Dr. Rihab Faisal
HYPOTHYROIDISM
Definition:
Deficiency of thyroid hormone production that result from either defect in
thyroid gland itself (primary hypothyroidism, most common) or reduced TSH
stimulation (central hypothyroidism).
Classification:
•
Congenital hypothyroidism
a. Primary hypothyroidism
▪ Defect in fetal thyroid development (dysgenesis) 80%.
▪ Defect in thyroid hormone synthesis (dyshormonogenesis) 15%.
▪ TSH unresponsiveness.
▪ Maternal iodine deficiency.
▪ Maternal antibodies: thyrotropin receptor–blocking antibody.
▪ Maternal medication (iodide, amiodarone, antithyroid medication,
radioiodine).
b. Central hypothyroidism
▪ Isolated TSH or TRH deficiency.
▪ Multiple congenital pituitary hormones deficiency.
•
Acquired hypothyroidism
a. Primary hypothyroidism
▪ Autoimmune (most common).
▪ Drug induced (excessive iodide, amiodarone, antithyroid
medication, anticonvulsants).
▪ Postablative (irradiation, thyroidectomy).
▪ Systemic infiltrative disease.
b. Central hypothyroidism (head trauma, tumor, radiation).
Clinical features:
Congenital hypothyroidism: Most infants with congenital hypothyroidism are
asymptomatic at birth, attributed to partial transplacental passage of maternal
T4, which provides fetal levels that are approximately 33% of normal at birth.
Despite this maternal contribution, hypothyroid infants still have a low serum
T4 and elevated TSH level on screening programs (protect the infant but not
interfere with screening).
While breast milk contains significant amounts of
thyroid hormones, it neither protect the hypothyroid infant nor affect neonatal
thyroid screening tests.
At birth; birthweight and length are normal, but head size may be slightly
increased because of myxedema of the brain. The anterior and posterior
fontanels are open widely.
During the 1st mo of life; prolongation of physiologic jaundice (delayed
maturation of glucuronide conjugation), feeding difficulties (sluggishness, lack
of interest, somnolence, and choking spells during nursing), and respiratory
difficulties(apneic episodes, noisy respirations, and nasal obstruction) partly
caused by the large tongue.
During infancy; respiratory distress, cry little, sleep much, have poor appetites,
and are generally sluggish.
There may be constipation, large abdomen, umbilical hernia, subnormal
temperature (often <35°C), cold and mottled skin (particularly that of the
extremities), edema of the genitals and extremities, slow pulse, heart murmurs,
cardiomegaly, asymptomatic pericardial effusion.
Approximately 10% of infants with congenital hypothyroidism have associated
congenital anomalies, including: cardiac anomalies (most common), nervous
system and eye anomalies, hearing loss, cleft palate, genitourinary anomalies.
Because symptoms appear gradually, the clinical diagnosis is often delayed. If
congenital hypothyroidism goes undetected and untreated, these manifestations
progress. So there will be retardation of physical and mental development, and
by 3-6 mo of age the clinical picture is fully developed.
Fully developed clinical picture; growth will be stunted, the extremities are
short, the head size is normal or even increased, the anterior fontanel is large
and the posterior fontanel may remain open, the eyes appear far apart, the
bridge of the broad nose is depressed, the palpebral fissures are narrow and the
eyelids are swollen, the mouth is kept open, and the thick, broad tongue
protrudes, dentition will be delayed, the neck is short and thick, the hands are
broad and the fingers are short, the skin is dry and scaly, and there is little
perspiration, myxedema (particularly in the skin of the eyelids, the back of the
hands, and the external genitals), the skin shows general pallor with a sallow
complexion, carotenemia (yellow discoloration of the skin, but the sclerae
remain white), the scalp is thickened, and the hair is coarse, brittle, and scanty,
the hairline reaches far down on the forehead, which usually appears wrinkled,
especially when the infant cries, developmental delayed (late in learning to sit
and stand), the voice is hoarse, and they do not learn to talk. The degree of
physical and intellectual delay increases with age.
Sexual maturation may also be delayed or might not take place at all. The
muscles are usually hypotonic, but in rare instances generalized muscular
pseudohypertrophy occurs (Kocher-Debré-Sémélaigne syndrome): it affects
patients who have hypothyroidism of longer duration and severity. Boys are
more prone to development of this syndrome who presented with athletic
appearance because of pseudohypertrophy, particularly in the calf muscles. Its
pathogenesis is unknown, and it returns to normal with treatment.
Acquired hypothyroidism: deceleration of growth (usually the first clinical
manifestation, but often goes unrecognized), goiter (associated with Hashimoto
thyroiditis may be a presenting feature), weight gain (mostly fluid retention
(myxedema) not true obesity), myxedematous changes of the skin, constipation,
cold intolerance, decreased energy, and an increased need for sleep.
Surprisingly, schoolwork and grades usually do not suffer, even in severely
hypothyroid children.
Additional features include bradycardia, muscle weakness or cramps, nerve
entrapment, and ataxia.
About puberty:
• Older adolescent girls manifest menometrorrhagia.
• Adolescents typically have delayed puberty.
• Younger children might present with galactorrhea (increased TRH
stimulating prolactin secretion) or pseudoprecocious puberty characterized
by breast development and vaginal bleeding in girls and macroorchidism in
boys (high TSH concentrations binding to the FSH receptor with subsequent
stimulation).
Some children have headaches and vision problems; they usually have
hyperplastic enlargement of the pituitary gland due to long-standing primary
hypothyroidism. It may be mistaken for a pituitary tumor.
Investigations:
Congenital hypothyroidism:
The early approach to newborn screening began with measure of levels of T4,
followed by measurement of TSH when T4 is low. Over time, many neonatal
screening programs elsewhere in the world have switched to an initial TSH
measurement. Regardless of the approach used for screening, some infants
escape detection because of technical or human errors; clinicians must maintain
their vigilance for clinical manifestations of hypothyroidism. In identical twins;
transfusion of euthyroid blood from the unaffected twin may normalized the
serum levels of T4 and TSH in the affected twin at the initial screening
and the
diagnosis was not made until the infants were 4-5 mo of age. Many newborn
screening programs perform a routine second test in same-sex twins.
1. TFT
FT4: low
T3 may be normal and are not helpful in the diagnosis.
TSH: high in primary hypothyroidism, normal or low in central one.
2. Serum levels of thyroglobulin are usually low in thyroid agenesis or defects
of thyroglobulin synthesis or secretion.
3. Radiography:
The distal femoral and proximal tibial epiphyses, normally present at birth, are
often absent ( mean
retardation of osseous development which occurs in
approximately 60% of hypothyroid infants). Cardiac enlargement or pericardial
effusion may be present.
4. Scintigraphy pinpoint the underlying cause in infants with congenital
hypothyroidism, also ultrasonographic examination of the thyroid is helpful.
5. ECG: may show low-voltage P and T waves with diminished amplitude of
QRS.
6. Echocardiography can confirm a pericardial effusion.
7. EEG: often shows low voltage.
8. The serum cholesterol level is usually elevated
in children older than 2 yr of
age.
Acquired hypothyroidism:
1. TFT
FT4: low
TSH: high in primary hypothyroidism, normal or low in central one.
2. Thyroid antibodies: antithyroglobulin and antiperoxidase antibodies can
pinpoint autoimmune thyroiditis as the cause.
3. Thyroid sonography: generally, not indicated unless there is a suspicion of a
thyroid nodule on neck palpation
4. X ray for bone age:
osseous maturation is delayed, which is an indication of
the duration of the hypothyroidism.
5. Abnormal laboratory findings, include hyponatremia, macrocytic anemia
(refractory to treatment with hematinics), hypercholesterolemia, and elevated
creatine phosphokinase.
Treatment:
Oral levothyroxin once daily at fixed time (standard recommendation is on an
empty stomach, 0.5-1 hr before breakfast). BASIC (bile acid binding resine,
aluminum containing antiacid, soy, iron, calcium and caffeine) interfere with
thyroxin absorption.
levothyroxin doses per weight decrease with increasing age (for example,
neonates 10-15 Ug/kg/day, while those ≥ 10 yr 2-4 Ug/kg/day).
Treatment should be monitored by measuring serum free T4 and TSH every 4-6
mo as well as 6 wk after any change in dosage.
Note
In congenital hypothyroidism, rapid normalization of thyroid function (ideally
within 2 wk) is important in achieving optimal neurodevelopmental outcome.