复旦儿科学课件：内分泌-生长激素缺乏症

GrowthHormoneDeficiency,GHD

生长激素缺乏症DepartmentofEndocrinology

Children’sHospital

FudanUniversity

GHDisadisorderinvolvesthepituitaryglandPituitaryglanddoesnotproduceenoughGHGrowthvelocityisslowerthannormalGHDcanoccuratanyageIntroductionGrowthhormone(GH)isahormonethatstimulatesnormalgrowthofbonesandtissuesGHDmayresultfromdisruptionoftheGHaxisGHDmaybeisolated(isolatedGHD)orassociatedwithotherpituitarydeficienciesPathogenesisGHisstimulatedbyGH-releasinghormone(GHRH)fromthehypothalamusGHisstimulatedbycertainGH-releasingpeptides(GHRPs)SomatostatinissecretedbythehypothalamusinhibitsGHsecretionPathogenesisGHAxisBoneepiphysisHypothalamusAnteriorpituitarySS(-)GHRH(+)GHLiverIGF-1(-)GonadsTE2ThyroidglandT3T4insulinlikegrowthfactor1(IGF-1)issecretedandactslocallyatthesiteofgrowingboneIGF-1bindstooneofseveralIGF-bindingproteins(IGFBPs)andcirculatesalmostentirely(>99%)intheboundstateIGFBP-3accountsforthemajorityofIGF-Ibindingandthisbindingprotein’sactivitydependsdirectlyonGHPathogenesisMostcausesofGHDareidiopathicSecondarycausesBraintumors,mostcommonlycraniopharyngiomaCNSsurgeryCNSradiationAnatomicalabnormalities(eg,septoopticdysplasia,emptysellasyndrome)GeneticGHDEtiologyShortstatureLowgrowthvelocityforageandpubertalstageIncreasedamountofadiposetissuearoundthewaistThechildmaylookyoungerDelayedtoothdevelopmentDelayedonsetofpubertyEpisodesofhypoglycemiaClinicalPresentation1.GHstimulationtestProvocativestimuliincludeinsulin,arginine,levodopa(l-dopa),clonidineandglucagonGHresponsetoinsulinisthemostreliabletestforGHD.GHresponse(GHlevel<10ng/ml)aftergiven2provocativestimulidiagnosesGHdeficiencyLaboratoryStudies2.Boneage3.HeadMRIorCT4.IGF-1andIGFBP-3levelsLowvaluesofIGF-1andIGFBP-3suggestGHD5.Otherpituitaryhormones6.KaryotypeLaboratoryStudiesAheightbelowthe3rd

percentileor

lessthan2SDonagrowthchartThegrowthvelocityisslow(

4cm/yfromage2ytopuberty)Thepeakgrowthhormone<10μg/ＬDelayedboneageDiagnosis14岁患者（右）患侏儒症，与同年龄发育正常男孩（左）比较(left)Normal14yomale(right)14yoGHDmale7岁生长激素缺乏症患者腕部X线摄片－－腕部骨化中心的发育符合3岁年龄7yomalewith3yoboneagePatientResults

GHLevel 0’ 20’ 30’ 60’ 90’ 120’ Insulin

0.72 0.29 1.53 1.49 1.44 1.76

(

g/L)

Arginine

0.13 --- 3.69 1.52 2.20 0.22

(g/L)

Referencerange

IGF－1

30ng/ml >70ng/ml

IGFBP－3

1.05ng/ml >1.82ng/mlPatientResultsConstitutionalgrowthdelayFamilialshortstatureIntrauterinegrowthretardationChronicdiseasesandsystemicdisorders

AchondroplasiaBoneandcartilagedisordersGeneticsyndromesPsychosocialdwarfismDifferentialDiagnosisConstitutionalgrowthdelayMostcommoninmalesSeenin1/3ofpatientspresentingwithshortstatureFamilyhistoryofdelayedgrowthandpubertyBoneagemirrorsheightageinsteadofchronologicageFamilialshortstatureFamilyhistorysuggestiveofshortstatureClinicalfeatures:normalbirthweight,normalgrowthvelocityNormalGHlevelTurnerSyndromeIncidence1/2500–1/5000Chromosomes45XO,45XO/46XX, 46XXq-,46XXp-Clinicalfeatures:webbedneck,shieldchest,widely-spacednipples,streakovaries,amenorrhea,absenceofsecondarysexcharacteristics13yoTurnerSyndromefemaleAchondroplasiaIncidenceof1/5000–2/26000Clinicalfeatures:frontalbossing,midface

hypoplasia,normaltrunklength,shortenedlimbswithtridenthandsandbrachydactylyXrayswithcontractedskullbase,square-shapedlongbones,chevron-shapeddistalfemoralepiphysis,shortenedgrowthplatesGHreplacement

Thedrugisgivensubcutaneouslyonce dailyatadosageof0.1U/kgOtherpituitarydeficienciesshouldbetreatedSurgicalresectionofbraintumorsTreatment使用Pen（新型注射器）患儿可安全自行注射生长激素MostchildrenwithGHDreachnormaladultstatureInitiateGHtherapyasearlyasp