Journal of Medicine Vol 4 - Amrita Institute of Medical Sciences and ...

Amrita Journal of Medicine
Multiple Endocrine Neoplasia 2B
CT scan neck showed multiple nodules involving both
lobes of thyroid with evidence of multiple enhancing
lymphadenopathy in the submandibular level 2, 3, 4 right
side and level 1 and 5 on both sides. The 24-hour urinary
metanephrine and VMA were surprisingly normal. CT
abdomen showed a 6.2 x 5.8 cm sized heterogeneously
enhancing lesion with central necrosis on the left adrenal
gland. Right adrenal gland also showed evidence of 1.2 x
1.3 cm enhancing nodule (Fig.3).
Fig.3: CT chest showing bilateral adrenal mass lesion
In spite of normal VMA and metanephrine patient
underwent laparoscopic bilateral adrenalectomy in view
of presence of bilateral adrenal mass and strong possibility
of the pheochromocytoma in this clinical setting.
Before surgery he was adequately prepared with alpha
blockade and given peri and postoperative steroid coverage
and later on, after adrenalectomy, he was stabilised
on oral hydrocortisone and fludrocortisone. His diagnosis
was confirmed with histopathology showing bilateral
pheochromocytoma. After that he underwent total thyroidectomy
with bilateral modified radical neck
dissection. Histopathology confirmed the diagnosis of
MTC with metastasis to bilateral cervical lymph nodes.
Post operatively he was started on L-thyroxine replacement
and then fractionated radiotherapy was given to
tumor bed and nodal areas.
MUTATION ANALYSIS
His blood was sent for MEN2B mutation analysis
which was done by PCR DNA sequencing which revealed
a heterozygous M918T mutation in exon 16 of RET protooncogene
of chromosome 10. His diagnosis of MEN 2B
was confirmed.
CARRIER ASCERTAINMENT
His 3-year-old son’s blood was also sent to the same
laboratory and it also yielded the same M918T mutation.
The son had few mucosal neuromas in the tongue.
His BP was normal and basal calcitonin was 14 pg/mL.
He underwent total thyroidectomy with central compartment
dissection.
Histopathological examination showed C cell hyperplasia.
His urinary metanephrines and CT abdomen are
normal now.
DISCUSSION
Multiple endocrine neoplasia syndromes are classified
into two main categories: MEN type 1 and MEN
type 2
MEN 2 includes two forms:
MEN 2A (Werner’s syndrome)
-Medullary thyroid cancer (100%)
-Pheochromocytoma (50%) and
-Parathyroid tumors (10-20%)
MEN2A variants
-MEN2A with cutaneous lichen amyloidosis
-Familial Medullary thyroid cancer
-MEN2A with Hirschsprung’s disease
MEN2B
-Medullary thyroid cancer (100%)
-Pheochromocytoma (50%)
-Ganglioneuroma and mucosal neuromas (>98%)-
-Marfanoid habitus (>95%)
MEN2 related syndromes are uncommon with probably
fewer than 1500 kindreds worldwide 1 . Fewer cases
of MEN2 have been reported in Asia, except for Japan,
where many families exist 2 . They are autosomal dominant
conditions due to activating mutations of extracellular
cysteine domain or intracellular tyrosine kinase domain
of RET protooncogene with the result that the intracellular
tyrosine kinase is activated constitutively in the
absence of its natural ligand ‘Glial derived nerotropic
factor’. MTC occurs in all the patients of MEN2B. In
general MTC develops earlier and it is more aggressive in
MEN2B compare to MEN2A. Children have been described
with metastatic MTC shortly after birth 3,4 . Death
related to complications of metastatic MTC may occur
before onset of the third decade 5,6 . Pheochromocytomas
in MEN2B occur in more than 50% of affected individuals
and also may develop at an early age. Mucosal
neuromas located on the tongue tip, within the lips, and
on the eyelids makes for a characteristic facies identifiable
even in the childhood 7 . But because of the rarity of
the condition and unawareness amongst the doctors it is
often missed as in the present case.
The primary goal of screening for MEN2 is to identify
and treat the several manifestations of MEN2 before they
become life threatening. A secondary goal is to provide
genetic counseling to family members about the potential
for transmission to the next generation. The two
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