Last Updated:
Dec 2005

The Thyroid and Down Syndrome

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by Len Leshin, MD, FAAP

Copyright 1996-98, All rights reserved

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Normal Function

The thyroid gland sits at the base of the front of the neck and makes thyroid hormone from iodide, thyroglobulin and tyrosine. This results in the production of thyroxine (T4), which is a "prohormone" (it's inactive but just one step away from becoming a real hormone), and the actual thyroid hormone, T3. Both T3 and T4 are secreted by the thyroid into the blood stream. T4 is converted to T3 by the thyroid, kidneys, and liver. And it's the T3 that's so important for normal growth and development of infants and children, and normal metabolism of all ages.
Send Me Email So where does the Growth Hormone (GH) fit in? The GH, synthesized in the part of the brain called the pituitary, appears to be the mediator between the thyroid hormone and the individual tissues. You can also include somatomedins, a group of proteins under the control of GH, as mediators between T3 and body tissues.

Thyroid function is controlled by Thyroid Stimulating Hormone (TSH), a hormone made in the hypothalamus and pituitary. If the brain detects that T3 levels are low, more TSH is made which tells the thyroid to make more T4 and T3. If levels are too high, the brain slows down making TSH.



This is the state of not making enough thyroid hormone, and is the most common thyroid problem associated with DS. This can be present at birth (congenital) or may occur at any age (acquired). Every state in the US and many other countries routine screen all newborns for hypothyroidism. In newborns and infants with DS, the most common reason for hypothyroidism is that the thyroid did not form correctly in the fetus. In acquired hypothyroidism, the most common reasons in toddlers and older children with DS is (1) autoimmunity (where the body makes antibodies against its own thyroid) and (2) thyroiditis, where the thyroid tissue becomes replaced with white blood cells and fibrous tissue (Hashimoto thyroiditis).

The symptoms of low thyroid hormone are difficult to pick up, especially in infants. They include decreased growth, decreased development, an enlarged tongue, decreased muscle tone, dry skin and constipation -- all of which might be expected in an infant with DS. So, it is recommended that all infants with DS be checked at birth, 6 months of age, 1 year of age, and once a year thereafter for thyroid function, regardless of their growth.

Screening for thyroid function in infants usually involves only a TSH level; if the TSH is elevated, then the T4 will be checked. In older infants and children, a T4 and TSH is recommended, and some doctors include a measurement of T3 as well. Typically in hypothyroidism, the T4 will be low and the TSH will be elevated (as the brain is trying to tell the thyroid to get going).

Some infants and young children have blood tests that show a normal T4 but a high TSH. This condition is called "idiopathic hyperthyrotropinemia." While the cause isn't clear, this may reflect a regulatory defect of TSH, or it may be a sign of impending true hypothyroidism. Some endocrinologists will recommend retesting in 3 to 6 months, and others will recommend treating as if it were an early hypothyroid state.

Treatment is the replacement of thyroid hormone with synthetic thyroxine. The dose is managed by watching sequential blood tests to see how the thyroid responds. Treatment is usually needed for life. It should be noted that if the parents have become used to a calm, sedate child who is hypothyroid, the replacement will look as if the child has suddenly become hyperactive, when in fact the child is returning to his or her "natural" state.

Since T3 is the active hormone and the body converts T4 (thyroxine) to T3, a common question is why we supplement with T4 instead of T3. T3 has a very short life span in the body while T4 has a longer life span. People who take only T3 must take it several times a day, while T4 can be given just once a day. There are some preparations available that combine T3 and T4, such as Thyrolar®. A combination medication may be useful for people who have hypothyroidism but do not get satisfactory results with T4 alone. An older version of combined T4 and T3 under the name of Armour® is still available, and is made from thyroids from pigs; this used to be the most common treatment of thyroid disease before the individual thyroid hormones were determined. Animal thyroid isn't used much now due to the better results obtained from the synthetic versions.

For recent studies on hypothyroidism in Down syndrome, see the abstracts for May 2005 and August 2005



While not anywhere near as common as hypothyroidism, this condition does occur. The usual cause is, again, autoimmune disease, but in hyperthyroidism, the immune system cranks up the thyroid. (This is called Graves Disease.) Symptoms include rapid heart rate, nervousness, sweating, decreased attention span, flushed skin, always feeling hot and loss of hair. Often these children will have a noticeably enlarged thyroid.

Testing here includes TSH (low), T3 (elevated) and T4 (elevated).

There are three possible treatments of hyperthyroidism. One treatment is aimed at blocking the action of the thyroid hormone on body tissues. This involves the use of antithyroid drugs, and are often the first treatment used. However, almost all of these drugs can cause significant side effects. A second treatment is surgery to remove part or all of the thyroid; and then the child or adult is begun on thyroid replacement if needed. The third treatment is the use of radioactive iodide, which destroys the thyroid's ability to produce thyroid hormone. The patient then takes replacement thyroid hormone. However, radioactive iodide is not often used in children because of the risk of thyroid carcinoma.

At the present time, there is no clear consensus on the best way to treat hyperthyroidism in children with DS.


Thyroid, DS and Controversy

Before the genetic reason of Down Syndrome was known, many people thought that DS was caused by hypothyroidism. In 1896, 20 years after Langdon Down first described "mongoloids," Telford Smith reported that giving thyroid therapy improved physical and mental conditions of these children. For decades later, researchers argued if all children with DS had hypothyroidism or not. With improved lab tests, the true picture emerged of most children with Down syndrome having normal thyroids.

There have been many claims for giving all children with DS thyroid hormone replacement, regardless of their blood tests. Dr. Turkel included thyroid hormone in his "U" series, Harrell's paper in 1981 on vitamin and mineral replacement included thyroid hormone therapy, and one researcher, Clemens Benda, advocated giving all children with DS a mixture of thyroid and pituitary gland. However, there is no known benefit from giving thyroid hormone to children with DS who have normal thyroid function, and could be detrimental.

Some researchers have claimed that there is a "low-borderline" thyroid state, and the thyroid tests could be normal as the body is able to partially compensate. However, research shows that giving thyroid replacement to individuals with DS and low-normal thyroid tests had no cognitive improvement.

Other people have latched on to a condition called Wilson's syndrome, called after the Dr. Wilson who first described it. Dr. Wilson believes that thyroid disease can be present with normal blood test, and evidenced by a low blood temperature and a collection of signs and symptoms, and then treated with a special thyroid replacement product. This has little to do with Down syndrome, except that some people have recently come forward claiming that hypothyroidism in people with DS may not be picked up with routine blood tests. In reality, there is no scientific evidence supporting these claims. For more information on this topic, see the American Thyroid Association's statement on Wilson's syndrome.


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