congenital Hypothyroidism

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congenital Hypothyroidism

• Baylor College of Medicine
• Anoop Agrawal, M.D.

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Case study- C.V.

• C.V. is a FT, 4kg, 7 day old hispanic infant
  girl, born to a 22 yo female, NSVD, GBS negative,
  APGARS 9/9. You receive a call from the Texas
  Department of Health stating C.V. has an abnormal
  thyroid study on her newborn screen.
• What is your course of action?

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Background

• Thyroid development begins around 17th day of
  gestation.
• Hypothalamus releases TRH by 20th week of
  gestation. T3 levels remain relatively low until
  the 30th week.
• Fetus is protected by increased activity of
  deiodinase enzymes in the brain and maternal
  thyroid hormone transfer across the placenta.
• Placenta is impermeable to TSH.

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incidence

• In US - 1 3,500 live births
• Females to Males - 21 ratio
• Hispanic - 12000, White infants - 14000,
  African American - 132,000
• Children with Down syndrome have 35 fold increase
  risk.
• Congenital Hypothyroidism is the most common
  treatable cause of mental retardation.

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etiology of C.H.

• What are the causes that result in lifelong
  hypothyroidism?
• Thyroid Dysplasia (agenesis, hypoplasia, or
  ectopy) - incidence is sporadic in 85 of cases
• Dyshormonogenesis - inborn error of thyroxine
  synthesis - 10 of cases
• Secondary or Central Hypothyroidism (125,000 -
  100,000)

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Etiology of C.H.

• What are the causes of transient hypothyroidism?
• Maternal or neonatal drug exposure
• Iodine deficiency (in Europe 1100 vs. in US
  150,000 due iodized salt in foods)
• Maternal antibodies - this form resolves in 1 to
  3 months as antibodies are cleared
• Gestational hyperthyroidism

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Clinical manifestations

• macroglossia
• large fontanelles
• hypotonia
• umbilical hernia
• prolonged unconjugated hyperbilirubinemia
• hoarse cry

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Clinical Findings Finffmanifestations

• 95 of newborn will have no evidence of disease
• Can be associated with other congenital
  malformations - mainly cardiac
• renal and urologic deformities also seen

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Newborn screening

• All states screen for hypothyroidism - type of
  testing is variable T4 with TSH backup vs. TSH
  alone
• 4 million infants are screened annually in US, of
  which 1,600 will be diagnosed with congenital
  hypothyroidism

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Evaluation
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case - c.v.

• State TSH screen reported to be gt400.
• C.V. was called into the office the next day.
  Thyroid function tests were performed via
  venipuncture.
• TSH gt 54, free T4 - QNS, thyroglobulin lt1
• Started on thyroxine 10 mcg/kg/day - or 40 mcg
  per day. Referred to Endocrine Clinic.

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Treatment

• Start at 10-15 mcg/kg/day as single daily dose.
• Initiation of hormone replacement with
  l-thyroxine can wait until diagnostic labs
  completed.
• Certain milks and drugs can interfere with
  thyroxine absorption soy formulas, iron,
  calcium, sucralfate, aluminum hydroxide, bile
  acid sequestrants.

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Treatment

• How should thyroxine be administered to the
  infant?
• It is available only as a tablet
• DO NOT HAVE THE PHARMACY COMPOUND THE TABLET INTO
  A SOLUTION.
• Tablet should be crushed and given in a small
  amount of milk or water.

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Permanent vs. transient

• How do you determine if child has permanent vs.
  transient hypothyroidism?
• After 3 years of age, discontinue therapy for 30
  days. If low free T4 and high TSH are found,
  then permanent is confirmed.
• Thyroid scan or u/s - uncommonly performed.
• If TSH rises above 20 mU/L after the first year
  of life in setting of insufficient T4 therapy,
  then likely to be permanent.

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Follow-up care

• AAP recommends the following schedule
• at 2 and 4 weeks after initiation of T4 treatment
• every 1 to 2 months during first 6 mos.
• every 3 to 4 months between 6 mos and 3yrs
• every 6 to 12 months thereafter until growth is
  complete
• 2 weeks after any change in dose

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Follow up care

• Serum T4 concentration should become normal
  within 1-2 weeks of treatment.
• Serum TSH should be normal within 1 month of
  treatment.

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Pedi endocrine

• In HCHD, pediatric endocrinologist available at
  Casa de Amigos
• no outpatient pedi endo at BTGH
• Depending on the type of Medicaid, a child may be
  referred to either Casa de Amigos or Texas
  Childrens.

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conclusion

• Congenital hypothyroidism is seen most commonly
  in females, hispanics.
• Thyroid dysgenesis is most common cause in the
  US.
• Iodine deficiency in the maternal diet is 1
  cause worldwide.
• Initiation with hormone replacement should not be
  delayed.
• Overall, long term outcomes are good.