What is hypothyroidism?
Hypothyroidism is a deficiency in thyroid hormone secretion and a reduction of action
of its hormones on the cells of the body. In children, there are two forms: (1)
congenital hypothyroidism, present at birth; and (2) acquired hypothyroidism, a
disease with an onset at any time after birth, usually after six months of age.
In each of these two forms, there are two categories: (1) primary hypothyroidism,
a failure of secretion by a damaged, defective, or absent thyroid gland; and (2)
hypothalamic/pituitary hypothyroidism, a failure of the mechanism that stimulates
the thyroid gland from the base of the brain, called the hypothalamus and the pituitary
The thyroid hormones are called thyroxine, or T4, and triiodothyronine, or T3. The
pituitary hormone that stimulates the thyroid gland is called thyroid stimulating
hormone, or TSH.
What causes hypothyroidism?
In most cases, the cause of congenital hypothyroidism is not known. A few cases
of inherited hypothyroidism are caused by mutations in the genes producing specific
proteins (known as enzymes) that are required to make thyroid hormones. These mutations
are inherited as autosomal recessive traits, i.e., the parents are unaffected, and
the child is affected because the child receives a mutation from each parent. The
parents have a one-in-four chance of having an affected child. Occasionally, a maternal
disease or a medication can interfere with the thyroid gland of the unborn child.
In certain areas of the world, a dietary lack of iodine causes hypothyroidism.
Most cases of acquired hypothyroidism are caused by autoimmune thyroiditis, a self-inflicted
destruction of the thyroid by the body's immune system. The processes that cause
this condition are poorly understood. An inappropriate immune response is directed
against the thyroid; the body does not recognize its own thyroid gland and generates
an immune response against the normal thyroid cells to cause inflammation, irritation,
or damage. Infrequently, surgical removal of the thyroid, certain medications or
chemicals, or damage by radiation treatment for cancer may cause hypothyroidism.
Who gets hypothyroidism?
In most cases, congenital hypothyroidism is sporadic. It occurs worldwide, once
in every 4,000 newborn infants, and affects girls twice as often as boys. In the
inherited forms, an equal number of males and females are affected. An infant born
to a mother with iodine deficiency, or an infant receiving, or exposed to a mother
given, excessive amounts of iodine for antiseptic reasons may have hypothyroidism.
The problem will continue until exposure to deficient or excessive iodine is corrected.
The majority of cases of acquired hypothyroidism occur in females with autoimmune
diseases. It may occur: (1) as autoimmune thyroid disease only; (2) in association
with other autoimmune diseases, such as insulin-dependent diabetes mellitus, alopecia
(hair loss), rheumatoid arthritis, and lupus erythematous; or (3) in association
with other diseases, such as Down syndrome and Turner's syndrome.
How does hypothyroidism cause disease?
Thyroid hormones regulate metabolism, i.e., the amount of energy that is available
for body functions. The production of proteins, especially those called enzymes,
is controlled by thyroid hormones. They regulate how much sugar is converted to
energy, how much protein is converted into muscle, and how much fat is stored and
available for energy. From early in fetal life through two to three years of age,
thyroid hormones acquired from the mother and those produced by the unborn child
in the second and third trimesters of pregnancy are essential for normal brain development.
What are the common findings?
The common findings of hypothyroidism are summarized in the table. The appearance
of a specific symptom and sign depends upon the age when hypothyroidism develops
and its severity. Often, the findings in a child may not be obvious to the parents
or the physician.
Table. Common findings of hypothyroidism.
Findings during first two weeks of life - Prolonged yellow jaundice - Swelling
of the eyelids, hands, and feet - Gestation more than 42 weeks - Birth weight more
than 4 kg - Poor feeding - Low body temperature - An enlarged, swollen abdomen -
Large midline fontanelles
Findings beyond age one month - Darkening and mottling
of the skin - Stressful, frequent, and labored breathing - Failure to gain weight;
poor sucking ability - Decreased stool frequency - Decreased activity and lethargy
Findings after age three months - Swollen and protuberant umbilicus - Infrequent
and hard stools - Dry skin with yellow coloration - Large tongue - Generalized swelling
- Hoarse cry
Findings between six months and three years - Deceleration of linear growth
- Coarse facial features - Dry skin with yellow coloration - Hoarse cry and large
tongue - Swollen and protuberant umbilicus - Enlargement of the arm and leg muscles
Findings during childhood - Slow growth and short stature - Delay in eruption
of teeth and in shedding primary teeth - Muscle weakness; enlargement of the arm
and leg muscles - Infrequent and hard stools - Dry skin with yellow coloration -
Generalized swelling - Early sexual development
Findings during adolescence
- Late onset of puberty - Slow growth and short stature - Delay in eruption of teeth
and in shedding primary teeth - Infrequent and hard stools - Dry skin with yellow
coloration - Discharge from the breasts (in girls) - Generalized swelling
How is hypothyroidism diagnosed?
For newborns in many areas of the world, there are routine, mandated screening programs
for congenital hypothyroidism. An elevated TSH on the newborn screening test requires
that a repeat TSH test be performed. Other tests are performed to define the cause
(inherited or sporadic) and the severity of hypothyroidism. In older infants and
children, hypothyroidism is suspected by: (1) the presence of a large thyroid gland,
or goiter, on examination of the neck; (2) a failure to maintain a normal rate of
growth in height; (3) the symptoms and signs of hypothyroidism (see table); (4)
a suspicion of it because members of the family have thyroid diseases; or (5) a
routine screening for TSH in children at increased risk for hypothyroidism.
Hypothyroidism is diagnosed by blood tests for TSH and free T4. An elevated TSH
is the most sensitive test for thyroid gland failure. A low free T4 is the diagnostic
test for hypothalamic/pituitary hypothyroidism, and, usually, it is low in primary
hypothyroidism, except in mild cases. Typically, the cause of thyroid gland failure
is autoimmune thyroiditis, which is diagnosed by finding thyroid antibodies from
a blood test. When the TSH value is increased and the T4 value is decreased, treatment
with thyroxine is started. Thyroxine treatment usually is started when the TSH value
is increased, yet the T4 value still is normal, as long as the cause of hypothyroidism
In patients with hypothalamic/pituitary hypothyroidism, there usually are other
pituitary hormone deficiencies, such as low levels of growth hormone (when the patient
is subjected to growth hormone secretion tests); low levels of the sex hormones
at the pubertal ages; and, less often, low levels of hydrocortisone and high levels
of prolactin, which is the pituitary hormone that stimulates the secretion of milk
in the mother after delivery.
How is hypothyroidism treated?
Treatment for hypothyroidism is easy and inexpensive. Typically, levothyroxine (L-thyroxine)
is prescribed, and the tablets should be given at least 30 minutes before a meal
or infant feeding. The daily dose per body weight steadily decreases from early
infancy to childhood to an adult dose in adolescence. Treatment must be individualized;
the amount that is absorbed and handled by the body differs among individuals. Careful
monitoring of blood tests (TSH and free T4 or T4) until the values are normal, and
then annually after three years of age once the tests become normal, is essential
for optimal management.
What are the complications?
There are no complications from L-thyroxine treatment when the proper dose is taken
and the blood tests are monitored on a regular basis. There are complications associated
with unrecognized or inadequately treated hypothyroidism, and the worst outcome
occurs if treatment is delayed in early infancy. Severe hypothyroidism before birth,
and a delay of treatment after birth, is associated with an impaired intellect (as
determined by IQ tests) and other neuropsychological abnormalities. After two or
three years of age, there are adverse effects of untreated hypothyroidism; however,
in most cases, they are reversible with adequate treatment.
Usually, if hypothyroidism is not adequately treated within approximately the first
6 to 12 months after its onset, a decrease in the rate of growth and, in many instances,
shortness of stature occur. If prolonged into the adolescent years, the final adult
height may be less than expected despite appropriate treatment. Prolonged hypothyroidism
also is associated with high levels of cholesterol, slowing of mental function and
school performance, an occasional episode of hip or knee pain from a slippage of
the growth center of the hips (usually requires surgical intervention), and chronic
constipation. Except for the normalization in growth, these abnormalities should
disappear with appropriate treatment.
How can hypothyroidism be prevented?
Hypothyroidism cannot be prevented unless it is caused by a nutritional deficiency
of iodine; excessive iodine intake; certain drugs, like lithium, that block the
ability of the thyroid gland to produce thyroid hormones; or drugs that impair the
absorption of thyroxine in those individuals who are taking it for hypothyroidism.
If taken with thyroxine, iron medications and high fiber in food will prevent the
absorption of thyroxine. Calcium tablets also may interfere with its absorption.
What research is being done?
In congenital hypothyroidism, research is being focused on the mutations that cause
the familial thyroid disorders, the cause(s) of the sporadic disease, and the effects
of maternal hypothyroidism on the unborn child. There is considerable interest in
discovering the mechanisms that cause autoimmune diseases, with a focus on autoimmune
thyroid diseases, the occurrence of diabetes mellitus in specific families with
autoimmune thyroid diseases, and an understanding of those antibodies that injure
thyroid cells and other antibodies that bind to and block the TSH receptor.
Links to other information
Familial Thyroid Diseases Including Hypothyroidism
Vassart G, Dumont JE, Refetoff S. Thyroid disorders. In: Scriver CR, Beaudet AL,
Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease.
New York: McGraw-Hill, 1995:2883-2928.
Fisher DA. Management of congenital hypothyroidism. J Clin Endocrinol Metab
Foley TP Jr. Congenital hypothyroidism. In: Braverman LE, Utiger RD, eds. Werner
and Ingbar's The Thyroid. 8th ed. Philadelphia: Lippincott-Raven, 2000:chap
82, part B, 977-983.
Foley TP Jr. Acquired hypothyroidism in infants, children and adolescents. In: Braverman
LE, Utiger RD, eds. Werner and Ingbar's The Thyroid. 8th ed. Philadelphia:
Lippincott-Raven, 2000:chap 82, part C, 983-988.
Foley TP Jr. Hypothyroidism. In: Hoekelman RA, Friedman SB, Nelson NM, Seidel HM,
Weitzman M, eds. Primary Pediatric Care. 4th ed. St. Louis: Mosby-Year Book,
Inc., 2000:chap 218. In press.
LaFranchi S, Dussault JH, Fisher DA, Foley TP Jr, Mitchell ML. Newborn screening
for congenital hypothyroidism: recommended guidelines. Pediatrics 1993;91:1203-1209.
About the Author
Thomas P. Foley, Jr. MD is Professor of Pediatrics in the School of Medicine
and Professor of Epidemiology in the Graduate School of Public Health at the University
of Pittsburgh and a member of the Medical Staff of the Children's Hospital of Pittsburgh
since 1971. Areas of scientific interest include (1) pediatric thyroidology with
specific interests in congenital hypothyroidism, acquired hypothyroidism, hyperthyroidism
and thyroid cancer; (2) auxology; and (3) international pediatrics with specific
interests in radiation-induced thyroid cancer associated with the Chernobyl accident,
autoimmune thyroid diseases, iodine deficiency disorders, newborn screening, toxicology
and the effects of maternal hypothyroidism on fetal development. My personal interests
are my family (wife, son and step-children), music (opera, classical music and traditional
bluegrass music as lead vocal and guitar for The Allegheny River Boys, Revonah RS-506,
1978), sports (spectator and participant) and humanitarian assistance for children
and child health through Child Health International (web site of a subsidiary: trfn.clpgh.org/orgs/bach).
Copyright 2012 Thomas P. Foley, Jr., M.D., All Rights Reserved