ENDOCRINOLOGY DR.

ESGUERRA
THYROID GLAND
THYROID DEVELOPMENT
The fetal thyroid arises from an outpouching of the foregut at the base of the tongue (foramen
cecum). It migrates to its normal location over the thyroid cartilage by 8-10 wk of gestation. The
thyroid bilobed shape is recognized by 7 wk of gestation, and characteristic thyroid follicle cell
and colloid formation is seen by 10 wk.
Thyroglobulin synthesis occurs from 4 wk, iodine trapping occurs by 8-10 wk, and thyroxine (T4)
and, to a lesser extent, triiodothyronine (T3) synthesis and secretion occur from 12 wk of
gestation.
There is evidence that several transcription factorsTTF-1/NKX-2.1, TTF-2 (also termed FOXE1), NKX2.5,
and PAX8are important in thyroid gland morphogenesis and differentiation, and possibly also in its
caudal migration to its final location. These factors also bind to the promoters of thyroglobulin and thyroid
peroxidase genes and so influence thyroid hormone production.
Hypothalamic neurons synthesize thyrotropin-releasing hormone (TRH) by 6-8 wk, the pituitary portal
vessel system begins development by 8-10 wk, and thyroid-stimulating hormone (TSH) secretion is evident
by 12 wk of gestation
Maturation of the hypothalamic pituitary-thyroid axis occurs over the second half of gestation, but normal
feedback relationships are not mature until approximately 3 mo of postnatal life. Other transcription
factors, including PROP-1
and Pit-1, are important for differentiation and growth of thyrotrophs, along with somatotrophs and
lactotrophs

THYROID PHYSIOLOGY (Not discussed)

Function of thyroid gland is to synthesize T4 and T3
The only known physiologic role of iodine (or iodide [I] in its ionized form) is in the synthesis of these
hormones

RDA of iodine (iodized):

Infants - 30/kg/24hr
Children 90-120 /kg/24hr
Adolescents & adults 150 /kg/24hr

Approximately one-third of maternal T4 crosses the placenta and fetus

Maternal T4 plays a role in fetal development especially that of the brain, before the synthesis of
fetal thyroid hormone begins.
At birth, there is an acute release of TSH; peak serum concentrations reach 60 mU/L 30 minutes
following delivery in full-term infants.
HYPOTHYROIDISM

Most cases of congenital hypothyroidism are not hereditary and result from thyroid dysgenesis.
Some cases are familial; these are usually caused by one of the inborn errors of thyroid hormone
synthesis (dyshormonogenesis) and may be associated with a goiter

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ENDOCRINOLOGY DR. ESGUERRA

Thyroid dysgenesis MC cause of permanent congenital hypothyroidism accounting for 80-85% of

cases.

Aplasia, Hypoplasia, or an Ectopic gland

Detected by Newborn Screening - Blood obtained by heel-prick between 2 and 5 days of life is
placed on a filter paper card and sent to a central screening laboratory
Most infants with congenital hypothyroidism are detected by newborn screening programs in the 1st
few wk after birth, before obvious clinical symptoms and signs develop .
In approximately 33% of cases of dysgenesis, even sensitive radionuclide scans can find no
remnants of thyroid tissue (aplasia). In the other 66% of infants, rudiments of thyroid tissue
are found in an ectopic location, anywhere from the base of the tongue (lingual thyroid) to the
normal position in the neck (hypoplasia).

Clinical manifestations

Prolongation of physiologic jaundice, caused by delayed maturation of glucuronide conjugation,

may be the earliest sign.
Feeding difficulties especially sluggishness, Lack of interest, Somnolence, Choking spells

during nursing, are often present during the first month of life
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Respiratory difficulties partially caused by the large tongue , include apneic episodes , Noisy

respirations and nasal obstruction

Some infant may develop respiratory distress syndrome
Retardation of physical and mental development becomes greater during the following

months and by 3-6 months of age the clinical picture is fully developed
The muscles are hypotonic, but in rare general instances generalized Pseudohypertrophy
(Kocher-Debr-Smlaigne syndrome) occurs, particularly in the calf muscles
The temperature is subnormal, often <35C (95F), and the skin, particularly that of the
extremities, may be cold and mottled

Treatment: levothyroxine
Prognosis

Thyroid hormone is critical for normal cerebral development in the early postnatal months;
biochemical diagnosis must be made soon after birth, and effective treatment must be initiated
promptly to prevent irreversible brain damage.

HYPERTHYROIDISM
Excessive secretion of thyroid hormone; during childhood with few exceptions, it is caused by

Graves disease

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ENDOCRINOLOGY DR. ESGUERRA

Graves disease lymphocytic infiltration of thyroid gland; is an autoimmune disorder;

production of thyroid-stimulating immunoglobulin that binds to and activates the G-proteincoupled

thyroid-stimulating hormone (TSH) receptor results in diffuse toxic goiter

5% of all patients with hyperthyroidism are younger than 15 years of age

Peak incidence occurs during adolescence; The incidence is approximately 5 times higher in

girls than in boys.

Symptoms
- The earliest signs in children may be emotional disturbances accompanied by motor
Hyperactivity
- Irritability
- Altered mood
- Insomnia restless sleepers& they tend to kick their covers off
- Anxiety
- Poor concentration
- Heat intolerance
- Increased sweating
- Palpitations, fatigue
- Weakness, dyspnea
- Weight loss with increased appetite (weight gain in 10% of patients)
- Pruritus
- Increased stool frequency
- Thirst and polyuria
- Oligomenorrhea or amenorrhea

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ENDOCRINOLOGY DR. ESGUERRA

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ENDOCRINOLOGY DR. ESGUERRA

CONGENITAL GOITER
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ENDOCRINOLOGY DR. ESGUERRA

Goiter is the enlargement of thyroid gland. Persons with enlarged thyroids can have normal
function of the gland (euthyroidism), thyroid deficiency (hypothyroidism), or
overproduction of the hormones (hyperthyroidism)

Usually sporadic
Congenital goiter Result from a fetal T4 synthetic defect from administration of
anti-thyroid drugs or iodides during pregnancy for treatment of maternal thyrotoxicosis.

Goitrogenic drugs that cross the placenta at high doses can interfere with synthesis of thyroid
hormone, resulting in goiter and hypothyroidism in the fetus
Goiter is almost always present in the infant with neonatal Graves disease. Thyroid
enlargement results from transplacental passage of maternal thyroid-stimulating
immunoglobulin. These goiters usually are not large; the infant manifests clinical symptoms of
hyperthyroidism. The mother often has a history of Graves disease, or the diagnosis of
maternal Graves may be revealed through the evaluation of neonatal hyperthyroidism. TSH
receptoractivating mutations are also a recognized cause of congenital goiter and
hyperthyroidism
*Pendred syndrome
* Iodine deficiency

HYPOPARATHYROIDISM
Hypocalcemia is common in neonates between 12 and 72 hr of life, especially in premature infants,
in infants with asphyxia, and in infants of diabetic mothers (early neonatal hypocalcemia) After the
2nd to 3rd day and during the 1st wk of life, the type of feeding also is a determinant of the level of
aserum calcium (late neonatal hypocalcemia). The role played by the parathyroid glands in these
hypocalcemic infants remains to be clarified, although functional immaturity of the parathyroid
glands is invoked as 1 pathogenetic factor. In a group of infants with transient idiopathic
hypocalcemia (1-8 wk of age), serum levels of parathyroid hormone (PTH) are significantly lower
than those in normal infants. It is possible that the functional immaturity is a manifestation of a
delay in development of the enzymes that convert glandular PTH to secreted PTH; other
mechanisms are possible.

Aplasia or hypoplasia of the parathyroid glands is often associated with the DiGeorge
syndrome/velocardiofacial syndrome
Hypocalcemia vitamin D, magnesium
Manifestation
- Chvostek sign
Elicitation: Tapping on the face at a point just anterior to the ear and just below the

zygomatic bone

Positive response: Twitching of the ipsilateral facial muscles, suggestive of neuromuscular

excitability caused by hypocalcemia

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ENDOCRINOLOGY DR. ESGUERRA

Trousseau sign
- Elicitation: Inflating a sphygmomanometer cuff above systolic blood pressure for several
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minutes
Positive response: Muscular contraction including flexion of the wrist and
metacarpophalangeal joints, hyperextension of the fingers, and flexion of the thumb on the
palm, suggestive of neuromuscular excitability caused by hypocalcemia

Laryngeal or Carpopedal spasm

- Convulsions with or without loss of consciousness. These episodes can begin with abdominal
pain, followed by tonic rigidity, retraction of the head, and cyanosis. Hypoparathyroidism is
mistaken for epilepsy
- Headache, vomiting, increased ICP, and papilledema may be associated with convulsions
and might suggest a brain tumor.
- Calcium level is low (5-7 mg/dL)
- Elevated Phosphorus level (7-12 mg/dL)
Treatment
- Emergency treatment of neonatal tetany consist of 5-10 ml or 1-3 mg/kg of a 10%
solution of Calcium Gluconate (elemental calcium 9.3 mg/dL ) at the rate of 0.5-1.0
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mL/min while the heart rate is monitored and a total dose not to exceed 20 mg of elemental
calcium/kg. Additionally, 1,25 dihydroxycholecalciferol (calcitriol) should be given.
An adequate intake of calcium should be ensured. Supplemental calcium can be given in the
form of calcium gluconate or calcium glubionate to provide 800 mg of elemental calcium
daily, but it is rarely essential. Foods with high phosphorus content such as milk, eggs, and
cheese should be reduced in the diet.
Clinical evaluation of the patient and frequent determinations of the serum calcium levels
are indicated in the early stages of treatment to determine the requirement for calcitriol or
vitamin D2. If Hypercalcemia occurs, therapy should be discontinued and resumed at a
lower dose after the serum calcium level has returned to normal

ENDOCRINOLOGY DR. ESGUERRA

References:
Dr. Marivic Esguerras lecture
Nelson Textbook of Pediatrics 20E

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