THYROID PHYSIOLOGY

AND DEVELOPMENT
Thyrotropin-releasing hormone (TRH), a tripeptide synthesized
in the hypothalamus, stimulates the release of pituitary
thyroid-stimulating hormone (TSH). Pituitary TSH is a glycoprotein
that stimulates the synthesis and release of thyroid
hormones by the thyroid gland. Thyroid function develops
in three stages. At the end of the first trimester, the gland
descends from the floor of the primitive oral cavity to its
definitive position in the anterior lower neck. The hypothalamicpituitary-thyroid axis becomes functional in the second
trimester. Peripheral metabolism of thyroid hormones matures
in the third trimester.
Thyroxine (T4), triiodothyronine (T3), and TSH do not
cross the placenta in significant amounts. Concentrations in
fetal serum reflect primarily fetal secretion and metabolism.
Maternal thyroid antibodies, iodides (including radioactive
iodides), and medications given to mothers to treat hyperthyroidism
(methimazole and propylthiouracil) cross the
placenta and affect fetal thyroid function. An infant born prematurely
or with intrauterine growth restriction may have an
interruption of the normal maturational process and appear to
have hypothyroidism by standard tests.
The thyroid gland concentrates iodine and binds it to
tyrosine molecules to produce either monoiodotyrosine or
diiodotyrosine, with subsequent coupling of two tyrosines, T4
or T3. The major fraction of circulating T3 (approximately two
thirds) is derived from peripheral deiodination of T4 to T3, but
some is produced by the thyroid gland itself. The conversion of
T4 to T3 requires the removal of one iodine from the outer ring

Newborn screening is crucial to make an early

diagnosis and initiate thyroid replacement therapy by younger
than 1 month of age. Findings at various stages after birth
include hypothermia, acrocyanosis, respiratory distress, large
fontanels, abdominal distention, lethargy and poor feeding,
prolonged jaundice, edema, umbilical hernia, mottled skin,
constipation, large tongue, dry skin, and hoarse cry. Thyroid
hormones are crucial for maturation and differentiation of tissues,
such as bone and brain (most thyroid-dependent brain
maturation occurs 2 to 3 years after birth)
When treatment (with levothyroxine) is initiated within 1
month or less after birth, the prognosis for normal intellectual
development is excellent; screening programs usually
offer therapy within 1 to 2 weeks of birth.