congenital hypothyroidism

Question 1

1. Describe how the thyroid gland develops.

Answer 1

prolifeartion of endodermal epithelial cells on median surface of floor between 1st and 2nd pharyngeal arches

connected to tongue vua thyroglossal duct on its descent, completed at 7 weeks

10-12 weeks thyroid begins to trap iodide and secrete thyroid hormones at 10-12 weeks

TSH is detectable in serum at 12 weeks

HPA feedback at 25 weeks

***placenta allows passage of small quantities of maternal T4

30 minutes after birth TSH rises to levels of 60-80uU/ml

Question 2

2. List the major transcription factors involved in thyroid gland development and thyroid hormone synthesis.

Answer 2

PAX-8

• initiation of thyroid cell diffeentitation
• essential for cell proliferation
• AD inheritance
• mild to severe hypoplasia
• associated with renal agenisis

TITF-2

• migration of thyroid precursor cells
• transcription control of Thyroglubuloin
• transcription control of thyroperoxidase
• Homozygoud mut–> Bamforth-Lazarus syndrome
• –CH, cleft palate, spiky hair, bifid epiglottis

TITF-1

• homeobox gene
• similar to TiTF-2
• expressed in lung, forebrain, and pituitary
• mut–> respiratory distress, neurological disorders, CH combinations

TSH-R

NIS

SCL26A4- encodes pendrin which is important for efflux of iodide at the apical membrane
–> Pendreds syndrome, AR–> deafness foiter

TG

TPO

THOX1 and THOX2 –> involved in H202 generation by NADPH peroxidases in the thyroid

Question 3

3. Describe the two major causes (two major subgroups) of congenital hypothyroidism.

Answer 3

85% caused by abnormal thyroid gland development
-aplasia (nada), hypoplasia (small), ectopy (arrested migration)

15% due to inborn error of thyroid hormonogenesis (thyroid dyshormonogenesis)

Question 4

4. Describe the method used to screen newborns in the state of Colorado for congenital hypothyroidism.

Answer 4

T4 is checked on all babies

• each day the lowest 10% of T4’s then have a TSH done
• If TSH is above 20 thats abnormal
• if TSH is less than 20does not mean its banormal but PCP will not be called
• will miss central hypothyroidism

If abnormal screen- repeat labs
–> 90% have TSH greater than 50 and 75% have T4 less than 6.5

Question 5

5. Identify the normal changes in thyroid stimulating hormone (TSH) secretion in the first week of life and how they affect the interpretation of the first newborn screen.

Answer 5

TSH skyrockets in first day of life (70-80 ug/dL) and slopes down from there
T4 and T3 will be 15-19 ug/dL y 1 day

so its best to test at 3-5 days of age

Question 6

6. Explain how laboratory tests distinguish central hypothyroidism from thyroid binding globulin deficiency.

Answer 6

central hypo thyroidism has low TSH

Question 7

7. List the symptoms/signs of congenital hypothyroidism.

Answer 7

+/- goiter

• **baby usually appears entirely normal
• large posterior fontanel
• prolonged jaundice
• macroglossia
• Hoarse cry
• umbilical hernia
• hypotonia

Question 8

8. Develop a schedule for monitoring the treatment of a child with congenital hypothyroidism.

Answer 8

start tx with T4 as early as possible

monitor levels every 3 months for 3 years and 4 weeks after every dose change

Question 9

if T3 uptake and T4 are in same direction

Answer 9

thyroid disease–> low low–> hypothyroid

Question 10

if t3 uptake and T4 are in opposite directions

Answer 10

TBG abnormality, high uptake low T4