Hypothyroidism in Children: What Causes it?
In my last posting, I discussed how easy it is (usually) to diagnose hypothyroidism. I did not even mention what causes the condition. Probably the easiest way to think about causes is to divide them into those due to some problem within the thyroid gland itself and those caused by problems that affect an otherwise normal gland.
Problems within the thyroid gland: congenital hypothyroidism
Congenital hypothyroidism affects about one in every 5000 newborns. In most instances, the condition is the result of some mix-up in utero that affects development of the gland. Most often the gland is simply mssing or just a small remnant. Sometimes there is a gland, or part of a gland, but it is ectopic; the gland normally migrates from the base of the tongue down the neck to its usual location, but once in a while it “parks” before it gets to where it is supposed to go- sometimes still at the base of the tongue which is called a lingual thyroid. Anyway, congenital hypothyroidism is very important to detect and to detect quickly since hypothyroidism can cause irreversible brain damage during the first two years of life. It is not surprising that all 50 States in the U.S. require newborn screening for hypothyroidism. Treatment is easy- just a little pill every day for life (if you are wondering, the pill is crushed up and given with liquid in infants). A delay in treatment for even a month or two can be disasterous.
The typical form of congenital hypothyroidism is not considered genetic and we actually do not know what causes it. Rarely, congenital hypothyroidism is due to a genetic disorder. For example, some people have thyroid glands but are unable to make thyroid hormones. There are a number of steps in the formation of thyroid hormone and abnormalities in each of the steps have been described. The most common of these genetic causes of congenital hypothyroidism is called Pendred syndrome and was first described in a Swiss family. In this syndrome, congenital hypothyroidism is associated with deafness. Generally it is easy to tell if a newborn infant with congenital hypothyroidism has an abnormality in thyroid hormone synthesis- the thyroid gland is enlarged. Anyway, the treatment is exactly the same whatever the cause of the hypothyroidism.
Occasionally we do see congenital hypothyroidism that is transient; examples would include hypothyrpoidism due to a medication the mother took during pregnancy (e.g., medications to treat maternal hyperthyroidism, ingestion of large amounts of iodine during the pregnancy).
Chronic lymphocytic thyroiditis
By far the most common cause of hypothyroidism after the newborn period is chronic lymphocytic thyroiditis, or Hashimoto’s thyroiditis as it is usually called. This condition is an autoimmune disorder, where the body’s immune system attacks this or that part of the body. In this instance, the autoimmune process directs lymphocytes, a type of white blood cell, to attack the thyroid gland. In some instances this leads to complete destruction of the gland; in other cases, the gland shows only minor damage and its ability to crank out normal amounts of thyroid hormones is unaffected. I have made the diagnosis in children as young as 6 months of age, but typically the disorder is found much more often in older children and adults. The thyroid gland is usually enlarged but rarely tender. The diagnosis is usually easy to make once suspected; blood levels of free T4 and TSH (as discussed in my last posting) and thyroid antiperoxidase antibodies. The presence of the thyroid antibodies in the blood test pins down the diagnosis even if the free T4 and TSH are normal.
The condition is seen quite frequently in certain medical conditions including type 1 diabetes mellitus (about 25-30% of patients), the Turner syndrome (about 50% of patients), and Down’s syndrome (about 40% of patients). It is much more common in females than males as are all thyroid disorders except for thyroid cancer and congenital hypothyroidism. Treatment is generally simple- a small pill every day.
Other causes of hypothyroidism due to problems within the gland
There are many other causes of hypothyroidism but they are relatively rare compared to congenital hypothyroidism and Hashimoto’s thyroiditis. For example, subacute thyroiditis is a condition that can cause hypothyroidism. Typically, people develop pain and swelling in the thyroid gland which generally subsides over 2-3 months. Hypothyroidism is transient, lasting only a month or so and people with the condition often present with evidence of an overactive thyroid gland early on: the damaged gland releases large amounts of stored thyroid hormone. So the “classic” pattern is early hyperthyroidism leading to hypothyroidism after a few weeks, and eventually, back to normal. Much is written about this condition in endocrinology textbooks. I confess that I am not sure if I ever saw a single case in a child during the past 40 years.
Other causes of hypothyroidism include certain drugs, iodine deficiency (basically unheard of in the U.S.), and consumption of certain foods such as large amounts of soybean products: soy products inhibit absorption of iodine which is critical for thyroid hormone synthesis. Nowdays there is so much iodine in our diets (e.g., salt, bread) that even aggressive tofu eaters need not worry (in the 1940s when soy milks were first introduced for baby formulas, there was an “epidemic” of iodine-deficiency goiters- a goiter just means enlargement of the thyroid gland. The problem was sorted out very quickly and eliminated by adding iodine to soy milk formulas.
Hypothyroidism caused by problems outside the thyroid gland
Just for completeness, you should know that hypothyroidism can be caused by problems in the messenger system that controls how much throid hormone the gland produces. Up in the brain, the hypothalamus normally sends a hormone signal, thyrotropin-releasing hormone or TRH to the pituitary gland which in turn sends a hormone signal, thyrotropin, or thyroid-stimulating hormone or TSH to the thyroid gland (it’s not as complicated as it may seem). If there is anything wrong with this signalling system in getting the proper message to the thyroid gland, the person will develop hypothyroidism. This is called secondary hypothyroidsim to distinguish it from primary hypothyroidism, where the problem is with the thyroid gland itself. Typically causes of seconary hypothyroidism include a variety of brain tumors, radiation to the brain, head trauma, and hypopituitarism (often with a variety of hormone deficiencies which we will discuss in a future posting).
It is generally easy to diagnose secondary hypothyroidism ,although maybe not so easy to determine the underlying cause: blood levels of free T4 will be low and the TSH normal or low. It is important to measure the free T4 not just the “total T4” since the latter can be affected by the levels of the serum proteins that carry most of the circulating thyroid hormones; if the serum proteins that carry thyroid hormones are low, the total T4 level will be low but the free T4 level will not be affected. Now that we have reliable free T4 assays, life is good for pediatric endocrinologists.