【醫(yī)學課件】性早熟（英文版）

PrecociousPuberty

2024/1/12DiagnosisIntroductionTypesandCausesTreatment2024/1/12

PrecociousPuberty:

TheonsetofsecondarysexualcharacteristicsoccurringatanunusuallyearlyagePrecocious:

Girl:<8YBoy:<9Y

AmericanLawsonWilkinsPediatricEndocrineSociety

(LWPES)：Whitegirl＜7歲，Blackgirl＜6歲Definition2024/1/12

Definition

PubertyisadevelopmentalprocessdefinedasthetransitionfromchildhoodtoadolescenceandadultreproductivefunctionManifestations:BreastenlargementinfemalesBeginningofmenstruationinfemalesGenitaliagrowthinmalesGrowthofpublichair

2024/1/12Tanner’sscale

ofbreastdevelopment2024/1/12BreastdevelopmentinfemaleStageI(Preadolescent)-OnlythepapillaiselevatedabovethelevelofthechestwallStageII-(BreastBudding)-ElevationofthebreastsandpapillamayoccurassmallmoundsalongwithsomeincreaseddiameteroftheareolaeStageIII-Thebreastsandareolaecontinuetoenlarge,althoughtheyshownoseparationofcontourStageIV-TheareolaeandpapillaeelevateabovethelevelofthebreastsandformsecondarymoundswithfurtherdevelopmentoftheoverallbreasttissueStageV-Maturefemalebreastshavedeveloped.ThepapillaemayextendslightlyabovethecontourofthebreastsastheresultoftherecessionoftheaerolaeTanner’sscale2024/1/12PubichairgrowthinfemalesStageI(Preadolescent)-Velloshairdevelopsoverthepubesinamannernotgreaterthanthatovertheanteriorwall.ThereisnosexualhairStageII-Sparse,long,pigmented,downyhair,whichisstraightoronlyslightlycurled,appears.ThesehairsareseenmainlyalongthelabiaStageIII-Considerablydarker,coarser,andcurliersexualhairappears.StageIV-Thehairdistributionisadultintypebutdecreasedintotalquantity.StageV-Hairisadultinquantityandtypeandappearstohaveaninversetriangleoftheclassicallyfemininetype.

Tanner’sscale2024/1/12PubichairgrowthinmalesStageI(Preadolescent)-Velloshairappearsoverthepubeswithadegreeofdevelopmentsimilartothatovertheabdominalwall.StageII-Thereissparsedevelopmentoflongpigmenteddownyhair,whichisonlyslightlycurledorstraight.Thehairisseenchieflyatthebaseofpenis.StageIII-Thepubichairisconsiderablydarker,coarser,andcurlier.ThedistributionisnowspreadoverthejunctionofthepubesStageIV-Thehairdistributionisnowadultintypebutstillisconsiderablylessthatseeninadults.ThereisnospreadtothemedialsurfaceofthethighsStageV-HairdistributionisadultinquantityandtypeandisdescribedintheinversetriangleTanner’sscale2024/1/12GenitaliadevelopmentinmaleStageI(Preadolescent)-Thetestes,scrotalsac,andpenishaveasizeandproportionsimilartothoseseeninearlychildhoodStageII-Thereisenlargementofthescrotumandtestesandachangeinthetextureofthescrotalskin.ThescrotalskinmayalsobereddenedStageIII-Furthergrowthofthepenishasoccurred,initiallyinlength,althoughwithsomeincreaseincircumference.Therealsoisincreasedgrowthofthetestesandscrotum.StageIV-Thepenisissignificantlyenlargedinlengthandcircumference,withfurtherdevelopmentoftheglanspenis.Thetestesandscrotumcontinuetoenlarge,andthereisdistinctdarkeningofthescrotalskin.StageV-Thegenitaliaareadultwithregardtosizeandshape.Tanner’sscale2024/1/12Praderorchidometer

G1:<3mlG2:4-8mlG3:10-15mlG4:15-20mlG5:25ml1,2,3;4,5,6,8;10,12;15,20;252024/1/12Epidemiology

Increasedincidence

4-5%ofgirlsfrombothracial(In1999)Female:Male=4~5:12024/1/12Epidemiology

12024/1/12Epidemiology

2024/1/12Epidemiology

2024/1/12BasicTerminologychronologicage:CAboneage:BAAssessmentofboneageisaclinicalprocedureusedinpediatricradiologytoevaluateskeletalmaturityonthebasisofbonegrowthinthelefthandandwrist,asseenonaradiograph.

2024/1/12BAofachild（8years）

9ossificationcenterswereshowninthepalmandwrist;spondylo-epiphysealwasn’tinafusionBAofAnadult

10ossificationcenterswereshowninthepalmandwrist;spondylo-epiphysealwasinafusionsesamoidbone

radialepiphysisulnaepiphysisProximalphalanxdistalphalanxmetacarpal2024/1/12Clinicalandsocialsignificance

1Induceearlybonematurationandreduceeventualadultheight2Indicatethepresenceofatumororotherseriousproblem3Causethechild,particularlyagirl,tobecomeanobjectofadultsexualinterest

2024/1/12DiagnosisIntroductionTypesandCausesTreatment2024/1/12Types13Partialprecociouspuberty2Peripheralprecociouspuberty(PPP)Centralprecociouspuberty(CPP)2024/1/12

1.Thecausecanbetracedtothehypothalamusorpituitary2.Gonadotropin-dependent3.Earlymaturationoftheentirehypothalamic-pituitary-gonadal(HPG)axis,withthefullspectrumofphysicalandhormonalchangesofpubertyCentralprecociouspuberty(CPP)2024/1/12hypothalamic-pituitary-gonadal(HPG)axis2024/1/122024/1/12CausesofCPPIdopathic—80-90%ingirlsOrganic—25-90%inboysTumor：Astrocytoma

,Opticnerveglioma,

Germcelltumors,Pinealtumors

、HamartomaOthers：CNS

damage（Trauma,radiation,infection

）Congenitalmalformations:arachnoidcyst,Asseptalabnormalities,hydrocephalus

2024/1/12Centralprecociouspubertyduetohypothalamichamartomainaoneyearandninemonth-oldboyRarecongenitalnonneoplasticheterotopiasThemostcommontumoralcauseofCPP

Mostoftheneuronsinahamartomaaresimilartonormalhypothalamicneurons●Diagnosis:thecharacteristiclocation,isointensitytonormalbrain,lackofcontrastenhancement,andabsenceofchangeinsizeandmorphologyofthemassatthefollow-up(MRIorCT).2024/1/12Generalinformation

◆1.8yroldboy◆

chiefcomplaint

abnormalenlargedexternalgenitaliaformorethan9months◆Historyofpresentillness

NoseizuresNoextrahormonesadmissionNootherabnormalsymptoms

2024/1/12Physicalexamination

Height:93cm

weight:17kg(＞95percentile),genitalstageandpubichairstage:TannerstageII.testisvolume:10ml,penis:5cminlengthPhysicalexamination:nocoffeemacula,noSkinPigmentationandnoabnormalsigns.2024/1/122024/1/12LabtestsBaselineTestosterone416.0ng/dl(<20ng/dl)luteinizinghormone(LH)1.6mIU/ml(<0.4mIU/ml)folliclestimulatinghormone(FSH)2.1mIU/ml(1.8-12mIU/ml)prolactin(PRL)14.6ng/ml(4.3-13.7ng/ml)HCG<1mIU/ml17β-estradiol(E2)29.3pg/ml(<20pg/mL),progesterone(P)0.2ug/dlcortisol14.7ug/dl;ACTH30.0pg/ml17-alphahydroxyProgesterone(17a-OHP):1.35nmol/L2024/1/12luteinisinghormonereleasinghormone(LHRH)stimulationtest

peakLHlevels:21.7mU/ml

peakFSHlevels:3.8mU/mlTheratioofLH/FSH:5.7IGF-1:499.6ng/ml.ThyroidFunctionTest:normalBoneage-3-4yearsUltrasound:Noabnormalechogenicityonhistestisandadrenal

glands

2024/1/12Magneticresonanceimaging

Treatment----GnRHa(tillnow)2024/1/12Secondarysexualdevelopmentinducedbysexsteroidsfromotherabnormalsources2.Gonadotropin-independentPeripheralprecociouspuberty(PPP)

2024/1/12.Gonadaltumors.Adrenaltumors.Germcelltumor.Congenitaladrenalhyperplasia.McCune–AlbrightsyndromeExogenoushormones:EnvironmentalexogenoushormonesTreatmentforanotherconditionCausesofPPPEndogenoussources:Exogenoussources:2024/1/12McCune–AlbrightsyndromeZygoticmutationofthegeneGNAS1,whichisinvolvedinG-proteinsignallingPolyostoticfibrousdysplasiaSkinpigmentationAutonomousendocrinehyperfunction2024/1/12McCune–Albrightsyndrome2024/1/12

PrematurethelarchePrematureadrenarchePrematurepubarchePrematuremenarcheGynecomastiaPartialprecociouspuberty2024/1/12PrematurethelarcheAbenign,self-limitingconditionwhichischaracterisedbybreastdevelopmentNormalgrowthandboneageNoresponseofFSHandLHtoGnRHstimulationtest2024/1/12PrematureadrenarcheThemostcommoncauseoftheearlyappearanceofpubichair("prematurepubarche")DD:Congenitaladrenalhyperplasia,Androgen-producingtumorsoftheadrenalsorgonadsOccursmoreofteninchildrenwithintrauterinegrowthretardationandinoverweightchildren2024/1/12PrematurepubarcheTheprecociousappearanceofpubichair(P2)withoutothersignsofpubertyDD:CPP,nonclassicformsofcongenitaladrenalhyperplasia

2024/1/12Prematuremenarche

thefirstmenstrualcycle,orfirstmenstrualbleedingPartofpubertyIsolatedprematuremenarcheisrarelythefirstmanifestationofprecociouspuberty

2024/1/12GynecomastiaTheabnormaldevelopmentoflargemammaryglandsinmalesresultinginbreastenlargementThecauses:animbalanceofsexhormonesorthetissueresponsivenesstothem2024/1/12IntroductionDiagnosisTypesandCausesTreatment2024/1/12CPPdiagnosiscriteria

1.Earlyonsetofsecondarysexualcharacteristicsfemale<8Y，male<9Y2.Increasedbloodgonadotropinlevel:Baseline:LH>3.0~5.0IU/LGnRH

stimulationtest：GnRH2.5μg/kg(100μg/m2),iv,0,30,60mindrawblood,LH

peak>12IU/L(F)，>25IU/L(M)，LH/FSH>0.6~1.0(radioimmunoassay)LHpeak>3.3~5IU/L，LH/FSH>0.6(Chemiluminescence)2024/1/12CPPdiagnosiscriteria

3.Gonadenlargement：Ovarianvolume>1ml，d>4mmfollicle；4.Testicularvolume≥4ml,Progressiveincrease5.Acceleratedlineargrowth6.Boneage－actualage≥1Y7.Increasedbloodsexualhormones2024/1/12StepsofdiagnosisPhysicalexam—evaluateanychangesinthebody.Familyhistory—findoutifearlypubertymightruninthefamily.Bloodtests—hormonelevels.X-rays—boneage.MRIsofthebrain—ruleoutorganicCNScauses,liketumorsUltrasounds—oftheovaries，uterus2024/1/12Differentials

Peripheralprecociouspuberty

NoresponseofLHandFSHGnRH

stimulationtestPrematurethelarche

FSH↑↑，LH↑(<5IU/L),FSH/LH>1

GnRH

stimulationtestcanchangetoCPPFollowup2024/1/12DiagnosisIntroductionTypesandCausesTreatment2024/1/12ThegoaloftreatmentforCPPImprovetheeventualadultheightPreventmenarcheControlthedevelopmentofsecondsexualcharacteristicsPreventpsychosocialproblems2024/1/12GnRHanalogue(GnRHa)AsyntheticpeptidemodeledaftertheGnRH(Gonadotropin-releasinghormone)withspecificaminoacidsubstitutionstypicallyinposition6and10.Analoguewith2substitutions:leuprolide,buserelin,nafarelin,histrelin,goserelin,deslorelin2024/1/12HowitworksTheaminoacid

substitutionsinhibitrapiddegradation

DownregulationofGnRH-recepter

DecreasedreleaseofFSHandLH2024/1/12IndicationsToimproveadultheight:1)Boneage:female≤11.5,male≤12.5,Boneage-age>2(spondylo-epiphysealwasn’tinafusion)2)Predictedadultheight:female<150cm,male<160cm;3)Impairedgrowthpotential:Theheightofboneage<-2SDofnormalrange4)Improvementofboneage/improvementofage>12024/1/12DifferentPrepairationsPediatrics2009;123:e752–e7622024/1/12Administration

Dose:Firstdose:80~100μg/kg，repeatonceafter2w，then60~80μg/kg.q4W

Courseofthetreatment:≥2years(toimproveadultheight)