Pediatric Thyroid - Ali

Question 1

Given normal levels of TBG, total T4, free T4, and TSH, what would happen to each if…

• Immediately following an acute increase in TBG
• A short time after the increase in TBG
• A long time after the increase in TBG

Answer 1

Sudden increase in TBG

• [TBG] increased
• Total [T4] increases
• Free [T4] decreases

Initial response after increase in TBG

• [TSH] increases
• Increased T4 release from thyroid

Steady state after increase in TBG

• increased [TBG]
• increased total [T4]
• free [T4] normal
• [TSH] normal

Question 2

Congenital hypothyroidism

• Relative racial prevalence?
• Relative sex prevalance
• Major etiologies?

Answer 2

Hispanics/Asians/NativeAmerican > Whites > Blacks

Female > Male

Etiologies

• Absent or ectopic thyroid (75-85% dysgenesis, 2% familial)
• Iodine deficiency (rare in US, common worldwide)
• Central hypothyroidism (5%, usually multiple pituitary hormone deficiency)
• Transient (10%, late maturation, maternal antibodies, drugs, goitrogens)

Question 3

What symptoms of congenital hypothyroidism are present at birth?

What are the consequences of untreated congenital hypothyroidism?

Why is it really really bad when these symptoms present?

Answer 3

Most infants are asymptomatic at birth - hence the need to screen

Untreated: lethargy, slow movement, hoarse cry, feeding problems, constipation, macroglossia, umbilical hernia, large fontanelles, hypotonia, dry skin, hypothermia, prolonged jaundice

These symptoms are evidence that irreversible brain damage has already begun

Question 4

How are newborns screened for congenital hypothyroidism?

Why are false positives fairly common on first screening?

Answer 4

Measures T4 and/or TSH (many states rely on TSH -> can miss central hypothyroidism or delayed TSH rise)

False positive are common in early specimens due to a sharp spike in in TSH in the first few hours after birth)

Question 5

What is the primary treatment for congenital hypothyroidism?

When should treatment be started?

What are the key goals of therapy? Why is compliance so critical in the first three years of life?

Answer 5

Levothyroxine

Treatment should be started within 2-3 weeks of birth

Goals

• Serum Free T4 or Total T4 in the upper range of normal during the first year of life.
• Serum TSH kept under 5mU/L (optimal 0.5-2)

Compliance is important during the first 3 years of life because there is an inverse relationship between IQ and onset/success of therapy. Hypothyroidism after the age of 3 does not affect brain development.

Question 6

Describe the mechanism by which Iodine enters thyroid follicle cells

Answer 6

Via Na+/I- symporter (I-trap) in the basolateral membrane

Question 7

What catalyzes the attachment of iodine to thyroglobulin?

Answer 7

thyroid peroxidase

Catalyzes attachment of iodine to tyrosine residues on thyroglobulin

Question 8

Approximately what percentage of dietary iodine ends up in thyroid hormones?

Which is more potent, T3 or T4?

Answer 8

~15%

T3 > T4

Question 9

What percentage of T3 and T4 is bound to TBG in plasma?

What is the half-life of each?

Answer 9

>99%

T4: 6 days

T3: 1 day