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| *Multiple endocrine neoplasia type-1 occurs due to the mutations in gene MEN-1. This gene encodes for menin protein. Menin prevents the cells from growing and dividing aggressively. Menin is likely involved in cell functions such as copying and repairing DNA and regulating the activity of other genes. Inactivating mutations of both the copies of the MEN1 gene leads to lack of availability of menin to control cell growth and division. This leads to the formation of tumors characteristic of MEN-1 syndrome. Why these tumors preferentially affect endocrine tissues is unclear.
| | Toxic multinodular goiter is diagnosed with a physical examination which shows nodules in the throat and rapid heart rate, among other signs such as diaphoresis, tremors, blood screening includes tests for elevated T3 and T4 hormone levels that indicate hyperthyroidism. |
| | | Low levels of thyroid-stimulating hormone (TSH) are suggestive of hyperthyroidism |
| *MEN-1 syndrome is inherited in an autosomal dominant fashion. The altered gene is usually inherited from an affected parent. People with this condition are born with one mutated MEN1 gene copy in each cell. New mutations in MEN-1 without a family history can also occur in some patients.
| | overactive nodules are found on ultrasound scans of the thyroid to create images of the thyroid, which can reveal the conjunction with a special radioactive iodine test that involves swallowing a pill prior to special scans. |
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| *In most autosomal dominant conditions, in order to cause the disorder one altered copy of a gene in each cell is usually enough, two copies of the MEN1 gene must be altered to trigger tumor formation in multiple endocrine neoplasia type 1.
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| *In an individuals lifetime, in a small number of cells a mutation in the second copy of the MEN1 gene occurs. Individuals with one MEN1 mutation acquire a second mutation in few cells leading to form tumors as a result of the unregulated division of cells.
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| TABL E 408-1 Multiple Endocrine Neoplasia (MEN) Syndromes
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| Type (Chromosomal Location) Tumors (Estimated Penetrance)
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| Gene and Most Frequently Mutated
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| Codons
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| MEN 1 (11q13) Parathyroid adenoma (90%)
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| Enteropancreatic tumor (30–70%)
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| • Gastrinoma (>50%)
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| • Insulinoma (10–30%)
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| • Nonfunctioning and PPoma (20–55%)
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| • Glucagonoma (<3%)
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| • VIPoma (<1%)
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| Pituitary adenoma (15–50%)
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| • Prolactinoma (60%)
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| • Somatotrophinoma (25%)
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| • Corticotropinoma (<5%)
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| • Nonfunctioning (<5%)
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| Associated tumors
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| • Adrenal cortical tumor (20–70%)
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| • Pheochromocytoma (<1%)
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| • Bronchopulmonary NET (2%)
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| • Thymic NET (2%)
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| • Gastric NET (10%)
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| • Lipomas (>33%)
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| • Angiofibromas (85%)
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| • Collagenomas (70%)
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| • Meningiomas (8%)
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| MEN1
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| 83/84, 4-bp del (≈4%)
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| 119, 3-bp del (≈3%)
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| 209-211, 4-bp del (≈8%)
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| 418, 3-bp del (≈4%)
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| 514-516, del or ins (≈7%)
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| Intron 4 ss (≈10%)
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| MEN 2 (10 cen-10q11.2)
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| MEN 2A MTC (90%) RET
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| Pheochromocytoma (>50%) 634, e.g., Cys → Arg (~85%)
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| Parathyroid adenoma (10–25%)
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| MTC only MTC (100%) RET 618, missense (>50%)
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| MEN 2B (also known as MEN 3) MTC (>90%) RET 918, Met → Thr (>95%)
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| Pheochromocytoma (>50%)
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| Associated abnormalities (40–50%)
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| • Mucosal neuromas
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| • Marfanoid habitus
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| • Medullated corneal nerve fibers
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| • Megacolon
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| MEN 4 (12p13) Parathyroid adenomaa
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| Pituitary adenomaa
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| CDKN1B; no common mutations identified
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| to date | |
| Reproductive organ tumorsa (e.g., testicular
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| cancer, neuroendocrine cervical carcinoma)
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| ?Adrenal + renal tumorsa
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Toxic multinodular goiter is diagnosed with a physical examination which shows nodules in the throat and rapid heart rate, among other signs such as diaphoresis, tremors, blood screening includes tests for elevated T3 and T4 hormone levels that indicate hyperthyroidism.
Low levels of thyroid-stimulating hormone (TSH) are suggestive of hyperthyroidism
overactive nodules are found on ultrasound scans of the thyroid to create images of the thyroid, which can reveal the conjunction with a special radioactive iodine test that involves swallowing a pill prior to special scans.