بررسی اختلالات تیروئید در نوزادان

بررسی اختلالات تیروئید در نوزادان

اسلاید 1: Evaluation of Thyroid Disorders in NeonatesFereidoun AziziResearch Institute for Endocrine SciencesShahid Beheshti University of Medical ScienceTehran, I.R.Iranبیست و هشتمین همایش بین المللی بیماری های کودکان29مهر تا 2 آبان ماه 1395

اسلاید 2: AgendaDefinitionsCongenital hypothyroidismPrevalenceScreening managementNeonatal thyrotoxicosis

اسلاید 3:

اسلاید 4: TRANSITIONS FROM EUTHYROIDISM TO HYPOTHYROIDISM OR HYPERTHYROIDISM N = normal, ↓=decreased, ↑ = increased

اسلاید 5: کم کاری تيروييد نوزادان

اسلاید 6: Causes of Congenital HypothyroidismDevelopmental defects1 every 4000 newborns; In Iran >1/1000Complete absence of thyroid tissueFailure of thyroid to descend properly during embryologic developmentRoute of descent (foramen caecum at the junction of anterior two thirds and posterior third of tongue to normal site or below)Biosynthetic defects in the thyroidPituitary or hypothalamic failureFamily with mutation in gene coding TSH β subunit

اسلاید 7: Thyroid disorders and their approximate prevalence in the neonatal periodThyroid dysgenesis>1:1000-1:4000AgenesisHypogenesisEctopiaThyroid dyshormonogenesis 1:40,000Thyroid-stimulating hormone unresponsivenessIodide trapping defectOrganification defectDefect in thyroglobulinIodotryrosine deiodinase deficiencyTransient hypothyroidism 1:40,000 Drug inducedMaternal antibody inducedIdiopaticHypothalamic-pituitary hypothyroidism 1:100,000Hypothalamic-pituitary anomalyPanhypopituitarismIsolated thyroid-stimulating hormone deficiencyThyroid hormone resistance

اسلاید 8: Differential diagnosis of transient congenital hypothyroidism Primary hypothyroidismPrenatal or postnatal iodine deficiency or excessMaternal antithyroid medicationMaternal TSH receptor blocking antibodiesSecondary or tertiary hypothyroidismPrenatal exposure to maternal hyperthyroidismPrematurity (particularly <27 weeks’ gestation)DrugsSteroidsDopamineMiscellaneousIsolated TSH elevationLow T4 with normal TSHPrematurityUndernutritionLow-T3 syndrome

اسلاید 9: Importance of iodine in brain development 50,000 brain cells produced/second in developing fetal brain 100 billion brain cells in adult One million billion connections between these brain cells: Determine IQ

اسلاید 10: Importance of iodine in brain development 90 % of human brain development occurs between 3rd month of pregnancy & 3rd year of life (Critical period)

اسلاید 11: Goiter has been known since the days of Lord Buddha and beforeEarliest evidence of goiter: 3000 BCCretinism, Tip of the IcebergWorld wide prevalence of goiter

اسلاید 12:

اسلاید 13: Total goiter rate in 4 national surveys in the I.R. Iran Median urinary iodine excretion in 4 national surveys in the I.R.IranAzizi F. Thyroid International 2009;4:1

اسلاید 14: پيشگيري از بروز گواتر در بيش از 25 ميليون متولدين 23 سال اخير افزايش 66،000،000 ضريب هوشي در كودكان و نوجوانان صرفه جويي 17،500،000،000،000ريال (12،000،000،000 يورو) در هزينه هاي بهداشتي درمانيتاثير حذف كمبود يد در سلامت جامعه ايراني

اسلاید 15: راهنمای تشخیص و درمان بیماری‌های تیروئید در بارداری و پس از زایمان انجمن متخصصین غدد درون ریز و متابولیسم ایرانانجمن علمی متخصصین زنان و مامایی و نازایی ایران انجمن آسیب شناسی ایرانانجمن علمی دکترای علوم آزمایشگاهی تشخیص طبی ایران1394

اسلاید 16:

اسلاید 17: CH ScreeningSince 1975Highly sensitive immunoassay methodsDirect measurement of serum thyroxine and TSHFilter paper blood spotsGurantee detection and treatment from the first weeks of lifeMajority of children who were treated early experienced normal growth and neurologic development and normal-range IQ values

اسلاید 18: Serum T4, TSHNormal/Low TSHT4NormalLowFT4High TSHT4Normal or lowScanNormalLowTBGGH/CortisolNormalLowNormalLowPrematurityTBGDeficiencyIsolated TSHDeficiencyCentral CHEctopicGlandNormal scanTGAbsentTG DeficiencyNormal/HighTBIIPositiveTransientCHNegativeGoitrous CHAntithyroid DrugsNo uptakeThyroid U/SNo ThyroidNormalAgenesisThyroidTBIIPositiveTransientCHNegativeTSH ResistanceIodine Trapping DefectIodine BlockadeAlgorithm for evaluating abnormal thyroid screening testsPositive screening test

اسلاید 19: تاريخچه غربالگري CH در ايراناولين اقدام براي غربالگري كم‌كاري مادرزادي نوزادان در سال 1366 توسط دفتر تحقيقات غدد دانشگاه علوم پزشكي شهيد بهشتي انجام گرفت ولي به دليل فراواني ميزان فراخوان (به علت كمبود يد در كشور) اين مطالعه پس از دو سال متوقف شد. با رفع كمبود يد در كشور، مركز تحقيقات غدد درون‌ريز دانشگاه علوم پزشكي شهيد بهشتي با همكاري سازمان انرژي اتمي ايران و آژانس بين‌المللي انرژي اتمي مجدداٌ برنامه غربالگري كم‌كاري مادرزادي تيروئيد را از سال 1376 در بعضي از بيمارستان‌هاي شهر تهران و سپس شبكه دماوند اجرا كرد .

اسلاید 20: نتايج مطالعات مركز تحقيقات غدد دانشگاه شهيد بهشتي و مطالعه شيراز شيوع بالاي كم‌كاري مادرزادي نوزادان در كشور را نشان مي‌دهد. اين شيوع به ترتيب يك در 914 و 1433 تولد گزارش شده بود. مطالعه ديگري شيوع بسيار بالاي كم‌كاري مادرزادي تيروئيد برابر يك در 370 نوزاد در اصفهان را گزارش نمود.

اسلاید 21: High prevalence of consanguineous and congenital hypothyroidism in Iran

اسلاید 22: تاريخچه برنامهطراحي برنامه: سال 1382 اجراي آزمايشي (پايلوت) در 3 استان: سال 1383 ادغام در سيستم سلامت كشور: مهر ماه 1384

اسلاید 23: اجزای تشکيل دهنده برنامه غربالگری نوزادانآموزش (پرسنل بهداشتی درمانی و اجرائی، والدين، عموم جامعه، سياستگذاران)آزمون غربالگری (اصول نمونه گيری، نوع آزمون غربالگري، انتقال نمونه ها، انجام آزمون غربالگری ، گزارش دهی )پيگيری اوليه (فراخوان موارد مشكوك) تشخيص بيماريمراقبت (درمان، پيگيري هاي لازم و مشاوره هاي تخصصي لازم)ارزشيابی برنامه (داخلي و خارجي)

اسلاید 24: هدف اصلی برنامه شناسايی و کنترل متابوليك نوزادان مبتلا به بيماری کم کاری تيروييد، درمان و پيشگيری از عوارض آنبازده نهايی اجراي برنامهکاهش هزينه های اقتصادی ناشی از بيماری کاهش ناتواني‌های حاصل از بيماری ارتقا کيفيت زندگی بيماران و خانواده آنها ارتقا ميانگين ضريب هوشی افراد جامعه ازطريق پيشگيری از کاهش ضريب هوشی مبتلايان

اسلاید 25: شاخص هاي اجرايي برنامهپوشش برنامه در سطح ملي: 97.3 درصدتعداد نوزادان غربالگري شده: 8 ميليونتعداد بيماران شناسايي شده: بيش از 20000 بيمار (گذرا و دائمی)نوع گذرای بیماری = 29 درصد بروز بيماري: 1در 600 نوزاد غربالگري شده

اسلاید 26: زمان انجام نمونه گيری برحسب سن نوزادزمان انجام نمونه گيری برحسب سن نوزادزمان انجام نمونه گيری برحسب سن نوزاد22 و بيشتر6-21 روز3- 5 روز2%20%78%شاخص هاي اجرايي برنامه ...زمان شروع درمان برحسب سن نوزادزمان شروع درمان برحسب سن نوزادزمان شروع درمان برحسب سن نوزاد41 و بيشتر 40-28 روزكمتر از 28روز5%18%77% شاخص زمان شروع درمان در بيماران شناسايي شده: 95 درصد در زمان مناسبدر 77 درصد بيماران شروع درمان در سن قبل از 28 روزگي (مطلوب)در 18 درصد بيماران شروع درمان در سن قبل از 29 تا 40 روزگي (قابل قبول)

اسلاید 27: حدود غیرطبیعی آزمایش های تیروئید نوزادان در برنامه کشوری

اسلاید 28: Signs and Symptoms of HypothyroidismAt Birth postmaturity macrosomia open posterior fontanel, large head circumference generalized delay in skeletal maturation (but normal or near-normal length)During Early Infancy decreased muscle tone, lethargy, poor feeding hypothermia constipation prolonged jaundice abdominal distension, umbilical hernia dry and mottled skin macroglossia hoarse cry myxedematous appearance

اسلاید 29: Algorithm for the diagnostic evaluation of an infant with suspected congenital hypothyroidism.

اسلاید 30: Congenital Hypothyroidism: OutcomeDisease-Related Variables:Etiology of hypothyroidismSkeletal maturityThyroid hormone levels at diagnosisAge at onset of therapyStarting doseTime to achieve normalizationSubsequent treatment and outcomeCompliance and treatment adequacyGender Social, genetic and environmental factors

اسلاید 31: Thyroid function, physical development and intelligence quotient in various types of congenital hypothyroidism

اسلاید 32: Intelligence and Achievement Test Result by Etiology in Congenital Hypothyroidism

اسلاید 33: Congenital Hypothyroidism: OutcomeDisease-Related Variables:Etiology of hypothyroidismSkeletal maturityThyroid hormone levels at diagnosisAge at onset of therapyStarting doseTime to achieve normalizationSubsequent treatment and outcomeCompliance and treatment adequacyGender Social, genetic and environmental factors

اسلاید 34: Reference intervals for TSH of age groupsKapelari K, et al. BMC Endocrine Disorders 2008; 8: 15-25

اسلاید 35: Age-related reference values for fT4 (both sexes)Kapelari K, et al. BMC Endocrine Disorders 2008; 8: 15-25

اسلاید 36: Percentiles for TSH (mU/L) of children And adolescentsKapelari K, et al. BMC Endocrine Disorders 2008; 8: 15-25

اسلاید 37: Effect of Delay Treatment on Eventual IQ Klein et al: A 5-6 month delay in treatment with an average IQ approximately 70 Loss of 5-6 IQ points per month (linear effect)Bonger-Schoking et al: Delay treatment in early weeks Most impact Lower IQ several points per weekJ pediatr 1972J pediatr 2000

اسلاید 38: Congenital Hypothyroidism: OutcomeDisease-Related Variables:Etiology of hypothyroidismSkeletal maturityThyroid hormone levels at diagnosisAge at onset of therapyStarting doseTime to achieve normalizationSubsequent treatment and outcomeCompliance and treatment adequacyGender Social, genetic and environmental factors

اسلاید 39: Congenital Hypothyroidism: OutcomeDisease-Related Variables:Etiology of hypothyroidismSkeletal maturityThyroid hormone levels at diagnosisAge at onset of therapyStarting doseTime to achieve normalizationSubsequent treatment and outcomeCompliance and treatment adequacyGender Social, genetic and environmental factors

اسلاید 40: Congenital Hypothyroidism: OutcomeDisease-Related Variables:Etiology of hypothyroidismSkeletal maturityThyroid hormone levels at diagnosisAge at onset of therapyStarting doseTime to achieve normalizationSubsequent treatment and outcomeCompliance and treatment adequacyGender Social, genetic and environmental factors

اسلاید 41: CH: Treat Children But Don’t Forget Their ParentsEvaluate the IQ development in CH children detected by neonatal screening in an attempt to identify factors that may affect the IQ developmentThree educational-affective attitudes in the parents1) 38% appropriate coping with emotional distress2) 51% reacted with anxiety resulting in overstimulation of the child3) 11% completely refused the disease Psychological counselling of parentsEurop J Endocrinol 1999;141: 101-104

اسلاید 42: Management of Congenital HypothyroidismMedicationsL-T4: 10–15 µg/kg by mouth once dailyMonitoringRecheck T4, TSH2–4 wk after initial treatment is begunEvery 1–2 mo in the first 6 moEvery 3–4 mo between 6 mo and 3 y of ageEvery 6–12 mo from 3 y of age to end of growthGoal of therapyNormalize TSH and maintain T4 and FT4 in upper half of reference rangeAssess permanence of CHIf initial thyroid scan shows ectopic/absent gland, CH is permanentIf initial TSH is 50 mU/L and there is no increase in TSH after newborn period, then trial off therapy at 3 y of ageIf TSH increases off therapy, consider permanent CHRose S & Brown R. Pdiatric 2006; 117: 2290

اسلاید 43: IQ scores are in the normal range of tests in almost all adequately treated CH children.Selected tests of motor proficiency are indicated at 3 and 5 years of age.Language performances are at particular risk in CH children, and language achievements should be regularly reevaluated at 6-month intervals and, if no spontaneous improvement is observed, they should receive specific rehabilitation treatment. No further motor and language evaluation is warranted in CH children with normal tests at age 5 years. Facts and Recommendations for neuropsychological follow up in CH

اسلاید 44: Health care professionals must both remain alert to parents’ perceptions, which may be different than those of their affected children, and promote the need for patient adherence to treatment throughout life, if confirmed to have permanent CH, using a standard clinical protocolLeger J, et al. JCEM 2011; 96: 1771.

اسلاید 45: NeonatalHyperthyroidism

اسلاید 46: Low birth, prematurityMicrocephaly, frontal bossing, triangular faciesIrritablelity, fever, diarrheaProminent eyes, diffuse goiterTachycardia, bonding pulsesCardiomegaly, EHF, arrhythmiasJaundice, hepatosplenomegaly, thrombocytopeniaAccelerated skeletal maturationClinical manifestations of neonatal hyperthyroidism

اسلاید 47: Management of thyrotoxicosis in pregnancyConfirm diagnosisStart propylthiouracil in first trimester; methimazole in the 2nd and 3nd trimesterRender patient euthyroid: continue with low-dose ATD up to and during labor and postpartumMonitor thyroid function: Throughout gestation; adjust ATD if necessary to maintain T4 at upper level of normal Check TSHRAb at 26 weeksDiscuss treatment with patient effect on patient effect on fetus breast feedingInform obstetrician and pediatricianReview postpartum-check for exacerbation

اسلاید 48: WHAT IS THE VALUE OF TSHRAB MEASUREMENT IN THE EVALUATION OF A PREGNANT WOMAN WITH GRAVES’ HYPERTHYROIDISM?If the patient has a past or present history of Graves’ disease, a maternal serum measure of TSHRAb should be obtained at 24-28 weeks gestation. Lution O et al. J Clin Endocrinol Metab 2005; 90: 6093Laurberg P et al. Europ J Endocrinol 2009;160: 1-8Zwaveling- Soonawala N et al. Thyroid 2009; 19: 661-2.

اسلاید 49: TSH receptor antibody in pregnancyA significant decrease in TRAb during pregnancyEuthyroid or hypothyroid GD patients may still have high TRAbHigh TRAb is more common after radioiodine therapyFetal and neonatal thyrotoxicosis occur in 1-5% of mothers with current or past GD.TRAb is the best predictor (predictive value 42%)Over 3 times UNL of TRAb at 24-28 weeks close follow-up of the fetus.Barbesino G, et al. J Clin Endocrinol Metab 2013; 98: 2247.Kamijo K. Endocr J 2007;54:619–624.Laurberg P, et al. Eur J Endocrinol 2009; 160: 1–8.

اسلاید 50: UNDER WHAT CIRCUMSTANCES SHOULD ADDITIONAL FETAL ULTRASOUND MONITORING FOR GROWTH, HEART RATE, AND GOITER BE PERFORMED IN WOMEN WITH GRAVES’ HYPERTHYROIDISM IN PREGNANCY?Fetal surveillance should be performed in women who have uncontrolled hyperthyroidism or who have highly elevated TSHRAb titers. Such monitoring may include ultrasound monitoring for heart rate, growth, and fetal goiter. Papendieck P et al. J Ped Endocrinol Metabol 2009; 22: 547

اسلاید 51: Treatment of neonatal hyperthyroidismMethimazole (not PTU) 0.25-1 mg/kg/dPropanolol 2 mg/kg/dLugol’s solution or potassium iodide on ipanoic acide 100-200 mg/dGlucocorticoids, in severe cases Digoxine, if neededBarbesino G, et al. J Clin Endocrinol Metab 2013; 98: 2247.Kamijo K. Endocr J 2007;54:619–624.Laurberg P, et al. Eur J Endocrinol 2009; 160: 1–8.