病理學教學課件：內(nèi)分泌系統(tǒng)疾病Diseases of Endocrine System

DiseasesofEndocrineSystem

PathologyDepartment,SchoolofBasicMedicalSciences,FudanUniversitycorpuspineal松果體Pituitary垂體thyroid甲狀腺Adrenals腎上腺isletofpancreas

胰島Testis睪丸Ovary卵巢HormonesMetabolicequilibrium/homeostasis維持代謝平衡和穩(wěn)態(tài)內(nèi)分泌系統(tǒng)包括：內(nèi)分泌腺內(nèi)分泌組織神經(jīng)內(nèi)分泌細胞：APUD細胞內(nèi)分泌系統(tǒng)的疾病多種多樣

1.先天性畸形或酶缺乏

2.免疫反應性炎癥

3.增生性疾病

4.腫瘤等影響激素的合成和分泌Classification1.Diseasesofunder/over-productionofhormonesandtheirresultantbiochemicalandclinicalconsequences激素分泌過多引起功能亢進；過少導致功能低下2.Diseasesassociatedwiththedevelopmentofmasslesions.占位病變morphologicfindingshormonelevelregulatormetabolites內(nèi)分泌疾病特點發(fā)病年齡不同，表現(xiàn)和后果有很大差別

內(nèi)分泌功能異?？衫^發(fā)于許多非內(nèi)分泌系統(tǒng)疾病ExcessInsufficiencyAdrenalcortisolaldosterone…Cushingsyndromehyperaldosteronism

原發(fā)性醛固醇增多癥AddisondiseaseIsletofpancreasinsulin

胰島素Hypoglycemia低血糖Diabetesmellitus糖尿病Thyroidthyroxine(T4)triiodothyronine(T3)Hyperthyroidism

甲亢Hypothyroidism

甲減Cretinism

呆小病Pituitarygrowthhormone…Gigantism巨人癥Acromegaly肢端肥大癥Dwarfism

侏儒癥PituitaryadenomaGrowthHormoneGigantism巨人癥

prepubertalchildrenbeforeepiphyses

closeAcromegaly肢端肥大癥softtissuesskinviscerabonesoftheface,hands&feetAdultsThyroid甲狀腺TheneteffectofT4T3:basalmetabolicrate (BMR)TRH:thyrotropin-releasinghormoneTSH:thyroid-stimulatinghormoneT4:thyroxineT3:triiodothyroninehypothalamus-pituitary-thyroidaxisThyroidFolliclesepitheliumthyroglobulin-richcolloidNormalfollicularcellsSynthesisandStorageofthyroidhormones合成，儲存，碘化，重吸收、分解FunctionlownormalhighEpitheliumflatcuboidalcolumnarColloidthickeventhinpuberty,pregnancy,physiologicstressTransienthyperplasiaInvolution復舊Thyroidparafollicularcells(“C”cells)濾泡旁細胞

calcitonin

降鈣素reabsorptionofbonebyosteoclastsabsorptionofcalcium(skeletalsystem)ThyroiddiseasesHyperthyroidism甲亢

Hypothyroidism甲減MasslesionsGraves

diseasenontoxicgoiter（simplegoiter）ThyroiditisNeoplasmsofthyroidIn1835,RobertGravesreported“violentandlongcontinuedpalpitationsinfemales”associatedwithenlargementofthethyroidgland20-40,womengeneticfactorsGravesDiseaseDiffusetoxicgoiter彌漫性毒性甲狀腺腫diffusesymmetricenlargementbeefydeepredparenchyma甲狀腺彌漫對稱性增大，質(zhì)如肌肉GravesDiseasePathogenesis:autoimmunedisorder

Inserum,antibodiestoTSHreceptor thyroidperoxisomes thyroglobulinThyroid-stimulatingimmunoglobulin(TSI)Thyroidgrowth-stimulatingimmunoglobulin(TGI)TSH-bindinginhibitorimmunoglobulins(TBIIs)GravesDiseaseReleaseofHFollicularE.proliferationPathogenesis:autoimmunedisorderGeneticfactorsHLA-B8 HLA-DR3

GravesDiseaseMorphologyGross:thyroidgland--diffuselyenlarged.為正常的2-3倍Thecutsurfaceofthethyroidhasafleshyappearance.GravesDiseaseDiffusehyperplasiainapatientwithGrave’sdisease.切面灰紅呈分葉狀，膠質(zhì)少，棕紅色，質(zhì)如肌肉Microscope:hyperplasticfollicleslinedbytall,columnarepith.crowded,enlargedepithelialcells---smallpapillaethescallopedappearanceoftheedgesofthecolloid(follicularcellsactivelyresorbcolloid)lymphoidinfiltratesininterstitium,germinalcenterGravesDisease(1)濾泡上皮增生，呈高柱狀(2)上皮細胞增生形成乳頭而向腔內(nèi)突出(3)吸收空泡(4)間質(zhì)淋巴細胞浸潤，有淋巴濾泡形成lymphoidinfiltrationgerminalcenterGravesDiseasehyperplasticfollicularcells,smallpapillaeareasofcolloidresorptionGravesDiseaseabundantbloodsupplyClinicalfeatures：GravesDisease3manifestations:Thyrotoxicosis甲狀腺毒癥infiltrativeophthalmopathy浸潤性眼病Myxedema粘液性水腫Thyrotoxicosis甲狀腺毒癥hypermetabolicstatefreeT3T4hyperfunctionofthethyroidgland(hyperthyroidism)hormoneexcessiveleakageoutofthyroidglandCausesofThyrotoxicosisAssociatedwithhyperthyroidismGravesdisease85%Hyperfunctioning(toxic)multinodulargoiterHyperfunctioning(toxic)adenomaTSH-secretingpituitaryadenomaNotAssociatedwithhyperthyroidismThyroiditis(earlystage,causehypothyoidismeventually)Strumaovarii(ovarianteratomawithectopicthyroid)卵巢甲狀腺瘤ExogenousthyroxineintakeThyrotoxicosishypermetabolicstate高代謝狀態(tài)overactivityofthesympatheticnervoussystem交感神經(jīng)過度興奮ThyrotoxicosisClinicalmanifestations:Clinicalmanifestations:Constitutionalsymptoms— warmskin,heatintolerance,excessivesweating, weightlosswithgoodappetite

全身癥狀：心悸、煩熱、多汗、多食、消瘦、乏力Gastrointestinal–hypermotility,malabsorptiondiarrhea胃腸蠕動加快，吸收不良性腹瀉。

ThyrotoxicosisCardiac–palpitations,tachycardia,cardiomegaly

心悸、心動過速、心臟肥大

Neuromuscular—

afinetremorofthehand,emotionalliability,anxiety,inabilitytoconcentrate,insomnia.muscleweakness

手震顫、情緒不穩(wěn)定、焦慮、注意力不集中、失眠、乏力ThyrotoxicosisClinicalmanifestations:Ocularchange—

awide-eyed,staringgazeandlidlag凝視、眼瞼后退

thyroidophthalmopathy(onlyinGravesDis.)Thyroidstorm甲狀腺危象—

abruptonsetofhyperthyroidism cardiacarrhythmias心律失常ThyrotoxicosisClinicalmanifestations:Clinicalfeatures：Thyrotoxicosisthyroidenlargementaudiblebruit(bloodflow)(withstethoscope)甲狀腺聽見血管雜音，觸診時可有震顫

diffusetoxicgoiterGravesDiseaseClinicalfeatures：

infiltrativeophthalmopathy40% awide-eyed,staringgazeandlidlag thyroidophthalmopathy(eyeballprotrusion,exophthalmos眼球突出)sympatheticnervoussystemlooseconnectivetissuebehindtheeyeballs(Gravesdis.)cornealinjuryGravesDiseaseClinicalfeatures：myxedemapretibialmyxedema---glycosaminoglycansininterstitium部分病人出現(xiàn)脛骨前粘液性水腫真皮和皮下組織糖胺聚糖沉積GravesDiseaseDiagnosis:

Clinicalfeatures

Laboratorydata—FreeT4andT3TSHAbtoTSHreceptorthyroidperoxisomes

thyroglobulinRadioactiveiodineuptakediffuselyincreaseduptake--Gravesdiseaseincreaseduptakeinsolitarynodule--toxicadenomadecreaseduptake--thyroiditisGravesDisease

轉(zhuǎn)歸內(nèi)科抗甲亢藥物治療;手術治療;放射性碘治療失明合并甲狀腺癌甲狀腺毒性心肌病nontoxic/simplegoiter單純性甲狀腺腫(diffusenontoxicandmultinodulargoiter)彌漫性非毒性甲狀腺腫goiter--enlargmentofthethyroidSimpleenlargmentofthethyroid(withoutthyrotoxicosis)twokinds:

endemic地方性(lowiodine)

sporadic散發(fā)性EtiologyandPathogenesisFoodsupplycontainlowlevelofiodineIngestionofsubstances(brassicacruciferaevegetables)HereditaryenzymaticdefectsNotapparent,iodineexcessgoiter高碘甲狀腺腫SynthesisofthyroidhormonecompensatoryinTSHFollicularcellhypertrophyhyperplasiaGoitrousenlargementcassavaMorphology 3stagesStageofhyperplasiaordiffusehyperplasticgoiter彌漫性增生性甲狀腺腫thyroidglandisdiffuselyandsymmetricallyenlargedFolliclesarelinedbycrowdedcolumnarcells,whichmaypileupandformprojections肉眼：甲狀腺彌漫腫大，對稱。

鏡下：濾泡上皮增生。2.Stageofstoredcolloidordiffusecolloidgoiter

彌漫性膠樣甲狀腺腫Gross:diffuseenlargementofthyroid.Thecutsurfaceisbrown,somewhatglassy,andtranslucent.Microscopically, follicularE.hyperplastic(earlystage) flattenedandcuboidalepith.(involution) abundantcolloid(involution)flattenedandcuboidalepith,abundantcolloiddiffuseenlargementofthyroidColloidgoiter彌漫對稱顯著增大，正常的10倍切面褐色，半透明膠凍狀。鏡下：扁平、立方狀，濾泡腔擴張，腔內(nèi)大量膠質(zhì)儲積3.Stageofmultinodulargoiter結(jié)節(jié)性甲狀腺腫Gross:therearemanynodulesintheenlargedthyroid.Microscope：regressivechangesarequitecommon.

（fibrosis,hemorrhage,calcification,cysticchange）

proliferationlesions后期濾泡上皮局灶性增生、復舊或萎縮不一致，分布不均，形成結(jié)節(jié)multinodulargoitermultinodulargoitercystformationnontoxic/simplegoiter肉眼：甲狀腺不對稱結(jié)節(jié)狀增大folliclesarrangedintoclustershemorrhagechronicinflammationnontoxic/simplegoitermultinodulargoiterhyperplasticnoduleMultinodulargoiterfibrosisandcysticchangehyperplasticnodulecompressedresidualthyroidnocapsule(diff.fromfollicularneoplasms)nontoxic/simplegoitercalcifiedwhitenodulenontoxic/simplegoitercystsandmuchfibrosisfocalcalcificationcalcificationnontoxic/simplegoiterClinicalfeatures alargeneckmassairwayobstruction,dysphagia,吞咽困難，呼吸困難Compressionoflargevesselsintheneckandupperthoraxnontoxic/simplegoiter不伴有內(nèi)分泌失調(diào)少數(shù)有毒性甲狀腺腫極少癌變Thyroiditis甲狀腺炎Chroniclymphocytic(Hashimoto)thyroiditisSubacuteGranulomatous(deQuervain)ThyroiditisSubacuteLymphocyticthyroiditisFibrous(Riedel’s)thyroiditisDuration---acute,subacute,orchronicInflammation---lymphocyticorgranulomatousDr.HakaruHashimoto日本學者Hashimoto于1912年首先報道patientswithgoiterandintenselymphocyticinfiltrationofthethyroid甲狀腺彌漫對稱腫大，間質(zhì)單核細胞浸潤chroniclymphocytic(Hashimoto)thyroiditis慢性淋巴細胞性甲狀腺炎，橋本甲狀腺炎themostcommoncauseofhypothyroidismanautoimmuneinflammatorydisorder45-65y/ofemalechildren(nonendemicgoiter)Painlessenlargementofthethyroid早期會出現(xiàn)甲亢癥狀，晚期會出現(xiàn)甲減癥狀。

“橋本氏病伴甲亢”、“喬本氏病伴甲低”PathogenesisBreakdownofselftolerancetothyroidauto-antigens血中抗甲狀腺球蛋白抗體（TGA)、甲狀腺微粒體(過氧化物酶)抗體(TMA)滴度明顯升Gross:thethyroidisusuallydiffuselyandsymmetricallyenlarged.Microscope:1.extensiveinfiltrationoftheparenchymabymononuclearinflammatory.2.folliclesatrophyandfibrosis3.Hürthle/oxyphilcells部分甲狀腺濾泡上皮變?yōu)轶w積增大、胞質(zhì)顆粒豐富的嗜酸性細胞(metaplasia)Morphologydiffusethyroidenlargementwithgrayishfleshycutsurface切面分葉，色灰白lymphoidinfiltrategerminalcentersHürthlecells(granulareosinophiliccytoplasm)adenselymphocyticinfiltratewithgerminalcentersresidualthyroidfolliclesHürthlecells30-50ywomenViralinfection(precededbyanupperrespiratorytractinfection)Painintheneckself-limiteddiseasegranulomaformationSubacuteGranulomatousThyroiditis

(deQuervain)亞急性肉芽腫性甲狀腺炎subacutegranulomatousthyroiditisfirm,enlargeddisruptionofthyroidfollicleschronicinflammatoryinfiltratemultinucleategiantcellchronicinflammatoryinfiltratemultinucleategiantcellsubacutegranulomatousthyroiditis“slient”or“painless”thyroiditisMildhyperthyroidismgoitrousenlargementMiddleagedwomenpostpartumthyroiditis產(chǎn)后甲狀腺炎self-limiteddiseaseUnlikeHashimotothyroiditis,follicularatrophyandoxyphilcellsarenotcommonlyseen.SubacuteLymphocyticthyroiditis

亞急性淋巴細胞性甲狀腺炎lymphocyticinfiltrationwithgerminalcentermildenlargementnormalappearanceSubacutelymphocyticthyroiditispatchdisruptionofthyroidfolliclesFibrousthyroiditis(Riedel’sthyroiditis)慢性纖維性甲狀腺炎、慢性木樣甲狀腺炎

AraredisorderofunknownetiologyCharacterizedbyextensivefibrosisinvolvingthethyroidandcontiguousneckstructures甲狀腺和周圍組織粘連。廣泛纖維化progressiveatrophyandscarringofthyroidtissueatrophicthyroidfollicleslymphocyticinfiltrationfibrosis(scarring)fibrousthyroiditis(Riedel’sthyroiditis)NeoplasmsofthethyroidBenign:adenomasMalignant:carcinomasAdenomas甲狀腺腺瘤BenignneoplasmsderivedfromfollicularepitheliumPainlessnodulesinthyroidFourthandfifthdecadesfemale-to-malerate=7:1FollicularadenomaofthethyroidMorphology:Asolitarysphericalencapsulatedlesion(multiplenodulesarealmostalwaysnodularhyperplasia)Aintact,well-formedcapsule.包膜完整CompresstheadjacenttissueHemorrhage&fibrosiscysticchangearecommonvarioushistologicsubtypes(trabecular,microfollicular,macrofollicular)nobiologicsignificance濾泡的形態(tài)可多樣welldevelopedfibrouscapsulesharpdemarcation分界清楚(encapsulation)andcolloidshineHürthlecell(oxyphil)adenoma.許特萊細胞腺瘤abundanteosinophiliccytoplasmandsmallregularnuclei

adenomasadenomasHemorrhagedegenerationfocalcalcificationcapsuleadenomas部分甲狀腺腺瘤可發(fā)生癌變。具有下列情況者，應當考慮惡變的可能性：1.腫瘤近期迅速增大。2.瘤體活動受限或固定。3.出現(xiàn)聲音嘶啞、呼吸困難等壓迫癥狀。4.腫瘤硬實、表面粗糙不平。5.出現(xiàn)頸淋巴結(jié)腫大。CarcinomaofThyroid1.papillarycarcinoma乳頭狀癌：75%to85%2.Follicularcarcinoma濾泡狀癌:10%to20%3.Medullarycarcinoma髓樣癌:5%(derivedfromCcells)4.Anaplasticcarcinoma未分化癌:<5%1.Papillarycarcinoma乳頭狀癌mostcommonformofthyroidcanceranyagebutmostofteninthetwentiestofortiesexposuretoionizingradiationverygoodprognosis

20-ysurvivalrates92%

Gross:solitaryormultifocallesions,wellcircumscribedorill-definedmargins

病灶單發(fā)或多發(fā)，甚至可有完整包膜，多數(shù)病例境界不清，浸潤周圍組織Wellcircumscribedlesionsuspicioussatellitenodule腫瘤呈囊狀，囊內(nèi)形成許多乳頭狀結(jié)構(gòu)Microscope:

papillaryarchitecture“ground-glass”nucleipsammomabodies癌細胞核呈毛玻璃樣，有乳頭結(jié)構(gòu)，有時有砂粒體（同心圓狀鈣化小體)

papillaryarchitecturefibrovascularcore“groundglassnuclei”(OrphanAnnieeye)Veryfinelydispersedchromatin癌細胞核染色質(zhì)少，呈透明狀或毛玻璃狀，無核仁thediagnosisisbasedonnuclearfeatures

(evenintheabsenceofapapillaryarchitecture)Pseudo-inclusionsinvaginationsofthecytoplasm---intranuclearinclusionsorintranucleargrooves細胞漿內(nèi)陷，形成假包涵體,或有核溝。follicularvariantpapillarycarcinoma

Psammomabodies砂粒體concentricallycalcifiedstructures同心圓狀鈣化小體neverfoundinfollicularandmedullarycarcinomas2.FollicularCarcinoma濾泡狀癌Thisisverymalignantcarcinoma,the5-yearsurvivalratesareonly30-40％，易血道轉(zhuǎn)移。Gross:maybegrosslyinfiltrativeorwellcircumscribed.Microscope:tumorcellinfiltratethecapsuleoradjacentthyroidparenchyma肉眼：境界不清或清楚鏡下:形態(tài)多樣，最重要的改變?yōu)槟[瘤侵犯包膜或周圍甲狀腺組織，follicularcarcinoma腫瘤無包膜，淺黃色，有小灶性出血。腫瘤為分化好的濾泡，腔內(nèi)有膠質(zhì)。與濾泡狀腺瘤鑒別FollicularcarcinomaFollicularadenomaadenomasfibrouscapsulenocapsularinvasionfollicularcarcinomascapsularinvasionfollicularcarcinomaFollicularcarcinoma,minimallyinvasivetype.follicularcarcinoma3.Medullarycarcinoma髓樣癌----Parafollicularcells,Ccells----prognosisFollicularca.<Medullaryca.<Papillaryca.----metastasislymphnodes起源于濾泡旁細胞（又稱C細胞），預后介于乳頭狀癌和濾泡癌之間，最常見的轉(zhuǎn)移方式為淋巴結(jié)轉(zhuǎn)移。

Gross:solitarynoduleormultiplelesionsMicroscope:polygonaltospindle-shapedcellsnests,trabeculae,andevenfolliclesAcellularamyloiddeposits(alteredcalcitoninmolecules)細胞外有淀粉樣物質(zhì)（降鈣素）沉積solidpatternofgrowthnoconnectivetissuecapsules實性生長，無包膜abundantdepositionofamyloid間質(zhì)有大量淀粉樣物質(zhì)沉積medullarycarcinomaamyloiddepositsKongoredstainbirefringenceonpolarizationCalcitonin(+)降鈣素(+)甲狀腺球蛋白(--)medullarycarcinoma4.AnaplasticCarcinoma未分化癌Undifferentiatedfollicularepitheliummeanage65yaggressive(mostdiein1year)Gross:bulkymassesintoadjacentneckstructures生長迅速呈大塊狀，穿過甲狀腺包膜侵犯周圍組織Microscope:highlyanaplasticcells

1.Large,polymorphicgiantcells 2.Spindlecells 3.LittleroundappearanceundifferentiatedpleomorphiccellswithmultiplemitoticfiguresanaplasticcarcinomaQuestionsWhatisthemostcommoncauseofgoiterworldwide?

Ingestionofsubstancesthatinterferewiththyroidhormonesynthesis.Anincreasedphysiologicdemandforthyroxine.Iodinedeficiency.Deficiencyofenzymesnecessaryforsynthesisofthyroidhormones.Maldevelopmentofthethyroidgland.

(c)Q1Whatconditionismostcommonlyassociatedwithhyperthyroidism?AdenomaofthyroidGranulomatousthyroiditisCretinismHashimotothyroiditisDiffusetoxicgoiter(Gravesdisease)(e)Q2Gravesdisease:Usuallyoccurswithathyroidofnormalsize.Iscausedbyanexcessofthyroid-stimulatinghormone(TSH).Iscausedbyexcessiveingestionofiodine.Hasahistologicalpictureofhypoplasticacinarepithelium.Hasapositiveassociationwithexophthalmos.

(e)Q3Gravesdiseaseischaracterizedclinicallybyfinding

a.Centralobesity,“moon”face,andabdominalstriaeb.Hyperthyroidism,exophthalmus,andpretibialmyxedemac.Polyuria,polydipsia,andhyponatremiad.Polyuria,polydipsia,andpolyphagiae.Progressivelethargy,coldintolerance,andmyxedema(b)Q4WhichofthefollowinghistologicfindingsismostconsistentwithadiagnosisofHashimotothyroiditis?

DiffusefibrousdepositionbetweenatrophicfolliclesFollicularcellhyperplasiawithscallopingofcolloidGranulomatousinflammationwithmultinucleatedgiantcellsLymphoidinfiltratewithscatteredHurthlecellParafollicularhyperplasiawithdepositionofam