Endocrine Series #6

The Thyroid Gland:

Physiology and Pathophysiology
Denise Kirsten, ND, RNC, NNP

T HE THYROID GLAND IS ONE OF THE LARGEST ENDOCRINE

glands in the body, weighing approximately 15 to 20
grams in the normal adult. It secretes two major hormones,
from the second to fourth tracheal cartilages (Figure 1).3
The lobes of the thyroid contain many hollow, spherical
structures called follicles, which are the functional units of the
which are required for the normal operation of a variety of thyroid gland (Figure 2). Each follicle is filled with a thick,
physiologic processes affecting virtually every organ system in sticky substance called colloid. The major constituent of col-
the body.1 Regulation of thyroid loid is a large glycoprotein called
hormone secretion occurs ABSTRACT thyroglobulin. Unlike other
through the hypothalamic- endocrine glands, which secrete
The thyroid gland contains many follicular cells that
pituitary-thyroid (HPT) system. store the thyroid hormones within the thyroglobulin
their hormones once they are
A deficiency of thyroid hor- molecule until they are needed by the body. The thyroid produced, the thyroid gland
mones, caused by a variety of hormones, often referred to as the major metabolic hor- stores considerable amounts of
conditions, results in many mones, affect virtually every cell in the body. Synthesis and the thyroid hormones in the col-
pathophysiologic processes, secretion of the thyroid hormones depend on the presence loid until they are needed by the
some of which have potentially of iodine and tyrosine as well as maturation of the hypotha- body.2,4
serious outcomes if left untreat- lamic-pituitary-thyroid system. Interruption of this devel- The thyroid gland secretes
ed. This article discusses the opment, as occurs with premature delivery, results in two thyroid hormones, thyrox-
anatomy and physiology of the inadequate production of thyroid-stimulating hormone and ine (T4) and triiodothyronine
thyroid gland, the regulation of thyroxine, leading to a variety of physiologic conditions. (T3). It also secretes the hor-
Pathologic conditions occur in the presence of insufficient
the thyroid hormones by the mone calcitonin. Of the two
thyroid production or a defect in the thyroid gland.
HPT system, and laborator y Laboratory tests are important in diagnosing conditions of
thyroid hormones, T4 is more
tests used in the evaluation of the thyroid gland. A thorough history in combination with abundant, but T3 is the more
thyroid function. The impact of clinical manifestations and radiologic findings are also potent and is considered to be
prematurity on this system is also useful in diagnosing specific thyroid conditions. Nurses play the principal thyroid hormone.5
reviewed, and several thyroid dis- an important role in identifying and managing thyroid Many bodily functions are
orders are discussed. The article disorders and in providing supportive care to infants and influenced by thyroid hormones.
concludes with implications for their families. Although thyroid hormones do
nursing care of the infant with not target a specific site, they
thyroid disorders. affect nearly every tissue in the
The thyroid gland is located immediately below the larynx body, causing a variety of physiologic responses (Table 1).
and anterior to the upper part of the trachea. It consists of two One of the most significant effects is on the basal metabolic
lateral lobes connected by a narrow band of thyroid tissue rate (BMR), which is defined as the measure of oxygen con-
called the isthmus.2 The isthmus usually overlies the region sumption during rest.1 Thyroid hormones influence the BMR

Accepted for publication June 2000. Revised July 2000.

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VOL. 19, NO. 8, DECEMBER 2000 11
 FIGURE 1 ■ The thyroid gland.
Adapted and redrawn from: Seeley R, Stephens T, and
Tate P. 1998. Anatomy and Physiology, 4th ed. Boston:
WBC McGraw, 550.
through oxygen consumption and heat produc-
tion. Through the actions of thyroid hormones,
cellular oxidation is stimulated in most tissues,
which leads to an increase in oxygen consump-
tion and heat production. As metabolism is
increased, there is a greater utilization of oxygen
by the cells, which in turn increases the amount
of metabolic end-products released from the
body’s tissues. Thermogenesis is also regulated
by the thyroid hormones. The increased secre-
tion of thyroid hormones after birth stimulates
catecholamine-mediated brown adipose tissue
thermogenesis and mobilization of fatty acids
from the infant’s fat stores.6,7 Thus, thyroid hor-
mones are said to have a “calorigenic effect”
because they produce heat. The calorigenic
actions of thyroid hormones as well as an
increase in BMR cause vasodilatation of most
tissues to occur, thus increasing blood flow.
There is also an increase in heart rate and stroke
volume.1,4,8–11
Thyroid hormones stimulate almost all
aspects of carbohydrate metabolism. The use of
glucose by the cells is increased, as is the rate of
glucose absorption by the gastrointestinal tract.
Calcium, water balance, and liver function are
also influenced by thyroid hormones. In
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12
FIGURE 2 ■ The thyroid follicle.
Adapted and redrawn from: Seeley R, Stephens T, and
Tate P. 1998. Anatomy and Physiology, 4th ed. Boston:
WBC McGraw, 550.
hypothyroid conditions, hypercalcemia occurs
and the glucuronic acid conjugation mechanism
of the liver may be impaired. In addition, water
is retained in the extracellular compartments. In
hyperthyroidism, urinary and fecal calcium
excretion are enhanced. Bone demineralization
occurs, and there is an efflux of calcium from the
bones, which leads to elevated serum ionized
calcium and phosphate concentrations and
decreased circulating levels of 1,25-dihydroxyvi-
tamin D. These effects lead to decreased intesti-
nal calcium absorption and a negative calcium
balance.1,4,10
All aspects of fat metabolism are enhanced by
thyroid hormones. Although glucose is the
major precursor for fatty acid synthesis, the
amount of carbohydrate or insulin is the primary
determinant of lipogenesis. Because thyroid hor-
mones stimulate carbohydrate metabolism, they
are necessary for lipogenesis in both liver and fat
cells. Mobilization of fatty acids from fat tissue
occurs in the presence of thyroid hormones,
which increases the free fatty acid concentration
in the plasma. Thyroid hormones also influence
cholesterol levels. In patients with hypothy-
roidism, cholesterolemia occurs secondary to a
decreased ability to excrete cholesterol in bile
rather than because of overproduction of choles-
terol. Conversely, a decreased quantity of choles-
terol is noted in hyperthyroidism.1,4
DECEMBER 2000, VOL. 19, NO. 8
TABLE 1 ■ Physiologic Effects of Thyroid Hormones1,4,7 TA

System Effects Tra

Cardiovascular Increases heart rate Inc
Increases the force of cardiac contractions Inc
Increases cardiac output as a result of the previous two effects
Act
Promotes peripheral vasodilation
Central nervous Essential for normal brain development, such as cerebellar growth and nerve myelination
Necessary for normal intellectual development in infants
Necessary for emotional stability in adults
Gastrointestinal Increases appetite
Increases secretion of “digestive juices”
Increases gastric motility
Hematopoietic Influences erythropoiesis
Metabolic Profoundly affects oxidative metabolism
Increases oxygen consumption in all tissues except the brain, gonads, and spleen
Promotes heat production
Influences synthesis and degradation of carbohydrate, fat, and protein
Respiratory Influences lung development
Necessary for surfactant production Fro
Increases rate and depth of respirations
Skeletal Indirectly promotes growth formation by actions on the pituitary gland
Acts synergistically with growth hormone and other growth factors that promote bone formation
Directly affects skeletal maturation
Necessary for progression of tooth development and eruption
Skin Necessary for growth and maturation of the epidermis and hair follicles

Thyroid hormones are essential for normal
growth and development and are most obvious
during infancy and early childhood. Body
growth, bone growth and maturation, and tooth
development and eruption are all dependent on
thyroid hormones. Skeletal maturation occurs
through the synergistic relationship between
thyroid hormones and growth hormone,
somatomedin, and other growth factors.
Thyroid hormones also promote bone forma-
tion indirectly through actions on the pituitary
gland. Ossification and fusion of the cartilagi-
nous growth plates result in bone maturation
and are dependent on thyroid hormones. A defi-
ciency of thyroid hormones after three to four
years of life results in delayed skeletal and bone
maturation as well as delayed eruption of perma-
nent teeth. Characteristically, these infants have
immature skeletal proportions and facial fea-
tures, and there is a reduction in epiphyseal
growth and bone mineralization, which leads to
the radiographic findings of dysgenesis of the
ossifying epiphyseal centers of the bone.1,7,10
Postnatal maturation of the central nervous
system is dependent on the presence of thyroid
hormones. In hypothyroid subjects, cerebral and
cerebellar growth and nerve myelination are
severely delayed. Overall, brain size and vascular-
ity are reduced. During infancy, an absence or
deficiency of thyroid hormones is catastrophic
and results in permanent, irreversible mental
retardation, even when treated later in child-
hood.1,10 Exaggeration of some of these physio-
logic responses is often a manifestation of
thyroid disease (Table 2).
EMBRYOLOGY AND FUNCTIONAL
DEVELOPMENT
The thyroid gland is the first endocrine gland
to appear in embryonic development. Fetal thy-
roid maturation can be divided into two phases.
Phase 1 consists of anatomic development and
embryogenesis of the HPT system and occurs
during the first trimester of gestation. Phase 2 is
characterized by the maturation of the HPT sys-
tem, including hormone production and control.
At approximately 24 days after fertilization,
the thyroid gland begins to develop from a small
solid mass of endoderm, forming a thickened
pouch called the thyroid primordium, located in
the floor of the primitive pharynx and at the tip
of the foramen cecum (Figure 3). As the embryo
elongates, the developing thyroid gland
descends through the tissues of the neck but
remains connected to the foramen cecum by a
narrow tube called the thyroglossal duct. The
thyroglossal duct atrophies and disappears by the
seventh week of gestation. By this time, the

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VOL. 19, NO. 8, DECEMBER 2000 13
 TABLE 2 ■ Pathophysiologic Effects of Thyroid Hormones1,4,10,11
System Hyposecretion
Basal metabolic rate (BMR)/ BMR below normal
temperature regulation Decreased body temperature
Cold intolerance
Decreased appetite
Weight gain
Reduced sensitivity to catecholamines
Carbohydrate metabolism Decreased glucose metabolism
Delayed degradation of insulin
Increased risk of hypercalcemia
Impaired glucuronic acid conjugation
mechanism of the liver
Cardiac Decreased voltage of all complexes
Prolonged PR interval
Depressed or inverted T wave
Decreased efficiency of pumping
action of heart
Low heart rate
Low blood pressure
Central nervous Slowed/deficient brain development
in infants
Mental retardation
Gastrointestinal Decreased GI motility
Decreased GI tone
Constipation
Hematopeoitic Anemia
Muscular Extremely sluggish muscles
Slow relaxation after contraction
Respiratory
Skeletal Growth retardation in children
Skeletal stunting and retention of
child’s body proportions
Retardation of dental growth
Hypersecretion
BMR above normal
Increased body temperature
Heat intolerance
Increased appetite
Weight loss
Increased sensitivity to
catecholamines, which may lead to
elevated blood pressure
Enhanced glucose catabolism
Enhanced glycolysis
Enhanced gluconeogenesis
Increased rate of gastrointestinal (GI)
absorption
Increased insulin secretion
Negative calcium balance
Enhanced urinary and fecal calcium
excretion
Demineralization of bone
Elevated plasma-ionized calcium and
phosphate levels
Decreased 1,25-dihydroxy-vitamin D
levels
Decreased intestinal calcium
absorption
Increased heart rate
Increased stroke volume
Increased cardiac output
Wide pulse pressure
Possible palpitations
Elevated blood pressure
Heart failure if prolonged
Irritability
Restlessness
Insomnia
Excessive GI motility
Diarrhea
Increased secretion of digestive juices
Muscle atrophy and weakness
secondary to excess protein
catabolism
Increased utilization of oxygen
Increased rate of carbon dioxide
production
Increased rate and depth of
respirations
Excessive skeletal growth initially
followed by early epiphyseal
closure and short stature

thyroid gland has descended to its final location
in the neck, covering both sides of the lower
part of the larynx and the upper part of the
trachea.12,13
By ten weeks gestation, the thyroid gland is
both functional and mature. At the end of the
first trimester, histologic differentiation of the
thyroid and pituitary glands has occurred. At
this stage of development, both T4 and thyroid-
stimulating hormone (TSH) can be measured in
fetal tissue, the thyroid gland can concentrate
iodine and synthesize T4, and the pituitary tissue
can synthesize TSH.7,9,14
By the end of the first trimester, the fetal

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14 DECEMBER 2000, VOL. 19, NO. 8
FIGURE 3 ■ Thyroid gland development.
Adapted and redrawn from: Larsen W. 1997. Human Embryology, 2nd ed. New York: Churchill Livingstone, 372.
HPT system is structurally intact, with matura-
tion continuing into the second trimester. Prior
to 18 weeks gestation, the HPT system is rela-
tively quiet and fetal thyroid hormone produc-
tion is limited. During the second half of
gestation, however, the endocrine pathway from
the hypothalamus to the pituitary and thyroid
glands becomes functional under the influence
of increasing serum TSH levels and produces
increasing amounts of T3 and T4.15 Fetal serum
TSH levels continue to increase progressively, so
that at 40 weeks gestation, they are higher than
adult values; concentrations of T3 are lower at
term than adult levels.8,14 Fetal T3 concentra-
tions are low probably because the processes for
the conversion of T3 from T4 during intrauter-
ine life are immature or lack the necessary stimu-
lation for their activation. After delivery, there is
a dramatic increase in the ability of the liver to
convert T 4 to T 3 that leads to a significant
increase in T3 levels. A progressive increase in T4
also occurs, reaching adults levels at 36 weeks
gestation.16
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VOL. 19, NO. 8, DECEMBER 2000
The increase in fetal serum concentrations of
TSH, T 4 , and T 3 during gestation reflects
increasing stimulation and maturation of the
fetal thyroid gland as well as increasing serum
thyroxine-binding globulin (TBG) concentra-
tions. Fetal serum concentrations of TBG
increase with advancing gestation, reaching
adult levels during the third trimester. Increases
in TBG presumably reflect the functional matu-
rity of the fetal liver and its increased capacity to
manufacture proteins.16
The fetal HPT system develops independent-
ly of the maternal system. The placenta is not
only impermeable to TSH, but poses a barrier to
the thyroid hormones with limited transfer of T4
and T3 from the mother to the fetus.17 Both
thyrotropin-releasing hormone (TRH) and
iodine freely cross the placenta. Because there is
very little TRH in maternal circulation and most
of it is degraded within the placenta, maternal
TRH has little influence on the fetal HPT sys-
tem. Instead, fetal TRH levels are high sec-
ondary to increased production of TRH by the
15
FIGURE 4 ■ Synthesis and secretion of thyroid hormones.
Please refer to the print version of
Neonatal Network
placenta and selected fetal tissues, particularly
the pancreas. The placenta is also permeable to
antithyroid drugs, and these can compromise
fetal and neonatal thyroid function.15,17
SYNTHESIS AND SECRETION
Thyroid hormone synthesis occurs on the
thyroglobulin molecules within the colloid.
Synthesis of the thyroid hormones by the thy-
roid gland is a ver y complex process that
depends on the presence of iodine and tyrosine
(Figure 4). Tyrosine, an amino acid that is syn-
thesized in sufficient amounts by the body, is the
major substrate that combines with iodine to
form thyroid hormones. Unlike tyrosine, which
is not an essential dietary requirement, iodine is
supplied to the body primarily through the diet,
although it is also readily absorbed from the skin
N E O N ATA L N E T WO R K
16
and lungs. The only purpose of iodine is the syn-
thesis of the thyroid hormones.8,10
The initial step in the formation of thyroid
hormones is the absorption and concentration of
iodide, an iodine compound, by the thyroid folli-
cle cells. The thyroid follicle actively pumps
iodide against a large concentration gradient
from the extracellular fluid to the interior of the
thyroid follicular cell, in a process called iodide
trapping. Once inside the follicular cell, iodide is
converted to iodine by oxidation. Oxidation of
iodide to iodine is facilitated by the enzyme
iodide peroxidase, which is located within the
follicular cells. The iodine concentration in the
thyroid gland then increases to about 30 times its
concentration in the blood, but during times of
active stimulation, the concentration of iodine
can be as high as 250 times that of plasma.1,4,18,19
DECEMBER 2000, VOL. 19, NO. 8
 Once formed, iodine attaches to tyrosine,
forming part of the thyroglobulin colloid. When
iodine attaches to tyrosine in the thyroglobulin
molecule, two iodotyrosines are formed:
monoiodotyrosine (MIT) and diiodotyrosine
(DIT). Several minutes, hours, or days later, in a
process called coupling, the iodotyrosines com-
bine to form iodothyronines, two of which are
the active thyroid hormones. The exact mecha-
nism for coupling is not understood. It is
believed that two DIT molecules are coupled to
form T4, and one DIT and MIT molecule are
joined to form T3. Only about 20 percent of
iodinated tyrosine undergoes coupling, with the
rest remaining as MIT and DIT. After coupling
is complete, each thyroglobulin molecule con-
tains one to three T 4 molecules and lesser
amounts of T3. In this form, the thyroid hor-
mones are often stored in the follicles for several
months until they are split off and secreted into
the bloodstream for use.1,4,19
The release of the thyroid hormones into the
systemic circulation is a very complex process.
One reason is that prior to the release of the thy-
roid hormones, T4 and T3 remain bound within
the thyroglobulin molecule. Secondly, these hor-
mones, which are stored deep within the thyroid
follicle, must be transported across the follicular
cells before they can enter the bloodstream.8
Because thyroglobulin is not released into the
circulation, the thyroid hormones must break
away from the thyroglobulin molecule. In the
first step of thyroid hormone secretion, the fol-
licular cell “bites off” and ingests a piece of col-
loid to form a colloid droplet. Within the cell,
the colloid droplet is ingested by lysosomes,
whose enzymes break down the thyroglobulin
molecule into its biologic active thyroid
hormones, T4 and T3, as well as the inactive
iodotyrosines, MIT and DIT. The thyroid hor-
mones, after passing to the outer membranes of
the follicular cells, are released into the blood.
The MIT and DIT have no endocrine value.4,8
Approximately 90 percent of the hormones
released from the thyroid gland initially appear
in the form of T4. However, a majority of the T4
that is secreted from the thyroid gland is subse-
quently converted to T3. The major portion of
the circulating T3 is derived from secreted T4,
rather than from thyroid secretion.6,8 T3 is four
times more potent in its biologic form than T4
and is the major hormone that interacts with the
target cells.8,18
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VOL. 19, NO. 8, DECEMBER 2000
Under normal conditions, 99 percent of the
thyroid hormones are bound to plasma proteins
once in the bloodstream. Of these, 70–80 per-
cent of the thyroid hormones are bound to
TBG, which is synthesized in the liver, and the
rest are bound to albumin and to a thyroid-
binding prealbumin (TBPA). These protein-
bound thyroid hormones are biologically
inactive.6,8
Less than 1 percent of the total plasma T4
and T3 exists in a free state, unbound to pro-
teins. These free T4 (FT4) and T3 (FT3) compo-
nents are biologically active, and it is these
components that produce the effects of the thy-
roid hormones on peripheral tissues and on the
pituitary feedback mechanism.1,6,10
The plasma proteins serve as a storage pool
for secreted thyroid hormones. The total
amount of thyroid hormone bound to plasma
proteins is about three times as much hormone
as is secreted and broken down in a day. Because
of this storage capacity, there is very little diurnal
variation. Unlike in other hormonal systems,
release of thyroid hormones and plasma concen-
trations remain relatively constant without sud-
den, wide swings in secretion. 6,8 The only
known factor that increases secretion of TRH
(and, hence, TSH and thyroid hormone) in
infants is exposure to cold. It is postulated that
this is an adaptive mechanism in newborns to
maintain body temperature as the infant goes
from the warmth of the mother’s womb to the
cold extrauterine environment. Various types of
stress are known to inhibit TSH and thyroid
hormone secretion, probably through neural
influences on the hypothalamus. The exact adap-
tive importance of this inhibition is unclear.1,8
REGULATION OF THYROID
HORMONE SECRETION
The most important regulator of thyroid hor-
mone secretion is TSH, which is secreted from
the anterior pituitary gland. Almost every step of
thyroid hormone synthesis and secretion is stim-
ulated by TSH. TSH stimulates the process of
iodide trapping and each step in T4 and T3 syn-
thesis. It also stimulates the endocytosis of the
colloid, the breaking apart of the thyroglobulin
into the two thyroid hormones, and the ultimate
release of T4 and T3 into the circulation.6,8
In addition to enhancing thyroid hormone
secretion, TSH is also responsible for maintain-
ing the structural integrity of the thyroid gland.
17
FIGURE 5 ■ Regulation of thyroid hormone secretions. When TSH is absent, the thyroid gland atro-
phies and secretes its hormones at a very low
rate. Conversely, sustained TSH stimulation
leads to an increase in the size of each follicular
cell (hypertrophy) as well as an increase in the
number of follicular cells (hyperplasia).6,8
Thyroid hormone secretion is regulated by a
negative feedback process involving the
hypothalamus, the anterior pituitary, and the
thyroid gland (Figure 5). The initiating hor-
mone in this process, TRH, is synthesized and
stored within the hypothalamus. When serum
thyroid hormone levels decline, TRH is released
into the HPT system and circulates to the
anterior pituitary gland to stimulate the secre-
tion of TSH. Release of TSH by the pituitary
gland stimulates the thyroid gland to produce
thyroid hormones and secrete them into the cir-
culation. Conversely, circulating T 4 and T 3
inhibit TSH secretion, thereby decreasing thy-
roid hormone synthesis and secretion.6,8,19

THYROID FUNCTION IN INFANTS

Term Infants
Thyroid function in term infants is altered
transiently and permanently by delivery into the
1. TRH is released from the hypothalamus to stimulate the anterior pituitary gland. extrauterine environment (Table 3). Exposure of
2. Once at the pituitary gland, TRH stimulates TSH secretion. the infant to the cold environment results in an
3. TSH then stimulates the thyroid gland to synthesize and secrete the thyroid hormones acute release of TSH from the anterior pituitary
T4 and T3.
4. T4 and T3 secretion inhibit secretion of TSH from the anterior pituitary gland and TRH
gland. Serum TSH concentrations peak 30 min-
from the hypothalamus. utes after birth and then rapidly decline during
the first 24 hours of life. This surge in TSH
Adapted and redrawn from: Seeley R, Stephens T, and Tate P. 1998. Anatomy and stimulates the thyroid gland to release both T4
Physiology, 4th ed. Boston: WBC McGraw, 554; and Sherwood L. 1997. Human and T3, resulting in a permanent increase of
Physiology: From Cells to Systems, 3rd ed. Boston: Wadsworth, 658.
these hormones during the first 36 to 48 hours
of postnatal life. Serum levels of bound and free
TABLE 3 ■ Postnatal Changes in Thyroid Function
T 4 peak at 24 hours of life and then slowly
Transient Changes Permanant Changes decrease over the first weeks of life. Serum con-
Increase in serum TSH Increased serum T3 and free T3 centrations of bound and free T3 increase three
Increased T3 and T4 production concentrations to six times within 4 hours after delivery sec-
Activation of BAT thermogenesis Increased conversion of T4 to T3 ondary to an abrupt increase in the conversion
Increased Type I MDI activity of T4 to T3. An additional sustained increase in
Absent placental degradation of thyroid serum concentrations of bound and free T 3
hormones
occurs between 2 to 4 hours and 24 to 36 hours
Decreased TSH concentration
of life. This second peak in T3 concentration
Decreased hypothalamic TRH production
coincides with elevated levels of T4 secreted
Increased serum free T4 concentrations
from the thyroid gland and to an elevation in
Resetting of hypothalamic-pituitary
setpoint for free T4 feedback control of the availability of the T4 hormone for conversion
TSH secretion to T3.15,20
Postnatally, during the first two to three days,
Key: BAT = brown adipose tissue; MDI = monodeiodinase TSH concentrations continue to progressively
Adapted from: Fisher D. 1998. Thyroid function in premature infants: The hypothyroxine- decline, falling to permanent levels significantly
mia of prematurity. Clinics in Perinatology 25(4): 1004–1005. Reprinted by permission.

N E O N ATA L N E T WO R K
18 DECEMBER 2000, VOL. 19, NO. 8
below cord concentrations, but normal for the TABLE 4 ■ Recommended Values for Serum Thyroid Hormone Concentrations3,7,25
extrauterine environment. Although the exact T4 Free T4 T3 TSH TBG
mechanism for this reduction remains unclear, it Age (µg/dl) (ng/dl) (mg/dl) µU/ml) (mg/dl)
is thought to be related to the increase in serum Cord:
T3 and T4 levels as well as continued maturation 30 weeks 9.4
(5.7–15.6)
of the feedback control of TSH by the thyroid
35 weeks 10.1
hormones.15,21 (6.1–16.8)
Term 10.8 1.7 50 9.0 3.0
Premature Infants (6.5–17.5) (2.0–4.5) (14–86) (<2.5–17.4) (0.7–5.2)
At birth, the premature infant experiences 1–3 days 16.5 4.2 220 8.0 3.0
thyroid system changes similar to those in term (11.0–22.0) (110–330) (49–281) (<2.5–13.3) (0.8–5.2)
infants; however, the HPT system remains 1–4 weeks 13.0 2.0 175 4.0 2.5
(8.0–17.2) (1.9–2.3) (100–300) (0.6–10.0) (0.5–5.0)
immature. The early TSH surge is blunted in
1–12 months 11.0 175 2.1 2.8
preterm infants, and there is a decrease in bound (5.9–16.3) ___ (100–260) (0.6–6.3) (1.6–3.6)
T4, free T4, and T3 concentrations. The extent
of these responses varies, depending on gesta-
tional age. In preterm infants born at 30 weeks
or more, serum T4 and free T4 levels increase because of immature metabolic processes and
transiently in the early neonatal period in nutritional deficiencies characteristic of prema-
response to the TSH surge. Although they grad- ture infants during the neonatal period. This
ually increase over the next several weeks, bound causes a reduction in the conversion of T4 to T3.
and free T4, serum TBG, and free T3 concentra- Hypoxia has also been shown to reduce serum
tions remain below those seen in full-term TSH concentrations and inhibit the conversion
infants throughout the first weeks of life, reach- of T4 to T3. The immature liver function of the
ing term infant values by 38 to 42 weeks post- preterm infant results in decreased serum pro-
conceptional age. There is an early increase in tein levels, which also lead to reduced T4 levels,
serum T3 concentrations at two to four hours of although free T4 concentrations are not affected.
life but shortly thereafter, the levels begin to The extent of these effects is related to the
decline. Later, when TSH secretion by the pitu- degree of immaturity.15,21
itary gland allows a progressive maturation of
the thyroid gland, serum T3 levels increase slow- LABORATORY TESTS USED IN THE
ly to normal postnatal values. These increasing EVALUATION OF THYROID
values indicate a progressive maturation of the FUNCTION
thyroid gland to respond to TSH.15,20 Thyroid tests are performed to determine the
In infants born at less than 30 weeks gesta- level of thyroid activity or to identify the cause of
tion, thyroid hormone responses are more pro- thyroid dysfunction. Although normal ranges
nounced because the HPT system is more have been defined for all age levels, discrepancies
compromised than in more mature infants. may exist between different laboratories and
During the early neonatal period, the TSH surge among age groups (Table 4). It is important that
and the ability of the thyroid gland to respond each laboratory provide its own normal values to
to TSH are limited. There is a progressive ensure accurate interpretation of results. When
decline in bound T4 and free T4 concentrations, interpreting results, keep in mind that a variety of
reaching a nadir at 1 to 2 weeks postnatal age. conditions and medications can alter thyroid hor-
By 3 to 4 weeks of life, T4 concentrations tend mone concentrations (Tables 5 and 6).
to re-equilibrate. Circulating T3 levels increase
slightly but remain low compared to levels in Thyroxine
premature infants born at a later gestational Routine assessment of thyroid function
age.15 should begin with the measurement of serum T4
There are several reasons for the relative and free T4. Unlike serum total T4 assays, which
hypothyroid state of premature infants. The measure both free and protein-bound hormone
HPT system in the premature infant is relatively levels, FT 4 measures only circulating T 4 .
immature, as are the enzymes involved in the Because free T4 is not affected by alterations in
synthesis of the thyroid hormones, in part the thyroid hormone–binding proteins in serum,

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VOL. 19, NO. 8, DECEMBER 2000 19
TABLE 5 ■ Factors Influencing Thyroid Hormone Concentrations TABLE 6 ■ Factors Influencing Impaired Peripheral
Hormone Increase Decrease
Thyroxine Thyrotoxicosis Severe hypothyroidism
Increased TBG Iodine deficiency
concentrations Moderate thyroid
T4 toxicosis insufficiency
Heparin (increases free T4) Salicylates Please refer to the print
Amiodarone administration Phenytoin version of Neonatal Network
Rifampicin
Glucocorticoids
Phenobarbital
Triiodothyronine Thyrotoxicosis Severe hypothyroidism
Increased TBG Acute illness or surgery
concentrations Amiodarone
T3 toxicosis Salicylates
Iodine deficiency Glucocorticoids
Propranolol
TBG Hepatitis Protein-losing enteropathy
Estrogens/pregnancy Protein-calorie malnutrition TSH
Biliary cirrhosis Nephrotic syndrome Measurement of serum TSH has become one
Prematurity Genetic abnormality
Heroin/methadone Glucocorticoids of the primary screening tests used in the diag-
5-fluorouracin Hyperthyroidism nosis and management of thyroid disorders. The
new assays are highly reliable and allow the prac-
Adapted from: Bertrand J, Rappaport R, and Sizonenko P. 1993. Assessment of endocrine titioner to distinguish between euthyroid infants
functions. In Pediatric Endocrinology: Physiology, Pathophysiology and Clinical Aspects,
Bertrand J, Rappaport R, and Sizonenko P, eds. Philadelphia: Lippincott Williams &
and hyperthyroid newborns with low or sup-
Wilkins, 658–681; and Domohove P. 1994. The thyroid gland. In Principles and Practices pressed TSH levels. The sensitive TSH assays are
of Pediatrics, 2nd ed., Oski F, ed. Philadelphia: Lippincott Williams & Wilkins, 1992–2001. also less affected by nonthyroidal illness and
remain unaltered by changes in thyroid hormon-
al binding protein. After the initial postnatal
TSH surge, serum TSH levels do not change
its measurement is one of the most important much with age.3,25
parameters used in the evaluation of thyroid sta-
tus. FT4 levels appear to be the best indicator of TBG
how much hormone is available to peripheral tis- Measurements of TBG concentrations are
sues. Measurement of FT4 is often used as a useful in the interpretation of abnormal thyroid
first-line test to document thyroid status in hormone levels. However, TBG levels may be
infants and children.3,22,23 altered by a variety of physiologic conditions and
medications (see Table 5).3,25
Triiodothyronine
Serum total T3 assays measure both protein- T3 Resin Uptake
bound and free T3 levels and are affected by The T3 resin uptake (T3RU) is commonly
alterations in serum thyroid–binding proteins. used to estimate the proportion of T4 that is not
Serum total and FT3 concentrations are not rou- bound to protein. It is not a measurement of
tinely measured in the assessment of thyroid serum T3 concentration. In this test, radiola-
function. Measurement of T3 levels is seldom beled T3 is added to the infant’s serum, where it
used for the detection of hypothyroidism competes with the serum-binding proteins for
because there is an overlap between the low- thyroid hormones. As the concentration of FT4
normal range and levels present in hypothyroid rises, the number of available unoccupied bind-
conditions. Consequently, measurements of ing sites decreases. Because TBG has a greater
serum total T3 and FT3 are not reliable for dis- affinity for T4 than for T3, the radioactive T3
tinguishing between normal and hypothyroid does not displace T4 from the TBG molecule.
conditions.24 In addition, because a majority of The unbound, radioactive T3 is then taken up
T3 is derived from T4, T3 concentrations may by a resin that is added to the infant’s serum.
not fall below normal until there is a reduction The percentage of this T3 varies inversely with
in plasma T4 levels.21 the concentration and affinity of unoccupied
binding sites on the serum TBG proteins; as the

N E O N ATA L N E T WO R K
20 DECEMBER 2000, VOL. 19, NO. 8
TABLE 7 ■ Causes of Hypothyroidism3,9,13,14
Thyroid agenesis or dysgenesis
HPT axis abnormalities
• TRH deficiency
• TSH deficiency
• Unresponsiveness of thyroid gland to TSH
Inborn error of hormone synthesis or metabolism
Iodine deficiency
Goitrous cretinism (caused by maternal ingestion of
goitrogens)
Transient hypothyroxinemia
Transient neonatal hypothyroidism
number of available TBG sites decreases, the
percentage of unbound radioactive T3 taken up
by the resin increases. This test is useful only if
the total T4 concentration is known.23,25
DISORDERS OF THYROID
FUNCTION
Congenital Hypothyroidism
Congenital hypothyroidism is defined as a
state in which there is a deficiency of thyroid hor-
mones that develops prior to or at the time of
delivery secondary to a variety of conditions
(Table 7). Because the placenta is relatively
impermeable to the transfer of T4, T3, and TSH,
hypothyroidism in the infant usually occurs as a
result of maldevelopment of the thyroid gland or
the HPT system and deficiencies in the enzymes
that synthesize thyroxine. Less frequently, mater-
nal iodine or antithyroid drugs used in the treat-
ment of thyrotoxicosis can be transferred
transplacentally during the first trimester, affect-
ing fetal thyroid development.9,25
Most infants with congenital hypothyroidism
deliver after 40 weeks gestation and are often
large for gestational age, weighing more than
4,000 grams at birth. Infants born hypothyroid
may present with defective skeletal maturation
and growth that occurred in utero, and they
manifest clinical signs and symptoms of thyroid
dysfunction. Many infants, however, exhibit no
symptoms or may have subtle, nonspecific clini-
cal manifestations (Table 8). Caution should be
exercised when diagnosing hypothyroidism in
premature infants because many of the clinical
manifestations are common findings in infants of
early gestation. The severity of clinical manifesta-
tions is related to thyroid function, thyroid hor-
mone interaction, and other body processes.9,14
N E O N ATA L N E T WO R K
VOL. 19, NO. 8, DECEMBER 2000
TABLE 8 ■ Clinical Manifestations Associated with Congenital Hypothyroidism
Respiratory difficulty Mottled skin
Hoarse cry Hypotension
Temperature instability Pallor
Lethargy Hypotonia
Peripheral cyanosis Late findings:
Poor feeding Enlarged tongue
Failure to thrive Elongated nasal bridge
Prolonged jaundice >2 weeks Narrow forehead
Large posterior fontanel, >1 cm diameter Eyelid edema
Protuberant abdomen with umbilical Thick, dry skin
hernia Long, coarse hair
Palpable goiter Anemia
Constipation; delay in passage of Large goiter
meconium
Adapted from: Miculan J, Turner S, and Paes B. 1993. Congenital hypothyroidism:
Diagnosis and management. Neonatal Network 12(6): 25–34; and Harrell G, and
Murray P. 1998. Diagnosis and management of congenital hypothyroidism. Journal of
Perinatal and Neonatal Nursing 11(4): 75–83.
Diagnosing hypothyroidism requires a thor-
ough history taking and physical examination,
followed by diagnostic tests. The principal
method for diagnosing hypothyroidism is the
newborn screen that is in place in the U.S. and
Canada. Most North American programs either
screen initially to measure values or use a two-
tiered approach, whereby a T4 measurement is
obtained first, followed by TSH assessment in
infants with abnormally low T4 levels. Blood
samples are collected between the second and
fifth day of life, which coincides with the physio-
logic TSH surge that occurs after birth. At
times, though, samples drawn between 24 and
48 hours after birth, during this TSH surge, may
be falsely positive for hypothyroidism and
require re-evaluation.9 In those infants exhibit-
ing physical manifestations of hypothyroidism,
additional laborator y tests as previously
described should be done before results of the
neonatal screen return.14
In addition to laboratory testing, x-rays of the
long bones are helpful in assessing bone age and
can be used to show the duration and severity of
thyroid function. The extent of bone maturation
is determined by the presence, size, and shape of
ossification centers in the knee and foot and by
the level of skull maturation.9,14
The best method for delineating the anatomy
and location of the thyroid gland is radioisotope
scanning. This scan is useful in differentiating
defects in thyroid development from other eti-
ologies. For infants clinically unstable for
radioisotope scanning, an ultrasound of the thy-
roid gland may be performed as a preliminary
21
TABLE 9 ■ Clinical Manifestations Associated with Hyperthyroidism3,7,25
Marked irritability Heat intolerance
Intrauterine growth retardation Prominent eyes
Low birth weight Thyroid enlargement
Microcephaly Failure to thrive
Hyperactivity Vomiting
Tachycardia Severe diarrhea
Tachypnea Hepatosplenomegaly
Jaundice Thrombocytopenia
Cardiac failure Goiter
test to identify the presence (or absence) of the
thyroid gland.9,14
Once hypothyroidism is confirmed, treatment
should be started to prevent mental retardation,
delayed physical growth and skeletal maturation,
and inappropriate neurodevelopment. In infants
who present with clinical manifestations associat-
ed with hypothyroidism, early treatment with L-
thyroxine (or levothyroxine) should be initiated
even before the newborn screen results are
returned.9,14 Controversy exists regarding the L-
thyroxine dose that provides optimal treatment
without producing toxic side ef fects.
Asymptomatic infants or those with minimal
clinical manifestations of hypothyroidism may be
placed on L-thyroxine at 10–15 µg/kg/day,
given orally once daily. For full-term infants with
a diagnosis of congenital hypothyroidism, the
recommended initial L-thyroxine dose is 25 to
50 µg/day, and for preterm infants, the recom-
mended starting dose is 25 µg/day.7,9,10 After
the initiation of replacement therapy, the L-thy-
roxine dose should be adjusted to maintain
serum T4 levels at high normal adult levels of
above 10 µg/dl during the first two years of life.
Thereafter, serum T4 levels should be kept at
age-appropriate values. Therapy should be
monitored monthly for the first six months of
life, every two to three months until two years of
life, and at three- to six-month inter vals
thereafter.9,10,14
Hyperthyroidism
Hyperthyroidism in childhood is rare and
occurs when the thyroid gland secretes excessive
amounts of thyroid hormone. Like hypo-
thyroidism, hyperthyroidism can be congenital
or aquired.25
Congenital hyperthyroidism, often called
neonatal thyrotoxicosis, is almost exclusively
seen in infants of mothers with Grave’s disease
or Hashimoto’s disease. The condition may be
transient, lasting up to several weeks, or
N E O N ATA L N E T WO R K
22
prolonged, lasting over six months. The etiology
is related to transplacental passage of thyroid-
stimulating immunoglobulin (TSI), which is an
autoantibody of the class G immunoglobulin.
The TSI is capable of displacing radiolabeled
TSH from TSH receptors of the thyroid mem-
brane.7,10,25 Diagnosis of neonatal thyrotoxicosis
is made based on clinical findings (Table 9) and
elevated levels of free T4 and free T3. TSH con-
centrations are also below the normal range.
Initiation of treatment should be prompt to alle-
viate the symptoms and reduce the amount of
thyroid hormone being produced. Therapy con-
sists of a combination of Lugol’s solution (5 per-
cent iodine and 10 percent potassium iodide),
propylthiouracil (PTU), and propranolol.
Lugol’s solution is given in doses of one drop
three times a day. The recommended PTU dose
is 10 mg/kg/day orally in three divided doses
(every eight hours).3,7,10 Adverse reactions to
PTU therapy often occur early. These reactions,
which appear frequently at higher doses, include
rash, hives, joint pain, and arthritis. The most
common drug reaction is transient leukopenia,
which is benign. More serious adverse reactions
include thrombocytopenia, collagen-vascular-like
syndrome, toxic hepatitis, diffuse interstitial
pneumonitis, and agranulocytosis. Agranulo-
cytosis is characterized by fever, bacterial infec-
tion, and a granulocyte count below 250/mm3.
PTU should be discontinued when fever and
oral infection or upper respiratory infection
occur.3
For infants who exhibit severe thyrotoxicosis,
propranolol hydrochloride is often used in
combination with iodine to rapidly minimize the
untoward clinical manifestations of thyro-
toxicity. Propranolol hydrochloride blocks the
conversion of T4 to T3 and is given orally at
1–2 mg/kg/day in two or more divided doses.
Digitalization may be necessary for infants with
cardiac failure.7,25 Dexamethasone may be helpful
in some infants with severe thyrotoxicosis.
Glucocorticoids suppress the HPT system and,
when administered at anti-inflammatory doses,
lower serum TSH and T4 levels. T3 levels are also
affected and are decreased secondary to inhibition
of the conversion of T4 to T3.23 Close monitoring
of thyroid hormone levels is essential to ensure
adequate therapy and to avoid hypothyroidism.
Despite prompt and adequate treatment,
long-term complications from neonatal thyro-
toxicosis can occur. These include premature
DECEMBER 2000, VOL. 19, NO. 8
craniosynostosis and neurodevelopmental defects,
such as intellectual impairment.7,25
TRANSIENT DISORDERS OF
THYROID FUNCTION
Although preterm infants experience the
same pathophysiologic processes that affect full-
term infants, certain disorders of thyroid func-
tion are more common among this population
(Table 10).
Transient Hypothyroxinemia
Transient hypothyroxinemia is a syndrome
commonly seen in premature infants, affecting
all to some degree. It is thought to occur in
premature infants secondary to immaturity of
the HPT system. Because serum T4 concentra-
tions gradually increase with advancing gesta-
tional age, this syndrome is characterized by low
serum T4 and relatively low free T4 levels.17
These low T4 levels in premature infants are
associated with normal TSH and T4 responses
to TRH. The hypothyroxinemia is a transient
process that corrects spontaneously over four to
eight weeks as T4 levels rise, suggesting matura-
tion of hypothalamic function. Because growth
and development of these infants are often nor-
mal, medical intervention is not necessary. Thus,
these infants appear to manifest a state of
hypothalamic hypothyroidism or immaturity
that represents a normal stage of fetal thyroid
system development. Routine newborn screen-
ing fails to identify these infants unless T4 and
TSH results are reported.17,20,21
Transient Primary Hypothyroidism
Transient hypothyroidism is a temporary con-
dition that occurs in premature infants exposed
to reduced iodine. It occurs more often in
Europe than in North America. This condition,
which is characterized by normal cord blood T4
and TSH values, develops during the first one to
two weeks of extrauterine life and is often super-
imposed on the transient hypothyroxinemia
characteristic of premature infants. In iodine
deficient areas, immature neonates are at risk for
this condition because premature infants require
higher intake to maintain positive iodine balance
in the extrauterine environment. Urinary iodine
excretion and thyroid iodine content are low.
Often the hypothyroidism is transient, but it
may persist for two to three months. In this case,
treatment is recommended with iodine supple-
N E O N ATA L N E T WO R K
VOL. 19, NO. 8, DECEMBER 2000
TABLE 10 ■ Thyroid Disorders in Premature Infants
Disorder Serum Levels Etiology
T4 T3
Transient hypothyroxinemia Low Normal Immaturity of the HPT system
Transient primary hypothyroidism Low Elevated Maternal antithyroid therapy
Iodine deficiency
Iodine excess
Idiopathic
Low T3 syndrome in preterm infants Normal Normal Prematurity
Hypoglycemia
Hypocalcemia
Infections
Surgical stress
Malnutrition
Acidosis
Hypoxia
Adapted from: Fisher D. 1998. Thyroid function in premature infants: The hypothyroxine-
mia of prematurity. Clinics in Perinatology 25(4): 999–1014; and Polk D, and Fisher D.
1998. Disorders of the thyroid gland. In Avery’s Diseases of the Newborn, 7th ed.,
Tauesch AW, and Ballard R, eds. Philadelphia: WB Saunders, 1224–1234.
mentation or T4. Although there is no standard
recommended T4 dose, 8 µg/kg/day adminis-
tered for six weeks has been found to improve
T4 levels.15,17,21
Transient hypothyroidism may also occur in
infants exposed to excess iodine or antithyroid
medications or through placental transfer of
TSH-receptor-blocking antibodies. The latter
produce a hypothyroid state that lasts until
maternal immunoglobulin is reduced. Premature
infants are at greatest risk for this condition
because of their limited thyroglobulin and
iodine stores, associated with an increase in the
utilization of T 4 . Thus, transient hypothy-
roidism, with or without a goiter, is character-
ized by low ser um total T 4 and free T 4
concentrations and increased serum TSH levels.
Treatment of these infants with iodine at 50 to
100 µg/kg/day with T4 is indicated and should
be continued for two to three months or until
the goiter disappears.15,17,21
Low T3 Syndrome in Premature Infants
Low T3 syndrome is a physiologic condition
that occurs in premature infants. Because the
neonatal TSH surge and T 4 and T 3 peak
responses increase with increasing gestational
age, premature infants present with lower T3
values than do full-term infants. This transient
“decrease” in T3 levels, the characteristic feature
of this syndrome, is probably related to the rela-
tive undernutrition and feeding disorders that
are common among premature infants in the
neonatal period and that occur as a result of a
23
variety of conditions. These conditions include acidosis,
hypoxia, hypoglycemia, hypocalcemia, and infections. All of
these factors tend to inhibit the conversion of T4 to T3 and
aggravate the already existing low T3 levels. Serum T3 levels
may remain low in these infants for one to two months.17,20
In addition to low serum T3 levels, total T4 concentrations
are normal or low. Free T4 values are usually in the range of
values for healthy premature infants of the same gestational
age and weight. Serum TSH concentrations are normal in
these infants. No medical treatment is required.17,20
NURSING IMPLICATIONS
As caregivers, nurses are in a unique position to minimize
the infant’s risks for thyroid deficiencies. Prior to invasive pro-
cedures, the skin is often cleansed with a variety of solutions
to reduce the risk of infection. One commonly used in the
NICU to decontaminate the skin is providone-iodine
solution. Its use in premature infants has been associated with
a variety of complications, including prolonged elevation in
plasma and urinary iodine, transient hypothyroxinemia,
hypothyroidism, and goiter. Therefore, solutions and com-
pounds containing iodine should be used sparingly in prema-
ture infants to minimize the risks associated with them. All
solutions used should be thoroughly washed off with comple-
tion of the procedure.26,27
Through communication with families, nurses can identify
those infants at risk for thyroid disorders. Prompt recognition
of clinical manifestations associated with specific thyroid condi-
tions can lead to early diagnosis. Early identification of specific
thyroid disorders reduces the delay in starting treatment and
facilitates the normalization of thyroid hormone levels.
Nurses also play a key role in monitoring tests and ensuring
compliance with mandated newborn screening. Newborn
screening should be done on every infant, and all tests should
be carefully documented. Because many infants are transport-
ed from referring hospitals, follow-up is necessary to ensure
that a newborn screen was completed. When the completion
of a newborn screen cannot be verified, screening should be
performed. For infants born at home, newborn screening
should be part of the routine admission lab work completed in
the NICU or in the pediatrician’s office. Critically ill or prema-
ture infants should all be screened prior to seven days of age
and before administration of blood transfusions. Adequate
documentation of the completion of the newborn screen is
especially important for these infants because the test often
gets overlooked during the acute phase of illness.
Early discharge is another factor that complicates the
screening process. Although all infants should have a new-
born screen prior to discharge, some may not be screened
because of early discharge from the hospital. For these infants,
the family physician or pediatrician should be notified
promptly to ensure that screening is done.9
Proper nursing technique in obtaining blood samples on
N E O N ATA L N E T WO R K
24
the designated forms reduces delay in the diagnosis of thyroid
disorders and provides accurate results. Blood specimens that
do not fully saturate the filter paper or that are contaminated
with other fluids will invalidate results. Nurses can reduce
sampling errors by ensuring that specimens are drawn correct-
ly in accordance with recommended guidelines.9
The nurse should teach and support parents of infants
diagnosed with a specific thyroid disorder prior to discharge.
Nurses need to teach parents about their infant’s condition
and the need for medication when indicated. In the case of
infants who require a lifetime of medication, compliance is
emphasized to prevent any associated untoward outcomes.
Parents need to be instructed on potential side effects associ-
ated with medications. Any significant reactions should be
reported to the family physician because they may be a sign of
improper dosing. Parents must be reassured that, with early
diagnosis, prompt treatment, and compliance with therapy,
optimal outcome is enhanced. Support for the family should
focus on the initial reactions of shock and sorrow that come
with the news that their infant has a lifelong illness. Parents
should be encouraged to speak openly about their feelings
and fears.
CASE STUDY
Baby girl HL was the third of quadruplets born at 28
weeks gestation by dates and 1,045 grams to a 47-year-old,
G3 P1 female whose laboratory studies were: O positive, anti-
body negative, rubella immune, PRP nonreactive, HBsAg
negative, GBBS negative. Maternal history significant for sys-
temic lupus erythematosus (SLE), Sjögren’s (a rare autoim-
mune disease that primarily affects the lacrimal and salivary
glands and results in lymphocyte infiltration of these organs),
hyperthyroidism, insulin dependent diabetes, anxiety disorder,
and untreated preeclampsia. Medications included prednisone
(for SLE and Sjögren’s), PTU (for hyperthyroidism), insulin,
and lorazepam as required. A cerclage was placed at 14 weeks
gestation. The mother was admitted for complaints of short-
ness of breath. After admission, she received 1.5 courses of
betamethasone. The infants were delivered by cesarean sec-
tion secondary to a nonreassuring fetal monitoring strip and
abnormal Doppler study on quadruplet A and poor growth of
quadruplets A and B. Apgar scores for baby girl HL were 8
and 9 at one and five minutes of life, respectively. The infant
cried spontaneously and had a good heart rate and respiratory
effort. Physical examination was unremarkable except for the
presence of a large goiter.
On admission to the special care nursery, the infant was
intubated secondar y to increased respirator y distress.
Beractant, 4 ml/kg, was given per protocol. The infant was
placed on initial ventilator parameters at a rate of 30
breaths/minute, pressure 24 cm H2O, peep 3 cm H2O, FiO2
0.40. Over the next several days, the infant required an
increase in ventilatory support. At two days of life, levothy-
DECEMBER 2000, VOL. 19, NO. 8
roxine (Synthroid) was started. Prior to initiation of
levothyroxine, T4 and TSH levels were drawn and revealed a
slightly low free T 4 value of 0.5 ng/dl (normal range:
0.7–1.6 ng/dl) and a significantly elevated TSH level of
134.45 microunit/ml (normal range: .38–6.15
microunit/ml). A cortisol level was also drawn, which was
low at 1 µg/dl. Hydrocortisone was started at 1 mg/kg/dose
three times a day.
By the third day of life, a significant improvement was
noted in the infant’s clinical condition. The ventilator param-
eters were aggressively weaned, and the infant was successfully
extubated at six days of age. Feedings were started on day 6
and advanced slowly with good tolerance. Once on full feed-
ings, the infant was placed on oral levothyroxine at 8
µg/kg/day.
Once baby girl HL was on levothyroxine, subsequent TSH
levels declined. On day 18, 31, and 52, levels were 1.78
microunit/ml, 0.40 microunit/ml, and 2.77 microunit/ml,
respectively. Repeat free T4 levels were 1.6 ng/dl on day 31
and 1.8 ng/dl on day 52.
The infant continued to improve. She was gradually
weaned off of hydrocortisone at 43 days of life and nasal can-
nula at 65 days of life. HL was discharged home at 75 days of
age on Synthroid. Physical examination prior to discharge
revealed a small but still palpable goiter.
This case illustrates the condition of transient hypothy-
roidism caused by the antithyroid drug PTU, which crosses the
placenta and interferes with the production of thyroid hor-
mones. This condition is characterized by low T4 concentra-
tions and very high TSH levels, as seen in this infant. At times,
these infants present with goiters.
Thyroid hormones are essential for surfactant production
because they enhance the phosphatidylcholine (PC), the
major phospholipid in surfactant. Often infants with low T4
and T 3 levels experience respiratory distress syndrome,
although the exact mechanism is unclear.28
The drug of choice for thyroid replacement is levothyrox-
ine because of its stability, low cost, easy laboratory measure-
ment of serum levels, and long half-life of seven days, which
permits once-daily administration.29 Once thyroid replace-
ment is begun, thyroid hormone concentrations increase and
TSH levels normalize. Synthroid therapy is continued for two
to three months or until the goiter disappears. Baby girl HL
will continue to be followed by an endocrinologist for evalua-
tion of her goiter and her thyroid hormone and TSH concen-
trations to determine length of treatment.
CONCLUSION
The thyroid gland contains many follicles that store thy-
roid hormones within the thyroglobulin molecule until they
are needed by the body. Thyroid hormone synthesis is a com-
plicated process that depends on the presence of iodine and
tyrosine as well as maturation of the HPT system. Stimulation
N E O N ATA L N E T WO R K
VOL. 19, NO. 8, DECEMBER 2000
of this system to secrete thyroid hormones is initiated by low
circulating T4 and T3 levels. A deficiency of thyroid hor-
mones results in a variety of pathologic conditions. Awareness
of the underlying physiology of thyroid functioning and clini-
cal manifestations of disease is important to identify infants at
risk for thyroid disorders. Early recognition and prompt treat-
ment are crucial to prevent the potentially devastating long-
term sequelae associated with thyroid hormone deficiency.
REFERENCES
1. Johnson L. 1992. Essential Medical Physiology. New York: Raven,
561–575.
2. Rhodes R, and Tanner G. 1995. Medical Physiology. Boston:
Little, Brown, 673–685.
3. Hung W. 1992. Clinical Pediatric Endocrinology. Chicago:
Mosby-Year Book, 1129–1178.
4. Guyton A, and Hall J. 1996. Human Physiology & Mechanisms
of Disease, 6th ed. Philadelphia: WB Saunders, 607–615.
5. Thibodeau G, and Patton F. 1997. The Human Body in Health
and Disease. St. Louis: Mosby-Year Book, 480–523.
6. Berne R, and Levy M. 1998. Physiology, 4th ed. St. Louis:
Mosby-Year Book, 910–929.
7. Fisher D. 1990. The thyroid gland. In Pediatric Endocrinology,
Kaplan S, ed. Philadelphia: WB Saunders, 87–126.
8. Sherwood L. 1997. Human Physiology: From Cells to Systems, 3rd
ed. Boston: Wadsworth, 655–699.
9. Miculan J, Turner S, and Paes B. 1993. Congenital hypothy-
roidism: Diagnosis and management. Neonatal Network 12(6):
25–34.
10. Foley T, and Morishima A. 1997. Thyroid disorders. In
Neonatal-Perinatal Medicine: Diseases of the Fetus and Infant,
6th ed., Fanaroff A, and Martin R, eds. St. Louis: Mosby-Year
Book, 1459–1563.
11. Marieb E. 1998. Human Anatomy and Physiology. New York:
Addison Wesley Education, 587–625.
12. Moore K, and Persaud TVN. 1998. The Developing Human:
Clinically Oriented Embryology, 6th ed. Philadelphia: WB
Saunders, 230–232.
13. Larsen W. 1997. Human Embryology, 2nd ed. New York:
Churchill Livingstone, 347–374.
14. Harrell G, and Murray P. 1998. Diagnosis and management of
congenital hypothyroidism. Journal of Perinatal and Neonatal
Nursing 11(4): 75–83.
15. Fisher D. 1998. Thyroid function in premature infants: The
hypothyroxinemia of prematurity. Clinics in Perinatology 25(4):
999–1014.
16. Thoerpe-Beeston JG, et al. 1991. Maturation of the secretion of
thyroid hormone and thyroid-stimulation hormone in the fetus.
New England Journal of Medicine 24(8): 532–536.
17. Polk D, and Fisher D. 1998. Disorders of the thyroid gland. In
Avery’s Diseases of the Newborn, 7th ed., Tauesch AW, and
Ballard R, eds. Philadelphia: WB Saunders, 1224–1234.
18. Seeley R, Stephens T, and Tate P. 1998. Anatomy and Physiology,
4th ed. Boston: WBC McGraw, 542–575.
25
19. Piano M, and Huether S. 1998. Mechanisms of hormonal regu-
lation. In Pathophysiology: The Biologic Basis of Disease in Adults
and Children, 3rd ed., McCance K, and Huether S, eds. St.
Louis: Mosby-Year Book, 625–655.
20. Fisher D, and Klein A. 1981. Thyroid development and disor-
ders of thyroid function in the newborn. New England Journal
of Medicine 304(12): 702–712.
21. Fisher D. 1990. Euthyroid low thyroxine (T4) and triiodothyro-
nine (T3) states in premature and sick neonates. Pediatric Clinics
of North America 37(6): 1297–1312.
22. Bertrand J, Rappaport R, and Sizonenko P. 1993. Assessment of
endocrine functions. In Pediatric Endocrinology: Physiology,
Pathophysiology and Clinical Aspects, Bertrand J, Rappaport R,
and Sizonenko P, eds. Philadelphia: Lippincott Williams &
Wilkins, 658–681.
23. Brunt L, and Halverson J. 1996. The endocrine system. In The
Physiologic Basis of Surgery, 2nd ed., O’Leary P, ed. Philadelphia:
Lippincott Williams & Wilkins, 312–348.
24. Tressler K. 1995. Clinical Laboratory and Diagnostic Tests.
Norwalk, Connecticut: Appleton & Lange, 265–338.
25. Domohove P. 1994. The thyroid gland. In Principles and
Practices of Pediatrics, 2nd ed., Oski F, ed. Philadelphia:
Lippincott Williams & Wilkins, 1992–2001.
26. Benis M. 1999. Newborn percutaneous absorption: Hazards and
therapeutic uses. Neonatal Network 18(8): 63–69.
N E O N ATA L N E T WO R K
26
27. Lund C, et al. 1999. Neonatal skin care: The scientific basis for
practice. Neonatal Network 18(4): 15–27.
28. Loper D. 1997. Physiologic principles of the respiratory system.
In Acute Respiratory Care of the Neonate, 2nd ed., Askin D, ed.
Santa Rosa, California: NICU INK, 1–30.
29. Greenspan F, and Dong B. 1995. Thyroid and antithyroid
drugs. In Basic and Clinical Pharmacology, 6th ed., Katzung B,
ed. Norwalk, Connecticut: Appleton & Lange, 578–591.
About the Author
Denise Kirsten works as a neonatal nurse practitioner at Rush
Presbyterian–St. Lukes Medical Center in Chicago. She also works part-
time at Rush University College of Nursing as an instructor in the
Neonatal Nurse Practitioner Program. She received her BSN from
Evansville University and her ND from Rush University in Chicago. She
is past president of the Chicago Area Association of Neonatal Nurses
(CANN) and a member of NANN and Sigma Theta Tau.
The author would like to thank Raymond Shields for providing illus-
trations for this article.
For further information, please contact:
Denise Kirsten, ND, RNC, NNP
Rush Presbyterian–St. Lukes Medical Center
1653 West Congress Parkway
Chicago, IL 60612-3864
E-mail: dkirsten@rush.edu
DECEMBER 2000, VOL. 19, NO. 8