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 gland.
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.
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.
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.
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.
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
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 is known.
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.
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.
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.
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.
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.
- American Thyroid Association www.thyroid.org
- Complete textbook available entitled "The Thyroid and Its Diseases" www.thyroidmanager.org
- Lawson Wilkins Pediatric Endocrine Society www.lwpes.org
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 1991;72:523.
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.
Copyright 2012 Thomas P. Foley, Jr., M.D., All Rights Reserved
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