病理学十二 内分泌系统疾病(中英文)

DiseasesofEndocrineSystem

corpuspineal松果体Pituitary垂体thyroid甲状腺Adrenals肾上腺isletofpancreas

胰岛Testis睾丸Ovary卵巢HormonesMetabolicequilibrium/homeostasisClassification1.Diseasesofunder/over-productionofhormonesandtheirresultantbiochemicalandclinicalconsequences2.Diseasesassociatedwiththedevelopmentofmasslesions.morphologicfindingshormonelevelregulatormetabolitesExcessInsufficiencyadrenalcortisolaldosterone…Cushingsyndromehyperaldosteronism

原发性醛固酮增多症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

prepubertalchildrenbeforeepiphyses

closeacromegalysofttissuesskinviscerabonesoftheface,handsandfeetAdultsThyroidTheneteffectofT4T3:basalmetabolicrate (BMR)TRH:thyrotropin-releasinghormoneTSH:thyroid-stimulatinghormoneT4:thyroxineT3:triiodothyroninehypothalamus-pituitary-thyroidaxisThyroidFolliclesepitheliumthyroglobulin-richcolloidNormalfollicularcellsSynthesisandStorageofthyroidhormonesFunctionlownormalhighEpitheliumflatcuboidalcolumnarColloidthickeventhinpuberty,pregnancy,physiologicstressTransienthyperplasiaInvolution复旧Thyroidparafollicularcells(“C”cells)

calcitonin

resorptionofbonebyosteoclastsabsorptionofcalcium(skeletalsystem)ThyroiddiseasesHyperthyroidism

HypothyroidismMasslesionsGraves

diseasenontoxicgoiter（simplegoiter）ThyroiditisNeoplasmsofthyroidIn1835,RobertGravesreported“violentandlongcontinuedpalpitationsinfemales”associatedwithenlargementofthethyroidgland20-40,womengeneticfactorsGravesDiseasePathogenesis:autoimmunedisorder

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

HLA-DR3

GravesDiseaseMorphologyGross:thyroidgland---diffuselyenlarged.Thecutsurfaceofthethyroidhasafleshyappearance.GravesDiseaseDiffusehyperplasiainapatientwithGrave’sdisease.diffusesymmetricenlargementbeefydeepredparenchymaGravesDiseaseabundantbloodsupplyMicroscope:hyperplasticfollicleslinedbytall,columnarepith.crowded,enlargedepithelialcells---smallpapillaethescallopedappearanceoftheedgesofthecolloid(follicularcellsactivelyresorbcolloid)lymphoidinfiltratesininterstitium,germinalcenterGravesDiseaselymphoidinfiltrationgerminalcenterGravesDiseaseClinicalfeatures：ThyrotoxicosishypermetabolicstatefreeT3T4hyperfunctionofthethyroidgland(hyperthyroidism)hormoneexcessiveleakageoutofthyroidglandGravesDisease3manifestations:Thyrotoxicosisinfiltrativeophthalmopathy

myxedemaCausesofThyrotoxicosisAssociatedwithhyperthyroidismGravesdisease85%Hyperfunctioning(toxic)multinodulargoiterHyperfunctioning(toxic)adenomaTSH-secretingpituitaryadenomaNotAssociatedwithhyperthyroidismThyroiditis(earlystage,causehypothyoidismeventually)Strumaovarii(ovarianteratomawithectopicthyroid)ExogenousthyroxineintakeThyrotoxicosisClinicalmanifestations:Constitutionalsymptoms—

warmskin,heatintolerance,excessivesweating, weightlosswithgoodappetiteGastrointestinal–hypermotility,malabsorptiondiarrheahypermetabolicstateoveractivityofthesympatheticnervoussystemThyrotoxicosisCardiac–palpitationstachycardiacardiomegaly

Neuromuscular—

afinetremorofthehand,emotionalliability,anxiety,inabilitytoconcentrate,insomnia. muscleweaknessThyrotoxicosisClinicalmanifestations:Ocularchange—

awide-eyed,staringgazeandlidlag thyroidophthalmopathy(onlyinGravesDis.)Thyroidstorm—

abruptonsetofhyperthyroidism cardiacarrhythmiasThyrotoxicosisClinicalmanifestations:Clinicalfeatures：Thyrotoxicosisthyroidenlargment

audiblebruit(bloodflow)(withstethoscope)

diffusetoxicgoiter3manifestations:Thyrotoxicosisinfiltrativeophthalmopathy

myxedemaGravesDiseaseClinicalfeatures：

eyechange awide-eyed,staringgazeandlidlag thyroidophthalmopathy(eyeballprotrusion,exophthalmos)sympatheticnervoussystemlooseconnectivetissuebehindtheeyeballs(Gravesdis.)cornealinjury3manifestations:Thyrotoxicosisinfiltrativeophthalmopathy40%myxedemaGravesDiseaseClinicalfeatures：pretibialmyxedema---glycosaminoglycansininterstitium3manifestations:Thyrotoxicosisinfiltrativeophthalmopathy

myxedemaGravesDiseaseDiagnosis:

Clinicalfeatures

Laboratorydata—FreeT4andT3TSHAbtoTSHreceptorthyroidperoxisomesthyroglobulinRadioactiveiodineuptakediffuselyincreaseduptake--Gravesdiseaseincreaseduptakeinsolitarynodule--toxicadenomadecreaseduptake--thyroiditisGravesDiseasenontoxic/simplegoiter(diffusenontoxicandmultinodulargoiter)goiter--enlargmentofthethyroidsimple

enlargmentofthethyroid(withoutthyrotoxicosis)twokinds:endemic(lowiodine)sporadicEtiologyandPathogenesisFoodsupplycontainlowlevelofiodineIngestionofsubstances(brassicacruciferaevegetables)HereditaryenzymaticdefectsNotapparentSynthesisofthyroidhormonecompensatoryinTSHFollicularcellhypertrophyhyperplasiaGoitrousenlargementcassavanontoxic/simplegoiterMorphology 3stages1.Stageofhyperplasiaordiffusehyperplasticgoiter

thyroidglandisdiffuselyandsymmetricallyenlargedFolliclesarelinedbycrowdedcolumnarcells,whichmaypileupandformprojectionsnontoxic/simplegoiterMorphology 3stages2.StageofstoredcolloidordiffusecolloidgoiterGross:diffuseenlargementofthyroid.Thecutsurfaceisbrown,somewhatglassy,andtranslucent.Microscopically, follicularE.hyperplastic(earlystage) flattenedandcuboidalepith.(involution) abundantcolloid(involution)nontoxic/simplegoiter3.MultinodulargoiterGross:therearemanynodulesintheenlargedthyroid.Microscope：regressivechangesarequitecommon.

（fibrosis,hemorrhage,calcification,cysticchange）

proliferationlesionsMorphology 3stagesnontoxic/simplegoiterColloidgoitermultinodulargoitermultinodulargoitercystformationnontoxic/simplegoiterMultinodulargoiterfibrosisandcysticchangehyperplasticnodulecompressedresidualthyroidnocapsule(diff.fromfollicularneoplasms)nontoxic/simplegoiterfolliclesarrangedintoclustershemorrhagechronicinflammationnodulargoiternontoxic/simplegoitermultinodulargoiterhyperplasticnodulecalcifiedwhitenodulenontoxic/simplegoitercystsandmuchfibrosisfocalcalcificationcalcificationnontoxic/simplegoiterClinicalfeatures alargeneckmassairwayobstruction,dysphagia,Compressionoflargevesselsintheneckandupperthoraxnontoxic/simplegoiterThyroiditisChroniclymphocytic(Hashimoto)thyroiditisSubacuteGranulomatous(deQuervain)ThyroiditisSubacuteLymphocyticthyroiditisFibrous(Riedel’s)thyroiditisduration-acute,subacute,orchronicinflammation-lymphocyticorgranulomatousthemostcommoncauseofhypothyroidismanautoimmuneinflammatorydisorder45-65y/ofemalechildren(nonendemicgoiter)PainlessenlargementofthethyroidChroniclymphocytic(Hashimoto)thyroiditisDr.HakaruHashimoto日本学者Hashimoto于1912年首先报道patientswithgoiterandintenselymphocyticinfiltrationofthethyroid.chroniclymphocytic(Hashimoto)thyroiditisPathogenesischroniclymphocytic(Hashimoto)thyroiditisBreakdownofselftolerancetothyroidauto-antigensGross:thethyroidisusuallydiffuselyandsymmetricallyenlarged.Microscope:extensiveinfiltrationoftheparenchymabyamononuclearinflammationcontainingsmalllymphocytes,plasmacells,andgerminalcenters.folliclesatrophyandfibrosisHürthle

/oxyphilcells(metaplasia)morphologychroniclymphocytic(Hashimoto)thyroiditisdiffusethyroidenlargementwithgrayishfleshycutsurfacelymphoidinfiltrategerminalcentersHürthlecells(granulareosinophiliccytoplasm)chroniclymphocytic(Hashimoto)thyroiditisadenselymphocyticinfiltratewithgerminalcentersresidualthyroidfolliclesHürthlecellschroniclymphocytic(Hashimoto)thyroiditis30-50ywomenViralinfection(precededbyanupperrespiratorytractinfection)Painintheneckself-limiteddiseasegranulomaformationSubacuteGranulomatousThyroiditis

(deQuervain)subacutegranulomatousthyroiditisfirm,enlargeddisruptionofthyroidfollicleschronicinflammatoryinfiltratemultinucleategiantcellchronicinflammatoryinfiltratemultinucleategiantcellsubacutegranulomatousthyroiditis“slient”or“painless”thyroiditisMildhyperthyroidismgoitrousenlargementMiddleagedwomenpostpartumthyroiditisself-limiteddiseaseUnlikeHashimotothyroiditis,follicularatrophyandoxyphilcellsarenotcommonlyseen.SubacuteLymphocyticthyroiditislymphocyticinfiltrationwithgerminalcentermildenlargementnormalappearancesubacutelymphocyticthyroiditispatchdisruptionofthyroidfolliclesFibrousthyroiditis(Riedel’sthyroiditis)AraredisorderofunknownetiologyCharacterizedbyextensivefibrosisinvolvingthethyroidandcontiguousneckstructuresprogressiveatrophyandscarringofthyroidtissueatrophicthyroidfollicleslymphocyticinfiltrationfibrosis(scarring)fibrousthyroiditis(Riedel’sthyroiditis)NeoplasmsofthethyroidBenign:adenomasMalignant:carcinomasadenomasBenignneoplasmsderivedfromfollicularepitheliumPainlessnodulesinthyroidFourthandfifthdecadesfemale-to-malerate=7:1FollicularadenomaofthethyroidMorphology:Asolitarysphericalencapsulatedlesion(multiplenodulesarealmostalwaysnodularhyperplasia)Aintact,well-formedcapsule.CompresstheadjacenttissueHemorrhagefibrosiscysticchangearecommonvarioushistologicsubtypes(trabecular,microfollicular,macrofollicular)nobiologicsignificanceadenomaswelldevelopedfibrouscapsulesharpdemarcation(encapsulation)andcolloidshineadenomasHürthlecell(oxyphil)adenoma.abundanteosinophiliccytoplasmandsmallregularnuclei

adenomasdegenerationfocalcalcificationcapsuleadenomasCarcinomaofThyroid1.papillarycarcinoma:75%to85%2.Follicularcarcinoma:10%to20%3.Medullarycarcinoma:5%(derivedfromCcells)4.Anaplasticcarcinoma:<5%1.Papillarycarcinomamostcommonformofthyroidcanceranyagebutmostofteninthetwentiestofortiesexposuretoionizingradiationverygoodprognosis20-ysurvivalrates92%Gross:solitaryormultifocallesionswellcircumscribedorill-definedmarginsWellcircumscribedlesionsuspicioussatellitenodulepapillarycarcinomaMicroscope:papillaryarchitecture

thediagnosisisbasedonnuclearfeatures

(evenintheabsenceofapapillaryarchitecture)

“ground-glass”/“OrphanAnnieeye”nuclei---finelydispersedchromatinopticallyclearoremptyappearance

psammoma

bodies-----concentricallycalcifiedstructurespapillarycarcinomapapillaryarchitecturefibrovascularcorepapillarycarcinoma“groundglassnuclei”(OrphanAnnieeye)VeryfinelydispersedchromatinpapillarycarcinomafollicularvariantpapillarycarcinomapsammomabodiesconcentricallycalcifiedstructurespapillarycarcinomaneverfoundinfollicularandmedullarycarcinomasPseudo-inclusionsinvaginationsofthecytoplasm---intranuclearinclusionsorintranucleargroovespapillarycarcinoma2.FollicularCarcinomaThisisverymalignantcarcinoma,the5-yearsurvivalratesareonly30－40％。Gross:maybegrosslyinfiltrativeorwellcircumscribed.Microscope:

tumorcellinfiltratethecapsuleoradjacentthyroidparenchymaFollicularcarcinomafollicularcarcinomaFollicularcarcinomaFollicularadenomaadenomasfibrouscapsulenocapsularinvasionfollicularcarcinomascapsularinvasionfollicularcarcinomaFollicularcarcinoma,minimallyinvasivetype.follicularcarcinoma3.Medullarycarcinoma----Parafollicularcells,Ccells----prognosisfollicularca.<medullaryca.<papillaryca.----metastasislymphnodesGross:solitarynoduleormultiplelesionsMicroscope:polygonaltospindle-shapedcellsnests,trabeculae,andevenfolliclesAcellularamyloiddeposits(alteredcalcitoninmolecules)medullarycarcinomasolidpatternofgrowthnoconnectivetissuecapsulesabundantdepositionofamyloidmedullarycarcinomaamyloiddepositsKongoredstainbirefringenceonpolarizationCalcitonin(+)medullarycarcinoma4.AnaplasticCarcinomaUndifferentiatedfollicularepitheliummeanage65yaggressive(mostdiein1year)Gross:bulkymassesintoadjacentneckstructuresMicroscope:highlyanaplasticcells 1.Large,polymorphicgiantcells 2.Spindlecells 3.LittleroundappearanceundifferentiatedpleomorphiccellswithmultiplemitoticfiguresanaplasticcarcinomaDiabetesMellitus

糖尿病Defectsininsulinsecretion,insulinactionormostcommonlybothDisordersofcarbohydrate,fat,proteinmetabolism三大物质代谢异常HyperglycemiaSystemicdiseaseTheinsulingeneisexpressedinthebetacellsofthepancreaticislets,whereinsulinissynthesizedandstoredingranulesbeforesecretion.

Normalinsulinphysiology5%~10%80%10%TypeITypeIIClinicalChildren>adultsNormalweightDecreasedbloodinsulinAnti-isletcellantibodiesKetoacidosiscommonAdults>childrenObeseNormalorincreasedbloodinsulinNoanti-isletcellantibodiesKetoacidosisrareGeneticsHLA-DlinkedNoHLAassociationPathogenesisAutoimmunitySevereinsulindeficiencyInsulinresistanceRelativeinsulindeficiencyIsletcellsInsulitisearlyMarkedatrophyandfibrosisSeverebeta-celldepletionNoinsulitisFocalatrophyandamyloiddepositsMildbeta-celldepletionPathogenesis

type1DMThreeinterlockingmechanisms:GeneticsusceptibilityAutoimmunityAnenvironmentinsultProgressivedestructionofβcellstype2DMPathogenesis

1.FormationofAdvancedglycosylationendproducts(AGE)糖基化终末产物

促进动脉粥样硬化DiffusethickeningofbasementmembranePathogenesisComplicationshyperglycemiaAGEreceptors巨噬c、内皮c、血管平滑肌cCross-linkwithECM2.ActivationofproteinkinaseC

PathogenesisComplications促血管生成分子促纤维化分子3.DisturbanceinpolyolpathwaysPathogenesisComplications葡萄糖→山梨醇→果糖消耗NADPH---细胞易受氧化应激损伤MORPHOLOGYPancreasArteries--macrovasculardiseasesmallvessels--microangiopathyKidneys—diabeticnephropathyRetina--retinopathyNerves--neuropathyOtherPancreasReductioninthenumberandsizeofisletsLeukocyticinfiltrationoftheislets(insulitis)intype1Intype2diabetes:AmyloiddepositionwithinisletsMORPHOLOGYMacrovascularDisease

•

Large-/medium-sizedarteries:acceleratedatherosclerosis

Myocardialinfarction---themostcommoncauseofdeathGangreneofthelowerextremities

•Smallarteries&arteriole:hyalinearteriolosclerosis

MORPHOLOGYmicroangiopathy

•

Diffusethickeningofbasementmembranes•UnderlyingthedevelopmentofdiabeticcomplicationsMORPHOLOGYnephropathyThreeimportantlesions(1)Glomerularlesions:(2)Renalvascularlesions:Hyalinearteriolosclerosisofbothafferent&theefferentarteriole(3)Pyelonephritis,includingnecrotizingpapillitis

AcuteorchronicMorecommonindiabetesMORPHOLOGYGlomerularlesions:

WidespreadthickeningofGBMandTBM肾小球基底膜正常厚度：约300nm

糖尿病肾病患者可达600nm

K-Wnodule:

AccumulationofhomogeneouseosinophilicmaterialwithinthemesangiumAroundedaccentuationofthemesangialexpansion

AdiffuseincreaseinmesangialmatrixalongwithmildMsCproliferationGlomerularlesions:Diffuse/NodularMesangialSclerosis

DiffusegranulartransformationofthesurfaceMarkedthinningofthecorticaltissueSomeirregulardepressionsTheresultofpyelonephritisOcularcomplications

Retinopathy,cataractformation,glaucomaMORPHOLOGY白内障青光眼Diabeticneuropathy•Aperipheral,symmetricneuropathyofthelowerextremitiesBothmotorandsensoryfunctionbutparticularthelatter•GeneralizedneuronaldegenerationofbrainMORPHOLOGYAnabolism

Catabolism

ClinicalFeaturesPolyuriaPolydipsiaPolyphagiaweightloss多尿烦渴多食合成代谢分解代谢HyperosmolarityAnyquestion?Whatisthemostcommoncauseofgoiterworldwide?

Ingestionofsubstancesthatinterferewiththyroidhormonesynthesis.Anincreasedphysiologicdemandforthyroxine.Iodinedeficiency.Deficiencyofenzymesnecessaryforsynthesisofthyroidhormones.Maldevelopmentofthethyroidgland.

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

acinarepithelium.Hasapositiveassociationwithexophthalmos.

(e)Q3Gravesdiseaseischaracterizedclinicallybyfinding

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

DiffusefibrousdepositionbetweenatrophicfolliclesFollicularcellhyperplasiawithscallopingofcolloidGranulomatousinflammationwithmultinucleatedgiantcellsLymphoidinfiltratewithscatteredHurthlecellParafollicularhyperplasiawithdepositionofamyloid(d)Q5AllthefollowingisfeatureofpapillaryadenocarcinomaofthethyroidEXCEPT