Multiple endocrine neoplasia type 2 (MEN2)

Sipple syndrome , Gorlin syndrome (not to be confused with the Gorlin-Goltz\/naevoid basal cell carcinoma syndrome)

Multiple Endocrine Neoplasia type 2 (MEN2) is defined by the association of C-cell tumors of the thyroid ( medullar thyroid carcinoma), tumors of the adrenal medulla ( pheochromocytoma) and parathyroid hyperplasia or adenoma in a single patient or in close relatives

MEN2 is an autosomal dominant disorder with a high penetrance. Expressivity is variable but phenotype-genotype correlations have been described. Incidence is estimated at 0.1\/10^{5\/year. It is generally assumed that 20 to 25% of medullar thyroid carcinomas (MTC) are heritabl}

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653 Multiple endocrine neoplasia type 2

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Three subtypes have been described:

MEN2A (Sipple syndrome) is the most frequent form, characterized by MTC in 95% of cases, phaeochromocytoma in 50% and parathyroid hperplasia or adenoma in 25%.

In familial MTC (FMTC), MTC is the only clinical manifestation.

MEN2B (Gorlin syndrome) is the least frequent variant defined by predisposition to MTC and phaechromocytoma and marfanoid habitus, mucosal neuromas and ganglioneuromatosis of the gastrointestinal tract.
C-cells secrete the hormon calcitonin which is a valuable marker for early diagnosis and for following the later course of the disease. There is no obvious syndrome of calcitonin overproduction.
Pheochromocytoma secrete adrenaline and noradrenaline which are responsible of hypertension but could be undetected and lead to fatal hypertensive episodes.
Parathyroid hyperplasia or adenoma lead to hyperparathyroidism; they are often clinically silent but could be revealed by symptomatic hypercalcemia or renal stones.

MTC is a malignant tumor, metastasizing at first locally within the neck and then to distant sites. Usually pheochromocytoma is non malignant; parathyroid hyperplasia or adenoma are benign

Total thyroidectomy with bilateral radical lymph node dissection is the treatment of MTC. Thyroidectomy is recommended for carriers of mutations, in the first years of life in MEN2A and MEN2B families, as soon as elevation CT during pentagastrin test in FMTC families.
Pheochromocytoma, hyperplasic parathyroid or adenoma should be surgically removed.

Pheochromocytoma could be letal by hypertension episodes but prognosis is essentially dependant from MTC.

21 exons; genomic sequence of 55kb

RET is expressed predominantly in the developing central and peripheral nervous system, the excretory system and the migratory neural-crest cells during embryogenesis.

Receptor tyrosine kinase

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http:\/\/sf-endocrino.net\/pathologies\/cancer\/articles\/contedevolx1.html NEM2 - SFE