Congenital Hypothyroidism ??????????? Xue Fan Gu, MD, PhD Xinhua Hospital Shanghai Jiao Tong University School of Medicine

1
Congenital Hypothyroidism??????????? Xue Fan
Gu, MD, PhDXinhua HospitalShanghai Jiao Tong
University School of Medicine

2
Incidence

• Thyroid hormone deficiency may or acquired
• Congenitalmost cases are hypoplasia or aplasia
  of the thyroid gland
• World 13 0005 000
• China 13 200

3

Thyroid Ontogenesis

• 8th gestational weeks synthesis of thyroglobulin
  
• 1012th gestational weeks pitutary gland begins
  to secrete TSH,thyroid gland synthesis of T3?T4
• 30th gestational weeks hypothalamic-pitutary-thyr
  oid axis is functioning and independent of the
  maternal axis

4

• After delivery, TSH rapidly rise reaching 6080
  uU/ml levels, and then slowly decline over the
  next few days(57d) to lt5 uU/ml levels

5
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

6
(No Transcript)
7

• T3 and T4
• Metabolic potency of T3 is 34 times that of T4.
  Only 20 of circulating T3 is secreted by the
  thyroid
• T3, T4 in circulation
• Binding form70with TBG ,other with Alb.
• Free formT4 0.03, T3 0.3

8

• TRH
• 
  TSH
• -

Hypothalamus
Anterior pituitary gland
Thyroid gland
rT3
T4
T3
Hypothylamic-pitutary-thyroid feedback regulation
9
Physiological of thyroid hormones

• Increase oxygen consumption
• Stimulate protein synthesis
• Influence growth and differentiation
• Affect carbohydrate, lipid and vitamine metabolism

10
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

11
Transient Hypothyroidism

• Premature
• Maternal medications (propylthiouracil,methimazol)
  
• Maternal antibody
• Iodine deficiency hypothyroidism in iodine
  deficiency area

12
Other Causes

• Pitutary/hypothalamis hypothyroidism
• Rare,lt5, measurement of TSH levels fail to
  revel patient with pitutary-hypothalamic
  hypothyroidism, since they have low TSH

13
Classification According To TSH Level

• TSH level rise
• Primary hypothyroidism
• Transient hypothyroidism
• TSH level in normal
• Pitutary/hypothalamis hypothyroidism
• low TBG

14
Clinical Findings In Newborns and Infants

• Absent symptom during the first few weeks of life
• A few have birth weightgt3.5kg prolongation of
  physiological icterus,constipation, hoarse cry,
  feeding or sucking difficulties

15

• Progress Manifestation
• Pulse is slow, heart murnures, cardiomegaly,hypoth
  ermia, hypotonia, enlarged tongue, skin cold and
  dry, umbilical hernia, hair is dry
• Mental retardation
• growth stunted

16
?????? 8y
17
Hypothyroidism caused by Pituitary-hypothalami
s

• Without symptom in neonatal period
• May be with other pituitaty hormone deficiency
• GH deficiency short stature
• ACTH deficiency hypoglycemia
• ADH deficiency diabetes incipidus

18
Laboratory findings

• TSH in neonatal screening programs lt1015 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)

19
Scintigraphy

• 99mTc?123I scintigraphy
• B ultrasound examination
• X ray retardation of skeletal maturation (bone
  age)

20
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 23 years old

21

• Dose of thyroxine(L-T4)
• ----------------------
• Age µg/day ug/kg/day
• ----------------------
• 06m 2550
  8.510
• 612m 50100
  58
• 15y 75100
  56
• 612y 100150
  45
• 12y to adult 100200
  23
• ----------------------

22
CH (4y) before treatment after one
year treatment
23
Flow Chart of Neonatal Screening for CH

• TSH of retesteted sample gt Cut off
  point
• Recall of
  neonate
• retested TSH levelgt Cut off point
• Serum FT3,FT4,TSH X-ray of knee
• FT4 TSH delayed BA FT4 normal,TSH
  normal BA
• CH
  Hyperthyrotropinemia

24