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33 Cards in this Set
- Front
- Back
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hyper function
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-excess of a hormone
-multiple endocrine neoplasia syndromes (MEN) |
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hypo function
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-deficiency of a hormone
-autoimmune polyglandular syndrome (APS) |
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MEN
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-1 & 2 most common
-affect multiple types of hormone -secreting organs and produce multiple hormonal syndromes |
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VonHippel-Lindau disease
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-hormone excess (catecholamines, insulin), malignant tumors, renal-cortex cancer, haemangioblastoma, retinal angioma
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Neurofibromatosis type 1:
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-duodenal carcinoid, catecholamine tumors, neurofibromas, freckling, café-au-lait spots, Lisch nodules (pigmented hamartomatous nevi in iris)
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MEN 1
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-association of tumors involving
1. Parathyroid gland 2. EnteroPancreatic 3. Anterior Pituitary (3 Ps) -2/3 main MEN-1 tumor types -familial = an index case with a relative who has 1 of the 3 main MEN-1 tumor types -simplex/sporadic form: no +FH -M=F; onset rarely <10 |
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MEN 1 endocrine features
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-parathyroidadenoma
-gastrinoma -prolactinoma |
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MEN 1- parathyroid/hyperplasia
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-hypercalcemia and increase PTH
-present in 20s, women slide13 |
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MEN 1- non-endocrine features
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1. Lipoma
2. Multiple facial angiofibromas 3. collagenoma |
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Lipoma
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-generally dermal, small and sometimes multiple
-frequency of lipomas in normal subjects has limited their use for MEN-1 carrier ascertainment |
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Multiple facial angiofibromas
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-found in 85% of MEN 1 pts but not in controls
-half of MEN1 pts have 5+ -Acneiform papules that do not regress and that can extend across the vermilion border of the lips |
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Collagenoma
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--Found in 70% of MEN-1 patients but not in control subjects
-whitish macular lesions about the trunk (sparing the face and neck) |
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MEN 2A
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-thyroid - medullary thyroid carcinoma
- parathyroid- hyperplasia - adrenals- pheochromocytoma |
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MEN 2B
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-thyroid - medullary thyroid carcinoma
-pheochromocytoma -marfoid habitus, GI, ganlioneuromatosis, mucosal neuromas |
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MTC only
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-thyroid- medullary thyroid carcinoma
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Why the specific glands involved?
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1. APUD Theory- specific polypeptide and biogenic amine producing cells derived embryologically from the neural crest
-Endodermal: pituitary, parathyroid and pancreas -Neuroectodermal: MCT, pheochromocytoma |
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genetics of MEN syndromes
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-autosomal dominant (FH impt!, screening family members!)
-specific gene defects identified 1. MEN 1: MEN1 gene, mutations, long arm of ch 11, gene product --> protein menin, tumor suppressor gene 2. MEN2: RET proto-oncogene on ch 10, activations promotes growth and differentiation signals in several tissues most derived from neural crest, thyroid "C" cells, parathyroid, adrenal medulla |
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Calcitonin
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-Calcitonin made by c cells of the thyroid, very specific to the thyroid; if someone has medullary carcinoma expect this to be elevated
-Good marker of recurrent disease -After surgery calcitonin level should be undetectable |
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genetic screening for MEN
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-MEN 1 screening useful for the pt/carrier state but not for therapeutic intervention
-MEN 1 gene mutations noted in only 70% of kindreds; 30% false neg -MEN 2 screening for RET mutations is a guide for successful mgmt of pts; almost 100% detection |
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prophylactic thyroidectomy
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-MEN 2A by age 5-6
-MEN 2B by age 1 -there are more specific guidelines based on genetics |
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gene carrier status
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slide 36
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Autoimmune polyglandular syndromes (APS)
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Type 1: Chronic mucocutaneous candidiasis(MC), chronic hyoparathyroidism(HP), Addison’s Disease (AI) (at least two present)
Type 2: Addison’s Disease (always present) and thyroid autoimmune diseases, and/or Type 1 diabetes Type 3: Thyroid autoimmune diseases associated with other autoimmune diseases (excluding Addison’s and /or hypoparathyroidism) Type 4: Combination of organ-specific autoimmune diseases not included in the previous groups |
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APS type 1
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-HAM
1. hypoparathyroidism- 80% 2. addisons dz- 72% 3. mucocutaneous candidiasis - 100% -APECED: Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dysplasia |
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APS type 1- associated endocrinopathies
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1. hypogonadism (F>M)
2. thyroidtis 3. type 1 DM |
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autoimmune polyglandular syndromes- type 1
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1. pernicious anemia
2. vitiligo 3. alopecia 4. karatopathy 5. hepatitis 6. ectodermal dystrophy: pitting of nails, calcification of TM, enamel hypoplasia |
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APS type 2
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-Schmidt's syndrome
1. thyroiditis or graves 2. type 1 DM 3. addisons- 100% -associated abnormalities 1. vitiligo 2. alopecia 3. hypogonadism -not associated 1. hepatitis 2. steatorrhea |
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APS epidemeology
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Type 1:
1. onset usually childhood 2. candidiasis often appears first 3. hypoparathyroidism often preceds adrenal failure 4. Abs herald organ failure 5. M=F Type 2: 1. adult onset 2. F>>M 3. DM often appears 1st 4. HLA association -ABs to target organs can predict disease |
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pathogenesis of APS
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-autoimmune diseases:as immunologic reaction against self-molecules resulting from a failure to maintain tolerance to self antigens
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APS organ specific ABs
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1. anti-adrenal Abs
2. anti-steroid cell AB 3. Anti-parital cell AB: predictive of pernicious anemia 3. Anti-melanocyte AB |
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APS non-organ specific ABs
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-ANA
-JRA, SLE, MS -Myositis -Steatorrhea |
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APS genetics
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Type 1: autosomal recessive
-AI regulator gene (AIRE), on ch21 -AIRE gene may function to enhance expression of “peripheral” antigens in the thymus, promoting tolerance; regulator of T-cell function Type 2: polygenic inheritance -altered by environmental factors |
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APS tx
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1. hormonal replacement therapy
2. anticipate organ failures 3. anti-candida meds 4. psyc support 5. immune modulation |
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Immunotherapy
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-Rituximab (anti-B cell AB) some efficacy in graves and type 1 DM
-anti-CD3 monoclonal ABs in type 1 DM -GAD65 injections in new onset T1DMLADA |
