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
? 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,hypothalamic-
pitutary-thyroid axis is functioning
and independent of the maternal axis
Thyroid 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
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 Pituitary-
hypothalamis
? 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/L
Normal range for neonate
T4 84-210 nmol/l(6.5-16.3ug/dl)
FT4 12-28 pmol/l(0.9-2.2ng/dl)
TSH 1.7-9.1 mu/L(1.7-9.1 uU/ml)
Laboratory findings
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
DDDD DDDD
Thank youThank you
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
? 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,hypothalamic-
pitutary-thyroid axis is functioning
and independent of the maternal axis
Thyroid 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
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 Pituitary-
hypothalamis
? 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/L
Normal range for neonate
T4 84-210 nmol/l(6.5-16.3ug/dl)
FT4 12-28 pmol/l(0.9-2.2ng/dl)
TSH 1.7-9.1 mu/L(1.7-9.1 uU/ml)
Laboratory findings
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
DDDD DDDD
Thank youThank you
