Transcript 先天性甲状腺功能减低症
Congenital Hypothyroidism 先天性甲状腺功能减低症 Xue Fan Gu, MD, PhD Xinhua Hospital Shanghai Jiao Tong University School of Medicine Incidence • Thyroid hormone deficiency may: or acquired • Congenital:most cases are hypoplasia or aplasia of the thyroid gland World: 1:3 000～5 000 China: 1:3 200 Thyroid Ontogenesis 8th gestational weeks: synthesis of thyroglobulin 10~12th gestational weeks: pitutary gland begins to secrete TSH,thyroid gland synthesis of T3、T4 30th gestational weeks: hypothalamicpitutary-thyroid axis is functioning and independent of the maternal axis • After delivery, TSH rapidly rise reaching 60~80 uU/ml levels, and then slowly decline over the next few days(5~7d) to <5 uU/ml levels Thyroid hormone synthesis and metabolism • The thyroid follicle is stimulated by TSH by increase with TSH receptor • Iodine from the circulation is concentrated and rapidly oxidized by peroxidase to iodine • Iodine incorporated into tyrosyl residures on thyroglobuline • Iodothyrosines are couple an ether linkage to form T4 and T3 • T3 and T4 • Metabolic potency of T3 is 3~4 times that of T4. Only 20% of circulating T3 is secreted by the thyroid • T3, T4 in circulation Binding form：70％with TBG ，other with Alb. Free form：T4 0.03%, T3 0.3% Hypothalamus TRH Anterior pituitary gland TSH - Thyroid gland rT3 T3 T4 Hypothylamic-pitutary-thyroid feedback regulation Physiological of thyroid hormones • • • • Increase oxygen consumption Stimulate protein synthesis Influence growth and differentiation Affect carbohydrate, lipid and vitamine metabolism Etiology • The cause may be sporadic or familial, goitrous or nongoitrous • Defective embryogenesis 75% Agenesis, dysgenesis, ectopia • Dyshormonogenesis Pit-1, TSH, TSHR, TTF-I, TTF-II, Pax 8, TG, TPO defect, etc. Iodide transport defect, organification defect, coupling defect, iodothyrosine deiodinase defect, inability of tissueses to convert T4 to T3 • Deficiency or excess of iodine Transient Hypothyroidism • Premature • Maternal medications (propylthiouracil,methimazol) • Maternal antibody • Iodine deficiency hypothyroidism in iodine deficiency area Other Causes • Pitutary/hypothalamis hypothyroidism Rare，<5％, measurement of TSH levels fail to revel patient with pitutary-hypothalamic hypothyroidism, since they have low TSH Classification According To TSH Level • TSH level rise Primary hypothyroidism Transient hypothyroidism • TSH level in normal Pitutary/hypothalamis hypothyroidism low TBG Clinical Findings In Newborns and Infants Absent symptom during the first few weeks of life A few have birth weight>3.5kg prolongation of physiological icterus,constipation, hoarse cry, feeding or sucking difficulties Progress Manifestation • Pulse is slow, heart murnures, cardiomegaly,hypothermia, hypotonia, enlarged tongue, skin cold and dry, umbilical hernia, hair is dry • Mental retardation • growth stunted 甲低特殊外表 8y Hypothyroidism caused by Pituitaryhypothalamis • Without symptom in neonatal period • May be with other pituitaty hormone deficiency GH deficiency ： short stature ACTH deficiency ：hypoglycemia ADH deficiency ： diabetes incipidus Laboratory findings TSH in neonatal screening programs: <10~15 mu/L Normal range for neonate T4 FT4 TSH 84-210 nmol/l(6.5-16.3ug/dl) 12-28 pmol/l(0.9-2.2ng/dl) 1.7-9.1 mu/L(1.7-9.1 uU/ml) Scintigraphy • 99mTc、123I scintigraphy • B ultrasound examination • X ray: retardation of skeletal maturation (bone age) Treatment Principal • Give thyroxine as early as possible • TSH and FT4 should be monitored and maintained in the normal range • Confirmation of diagnosis may be necessary for some infant to rule out the possibility of transient hypothyroidism at 2~3 years old Dose of thyroxine（L-T4) ────────────────────── Age μg/day ug/kg/day ────────────────────── 0~6m 25~50 8.5~10 6~12m 50~100 5~8 1~5y 75~100 5~6 6~12y 100~150 4~5 12y to adult 100~200 2~3 ────────────────────── CH (4y) before treatment after one year treatment Flow Chart of Neonatal Screening for CH TSH of retesteted sample > Cut off point Recall of neonate retested TSH level> Cut off point Serum FT3,FT4,TSH X-ray of knee FT4 TSH delayed BA FT4 normal，TSH normal BA CH Hyperthyrotropinemia 谢 谢 Thank you