Download 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