and, more rarely, gynecomastia in men
Associated endocrine tumours
Adrenal cortical tumours hypercortisolaemia and Cushing's syndrome
Thyroid tumours may be incidental and not significant
Non-endocrine associated tumours
Carcinoid tumours generally silent and most patients are asymptomatic
Facial angiofibromas benign tumours comprising blood vessels and
connective tissue, and consist of acneiform papules
that do not regress
Facial collagenomas multiple, skin-coloured, sometimes hypopigmented
cutaneous nodules, symmetrical arrangement on the
trunk, neck and upper limbs,
Lipomas multiple benign fatty tissue tumours that are
subcutaneous or, rarely, visceral
Meningiomas mainly asymptomatic and in 60% of cases show no
growth.

Physical examination such as inspection, palpation, percussion and auscultation can also help us
in diagnosing patient with MEN 1. Physical examination is based on the characteristic of MEN 1
and the information that have been collected during the anamnesis. Inspection on the neck
abdomen or the other region can be done to determine whether there are any enlargement of the
organ. Basically the purpose of the physical exam is to find any abnormality objectively.
Biochemical test is one of the diagnosis method that usually performed in the patient with
MEN1. Increase of hormonal concentration above normal level is a clue of abnormality in the
organ that secrete the hormone. Hormonal concentration between normal people and MEN 1
patient can be seen on Table 2.
Table 2. Laboratory Test
[1.2]

Characteristic Substance Normal Range In MEN 1 Syndrome
Parathyroid tumours
Parathyroid Hormone
(PTH)
normal range 1060
pg/ml
Elevated
Calcium normal range
8.510.5 mg/dl or 2.1
2.6 mmol/l
Elevated
Pancreatic tumours
Gastrinomas Gastrin normal range <100
ng/l
Elevated
Insulinomas
Insulin reference values 220
U/ml or 14.35143.5
Elevated
pmol/l
C-peptide reference values 0.5
2.0 ng/ml or
0.170.66 nmol/l
Elevated
VIPoma VIP reference
value <75 pg/ml
Elevated
Anterior pituitary tumours
Prolactinoma Prolactin Reference alues:
premenopausal women
020 ng/ml; postmeno-
pausal women 015
ng/ml; men 015
ng/ml
Elevated

Early recognition of affected and at-risk individuals is now facilitated by DNA-testing, reducing
the morbidity and mortality of MEN 1 and providing the opportunity to initiate treatment at early
stages. Mutational analysis of the MEN 1 gene is recommended for patients who meet the
clinical criteria for MEN 1 and for those in whom a diagnosis of MEN 1 is suspected.
Identification of a mutation in a patient enables testing for relatives. Finding family members
without a mutation may lead to a decision for no further screening. Most laboratories currently
use direct DNA sequencing strategies of the MEN 1 gene coding region and intron-exon
junctions. This analysis requires a single blood sample, can be performed at any age and does not
need, in theory, to be repeated.
[1]

Imaging plays a vital role in the diagnosis and management of the disease. Characteristics of
MEN 1 Syndrome such as Parathyroid Tumor, Pancreas Tumor, Anterior Pituitary adenoma and
the other neoplasm can be detected using imaging method. Imaging is used to confirm the
diagnosis beside the anamnesis, physical examination and Laboratory test.
At ultrasonography (US), parathyroid adenomas typically appear as a well-dened, oval hypo-
echoic mass posterior to the thyroid gland. CT provides no additional information, but it can
maximizes the chances of localization. Magnetic resonance (MR) imaging has a slightly higher
sensitivity than CT for the localization of parathyroid masses but is not used as the rst-line
investigative modality.
[3]

Pancreatic tumors are characterized by multiple nodular lesions developed at an early age.
[1]

Most pancreatic tumors in MEN 1 are functional, with less malignant potential than sporadic
pancreatic tumors.
[3]
Endoscopic ultrasonography (EUS) examination is the most sensitive
imaging procedure for the detection of small (10 mm) pancreatic endocrine tumors in
asymptomatic MEN1 patients; its sensitivity is higher than 75%. The use of EUS in association
with Octreoscan scintigraphy increases the pancreatic tumoural detection rate to 90%; EUS
allows precise localization of the tumors, while Octreoscan scintigraphy gives much more
information about the spread of the disease and detects liver metastases with a sensitivity of
92%.
[1]
CT is also useful in the diagnosis of local spread and liver involvement. The overall
sensitivity of CT for localizing pancreatic adenomas is 70%80%. MRI also can be used and has
a greater sensitivity than CT for identifying small islet cell tumors.
[3]

Pituitary tumours can be detected by computed tomography (CT) scanning and nuclear magnetic
resonance imaging (MRI).
[1]
A microadenoma may not be clearly visualized, but suggestive
signs include focal convexity of the superior margin of the gland and erosion of the sellar oor.
Deviation of the pituitary stalk is a nonspecic and unreliable sign. Macroadenomas (>10 mm)
may compress adjacent structures. Very rarely, bilateral pituitary adenomas may occur in MEN
1.
[3]


Reference
[1] Marini F, Falchetti A, Del Monte F, Sala SC, Gozzini A, Luzi E, Brandi ML. Multiple
endocrine neoplasia type 1. Orphanet Journal of Rare Diseases. 02 October 2006; 1(38):
1-9.
[2] Callender GG, Rich TA, Perrier ND. Multiple endocrine neoplasia syndromes. Surgical
Clinic of North America. 2008; 88: 863895.
[3] Scarsbrook AF, Thakker RV, Wass JAH, Gleeson FV, Phillips RR. multiple endocrine
neoplasia: spectrum of radiologic appearances and discussion of a multi technique
imaging approach. Radio Graphics. 2006; 26:433451