Endocrine Uii 2011

*T. UtoroDepartment of PathologyGadjah Mada University School of Medicine

PATHOLOGY ENDOKRINOLOGY

*PATHOLOGY OF THE

T H Y R O I D

*T H Y R O I DNormally weighs between 20 and 30 g.Follicle is the functional unit of the thyroid composed of an epithelium-lined sac filled with colloid stores thyroid hormones in the form of thyroglobulin T4 (thyroxine) and T3 (triiodo-thyronine) regulated by TSHSerum T4 and T3 are bound to thyroid-binding globulin (TBG)

*Homeostasis in the hypothalamus-pituitary-thyroid axis, and mechanism of action of thyroid hormonesCellular effects of thyroid hormonesup-regulation of carbohydrate and lipid catabolismStimulation of protein synthesis in wide range of cells

Net result:Increased the basal metabolic rate

*Pathology of thyroidCONGENITAL ANOMALYGOITERHYPOTHYROIDISMHYPERTHYROIDISMTHYROIDITISBENIGN TUMORS (ADENOMAS)MALIGNANT TUMORS

*Pathology of thyroidA. CONGENITAL ANOMALY1. Thyroglosal duct cyst- is a remnant of the thyroglossal duct- is the most common thyroid anomaly- does not lead to alterations in thyroid function2. Ectopic thyroid tissue- may be found anywhere along the course of the thyroglossal duct

*Pathology of thyroid B. GOITERA chronic enlargement of thyroid gland due to other than neoplasm

Synonim: STRUMA

*Pathology of thyroid B. GOITERA.CAUSESa. Physiologic enlargement- is not uncommon in puberty and pregnancy b. Iodine deficiency- occurs in geographic areas where diet is deficient in iodinec. Hashimoto thyroiditisd. Goitrogens- foods or drugs that suppress synthesis of thyroid hormonee. Dyshormogenesis- partial or complete failure of thyroid hormone synthesis; can be caused by various enzyme deficiencies

*Pathology of thyroid B. GOITERB.TERMINOLOGYa. Simple goiter (nontoxic goiter)- is goiter without thyroid hormone dysfunction b. Toxic goiter- is goiter associated with hyperthyroidismc. Endemic goiter- goiter occurring with high frequency in iodine-deficient geographic areasd. Nodular goiter- irregular enlargement of the thyroid nodule formation- nodular colloid goiter: late stage simple goiter, in which goiter is most often nodular (most nodules are hypoplastic and do not take up radioactive iodine cold nodule)

*Non-toxic goiterIrregular nodulesMarked variation in the size of follicles

*Nodular (non-toxic) GoiterThe gland is coarsely nodular and contains areas of fibrosis and cystic change.

*Pathology of thyroid C. HYPOTHYROIDISMDiminished production of thyorid hormone, leadingto clinical manifestation of thyroid insufficiency.It can be the consequences of three general processesDefective synthesis of thyroid hormone, with compensatory goitrogenesis (goitrous hypothyroidism)Inadequate function of thyroid parenchyma (usually as a result of thyroiditis, surgical resection, or radioiodine therapy)Inadequate secretion of TSH by the pituitary or TRH by the hypothalamus

*Pathology of thyroidC. HYPOTHYROIDISM

Dominant clinical manifestation

*Pathology of thyroid C. HYPOTHYROIDISMLaboratory abnormalities1. Decrease serum free T4, increased serum TSH2. Increase serum cholesterol3. Classic thyroid test-T3 resin uptake decreased- Total T4 decreased

*Pathology of thyroid C. HYPOTHYROIDISMClinical syndromesHypothyroidism is manifest as Myxedema in adults or as Cretinism in children

*Pathology of thyroid: C. HYPOTHYROIDISM: MyxedemaA. More common in womenB. Etiology: 1. Therapy for hyperthyroidism with surgery, irradiation, or drugs 2. Hashimoto thyroiditis3. Unknown primary idiopathic myxedema is a poorly defined form of myxedema : TSH receptor blocking antibodies have been identified.4. Iodine deficiency is the most important cause in non-iodine deficient geographic regions

*Pathology of thyroid: C. HYPOTHYROIDISM: MyxedemaC. Clinical charateristics1. Incidious onset 2. Cold intolerance3. Tendency to gain weight because of a low metabolic rate4. Lowered pitch of voice5. Mental and physical slowness6. Menorrhagia7. Constipation8. Abnormal physical findings:- puffiness of face, eyelids, and hands- dry skin- hair loss; coarse and brittle hair; scant axillary and pubic hair; thinning of the lateral aspect of the eyebrows- increase in relaxation phase of deep tendon reflexes.

*Pathology of thyroid: C. HYPOTHYROIDISM: CRETINISMA. Etiology: 1. Iodine deficiency 2. Deficiency of enzymes necessary for the synthesis of thyroid hormones3. Maldevelopment of the thyroid gland4. Failure of the fetal thyroid to descend from its origin at the base of the tongue 5. Trans placental transfer fo antithyroid antibodies from a mother with autoimmune thyroid diseaseB. Characteristics:1. Severe mental retardation2. Impairment of physical growth with retarded bone development and dwarfism3. Large tongue4. Protuberant abdomen

*Pathology of thyroidHYPERTHYROIDISM (THYROTOXICOSIS)A. Clinical Features1. Restlessness, irritability, fatigability2. Tremor3. Heat intolerance; sweating; warm, moist skin (especially palms)4. Tachycardia, often with arrythmia and palpitation, sometimes with high-output cardiac failure5. Muscle wasting and weight loss despite increase appetite6. Fine hair7. Diarrhea8. Menstrual abnormalities, commonly amenorrhoea or oligomen.9. Greatly increased free T4 and reduced TSH ------ and less commonly employed are increased total T4&T3, and resin uptake

*Graves disease, hyperthyroidismExophthalmos Thyroid mass

*Major clinical manifestations of Graves disease

*Pathology of thyroidHYPERTHYROIDISM (THYROTOXICOSIS)B. Graves DiseaseGeneral Charcteristics1. Hyperthyroidism caused by diffuse toxic goiter2. Associated with striking exophthalmos autoimmune?3. More in women4. incidence increased in HLA-DR3 and HLA-B8 positive individualMechanism1. Thyroid-stimulating-immunoglobulin (TSI) reacts with TSH receptors stimulates thyroid hormone production2. Thyroid-growth-immunoglobulin (TGI) stimulates glandular hyperplasia and enlargement 3. Antimicrosomal and other autoantibodies are characteristic

*Pathology of thyroidHYPERTHYROIDISM (THYROTOXICOSIS)B. Other causes of hyperthyroidism1. Plummer Disease- the combination of hyperthyroidism, nodular goiter, and absence of exophthalmos- the hot nodules can be adenomas or non-neoplastic areas of nodular hyperplasia2. Pituitary hyperfunction- can cause excess production of TSH and secondary hyperthyroidism3. Struma ovarii- ovarian teratoma made up of thyroid tissue, can be hyperfunctional4. Exogenous administration of thyroid hormone

*Graves DiseaseDiffusely hyperplastic thyroid with follicle are lined by tall, columnar epithelium, and scalloped (moth eaten) appearance of the edge of the colloid.

*Graves disease, hyperthyroidismThe follicles are lined by hyperplastic, tall columnar cells

*Immune mechanism of Graves Disease and Hashimoto Thyroiditis

*Pathology of thyroid E. THYROIDITISInflammation of the thyroid gland(encompasses a heterogenous group of inflammatory disorders of thethyroid gland, including those that are caused by autoimmunemechanisms and infectious agents)

A. Acute suppurative thyroiditis: a bacterial infection, usually occurs in young children or debilitated patients. It is rareB. Subacute granulomatous thyroiditis (De Quervain thyroiditis)C. Chronic thyroiditis (Hashimoto thyroiditis, Struma lymphomatosa, autoimmune thyroiditis)D. Riedels struma (Riedels disease)

*Subacute/De Quervain/granulomatous ThyroiditisIs characterized by focal destruction of thyroid tissue and granulomatous inflammationEtiology: variety of viral infections such as mumps or coxsackie virusFollows a limited course several weeks of duration consisting of flu-like illness along with pain and tenderness of the thyroid, sometimes with transient hyperthyroidismMore common in women

*Subacute/De Quervain/granulomatousThyroiditisThe release of colloid into the interstitial tissue has elicited a prominent granulomatous reaction, with numerous foreign body giant cells

*Subacute/De Quervain/granulomatous ThyroiditisThe parenchyma contains chronic inflammatory infiltrate with a multinucleate giant cells and colloid folicles

*Chronic autoimmune (Hashimoto) thyroiditisAutoimmune disorder that occur more often in womenCommon cause of hypothyroidism, may occasionaly have an early transient hyperthyroid phaseCharacterized histologically by massive infiltrates of lymphocytes with germinal center formation, thyroid follicles are atrophic, and Hurthle cells are prominentAssociated with various antibodies (antithyroglobulin, antithyroid peroxidase, anti TSH-receptor, anti-iodine receptor antobodies)May be associated with other autoimmune disorders: pernicious anemia, DM, Sjogren syndrome the incidence is increased in HLA-DR5 and HLA-B5 positive

*Chronic autoimmune (Hashimoto) thyroiditisThe thyroid gland is symmetrically enlarged and coarsely nodular.Coronal section irregular nodules and an intact capsule

*Chronic autoimmune (Hashimoto) thyroiditisAtrophic thyroid follicles with conspicuous chronic inflammatory infiltrate(the inflammatory cells form prominent lymphoid follicles with germinal centers)

*Hashimoto ThyroiditisDense lymphocytic infiltrates with germinal centersResidual thyroid follicle lined by Hurthle cells are also seen

*Riedel thyroiditisCharacterized by thyroid replacement of fibrous tissueEtiology is unknown, does not appear to be related to other thyroiditisAlso involves extra thyroidal soft tissue of the neck, often associated with fibrosis in other location (retroperitoneum, mediastinum, orbit)May clinically mimick carcinoma

*Riedel thyroiditisThe thyroid parenchyma is largely replaced by dense, hyalinized fibrous tissue and a chronic inflammatory infiltrate

*Pathology of thyroidF. BENIGN TUMORS (ADENOMAS)Are most often solitaryPresent clinically as nodulesCan occur in a variety of histologic pattern (follicular, Hurthle cell)Are most often nonfunctional but can occasionally cause hyperthyroidismFemale:male is 7:1

*FOLLICULAR ADENOMAEmbryonal adenomaFetal adenomaSimple adenomaColloid adenomaHurthel cell adenomaAtypical adenoma

*Follicular adenomaEmbryonal adenomaThe tumor features a trabecular pattern with poorly formed follicles that contain little if any colloid

*Follicular AdenomaCOLLOID ADENOMAThe cut surface of an encapsulated mass reveals:Hemorrhage

Fibrosis

Cystic change

*Follicular AdenomaA solitary, well-circumscribed nodule is seen.Cystic

*Follicular AdenomaWell-differentiated follicles resembling normal thyroid parenchyma.

*Follicular adenomaFETAL ADENOMARegular pattern of small follicles

*Follicular adenomaHurthle cell AdenomaCells with abundant eosinophilic cytoplasm and small regular nuclei.

*Pathology of thyroid G. MALIGNANT TUMORSPapillary CarcinomaFollicular CarcinomaMedullary CarcinomaAnaplastic Carcinoma

*G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Is the most common thyroid cancer (90%)Most frequent between ages 20 50 yearsFemale:male is 3:1Papillary growth pattern with ground glass nucleiBetter prognosis than other forms of thyroid cancer , even when adjacent lymph nodes is involvedCan be long-term consequence of prior radiotherapy to the neckTypically invades lymphatics and spreads to regional lymph nodes

*G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Pathogenesis:Iodine excess Animal exp., in endemic goiter region addition of iodine increase incidenceRadiation Radiation therapy, and radioactive rayGenetic factorsFirst degree relatives of persons with tumor: 4-10 fold higher risk Somatic mutationSomatic rearrangement of RET protooncogene in chromosome 10 (10q11.2)

*G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Macroscopic appearance with grossly discernible papillary structureFNAB - BAJAH

*G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Cut surface diplays a circumscribed pale tan mass with foci of cystic change

*G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC)Well-formed papillaeOrphan Annie eye, or ground-glass nuclei, or empty appearing nuclei

*G. MALIGNANT TUMORSPapillary Thyroid Carcinoma (PTC) the most common thyroid cancerBrancing papillae are lined by neoplastic columnar epithelium with clear nuclei. A calcospherite (psammoma body) is evident..

*G. MALIGNANT TUMORSFollicular Thyroid Carcinoma (FTC)FTC ia defined as a malignant neoplasm that is purely follicular and does not contain papillary or any other elementsMostly are detected as a palpable nodule or enlarged thyroid, or as advanced form as bone (pathological fracture), or lung metastasisPoorer prognosis than PTCDiffers from PTC in that metastses are blood borne rather than lymphatic, directed principally to the bones of shoulder and pelvic girdles, sternum, and skull

*G. MALIGNANT TUMORSFollicular Thyroid Carcinoma FTC)Cut surface of follicular carcinoma with the substantial replacement of the lobe of the thyroid.

The tumor has a light-tan appearance and contains small foci of hemorrage

*G. MALIGNANT TUMORSFollicular Thyroid Carcinoma (FTC)Glandular lumen contains recognizable colloid

*G. MALIGNANT TUMORSFollicular Thyroid Carcinoma (FTC)Capsular integrity in follicular neoplasm is critical in distinguishing follicular adenoma from carcinoma.Follicular adenoma: capsule is usually thin, occasionally more prominent; no capsular invasion is seen (arrows).Follicular carcinoma: capsular invasion (arrows)ADENOMACARCINOMA

*G. MALIGNANT TUMORSFollicular Thyroid Carcinoma (FTC)A microfollicular tumor has invaded veins in the thyroid parenchyma.

*G. MALIGNANT TUMORSMedullary Thyroid Carcinoma (MTC)MTC is distinguished by its secretion of the calcium-lowering hormone (calcitonin)Reprsents no more than 5% of all thyroid cancers80% are sporadic form: RET protooncogene mutation are detected in 25-70% of cases20% are familial form: afflicted by MEN type 2 includes phaeochromocytoma and parathyroid hyparplasia, adenomaThe mean age: 50 years (familial case 20 years)

*G. MALIGNANT TUMORSMedullary Thyroid Carcinoma (MTC)Tends to arise in superior portion (the region that are richest in C cells--parafollicular)Often multicentric and bilateral (MEN setting)Conspicuous feature: the presence of stromal amyloid, representing the disposition of calcitoninThe preccursor of the familial form MTC is C cell hyperplasiaTumor markers: Calcitonin, CEA, Chromogranin

*G. MALIGNANT TUMORS: Medullary Thyroid Carcinoma (MTC)Clinical FeaturesSymptoms related to endocrine secretion: carcinoid syndrome (calcitonin), Cushing syndrome (ACTH)Watery diarhea in 1/3 cases, caused by secretion of vasoactive intestinal peptide, pros-taglandin, and several kininsFamilial MTC: hypertension, episodic hypertension, symptoms attributable to the secretion of catechol-amines and phaeochromocytomaTherapy: thyroidectomy local recurrencies 1/3 5-year survival rate is 75%

*G. MALIGNANT TUMORS: Medullary CarcinomaSolid pattern of growth and do not have connective tissue capsule.Coronal section total (bilateral) involvement by a firm, pale tumor.

*G. MALIGNANT TUMORS: Medullary Thyroid CarcinomaNest of polygonal cells embedded in a collagenous framework.

*G. MALIGNANT TUMORS: Medullary Thyroid CarcinomaAmyloid: Congo red staining polarized light microscope pale green birefringent

*G. MALIGNANT TUMORS: Medullary CarcinomaTypically contain amyloid, visible here as homogenous extracellular material, derived from calcitonin molecules secreted by the neoplastic cells

*G. MALIGNANT TUMORS: Anaplastic (Undifferentiated) Carcinoma of the ThyroidUsually fatal, principally afflict women (4:1) over the age of 60 yearsConstitutes 10% of thyroid cancersIt seems likely that the anaplastic carcinoma represent the transformation of a benign or lower grade thyroid neoplasm into poorly differentiated and highly aggressive cancerMutation of p53 is common5-year survival rate less than 10%

*G. MALIGNANT TUMORS: Anaplastic Carcinoma of the ThyroidThe tumor in traverse section partially surround the trachea and extend into the adjecent soft tissue.

*G. MALIGNANT TUMORS: Anaplastic CarcinomaThe tumor is composed of bizarre spindle and giant cells with numerous mitoses

*G. MALIGNANT TUMORS: Lymphoma of the thyroidAre largely B-cell tumorsAccounts for 2% of all thyroid cancersMost if not all cases arise in the setting of chronic thyroiditisMore in women (4:1), the mean age is older than manMacros: large, soft, tannish masses of thyroid, usually extending beyond the confines of glandMicros: same spectrum as other sites, mostly diffuse large cell pattern

PANKREAS ENDOKRINDiabetes mellitusTumor endokrin (islet cell tumors)

Secretory Products of Islet Cells and Their Physiologic Actions

CellSecretory ProductMol. Wt.Physiological ActionAlphaGlucagon 3500Catabolic, stimulates glycogenolysis & gluconeogenesis, raises blood glucoseBetaInsulin 6000Anabolic, stimulates glycogenesis, lipogenesis, protein synthesis, lowers blood glucose. Inhibits secretion of alpha, beta, D1, acinar cellsDeltaDSomatostatin1600DeltaD1Vasoactive Intestinal Polypeptide (VIP)3800Same as glucagon, regulates tone & GE tract motility, activates cAMP of intestinal epitheliumPPHuman pancreatic polypeptide (ppp)4300Stimulates gastric enzyme secretion, inhibits intestinal motility & bile secretionECSerotonin, substance P (motilin)176Induce vasodilatation, increases vascular permeability, stimulates motility of gastric muscle and tone of lower esophageal sphincter

PAFKUGM

NORMAL PANCREAS

Staining of immunoperoxidase technique for insulin insulin containing cells are darkly stained

DIABETESKlasifikasi & gambaran umum1. DM Tipe 12. DM Tipe 23. Maturity-onset DM of the young (MODY)4. DM sekundera. Penyakit pankreas(1) Hemokromatosis Herediter (bronze diabetes)(2) Pankreatitis(3) Ca pankreasb. Penyakit endokrin lainc. Kehamilan Patofisiologi

DIABETES Tipe 1Kalau tidak diberikan insulin akan terjadi Intoleransi karbohidrat dengan hiperglikemia poliuri, polidipsi, penurunan berat badan / nafsu makan naik, ketoasidosis, koma kematianKetoasidosis akibat dari meningkatnya katabolisme lemak keton bodies (yang tidak terbatas pada ketoasidosis tetapi juga pada kelaparan jauh lebih ringan)

DIABETES Tipe 2Jauh lebih banyak dari pada tipe 1Mulai pada umur pertengahan (paling sering)Mekanisme: 1. peningkatan resistensi terhadap insulin akibat dari penurunan reseptor insulin di membran atau 2. karena disfungsi pos-reseptor; atau 3. dapat berhubungan dengan terganggunya proses perubahan proinsulin insulin4. Penurunan sensing glukosa oleh sel beta5. Gangguan fungsi protein pembawa intraselular

DIABETES Tipe 2Faktor etiologik:Riwayat keluarga positive lebih sering dari pada tipe 1Paling sering dihubungkan dengan obesitas sedang sampai beratGejala / karakteristik:Kadar insulin plasma normal atau meningkatIntoleransi karbohidrat ringan diet dan OAD, insulin biasanya tidak diperlukanKetoasidosis tidak biasa kecuali pada keadaan stress tertentu misalnya pada infeksi dan operasi

Maturity-onset diabetes mellitus of the youngMODYSindroma autosom dominan ditandai dengan hiperglikemia ringan dan hiposekresi insulin, tanpa hilangnya sel betaOnset lebih dini dari pada tipe 2Disebabkan karena keaneka-ragaman kelompok dari defek gena tunggal pada

DM SekunderMuncul sebagai manifestasi sekunder dari pankreas dan penyakit endokrin yang lain dan kehamilan

1. Penyakit pankreas2. Penyakit endokrin lain3. Kehamilan

DM Sekunder1. Penyakit pankreas1.Hemokromatosis herediter (bronze diabetes)Ditandai oleh absorpsi besi berlebihan dan deposisi hemosiderin parenkimal, dengan fibrosis reaktif pada berbagai organ terutama pankreas, hati, jantung2.PankreatitisRadang akut ditandai hiperglikemi; radang kronis berakibat destruksi pulau Langerhans DM sekunder3.Ca pankreasDiabetes bisa sebagai gejala

DM Sekunder2. Penyakit endokrin lain1.Cushing SyndromeBerakibat hiperglikemia dan peningkatan glukoneogenesis dan gangguan pemakaian glukosa perifer2.AkromegaliBerakibat hiperglikemia karena efek laksana-anti insulin dari GH (hormon pertumbuhan)3.Hipersekresi glukagonMenyebabkan glikogenolisis karena tumor sel alfa (glukagonoma)4.Kelainan endokrin lainFeokromositoma & hipertroidisme kadang dihubungkan dengan hiperglikemia

Patofisiologi DM1.Pulau-pulau Langerhansa. DM tipe 1Pulau-pulau kecil dan sel-sel beta sangat berkurang atau hilangAdanya radang dengan sebukan limfosit padat sangat spesifik pada tingkat awal b. DM tipe 2Fibrosis dan hialinisasi fokal pada pulau2 (karena deposit amilin) cukup karakteristik tapi tidak spesifikDepoisisi amylin (islet amyloid polypeptide, IAPP) dalam pulau-pulau karakteristik untuk DM tipe 2 mengganggu perubahan proinsulin ke insulin atau sensing insulin oleh sel beta

Amyloid of a pancreatic islet

Patofisiologi DM2.GinjalManifestasi awal pada ginjal yang sering: penebalan membrana basalisAkibat umum: glomerulosklerosis difus, fokal (penyakit Kimmelstiel-Wilson), lesi arteriolar, lesi eksudatifHiperglikemi lama tanpa terapi lesi Armani-Ebstein (deposisi glikogen tubular)Pielonefritis: komplikasi yang sering, kadang bersama nekrosis papilar renal

Hyaline arteriolosclerosis of afferent arteriolae of kidney

Nodular glomerulosclerosis

Nephrosclerosis in long standing diabetes

Patofisiologi DM3. Sistem kardiovaskularInsiden aterosklerosis sangat meningkat, pada usia lebih muda, dan meningkat tinggi pada wanita pre & post menopausalKomplikasi: infark miokard dan insufisiensi vaskular perifer (sering dengan gangren tungkai bawah)Penebalan membrana basalis kapilar organ multipel dan diperkirakan karenaglikosilasi protein membran non-enzimatik

Patofisiologi DM4.MataPaling sering: katarakRetinopati proliferatif (eksudat retina, edema, hemoragi, mikroaneurisma vasa kecil)5.Sistem syarafPerubahan: neuropati perifer, otak, dan medula spinalis6.HatiPerlemakan hati7.Kulit:XantomaFurunkel dan abses, infeksi jamur

Diabetic retinopathy

TYPE I VERSUS TYPE II DM

TUMOR ENDOKRIN PANKREAS1.Insulinoma (tumor sel beta)Paling banyak, bisa jinak atau ganasSekresi insulin berlebihan (mengandung C-peptide) harus dibedakan dengan insulin eksogen (terapi tidak mengandung C-peptide)Trias Whipple:Hiperinsinemia & hipoglikemia episodikDisfungsi CNS sementara karena hipoglikemia (confuse, anxiety, stupor, convulsion, coma)Segera menjadi normal kembali dengan pemberian glukose

Insulinoma : ribbon or brown stained cells resembling those of the normal islet of Langerhans

TUMOR ENDOKRIN PANKREAS2.Gastrinoma Tumor ganas, bisa ekstra pankreasSekresi gastrinBerhubungan dengan sindroma Zolinger-Ellison3.Glukagonoma (tumor sel alfa)Jarang, berakibat DM sekunder dan lesi kulit khas: eritema migratori nekrolitik4.VipomaJarang, sekresi vasoactive intestinal peptide (VIP)Berhubungan dengan sindroma WDHA (Watery Diarrhea Hypokalemia and Achlorhydria) = sindroma Verner-Morrison = kolera pankreatik

Multiple Endocrine Neoplasia (MEN)Kelompok sindroma autosomal dominan dengan hiperfungsi lebih dari satu organ endokrinKemungkinan berhubungan dengan hiperplasia atau tumorJenis: 1. MEN I (sindroma Werner) 2. MEN IIa (sindroma Sipple)3. MEN IIb (MEN III)

MEN I (WERMER SYNDROME)Termasuk hyperplasia tumor hipofisis, paratiroid, atau pankreas endokrin (3Ps)Bisa tambah hyperplasia atau tumor tiroid atau adrenal cortexKomponen pankreatiknya dapat bermanifestasi sebagai sindroma Zollinger-Ellison, hiperinsulinisme, atau cholera pankreatikBerhubungan dengan mutasio pada gena MEN I

MEN IIa (Sipple syndrome)Termasuk pheochromocytoma, medullary carcinoma tiroid, dan hiperparatiroidisme karena hiperplasia atau tumor Berhubungan dengan mutasi onkogena ret

MEN IIb / IIIIncludes pheochromocytoma, medullary carcinoma, and multiple mucocutaneous neuroma or ganglioneuroma. In contrast to MEN IIa, does not induce hyperparathy-roidism. - is linked to different mutations in the ret oncogene than is MEN IIa

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