1、（呆小病（呆小病 克汀病）克汀病）(Cretinism)先天性甲状腺功能减低症先天性甲状腺功能减低症 Congenital HypothyroidismOverviewCongenital Hypothyroidism is common disease of pediatric endocrinology.Congenital factors cause the insufficience of thyriod hormone,which result in the low metabolism,retardation of growth,and mental impairment.The
2、onset during inbore or newborn peroid,can lead to irreversible mental impairment.Disease incidence In American and Europe:Incidence of neonatal screening:1/3750In China:Incidence of neonatal screening:1/3624 -the nationwide neonatal screening from clinical examination center of Health Bureau in 1999
3、 CategorySporadical congenital hypothyroidism accounting for most patients,a few as family.Endemic congenital hypothyroidism Pregnant women live in iodine insufficient areas,which result in iodine deficiency.along with the population of iodine salt in dietary,the incidence is much lower.Synthesis an
4、d release of thyroid hormone(TH)Blood thyroid epithelial cell TSH hydrogen peroxidaseI I I O +tyrosineoxidization T1 +T2T3T4 TSH T2 +T2T3、T4 +iodizeiodinasecytolysosomeThyroglobulin (TG)hydrolyzeTGRegulation of thyroid hormone secretion thyroid-stimulating hormone-releasing hormone(TRH)Hypothalamus(
5、HT)thyroidthyroid stimulating hormone(TSH)T3、T4（+）（+）（）Pituitary Thyriod dysgenesis Athyreotic or hypothyreotic Ectopic Goitrous enzyme defect(thyriod hormone dysgenesis)Iodine deficiency or Iodine transporter defect peroxidase defct thyroglobulin synthetic defect Thyroid-stimulating hormone defect
6、TSH defect or TSH resistance P e r i p h e r a l t h y r i o d h o r m o n e inactivation Transient hypothyriodism maternal antithyriod medications or maternal antithyriod antibodiesEtiological factorThe role on metabolism of human bodyThe role on growth and development The role on function of organ
7、s and systemsphysiologic function of thyriod hormone The role on metabolism Oxidation basal metabolism,heat production protein promote protein synthesis fat promote lipoclasis liquid promote large molecular substance in lymphatic vessel into blood,maintain water balancemineral salt affect turnover r
8、ate of calcium and phosphonium Vitamin participate vitamin metabolismThe role on growth and development tissue Promote tissue,cell growth and development skeleton promote bone and cartilage growth and development,promote calcium and phosphonium deposit.Cerebrum promote proliferation,differentiation,
9、maturity of pallium cellular Differentiation,maturity process of infant palliumpallium Pregnant 2mo formation Pregnant 5mo DifferentiationLate foetal period peak period of proliferation,-8mo after birth differentiation and maturation Upto 3yr differentiation finishAttention:thyroid hormone is essent
10、ial for this processThe role on organ and systemcirculation system increase myocardial contractility digestive system promote digestive gland secretion,maintain normal enterokinesia.sexual gland promote sexual developmentClinical manifestationtypical symptom典型症状典型症状Special manifestation of neonatal
11、hypothyroidism新生儿甲低的特殊表现新生儿甲低的特殊表现Typical symptome(典型症状典型症状)Retardation of growth and development生长发育障碍生长发育障碍unusual facies and body carriage特殊面容体态特殊面容体态mental disable智能低下智能低下Physiologic Hypofunction生理功能低下生理功能低下 126cm85cm7yr6mo7yr6moRetardation of growth and developmentTypical symptome(典型症状典型症状)Reta
12、rdation of growth and development生长发育障碍生长发育障碍unusual facies and body carriage特殊面容体态特殊面容体态mental disable智能低下智能低下Physiologic Hypofunction生理功能低下生理功能低下 unusual facies and body carriageunusual facies6yr6yrunusual faciesunusual facies12 yr12 yr4 yr4 yr2mo2mo1yr6mo1yr6moTypical symptome(典型症状典型症状)Retardatio
13、n of growth and development生长发育障碍生长发育障碍unusual facies and body carriage特殊面容体态特殊面容体态mental disabe智能低下智能低下Physiologic Hypofunction生理功能低下生理功能低下 Very severe mental disable智力极度落后。智力极度落后。Very lower Memory and attention记忆力、注意力均低下。记忆力、注意力均低下。Disorder of motor development,delayed walking,poor fine activities
14、运动发育障碍，行走延迟，精细动作差。运动发育障碍，行走延迟，精细动作差。partial deafness,disesthesia听力减退听力减退、感觉迟钝。、感觉迟钝。Typical symptome(典型症状典型症状)Retardation of growth and development生长发育障碍生长发育障碍unusual facies and body carriage特殊面容体态特殊面容体态mentally disable智能低下智能低下Physiologic Hypofunction生理功能低下生理功能低下 Lower basal metabolic rate(基础代谢率低表基础
15、代谢率低表现现)Quiet and less activities,lower voice,limited food-intake,lower body temperature.安静少动、声音低哑、进食量少、体温偏低安静少动、声音低哑、进食量少、体温偏低;Lower cardiovascular function心心(血管功能血管功能低下表现低下表现)Bradycardia,lower cardiechema,hydropericardium,electrocardiogram show low tension,lengthened P-R interval,conduction blocka
16、de.心率缓慢、心音低钝心率缓慢、心音低钝、可有心包积液、心电图呈低电压、可有心包积液、心电图呈低电压、P-RP-R间期延长、传导阻滞间期延长、传导阻滞;Lower digestion function(消化功能低下表现消化功能低下表现)Decreased enterokinesia,abdominal distention,constipation,dry stool.肠蠕动减少、腹胀、便秘、大便肠蠕动减少、腹胀、便秘、大便干结干结Special manifestation of neonatal hypothyroidism新生儿甲低的特殊表现新生儿甲低的特殊表现Appearance of
17、 overall hypo-metabolic function全面代谢低下的表现全面代谢低下的表现 Special manifestation of neonatal hypothyroidism post-term birth,large for date infant,birth weight4000g,oedema,prolonged jaundice.过期产、巨大儿、体重过期产、巨大儿、体重4000g4000g、水肿、黄疸时间延长。、水肿、黄疸时间延长。Poor-feeding,poor-sucking,fewer food-intake,sleepiness,dull reacti
18、on,hoarse cry,lower body temperature,poor peripheral circulation,easy to stiff edema.喂养困难、吸吮差、少吃、多睡不动、对外界反应迟钝、喂养困难、吸吮差、少吃、多睡不动、对外界反应迟钝、哭声低微、低体温、末稍循环差、易发生硬肿；哭声低微、低体温、末稍循环差、易发生硬肿；Decreased enterokinesia,abdominal distention,constipation肠蠕动少、腹胀、便秘，易被误诊为巨结肠肠蠕动少、腹胀、便秘，易被误诊为巨结肠Laboratory examination Newbo
19、rn screening Time:23 days after birthMothed:use dry blood slip and detect TSH level.Results:positive:TSH 20uU/ml then detect T4 and TSH to further determineLaboratory examinationEvaluate thyriod function primarily hypothyriodism:T4 T3 TSH (甲状腺性甲低甲状腺性甲低)secondary hypothyriodism:T4 T3 TSH(垂体性甲低垂体性甲低)T
20、RH stimulating test(TRH刺激试验刺激试验)objective:suspected insufficient TSH or TRH objectivesmothed:TRH 7ug/kg,IV,detect TSH levelresults:normal:at 30 min appear TSH peak，at 90 min retum to basic level valu abnormal:dont appear TSH peak-pituitary disorder appaer delayed TSH peak-hypothalamic disorderLabora
21、tory examinationLaboratory examinationEvaluation bone ageObviously delayed bone age,almost lag 3years oldPosition of detect bone age:younger than 6 month:detect lap older than 6month:detect wrist diagnostic therapyOnly used in the condition that there is suspect clinical manifestation,but can not de
22、tect thyriod function.Laboratory examinationDiagnosis as early as possiblediagnostic criteriaChildren:typical symptom+T4 TSH+lag bone ageNeonate:Neonatal special manifestation +T4 TSHDifferential diagnosisCongenital megacolon 先天性巨结肠先天性巨结肠21-trisome 21-21-三体症三体症Bone dysgenopathy 骨发育障碍病骨发育障碍病 Achondro
23、plasty 软骨发育不全软骨发育不全 Mucopolyasccharidosis 粘多糖病粘多糖病Rickets 佝佝偻病偻病Anaemia 贫血贫血 21-trisome(21-21-三体症三体症)21-trisomeDifferential diagnosisCongenital megacolon 先天性巨结肠先天性巨结肠21-trisome 21-21-三体症三体症Bone dysgenopathy 骨发育障碍病骨发育障碍病 Achondroplasty 软骨发育不全软骨发育不全 Mucopolyasccharidosis 粘多糖病粘多糖病Rickets 佝佝偻病偻病Anaemia
24、贫血贫血 AchondroplastyAchondroplasty3yr6moMucopolyasccharidosisDifferential diagnosisCongenital megacolon 先天性巨结肠先天性巨结肠21-trisome 21-21-三体症三体症Bone dysgenopathy 骨发育障碍病骨发育障碍病 Achondroplasty 软骨发育不全软骨发育不全 Mucopolyasccharidosis 粘多糖病粘多糖病Rickets 佝佝偻病偻病Anaemia 贫血贫血 TherapyPrinciple Once diagnosis,immediately tr
25、eatmentLifetime substitute therapyStarted with lower doseRegulated dose along with increasing ageAttention the individual defference medicine thyroxin甲状腺素甲状腺素thyroxin T3 T4 40mg 60mglevothyroxine T4 25ug 50ug 100ug 100ug Sodium(L-T4)drugs component dosage form equivalent dose Method of take medicine
26、Start from lower dose,increasing gradually to maintenance dose,regulate per every 1-2 weeks.Dose of medicine neonate 10ug/kg.d bid or qd infant 6-8ug/kg.d bid or qd child 5ug/kg.d bid or qdmaintenance doseDisappear of clinical manifestation,growth advance,not appear hyperthyriodism,normal T4 TSH level.therapeutic reactionClinical manifestation improve around 2 weeks,Clinical manifestation disappear and growth advance around 2-3 months.AttentionSupplement nutrient substance and vitamins.
