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For further information, see CMDT Part 26-27: MEN Types 1–4
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Essentials of Diagnosis
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MEN 1: tumors of the parathyroid glands, endocrine pancreas and duodenum, anterior pituitary, adrenal, thyroid; carcinoid tumors; lipomas and facial angiofibromas
MEN 2 (formerly MEN 2A): medullary thyroid cancers, hyperparathyroidism, pheochromocytomas, Hirschsprung disease
MEN 3 (formerly MEN 2B): medullary thyroid cancers, pheochromocytomas, Marfan-like habitus, mucosal neuromas, intestinal ganglioneuroma, delayed puberty
MEN 4: tumors of the parathyroid glands, anterior pituitary gland, adrenal gland, ovary, testicle, kidney
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General Considerations
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MULTIPLE ENDOCRINE NEOPLASIA (MEN) 1 (WERMER SYNDROME)
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Parathyroid, enteropancreatic, and pituitary tumors
Nonendocrine tumors
Incidental adrenal nodules are found in about 50% of affected patients but are rarely secretory
Mutations in the menin gene (11q13) detectable in 60–95% of cases
Variants of MEN 1 occur, eg, kindreds with MEN 1 Burin have a high prevalence of prolactinomas, late-onset hyperparathyroidism, and carcinoid tumors, but rarely enteropancreatic tumors
In patients with MEN 1 gastrinomas, depending on the kindred, hepatic metastases tend to be less aggressive than in those with sporadic gastrinomas
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MEN 2 (FORMERLY MEN 2A; SIPPLE SYNDROME)
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Medullary thyroid carcinoma, hyperparathyroidism, pheochromocytomas
Nonendocrine: Hirschsprung disease
Caused by a mutation of the ret proto-oncogene (RET) on chromosome 10 (95%)
Each kindred has a certain ret codon mutation that correlates with the particular variation in the MEN 2 syndrome, such as the age of onset and aggressiveness of medullary thyroid cancer
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MEN 3 (FORMERLY MEN 2B)
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Adrenal pheochromocytomas, medullary thyroid carcinoma, mucosal neuromas
Nonendocrine manifestations
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Rare autosomal-dominant familial tumor syndrome caused by germline mutations in the gene CDKN1B
Affected patients are particularly prone to parathyroid adenomas (80%), pituitary adenomas (less aggressive than those seen with MEN 1), pancreatic neuroendocrine tumors, and adrenal tumors
They also appear to be prone to adrenal tumors, renal tumors, testicular cancer, neuroendocrine cervical carcinoma, and primary ovarian failure
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OTHER SYNDROMES RELATED To MEN
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Carney complex
Adrenocortical nodular hyperplasia that can produce skin abnormalities
Cushing syndrome
GH-secreting pituitary adenomas or hyperplasia with acromegaly
Thyroid tumors
Gonadal Sertoli cell tumors
Myxomas of heart and breast
Other malignancies
McCune-Albright syndrome:
Precocious puberty (particularly girls) due to gonadal hypersecretion
Cushing syndrome caused by multiple adrenal nodules
Hyperthyroidism from functioning thyroid nodules
Acromegaly caused by GH-secreting pituitary tumors may develop
Fibrous dysplasia of bones and hypophosphatemia, and bone fractures are common
Sudden death has been reported
Type 2 von Hippel Lindau (VHL) syndrome
Associated with pheochromocytomas, pancreatic/duodenal neuroendocrine tumors, hyperparathyroidism, and pituitary tumors
Hemangiomas and renal cell carcinomas
Hypoxia Inducible Factor 2A (HIF2A) germline mutations predispose to
Neurofibromatosis type 1 ...