病理学教学课件：内分泌系统疾病Diseases of Endocrine System

DiseasesofEndocrineSystem

PathologyDepartment,SchoolofBasicMedicalSciences,FudanUniversitycorpuspineal松果体Pituitary垂体thyroid甲状腺Adrenals肾上腺isletofpancreas

胰岛Testis睾丸Ovary卵巢HormonesMetabolicequilibrium/homeostasis维持代谢平衡和稳态内分泌系统包括：内分泌腺内分泌组织神经内分泌细胞：APUD细胞内分泌系统的疾病多种多样

1.先天性畸形或酶缺乏

2.免疫反应性炎症

3.增生性疾病

4.肿瘤等影响激素的合成和分泌Classification1.Diseasesofunder/over-productionofhormonesandtheirresultantbiochemicalandclinicalconsequences激素分泌过多引起功能亢进；过少导致功能低下2.Diseasesassociatedwiththedevelopmentofmasslesions.占位病变morphologicfindingshormonelevelregulatormetabolites内分泌疾病特点发病年龄不同，表现和后果有很大差别

内分泌功能异常可继发于许多非内分泌系统疾病ExcessInsufficiencyAdrenalcortisolaldosterone…Cushingsyndromehyperaldosteronism

原发性醛固醇增多症AddisondiseaseIsletofpancreasinsulin

胰岛素Hypoglycemia低血糖Diabetesmellitus糖尿病Thyroidthyroxine(T4)triiodothyronine(T3)Hyperthyroidism

甲亢Hypothyroidism

甲减Cretinism

呆小病Pituitarygrowthhormone…Gigantism巨人症Acromegaly肢端肥大症Dwarfism

侏儒症PituitaryadenomaGrowthHormoneGigantism巨人症

prepubertalchildrenbeforeepiphyses

closeAcromegaly肢端肥大症softtissuesskinviscerabonesoftheface,hands&feetAdultsThyroid甲状腺TheneteffectofT4T3:basalmetabolicrate (BMR)TRH:thyrotropin-releasinghormoneTSH:thyroid-stimulatinghormoneT4:thyroxineT3:triiodothyroninehypothalamus-pituitary-thyroidaxisThyroidFolliclesepitheliumthyroglobulin-richcolloidNormalfollicularcellsSynthesisandStorageofthyroidhormones合成，储存，碘化，重吸收、分解FunctionlownormalhighEpitheliumflatcuboidalcolumnarColloidthickeventhinpuberty,pregnancy,physiologicstressTransienthyperplasiaInvolution复旧Thyroidparafollicularcells(“C”cells)滤泡旁细胞

calcitonin

降钙素reabsorptionofbonebyosteoclastsabsorptionofcalcium(skeletalsystem)ThyroiddiseasesHyperthyroidism甲亢

Hypothyroidism甲减MasslesionsGraves

diseasenontoxicgoiter（simplegoiter）ThyroiditisNeoplasmsofthyroidIn1835,RobertGravesreported“violentandlongcontinuedpalpitationsinfemales”associatedwithenlargementofthethyroidgland20-40,womengeneticfactorsGravesDiseaseDiffusetoxicgoiter弥漫性毒性甲状腺肿diffusesymmetricenlargementbeefydeepredparenchyma甲状腺弥漫对称性增大，质如肌肉GravesDiseasePathogenesis:autoimmunedisorder

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

GravesDiseaseMorphologyGross:thyroidgland--diffuselyenlarged.为正常的2-3倍Thecutsurfaceofthethyroidhasafleshyappearance.GravesDiseaseDiffusehyperplasiainapatientwithGrave’sdisease.切面灰红呈分叶状，胶质少，棕红色，质如肌肉Microscope:hyperplasticfollicleslinedbytall,columnarepith.crowded,enlargedepithelialcells---smallpapillaethescallopedappearanceoftheedgesofthecolloid(follicularcellsactivelyresorbcolloid)lymphoidinfiltratesininterstitium,germinalcenterGravesDisease(1)滤泡上皮增生，呈高柱状(2)上皮细胞增生形成乳头而向腔内突出(3)吸收空泡(4)间质淋巴细胞浸润，有淋巴滤泡形成lymphoidinfiltrationgerminalcenterGravesDiseasehyperplasticfollicularcells,smallpapillaeareasofcolloidresorptionGravesDiseaseabundantbloodsupplyClinicalfeatures：GravesDisease3manifestations:Thyrotoxicosis甲状腺毒症infiltrativeophthalmopathy浸润性眼病Myxedema粘液性水肿Thyrotoxicosis甲状腺毒症hypermetabolicstatefreeT3T4hyperfunctionofthethyroidgland(hyperthyroidism)hormoneexcessiveleakageoutofthyroidglandCausesofThyrotoxicosisAssociatedwithhyperthyroidismGravesdisease85%Hyperfunctioning(toxic)multinodulargoiterHyperfunctioning(toxic)adenomaTSH-secretingpituitaryadenomaNotAssociatedwithhyperthyroidismThyroiditis(earlystage,causehypothyoidismeventually)Strumaovarii(ovarianteratomawithectopicthyroid)卵巢甲状腺瘤ExogenousthyroxineintakeThyrotoxicosishypermetabolicstate高代谢状态overactivityofthesympatheticnervoussystem交感神经过度兴奋ThyrotoxicosisClinicalmanifestations:Clinicalmanifestations:Constitutionalsymptoms— warmskin,heatintolerance,excessivesweating, weightlosswithgoodappetite

全身症状：心悸、烦热、多汗、多食、消瘦、乏力Gastrointestinal–hypermotility,malabsorptiondiarrhea胃肠蠕动加快，吸收不良性腹泻。

ThyrotoxicosisCardiac–palpitations,tachycardia,cardiomegaly

心悸、心动过速、心脏肥大

Neuromuscular—

afinetremorofthehand,emotionalliability,anxiety,inabilitytoconcentrate,insomnia.muscleweakness

手震颤、情绪不稳定、焦虑、注意力不集中、失眠、乏力ThyrotoxicosisClinicalmanifestations:Ocularchange—

awide-eyed,staringgazeandlidlag凝视、眼睑后退

thyroidophthalmopathy(onlyinGravesDis.)Thyroidstorm甲状腺危象—

abruptonsetofhyperthyroidism cardiacarrhythmias心律失常ThyrotoxicosisClinicalmanifestations:Clinicalfeatures：Thyrotoxicosisthyroidenlargementaudiblebruit(bloodflow)(withstethoscope)甲状腺听见血管杂音，触诊时可有震颤

diffusetoxicgoiterGravesDiseaseClinicalfeatures：

infiltrativeophthalmopathy40% awide-eyed,staringgazeandlidlag thyroidophthalmopathy(eyeballprotrusion,exophthalmos眼球突出)sympatheticnervoussystemlooseconnectivetissuebehindtheeyeballs(Gravesdis.)cornealinjuryGravesDiseaseClinicalfeatures：myxedemapretibialmyxedema---glycosaminoglycansininterstitium部分病人出现胫骨前粘液性水肿真皮和皮下组织糖胺聚糖沉积GravesDiseaseDiagnosis:

Clinicalfeatures

Laboratorydata—FreeT4andT3TSHAbtoTSHreceptorthyroidperoxisomes

thyroglobulinRadioactiveiodineuptakediffuselyincreaseduptake--Gravesdiseaseincreaseduptakeinsolitarynodule--toxicadenomadecreaseduptake--thyroiditisGravesDisease

转归内科抗甲亢药物治疗;手术治疗;放射性碘治疗失明合并甲状腺癌甲状腺毒性心肌病nontoxic/simplegoiter单纯性甲状腺肿(diffusenontoxicandmultinodulargoiter)弥漫性非毒性甲状腺肿goiter--enlargmentofthethyroidSimpleenlargmentofthethyroid(withoutthyrotoxicosis)twokinds:

endemic地方性(lowiodine)

sporadic散发性EtiologyandPathogenesisFoodsupplycontainlowlevelofiodineIngestionofsubstances(brassicacruciferaevegetables)HereditaryenzymaticdefectsNotapparent,iodineexcessgoiter高碘甲状腺肿SynthesisofthyroidhormonecompensatoryinTSHFollicularcellhypertrophyhyperplasiaGoitrousenlargementcassavaMorphology 3stagesStageofhyperplasiaordiffusehyperplasticgoiter弥漫性增生性甲状腺肿thyroidglandisdiffuselyandsymmetricallyenlargedFolliclesarelinedbycrowdedcolumnarcells,whichmaypileupandformprojections肉眼：甲状腺弥漫肿大，对称。

镜下：滤泡上皮增生。2.Stageofstoredcolloidordiffusecolloidgoiter

弥漫性胶样甲状腺肿Gross:diffuseenlargementofthyroid.Thecutsurfaceisbrown,somewhatglassy,andtranslucent.Microscopically, follicularE.hyperplastic(earlystage) flattenedandcuboidalepith.(involution) abundantcolloid(involution)flattenedandcuboidalepith,abundantcolloiddiffuseenlargementofthyroidColloidgoiter弥漫对称显著增大，正常的10倍切面褐色，半透明胶冻状。镜下：扁平、立方状，滤泡腔扩张，腔内大量胶质储积3.Stageofmultinodulargoiter结节性甲状腺肿Gross:therearemanynodulesintheenlargedthyroid.Microscope：regressivechangesarequitecommon.

（fibrosis,hemorrhage,calcification,cysticchange）

proliferationlesions后期滤泡上皮局灶性增生、复旧或萎缩不一致，分布不均，形成结节multinodulargoitermultinodulargoitercystformationnontoxic/simplegoiter肉眼：甲状腺不对称结节状增大folliclesarrangedintoclustershemorrhagechronicinflammationnontoxic/simplegoitermultinodulargoiterhyperplasticnoduleMultinodulargoiterfibrosisandcysticchangehyperplasticnodulecompressedresidualthyroidnocapsule(diff.fromfollicularneoplasms)nontoxic/simplegoitercalcifiedwhitenodulenontoxic/simplegoitercystsandmuchfibrosisfocalcalcificationcalcificationnontoxic/simplegoiterClinicalfeatures alargeneckmassairwayobstruction,dysphagia,吞咽困难，呼吸困难Compressionoflargevesselsintheneckandupperthoraxnontoxic/simplegoiter不伴有内分泌失调少数有毒性甲状腺肿极少癌变Thyroiditis甲状腺炎Chroniclymphocytic(Hashimoto)thyroiditisSubacuteGranulomatous(deQuervain)ThyroiditisSubacuteLymphocyticthyroiditisFibrous(Riedel’s)thyroiditisDuration---acute,subacute,orchronicInflammation---lymphocyticorgranulomatousDr.HakaruHashimoto日本学者Hashimoto于1912年首先报道patientswithgoiterandintenselymphocyticinfiltrationofthethyroid甲状腺弥漫对称肿大，间质单核细胞浸润chroniclymphocytic(Hashimoto)thyroiditis慢性淋巴细胞性甲状腺炎，桥本甲状腺炎themostcommoncauseofhypothyroidismanautoimmuneinflammatorydisorder45-65y/ofemalechildren(nonendemicgoiter)Painlessenlargementofthethyroid早期会出现甲亢症状，晚期会出现甲减症状。

“桥本氏病伴甲亢”、“乔本氏病伴甲低”PathogenesisBreakdownofselftolerancetothyroidauto-antigens血中抗甲状腺球蛋白抗体（TGA)、甲状腺微粒体(过氧化物酶)抗体(TMA)滴度明显升Gross:thethyroidisusuallydiffuselyandsymmetricallyenlarged.Microscope:1.extensiveinfiltrationoftheparenchymabymononuclearinflammatory.2.folliclesatrophyandfibrosis3.Hürthle/oxyphilcells部分甲状腺滤泡上皮变为体积增大、胞质颗粒丰富的嗜酸性细胞(metaplasia)Morphologydiffusethyroidenlargementwithgrayishfleshycutsurface切面分叶，色灰白lymphoidinfiltrategerminalcentersHürthlecells(granulareosinophiliccytoplasm)adenselymphocyticinfiltratewithgerminalcentersresidualthyroidfolliclesHürthlecells30-50ywomenViralinfection(precededbyanupperrespiratorytractinfection)Painintheneckself-limiteddiseasegranulomaformationSubacuteGranulomatousThyroiditis

(deQuervain)亚急性肉芽肿性甲状腺炎subacutegranulomatousthyroiditisfirm,enlargeddisruptionofthyroidfollicleschronicinflammatoryinfiltratemultinucleategiantcellchronicinflammatoryinfiltratemultinucleategiantcellsubacutegranulomatousthyroiditis“slient”or“painless”thyroiditisMildhyperthyroidismgoitrousenlargementMiddleagedwomenpostpartumthyroiditis产后甲状腺炎self-limiteddiseaseUnlikeHashimotothyroiditis,follicularatrophyandoxyphilcellsarenotcommonlyseen.SubacuteLymphocyticthyroiditis

亚急性淋巴细胞性甲状腺炎lymphocyticinfiltrationwithgerminalcentermildenlargementnormalappearanceSubacutelymphocyticthyroiditispatchdisruptionofthyroidfolliclesFibrousthyroiditis(Riedel’sthyroiditis)慢性纤维性甲状腺炎、慢性木样甲状腺炎

AraredisorderofunknownetiologyCharacterizedbyextensivefibrosisinvolvingthethyroidandcontiguousneckstructures甲状腺和周围组织粘连。广泛纤维化progressiveatrophyandscarringofthyroidtissueatrophicthyroidfollicleslymphocyticinfiltrationfibrosis(scarring)fibrousthyroiditis(Riedel’sthyroiditis)NeoplasmsofthethyroidBenign:adenomasMalignant:carcinomasAdenomas甲状腺腺瘤BenignneoplasmsderivedfromfollicularepitheliumPainlessnodulesinthyroidFourthandfifthdecadesfemale-to-malerate=7:1FollicularadenomaofthethyroidMorphology:Asolitarysphericalencapsulatedlesion(multiplenodulesarealmostalwaysnodularhyperplasia)Aintact,well-formedcapsule.包膜完整CompresstheadjacenttissueHemorrhage&fibrosiscysticchangearecommonvarioushistologicsubtypes(trabecular,microfollicular,macrofollicular)nobiologicsignificance滤泡的形态可多样welldevelopedfibrouscapsulesharpdemarcation分界清楚(encapsulation)andcolloidshineHürthlecell(oxyphil)adenoma.许特莱细胞腺瘤abundanteosinophiliccytoplasmandsmallregularnuclei

adenomasadenomasHemorrhagedegenerationfocalcalcificationcapsuleadenomas部分甲状腺腺瘤可发生癌变。具有下列情况者，应当考虑恶变的可能性：1.肿瘤近期迅速增大。2.瘤体活动受限或固定。3.出现声音嘶哑、呼吸困难等压迫症状。4.肿瘤硬实、表面粗糙不平。5.出现颈淋巴结肿大。CarcinomaofThyroid1.papillarycarcinoma乳头状癌：75%to85%2.Follicularcarcinoma滤泡状癌:10%to20%3.Medullarycarcinoma髓样癌:5%(derivedfromCcells)4.Anaplasticcarcinoma未分化癌:<5%1.Papillarycarcinoma乳头状癌mostcommonformofthyroidcanceranyagebutmostofteninthetwentiestofortiesexposuretoionizingradiationverygoodprognosis

20-ysurvivalrates92%

Gross:solitaryormultifocallesions,wellcircumscribedorill-definedmargins

病灶单发或多发，甚至可有完整包膜，多数病例境界不清，浸润周围组织Wellcircumscribedlesionsuspicioussatellitenodule肿瘤呈囊状，囊内形成许多乳头状结构Microscope:

papillaryarchitecture“ground-glass”nucleipsammomabodies癌细胞核呈毛玻璃样，有乳头结构，有时有砂粒体（同心圆状钙化小体)

papillaryarchitecturefibrovascularcore“groundglassnuclei”(OrphanAnnieeye)Veryfinelydispersedchromatin癌细胞核染色质少，呈透明状或毛玻璃状，无核仁thediagnosisisbasedonnuclearfeatures

(evenintheabsenceofapapillaryarchitecture)Pseudo-inclusionsinvaginationsofthecytoplasm---intranuclearinclusionsorintranucleargrooves细胞浆内陷，形成假包涵体,或有核沟。follicularvariantpapillarycarcinoma

Psammomabodies砂粒体concentricallycalcifiedstructures同心圆状钙化小体neverfoundinfollicularandmedullarycarcinomas2.FollicularCarcinoma滤泡状癌Thisisverymalignantcarcinoma,the5-yearsurvivalratesareonly30-40％，易血道转移。Gross:maybegrosslyinfiltrativeorwellcircumscribed.Microscope:tumorcellinfiltratethecapsuleoradjacentthyroidparenchyma肉眼：境界不清或清楚镜下:形态多样，最重要的改变为肿瘤侵犯包膜或周围甲状腺组织，follicularcarcinoma肿瘤无包膜，浅黄色，有小灶性出血。肿瘤为分化好的滤泡，腔内有胶质。与滤泡状腺瘤鉴别FollicularcarcinomaFollicularadenomaadenomasfibrouscapsulenocapsularinvasionfollicularcarcinomascapsularinvasionfollicularcarcinomaFollicularcarcinoma,minimallyinvasivetype.follicularcarcinoma3.Medullarycarcinoma髓样癌----Parafollicularcells,Ccells----prognosisFollicularca.<Medullaryca.<Papillaryca.----metastasislymphnodes起源于滤泡旁细胞（又称C细胞），预后介于乳头状癌和滤泡癌之间，最常见的转移方式为淋巴结转移。

Gross:solitarynoduleormultiplelesionsMicroscope:polygonaltospindle-shapedcellsnests,trabeculae,andevenfolliclesAcellularamyloiddeposits(alteredcalcitoninmolecules)细胞外有淀粉样物质（降钙素）沉积solidpatternofgrowthnoconnectivetissuecapsules实性生长，无包膜abundantdepositionofamyloid间质有大量淀粉样物质沉积medullarycarcinomaamyloiddepositsKongoredstainbirefringenceonpolarizationCalcitonin(+)降钙素(+)甲状腺球蛋白(--)medullarycarcinoma4.AnaplasticCarcinoma未分化癌Undifferentiatedfollicularepitheliummeanage65yaggressive(mostdiein1year)Gross:bulkymassesintoadjacentneckstructures生长迅速呈大块状，穿过甲状腺包膜侵犯周围组织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