Congenital HypothyroidismCongenital Hypothyroidism先天性甲状腺功能减低症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

IncidenceIncidence

• Thyroid hormone deficiency may: or acquired• Congenital:most cases are hypoplasia or apla

sia of the thyroid gland

World: 1:3 000 ～ 5 000

China: 1:3 2001:3 200

8th gestational weeks: synthesis of th

yroglobulin 10~12th gestational weeks: pitutary gl

and begins to secrete TSH,thyroid gland synthesis of T3 、 T4

30th gestational weeks: hypothalamic-pitutary-thyroid axis is functioning and independent of the maternal axis

Thyroid OntogenesisThyroid Ontogenesis

• 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%

TRH

TSH

-

Hypothalamus

Anterior pituitary gland

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

EtiologyEtiology• The cause may be sporadic or familial, goitrous or nongoitThe cause may be sporadic or familial, goitrous or nongoit

rousrous• Defective embryogenesis 75%Defective embryogenesis 75%

Agenesis, dysgenesis, ectopiaAgenesis, dysgenesis, ectopia• DyshormonogenesisDyshormonogenesis Pit-1, TSH, TSHR, TTF-I, TTF-II, Pax 8, TG, TPO defePit-1, TSH, TSHR, TTF-I, TTF-II, Pax 8, TG, TPO defe

ct, etc.ct, etc. Iodide transport defect, organification defect, coupling defIodide transport defect, organification defect, coupling def

ect, iodothyrosine deiodinase defect, inability of tissueses to ect, iodothyrosine deiodinase defect, inability of tissueses to convert T4 to T3convert T4 to T3

• Deficiency or excess of iodine

Transient Hypothyroidism

• Premature• Maternal medications (propylthiourac

il,methimazol)• Maternal antibody• Iodine deficiency hypothyroidism in iodine

deficiency area

Other Causes

• Pitutary/hypothalamis hypothyroidisPitutary/hypothalamis hypothyroidismm

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 hypothyroidismPitutary/hypothalamis hypothyroidism

low TBG

Clinical FindingsClinical FindingsIn Newborns and InfantsIn Newborns and Infants

Absent symptom during the first few wee

ks of life

A few have birth weight>3.5kg prolongati

on of physiological icterus,constipation, h

oarse cry, feeding or sucking difficulties

Progress Manifestation• Pulse is slow, heart murnures, cardiom

egaly,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 Pituitary-hypPituitary-hypothalamisothalamis

• Without symptom in neonatal period

• May be with other pituitaty hormone deficiency

GH deficiency ： short stature

ACTH deficiency ： hypoglycemia

ADH deficiency ： diabetes incipidus

TSH in neonatal screening programs: <10~15 mu/Lmu/L

Normal range for neonate

T4 84-210 nmol/l(6.5-16.3ug/dl) FT4 FT4 12-28 pmol/l(0.9-2.2ng/dl) 12-28 pmol/l(0.9-2.2ng/dl) TSHTSH 1.7-9.1 mu/L(1.7-9.1 uU/ml) 1.7-9.1 mu/L(1.7-9.1 uU/ml)

Laboratory findingsLaboratory findings

Scintigraphy

• 99mTc 、 123I scintigraphy

• B ultrasound examination

• X ray: retardation of skeletal maturation (bone ag

e)

TreatmentTreatmentPrincipal• 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 thyroxineDose 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 谢谢 Thank youThank you