儿科学课件 17 先天性甲状腺功能减低症（英文）-熊丰

(Cretinism)ProfFengXiongPediatricEndocrinologyDepartmentChildren’sHospitalofCMUCongenitalHypothyroidismLearningobjectivesYoushouldknow:TheclinicalfeaturesofcongenitalhypothyroidisminneonatesandchildrenBeabletodiscussthediagnosisandmanagementMajorcontentsOverviewofcongenitalhypothroidismEtiologyClinicalmanifestationLaboratoryexaminationDiagnosisanddifferentialdiagnosisTreatment

Abbreviation

CHcongenitalhypothyroidismTRHthyrotropin-releasinghormoneTSHthyrotropic-stimulatinghormoneT4thyroxineT3triiodothyronineMITmonoiodotyrosine(单碘酪氨酸）DITdiiodotyrosine（双碘酪氨酸）TGthyroglobulinTBGthyroxine-bindingglobulinTHthyroidhormoneOverviewHypothyroidismCongenitalhypothyroidismacquiredhypothyroidismIodinedeficiencyAutoimmunedisease—HashimotothyroiditisOverviewHypothyroidismCongenitalhypothyroidism

acquiredhypothyroidismIodinedeficiencyAutoimmunedisease—HashimotothyroiditisOverviewCongenitalHypothyroidism(CH)iscommondiseaseofpediatricendocrinology.Congenitalfactorscausetheinsufficiencyofthyroidhormone,whichresultinthelowmetabolism,growthretardation,andmentalimpairment.Theonsetduringinbornornewbornperiod,willleadtoirreversiblementalimpairment.

CHisoneofpreventablecausesofmentalretardation,earlytreatmentwillimprovetheprognosisthoroughly.Incidence

1in4000livebirths(inAmericaandEurope)Females:Maleis2:1InChina:IncidenceofCongenitalhypothyroidism（Fromtheneonatalscreening):1in3624

------thenationwideneonatalscreeningfromclinicalexaminationcenterofHealthBureauin1999ClassificationSporadicalCHMajorityCHpatientsaresporadical,afewisfamilial.EndemicCHPregnantwomenliveiniodineinsufficientareas,whichresultiniodinedeficiency.Alongwithfortifyingiodinesaltindietary,incidenceofendemicCHismuchlower.

EmbryologyofThyroidThyroidisthefirstendocrineglandtodevelopinembryoBegins

to

form

in

24

days

afterfertilizationForms

from

primordial

pharyngeal

floor（原始咽底部）

formingthyroid

diverticulum

（原基）Asembryo

and

tonguegrow,thyroiddescends

inanteriorneckandreachesitsnormalsite:theoppositecervicalvertebra5-7by7weeksofgestationPharynxfloorRoleofPlacenta

SubstancePlacentalpermeability

I-

++++

TRH

+++

IgGAntibodies

+++

T3

+

T4

+

TSH

0pituitary-thyroidhormoneproductionafterbirth

HormonesinfetalHormonesafterbirth(Hour)Within30minutesofdelivery,TSHabruptriseoccurs--asaprotectedresultsofchangeinenvironmentaltemperature.TSHlevels:first12hashighas70mU/L;after48h:<20;after120h:<5T4andT3:TSHsurgecausesmarkedincreaseinT4,T3by24hto48hCouplingOrganification/OxidationIodideTrappingHydrolyzeTSHTSHRegulationofTHsecretionDownloadedfrom:StudentConsult(on27January200809:43PM)©2005ElsevierThyroidDysgenesis

85-90%

Aplasia

HypoplasiaEctopicthyroidDyshormonogenesis

5%TSHunresponsiveness

lodidetrappingdefect

OrganificationdefectDefectinTG

DeiodinasedeficiencyEtiologyCentralHypothyroidism1in100,000livebirthsHypothalamic-pituiaryanomaly

PanhypopituitarismIsolatedTSHdeficiencyThyroxineReceptorRssistanceMaternalFactorsDruginduced:propylthiouracil(PTU,丙硫氧嘧啶)/

Methimazole(MM,他巴唑)/IodineAntibodyinduced:thyrotrophinreceptorblockingantibody(TRBAb)IodineDeficiencyEtiology

ThyroidGlandFunctionSynthesize,store,andreleaseT4andT3intocirculationT4isthemajorproductT3isconvertedfromT4

bydeiodinase

intheperipheraltissues

FunctionofThyroidHormoneNeurodevelopmentaleffectCellularMetabolismandProtein,Lipid,GlucoseMetabolism&vitaminsGrowthandDevelopmentOrgansandsystems

Function:

NeurodevelopmentalEffectPerinatalandpostnatalmaturationof

brain,retina,andcochlea（耳蜗）T3directlypromotesneuraldifferentiation

Differentiation,maturationofinfantpallium（大脑皮层）

Pregnant2moformationPregnant5moDifferentiation

Latefetalperiodpeakperiodof---8moafterbirthproliferation,differentiationandmaturationUpto3yrdifferentiationfinishedAttention:thyroidhormoneisessentialforthisprocessTheroleonmetabolism

Oxidationbasalmetabolism↑,heatproduction↑proteinpromoteproteinsynthesisfatpromotelipoclasis

liquidpromotelargemolecularsubstanceinlymphaticvesselintoblood,maintainwaterbalancemineralsaltaffectturnoverrateofcalciumand

phosphoniumVitaminparticipateinmult-vitaminmetabolism,especiallyvitaminAFunction:

GrowthandDevelopmentPostnatal

growth

is

dependentuponTHandGHwhicharemediatedthroughIGF-1receptorsPromotebone,cartilagegrowthanddevelopment,promotecalciumandphosphoniumdepositinbone.(Hypothyroidism

leads

to

delayeddentaleruption,

linear

growth,and

delayedskeletalmaturation)Promotealltissue,cellsgrowthanddevelopmentTheroleonorganandsystemcirculationsystemincreasemyocardialcontractilitydigestivesystempromotedigestivegland

secretion,maintainnormalenterokinesia.sexualglandpromotesexualdevelopmentClinicalmanifestationTypicalsymptomsofchildrenManifestationofneonatalhypothyroidismClinicalmanifestationTypicalsymptomofchildrenManifestationofneonatalhypothyroidismChildrenwithHypothyroidismTypicalsymptoms

RetardationofgrowthanddevelopmentCoarsefaciesandunusualbodyfeaturesMentalRetardationHypometabolismChildrenwithHypothyroidismTypicalsymptoms

RetardationofgrowthanddevelopmentCoarsefaciesandunusualbodyfeaturesMentalRetardation

Hypo-metabolismChildrenwithHypothyroidismTypicalsymptoms

RetardationofgrowthanddevelopmentCoarsefaciesandunusualbodyfeaturesMentalRetardation

Hypo-metabolismCoarsefaciesSparsehairPallorandjaundiceLowdorsumofnosemacroglossiaVacantexpressionCoarsefaciesSparsehairPallorandjaundiceLowdorsumofnosemacroglossia

VacantexpressionunusualbodyfeaturesMacrocephaly(巨头畸形)ShortneckabdominalbulgeUmbilicalherniaRough,dryskinChildrenwithHypothyroidismTypicalsymptoms

RetardationofgrowthanddevelopmentCoarsefaciesandunusualbodyfeaturesMentalRetardationHypo-metabolismVeryseverementalretardationVeryworsenMemoryandattentionDisorderofmotordevelopment,delayedwalking,hypotonia,poorfineactivitiespartialdeafness,disesthesia（感觉迟钝）MentalretardationChildrenwithHypothyroidismTypicalsymptoms

RetardationofgrowthanddevelopmentCoarsefaciesandunusualbodyfeaturesMentalRetardation

Hypo-metabolismLowerbasalmetabolicrateQuietandlessactivities,hoarsevoice,limitedfood-intake,lowerbodytemperature.

LowercardiovascularfunctionBradycardia

心动过缓,hydropericardium

心包积液,weakcardiechema

心音低顿。Electrocardiogramshowlowtension低电压,lengthenedP-Rinterval,conductionblockade传导阻滞Lowerdigestionfunctionconstipation,drystool,abdominaldistention.Hypo-metabolismClinicalmanifestationTypicalsymptomsofchildrenManifestationofneonatalhypothyroidismClinicalFeaturesofneonatalCH>95

percent

neonates

with

CH

have

few

clinicalmanifestations

(maternalT4crossestheplacenta,soeveninathyrosisthyroidhormoneumbilicalcordserumT4

levelare

about25to

50percentofthoseofnormalinfants).

Clinicalfindings:(happensin5%ofneonatalCH)Post-termbirth(>42weeks);largefordateinfant

Wt>4kgHypothermia,acrocyanosis手足发绀,respiratorydistress,lethargyandhoarsecry.poorfeeding,constipation.Jaundiceoftenprolongsover2weeks.Oedema,largeposteriorfontanel,macroglossia,abdominaldistension,umbilicalhernia脐疝,mottledskin.boneageisoftendelayedatbirth.LaboratoryexaminationAnelevatedTSHismostsensitiveandspecifictesttoconfirmdiagnosisRemember

that

TSH

surge

occurs

infirst12hours

of

life

and

may

remain

high

until

48hoursLaboratoryexamination

Newbornscreening

SuitableTime:2－3daysafterbirthMothed:usedrybloodslipanddetectTSHlevel.Results:positive:TSH>20uU/ml

thendetectT4andTSHforfurtherdetermineLaboratoryexamination

Evaluatethyroidfunction

primarilyhypothyriodism:T4↓T3↓TSH↑

secondaryhypothyriodism:T4↓T3↓TSH↓

TRHstimulatingtest

objective:suspectedinsufficientTSHorTRH

objectives

mothed:useTRH7ug/kg,IV,detectTSHlevel

results:

normal:at30minappearTSHpeak，

at90minretumtobasicvalue.

abnormal:

NoTSHpeakappear---pituitarydisorder

DelayedTSHpeakappear---hypothalamic

disorderLaboratoryexaminationRadiograph—infantandchildCHEvaluationboneageObviouslydelayedboneage,almostlags>3yearsoldPositionofdetect:youngerthan6month:takekneeX-rayolderthan6month:takewristX-rayNeonataldistalfemoralepiphysisossificationcenter

NormalneonateNeonatewithCHWristossificationcenter

NormalchildrenCHchildren

DiagnosisasearlyaspossiblediagnosticcriteriaNeonate:Neonatalspecialmanifestation+T4↓TSH↑Children:typicalsymptom+T4↓TSH↑+lagboneage

DifferentialdiagnosisCongenitalmegacolon

先天性巨结肠

21-trisome

21-三体症

Dysosteogenesis

骨发育障碍

Achondroplasia

软骨发育不全

Rickets

佝偻病

Anaemia

贫血DifferentialdiagnosisCongenitalmegacolon

先天性巨结肠

21-trisome

21-三体症

Dysosteogenesis

骨发育障碍

Achondroplasia

软骨发育不全

Rickets佝偻病

Anaemia

贫血CongenitalmegacolonVerysevereconstipation,abdominaldistensionandUmbilicalherniaWeightlossing

Normalfacial,voiceandphysicalfunction,X-rayshowenlargedcolon.NormalthyroidfunctionCongenitalmegacolon

XrayimagingDifferentialdiagnosisCongenitalmegacolon

先天性巨结肠

21-trisome

21-三体症

Dysosteogenesis

骨发育障碍

Achondroplasia

软骨发育不全

Rickets佝偻病

Anaemia

贫血21-trisome(21-三体症)SeverementalretardationTypicalfacialappearanceRoundface,epicanthicfold内眦赘皮,upwards

angulus

oculi

lateralis

外眦上翘，Depressionnasalbridgeandupwardsnostrils朝天鼻Protrudingtongue,舌外伸Chromosomeanalysis:21-trisome21-trisomekaryotypeDifferentialdiagnosisCongenitalmegacolon

先天性巨结肠

21-trisome

21-三体症

Dysosteogenesis

骨发育障碍

Achondroplasia

软骨发育不全

Rickets佝偻病

Anaemia

贫血Achondroplasia

ShortstaturewithlongtrunkandshortlimbsLargehead,frontalprotrusion,depressionofnasalbridgeShortandbroadhandsMarkedlumbarlordosisNormalskin,intelligenceandthyroidfunctionspecialX－rayfeaturesAchondroplasiaXrayimagingDifferentialdiagnosisCongenitalmegacolon

先天性巨结肠

21-trisome

21-三体症

Dysosteogenesis

骨发育障碍

Achondroplasia

软骨发育不全

Rickets佝偻病

Anaemia

贫血TreatmentTreatmentgoals

AssurenormalgrowthanddevelopmentNormalT4asrapidlyaspossibleAvoidhyperthyroidismMaintainclinicalandbiochemicaleuthyroidismEachwkdelayoftreatmentaffectsIQby1-2pointsTreatmentPrincipleOncediagnosed,immediatelytreatmentThyroidhormonesupplementinlifetimeRegulateddosealongwithincreasingageAttentiontheindividualdifferenceL-ThyroxineL-Thyroxineisthetreatmentofchoicelonghalf-lifeandinexpensiveexcellent

bioavailability

following

oralintakeProvidesstablelevelsofT4,T3andTSHovera24-hourperiodL-ThyroxineReplacementassoonaspossibleDoseofT4changeswithage:newborn10to15μg/kg.d,bidorqd

Infant:6-8ug/kg.d,bidorqd

laterinchildhood3-5μg/kg,bidorqd

Goal:serumT4upperhalfofnormalrangeDoNOTgivewithIron,soyorfibrePreferredcrushedtabletasliquidformslessstableMonitoring–guidelinesfromAmericanAcademyofPediatricsFollow-upinitially:2/52w-4/52w；Every1-2moduringthefirst6mo;Every3-4mobetween6moand3yofage;Every6-12mofrom3yofagetoendofgrowth.TherapeuticreactionClinicalsymptomesimprovearound2weeks,Clinicalmanifestationdisappearandgrowthadvancearound2-3months.AttentionSupplementofnutrientsubstanceandvitaminsareneeded.OutcomesTreatmentwithin3weeks(scree