Transcript Thyroid Function: Fetal, Maternal Relationship

Thyroid Function: Fetal, Maternal
Relationship
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Thyroid Function in Pregnant Women
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Thyroid gland increase in size by 10-20%.
Through monodeiodination the placenta provides
iodine to the fetus.
Estrogen stimulates an increase in Thyroid Binding
Globulin (TBG).
Hypothyroid mother have increased T4
requirements during pregnancy due to placental
degradation of T4 to rT3, transfer of T4 to the
fetus and increased maternal clearance of T4.
Placental Human Chorionic Gonadotropin (HCG)
increases maternal T4.
Thyroid Function: Fetal, Maternal
Relationship
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Stages of Neurological Development and Thyroid
Hormone:
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Phase I :
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Phase II:
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17 days in rat, 10-12 weeks in humans.
Probable role in brainstem and cerebral neurogenesis.
Thyroid hormones are from mother.
Fetal thyroid synthesizes and secretes thyroid hormone.
Brain is exposed to both fetal and maternal hormones.
Phase III:
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After birth. Brain depends on neonatal thyroid hormone.
Some in milk.
Cerebellar neuronal proliferation, migration and differentiation.
Myelination and gliogenesis.
Thyroid Function: Fetal, Maternal
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Key is maternal thyroid status during the first
trimester – during fetal brain development.
Hypothyroid or iodine (recommend 200
µg/day) deficient mother result in affected
fetus. Hypothyroid fetus may be minimally
effected.
Antibody transfer – Thyroid serum
immunoglobulin (TSI - hyperthyroidism) and
TSH-receptor antibody – TBII
(hypothyroidism)
Thyroid Function: Fetal, Maternal
Relationship
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T4, T3, FT4, and TSH – ALL in amniotic fluid. Less
than maternal and fetal serum levels.
Cordocentesis – more accurate levels.
Can treat in utero with T4 or T3.
T4 detectable in fetal serum by 12 weeks.
FT4 in cord blood is equal to or greater than
maternal blood.
Fetal T4 is mostly metabolized to rT3. Gradually
decreases after birth. rT3 has little metabolic
activity.
Cord blood T3 and FT3 are 30 to 50% of maternal
concentrations at term.
Thyroid Function: Fetal, Maternal
Relationship
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TSH present at 12 weeks.
Higher in fetus
Surge at term/delivery.
T4 binding proteins – pre-albumin, albumin and TBG.
Most bound to TBG. Estrogen causes increased
production of TBG.
At birth – TSH surges during the first 30 minutes.
Peak persists for 6 – 24 hours.
In response to TSH there is a peak in T4, FT4, and
T3. Peaks at 24 hours. Hyperthyroid state.
Gradual reduction in T4, T3, rT3 over 4 to 6 weeks.
Gradually goes to adult levels by puberty.
Thyroid Function: Fetal, Maternal
Relationship
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Preterm infants:
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Surge in TSH and TH occurs but is less
than seen in term infants.
TSH returns to normal at 3 to 10 days.
The concentration of T3 and rT3 in breast
milk is not sufficient to prevent
hypothyroidism.
Thyroid Function: Fetal, Maternal
Relationship
Congenital Hypothyroidism:
 Neonatal screening first done in 1972 in Quebec,
Canada.
 Primary Hypothyroidism
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Defective embryogenesis – agenesis, dysgenesis.
Inborn errors
Iodide trapping defect
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Iodide organification (oxidation) defect. Pendred’s Syndrome.
Coupling Defect
Deoiodination defect – deiodinases I, II, III.
TG synthetic defects
Goiter with calcifications
Peripheral tissue resistance to thyroid hormone
Unresponsiveness of thyroid to TSH.
Thyroid Function: Fetal, Maternal
Relationship
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Goitrous cretinism caused by maternal
goitrogens
Iodide deficiency
Thyroid Function: Fetal, Maternal
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Central hypothyroidism
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Midline defect
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Genetic mutation or deletion
Isolated deficiency of TSH ß-subunit.
Abnormal hypothalamus-pituitary development.
Cleft lip, holoprosencephaly, seto-optic
dysplasia.
Acquired birth injury
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Hemorrhage, meningitis, trauma.
Thyroid Function: Fetal, Maternal
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Female: male ratio 2:1. for CH.
Maternal ingestion of goitrogens
iodides, thiocarbamides, potassium
pechlorate. Expectorants with iodide,
amiodarone (contains Iodine)
Iodide Deficiency – goiter. Result is low
T4 level in developing brain.
Recommend Infant supplementation of
40 µg per day iodide.
Thyroid Function: Fetal, Maternal
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Central hypothyroidism
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Secondary – pituitary – TSH. Normal or
elevated TRH, low TSH, low T4.
Tertiary – hypothalamic – TRH. Low TRH,
low or normal T4, low or normal TSH.
Respond to TRH treatment.
Thyroid Function: Fetal, Maternal
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Neonatal Screening
Filter paper spot. Obtained at 24 hours to 5
days.
Measure TSH, screen for primary
hypothyroidism. Detects most cases of
primary hypothyroidism.
Incidence 1:3500-4000.
Secondary and Tertiary CH is 1:80-100,000.
Thyroid Function: Fetal, Maternal
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Clinical manifestations
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Appear gradually – lethargy, hypotonia,
periorbital edema, mottled skin, feeding
intolerance, hoarse cry, constipation,
hypothermia..
Clinical features - large tongue, umbilical
hernia, thick skin, dry skin, hyporeflexia,
umbilical hernia, coarse hair.
Lingual thyroid – base of tongue.
Goiters – large or small cervical mass.
Thyroid Function: Fetal, Maternal
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Laboratory
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Elevated TSH most sensitive for
primary hypothyroidism.
TSH surge at birth. Level gradually go
down after birth. Maybe higher than 10
mU/l at 24 hours. Samples taken before 24
hours maybe high in normal infant.
Primary hypothyroidism – high TSH
and low or low-normal T4 and FT4.
Thyroid Function: Fetal, Maternal
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Central hypothyroidism
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Low FT4, low-normal T4, and normal TSH.
Nonthyroidial illnesses – Respiratory
Distress – low or normal T4, normal FT4,
and normal TSH.
In severe myxedema get cardiomegaly,
and slowing of EEG pattern (brain).
Thyroid Function: Fetal, Maternal
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Transient Primary Neonatal Hypothyroidism
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Marked by persistent elevation of TSH.
Higher in areas with iodine deficiency
Low T4, low FT4, and high TSH.
May confuse with transient hypothyroxinemia.
Can be caused by transplacental antithyroid drugs,
excessive iodine.
Placental transfer of TRAb – TSH receptor
antibody. Persist for 2 to 3 months.
Thyroid Function: Fetal, Maternal
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Transient Hyperthyrotropinemia
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Elevated TSH, normal T4 and FT4.
May represent mild transient or permanent
hypothyroidism.
Cause is unknown.
Best outcomes if treated by 4 to 6 weeks.
Treat for 2-3 years.
Thyroid Function: Fetal, Maternal
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Transient Hypothyroxinemia
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Preterm infants
Immature hypothalamic-pituitary axis. Maybe normal for GA.
Low T4 and FT4 compared to term. Normal TSH.
TBG – slightly low.
Prevalence 1:6,000.
Shows response to TRH – increase T4 and TSH (tertiary)
T4 normalizes by 4- 6 months.
Developmentally normal at 1 year.
No effect of T4 administration on developmental outcome.
Thyroid Function: Fetal, Maternal
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Transient Hypothyroxinemia
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Screen preterm infants at 5 days. Repeat
at 2, 4, 6 weeks.
Supplementation at less than 28 weeks
showed improved mental outcome, less
morbidity. Infants greater than 28 weeks
showed greater morbidity.
T4 supplementation Currently not
recommended.
Thyroid Function: Fetal, Maternal
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Euthyroid Sick Syndrome
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Alterations in TH occur as an adaptive
response to decreased metabolic rates in ill
patients. Non thyroidal illness.
Low T3, high rT3, normal TSH, low normal
T4 and normal FT4.
Slowly normalizes.
Supplementation not indicated.
Thyroid Function: Fetal, Maternal
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Treatment
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Treat as quickly as possible following initial screening. A
delay of 8 days results in lower IQ scores.
Half life for T4 is 3-4 days in neonate but in adults it is 6
days.
In cases that are not clear cut – TREAT – 2-3 years.
L-thyroxine – 12-15µg/kg/day. Began as soon as possible –
optimally by 2 weeks. Pills.
Cerebral cortex get most of its T3 from deiodination of T4.
Goiters – if TSH is elevated and T4 low treat with Lthyroxine. Can be caused by antithyroid medications and
excessive iodide
Thyroid Function: Fetal, Maternal
Relationship
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Breast Milk
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Small amounts of PTU in milk.
Good concentration of iodides in BM.
Should NOT give methamizole to nursing
mothers.
Thyroid Function: Fetal, Maternal
Relationship
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Amniotic fluid - Measurement of
iodothyronines not good
Cord blood – measure TSH and
Iodotyroinines. Much better.
TRH to mother causes increase TSH
and T3 and does not reduce postnatal
surge of TSH.
Thyroid Function: Fetal, Maternal
Relationship
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Prognosis:
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Clinically improves quickly
Reduce goiter if present.
Improved growth rate – skeletal.
Normal neurological development is dependent on early
diagnosis and supplementation
80% supplemented before 3 months had IQ score greater
than 85 but 77% showed some problems with speech, math
ability and fine motor function.
BEST OUTCOMES IF STARTED BY ONE WEEK OF AGE. Minor
difference in school achievements and test scores.
First trimester T4 is derived from the mother – swallowing,
transdermal. Protects the fetal brain.
Overall good.
Thyroid Function: Fetal, Maternal
Relationship
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Thyrotoxicosis
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Occurs in infants born to mother with
active Graves disease (before or during
pregnancy), Hashimoto disease, or treated
Graves disease (surgical or ablation).
Due to placental transfer of TSH-receptor
immunoglobulin (TRAb) and TSI.
Infants born to mother with Graves can be
normal – depends on amount of antibody.
Thyroid Function: Fetal, Maternal
Relationship
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Thyrotoxicosis – clinically.
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Irritability, tremors, sweating, weight loss,
enlarged spleen and liver, exophthalmia,
hyperthermia, arrhythmias.
TSI level decrease over 3 weeks to 6
months.
Maternal antithyroid medications may
render the neonate euthyroid or
hypothyroid until the antithyroid
medications disappear. Late thyrotoxicosis.
Thyroid Function: Fetal, Maternal
Relationship
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Thyrotoxicosis
TRAb – a polyclonal antibody that
initially blocks the TSH receptor. A
second population of TRAb then
stimulates the receptor to cause
thyrotoxicosis.
Low TSH, high T4.
Palpable thyroid gland.
Thyroid Function: Fetal, Maternal
Relationship
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Thyrotoxicosis – treatment
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Lugol solution (Iodine) and PTU or MTZ.
May need supplement withT4.
ß-adrenergic drugs reduce symptoms.
Digoxin for failure.
Steroids in some cases.
Mortality rate – less than 15%.
Prenatal therapy with PTU.
Summary: Thyroid Function Fetal, Maternal Relationship
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Hypothyroid mothers have increased T4
requirements during pregnancy.
Key is maternal thyroid status during the first
trimester – during fetal brain development.
Cord blood – measure TSH and Iodotyroinines.
Much better than amniotic fluid.
Thyroid hormones are from mother - deficient
mother result in affected fetus.
Antibody transfer – Thyroid serum immunoglobulin
(TSI - hyperthyroidism) and TSH-receptor
antibody – TBII (hypothyroidism).
T4 & TSH detectable in fetal serum by 12 weeks.
Summary: Thyroid Function Fetal, Maternal Relationship
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At birth – TSH surges during the first 30
minutes. Hyperthyroid state.T4, T3, rT3 drop
over 4 to 6 weeks.
Neonatal Screening - Filter paper spot. Obtained
at 24 hours to 5 days.
Measure TSH, and screen for primary
hypothyroidism.
Screen preterm infants at 5 days. Repeat at 2, 4,
6 weeks.
Transient Primary Neonatal Hypothyroidism
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antithyroid drugs, excessive iodine, or TRAb – TSH
receptor antibody.
Summary: Thyroid Function Fetal, Maternal Relationship
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Transient Hypothyroxinemia
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Treat as quickly as possible following initial
screening. A delay of 8 days results in lower IQ
scores.
L-thyroxine – 12-15µg/kg/day. Began as soon as
possible – optimally by 2 weeks. Pills.
Thyrotoxicosis
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Occurs in infants born to mother with active
Graves disease (before or during pregnancy),
Hashimoto disease, or treated Graves disease
(surgical or ablation).