Key Points
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The thyroid gland is part of the endocrine system. It is a gland that is in the neck.
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Thyroid function affects or has an impact on many body functions and, therefore, abnormal thyroid function can cause many body and mind changes.
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Hypothyroidism (underactive thyroid) is much more common in people with Down syndrome compared to people without Down syndrome.
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Hyperthyroidism (overactive thyroid) is also more common in people with Down syndrome but not as common as hypothyroidism.
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When assessing thyroid function in people with Down syndrome, it is important to review symptoms that may be associated with thyroid function and to do lab tests.
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Hypothyroidism is typically treated with thyroid replacement medication (pills).
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Hyperthyroidism can be treated with pills but sometimes is treated with radioactive iodine or surgery.
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Thyroid gland
The thyroid gland is part of the endocrine system. The endocrine system consists of glands that produce hormones - chemical messengers that transport a signal from one cell to the other and affect the function of the receiving cell. When something goes wrong with a gland, the level of hormones made by that gland increases above or decreases below normal levels. This leads to endocrine disorders that can have a wide variety of symptoms.
The thyroid gland sits in the anterior (front) of the neck just below the Adam's apple. It is described as having a butterfly shape.
The thyroid has many important functions including:
How is thyroid function measured?
In the endocrine system, endocrine glands can affect the function of other endocrine glands. In the case of the thyroid, it is linked via hormones to other endocrine glands including the pituitary gland and the hypothalamus in the brain. Understanding the hormones that each secretes is helpful to understand the blood tests used to assess thyroid function. The figure below shows the interactions among the 3 glands.
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The human body produces two types of thyroid hormones - T3 (triiodothyronine) and T4 (thyroxine). T4 is converted to T3 in cells of the body, much of it in the liver. T3 is more active than T4 but, because changes are noted in T4 first, T4 is the thyroid hormone usually measured. T3 is occasionally measured, more commonly in assessing hyperthyroidism.
The thyroid gland is stimulated to make these hormones by thyroid stimulating hormone (TSH), which is made in the pituitary gland in the brain. TSH is the other commonly measured hormone to assess thyroid function.
The hypothalamus in the brain releases TSH-releasing hormone (TRH) that signals the pituitary gland to release TSH. Typically, when there is enough thyroid hormone (T3 and T4) present in the body, the thyroid hormones loop back to the hypothalamus to decrease TRH production and to the pituitary gland to reduce TSH production. This in turn reduces T3 and T4 production by the thyroid gland. TRH is less commonly measured because abnormal secretion of TRH is less common.
The following are possible patterns of TSH and thyroid hormones:
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normal TSH, normal thyroid hormones - normal thyroid function
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elevated TSH, low thyroid hormones - hypothyroidism (due to thyroid dysfunction)
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low TSH, low thyroid hormones - hypothyroidism (due to decreased pituitary production of TSH)
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high TSH, normal thyroid hormones - borderline (or subclinical or compensated) hypothyroidism
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low TSH, elevated thyroid hormones - hyperthyroidism
*We are sometimes asked if fasting is required for thyroid blood tests. Fasting (not eating for 8-12 hours before the test) is not typically required for thyroid blood testing. However, often other tests may be drawn at the same time and some of these tests may require fasting. It is acceptable to fast for a thyroid blood test if fasting is required for other tests.
Hypothyroidism
An underactive thyroid (hypothyroidism) is a common issue that affects many people with Down syndrome. In our practice, about 40% of the individuals we have cared for have hypothyroidism, which is about 11 times the rate in those without Down syndrome.
When do people with Down syndrome develop hypothyroidism?
People with Down syndrome, like people without Down syndrome, can develop hypothyroidism at any time of life. Some infants, including infants with Down syndrome, are born with hypothyroidism. That is why all newborns in the United States are tested for hypothyroidism shortly after birth. People with Down syndrome may also develop hypothyroidism later in their lives.
Why do people with Down syndrome develop hypothyroidism?
People with Down syndrome have more autoimmune conditions. Autoimmune conditions occur when the immune system is stimulated in such a way that it "attacks" parts of the body. Hashimoto's thyroiditis, an autoimmune condition, occurs when the immune system attacks the thyroid. This can cause hypothyroidism. It can also sometimes cause hyperthyroidism (overactive thyroid), which is discussed in the next section. When enough of the thyroid is damaged, the function of the thyroid drops into the subnormal range. This is the most common reason for hypothyroidism in people with Down syndrome.
Another cause of hypothyroidism is lack of iodine in the diet. This is much less common in the United States since iodine was added to table salt. However, theoretically, this may resurface as a cause of hypothyroidism as more non-iodized salt products are available and used.
Additional infrequent causes of hypothyroidism include dysfunction related to x-ray/radiation injury, surgical injury, medication side effects, and pituitary or hypothalamic disorders.
Symptoms and signs
Common symptoms of hypothyroidism include:
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Weakness
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Dry skin
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Fatigue
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Slowing of speech
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Mood changes, depression
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Puffy eyelids
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Increased sensitivity to cold temperatures
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Decreased ability to sweat
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Cold skin
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Thickened tongue
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Puffiness of the face
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Weight gain
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Coarse hair
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Pale skin
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Anemia
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Forgetfulness or difficulty with the thinking process
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Constipation and decreased rate of food passing through the GI tract
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Disturbances with menstruation in women
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Lower heart rate
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When severe, difficulty with breathing
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Change in sleep
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Change in sexual function
Early signs of these problems can be difficult to detect in people with Down syndrome, as some of the symptoms, such as dry skin, often occur in people with Down syndrome who do not have thyroid problems.
Screening
Because many of the signs and symptoms of hypothyroidism are common in people with Down syndrome even when they do not have hypothyroidism, just watching for symptoms is a difficult way to assess thyroid function in people with Down syndrome. For this reason, regular thyroid testing is recommended. Measuring thyroid function is relatively easy with blood testing. Screening can be done through thyroid blood tests of TSH and possibly T4 (and less commonly T3).
The GLOBAL Medical Care Guidelines for Adults with Down Syndrome recommend screening adults with Down syndrome for hypothyroidism every 1 to 2 years using a TSH test beginning at age 21. The American Academy of Pediatrics recommends at least annual screening up to age 21.
The screening is for hypothyroidism, but it will also find hyperthyroidism if it is present. However, hyperthyroidism is less common than hypothyroidism, so the guidelines are based on screening for hypothyroidism.
Treatment
If hypothyroidism is identified through testing of TSH (and possibly T4 and T3), it is important to correct the thyroid function. Treatment of hypothyroidism most commonly involves using synthetically prepared medications (e.g., levothyroxine, Synthroid, Levoxyl) to replace the body’s decreased thyroid hormone. The starting dose can be calculated based on the patient’s weight or based on nationally recognized “middle-of-the-road” doses such as 75 or 88 micrograms (for adults).
Important side effects to keep in mind with the medications are that they can increase the heart rate and the blood pressure. These side effects need to be monitored in people with high blood pressure, heart problems, or who are older in age. Some individuals become anxious when first starting the medication. Sometimes it is beneficial to start on a lower dose than will be expected to completely treat hypothyroidism to avoid these symptoms. The dose can be increased over several months.
The TSH (and possibly T4 and T3) level should be checked 6-8 weeks after starting the medication or changing the dose to document that normal hormone levels are achieved. If normal levels have not yet been reached, the dose should be adjusted, and the blood test should be repeated in another 6-8 weeks.
After the appropriate dose of medication has been achieved, the person will usually need to take the medication for the rest of their life. Usually, the person’s primary health care provider can appropriately manage hypothyroidism. In more complicated or difficult-to-manage cases, a referral to an endocrinologist may be necessary.
Once the medication brings hormone levels back to normal, the symptoms of hypothyroidism usually improve. However, as mentioned, many of the symptoms of hypothyroidism are also characteristic of people with Down syndrome. These concerns may improve but usually do not disappear. For example, dry skin is a symptom of hypothyroidism but also a common characteristic of Down syndrome. Treating hypothyroidism may improve the dry skin but probably will not resolve it.
Testing should be done any time there is a sudden onset or change in any symptoms that could be due to hypothyroidism, particularly if they are serious enough to interfere with the person's daily life.
Some individuals with Down syndrome do not seem to be able to tolerate the dose that normalizes the blood tests. For example, some individuals will become anxious, as if they have hyperthyroidism, when they go from thyroid function that is too low to normal levels (based on blood work). Sometimes, as noted above, starting the dose in a range that is sub-therapeutic (below what is expected to be the ultimate effective dose) and increasing the dose slowly over time helps. In other individuals, we have infrequently found that they only tolerate doses that are below that which is required to return the blood tests to the normal range. Their thyroid function is improved but not normalized but that is the best they can tolerate.
In the uncommon situation in which hypothyroidism is caused by iodine deficiency, adding iodine to the diet can treat the underactive thyroid. This is often addressed by adding iodized salt to the diet. Iodine-containing foods such as codfish, seaweed, and cranberries are an option as are iodine supplements. Another mineral, zinc, supports thyroid function. Zinc supplements or eating foods rich in zinc such as meat, seafood, nuts, seeds, and whole grains can increase zinc levels in the body. In our experience, for someone that has hypothyroidism, taking zinc supplements might be helpful but not enough to avoid taking thyroid hormone (levothyroxine, Synthroid, Levoxyl, etc.).
Sometimes a combination of T4 and T3 thyroid hormones is prescribed. Common names for this product are Armour thyroid or natural thyroid. While the T4-only products (e.g., levothyroxine) are most often prescribed and recommended, some individuals report they feel better if they take Armour thyroid rather than levothyroxine. Endocrinologists often report that it is more difficult to manage or regulate thyroid function with Armour thyroid, and our experience in people with Down syndrome is similar. While we more commonly prescribe a T4-only product like levothyroxine, some individuals with Down syndrome report they feel better on Armour thyroid, and we are successfully treating some individuals with it.
Borderline hypothyroidism
Borderline hypothyroidism (also called subclinical hypothyroidism or compensated hypothyroidism) is often seen in individuals with Down syndrome. In this condition, the level of TSH is high, but the T4 and/or T3 are not decreased. In hypothyroidism, usually the T4 and/or T3 are low. As noted above, the low level of the T4 and/or T3 loops back to the brain to signal it to raise the level of TSH, which functions to stimulate the thyroid to make more T3/T4. However, the significance of the situation in borderline hypothyroidism with the elevated TSH but normal T3 and T4 is less clear.
Endocrinologists disagree about treatment for borderline hypothyroidism. Some think it should be treated with thyroid hormone. Others think it should just be monitored. One reason for the uncertainty is that it is not uncommon for people with Down syndrome to have a slightly high TSH level (with normal T3/T4) and then later, without treatment, the TSH can become normal.
We typically approach borderline hypothyroidism in this way:
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If the person has symptoms consistent with hypothyroidism, treat with thyroid hormone.
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If the TSH is more than a little elevated, treat with thyroid hormone, even if the person does not have symptoms of hypothyroidism. For example, if normal is 1-5, consider treating if TSH is greater than 10.
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Consider drawing blood to test for thyroid antibodies (anti-thyroglobulin and anti-microsomal antibodies). An elevation of these antibodies is consistent with the person having Hashimoto's thyroiditis, and the anticipated ongoing autoimmune "attack" on the thyroid is likely the cause of the thyroid dysfunction. If people with Down syndrome who have an elevated TSH and normal thyroid hormone levels (T3/T4) also have elevated antibodies, they are likely to develop hypothyroidism (elevated TSH and low thyroid hormones). It is reasonable to consider treating for hypothyroidism if the antibodies are elevated, the TSH high, and the thyroid hormone (T3/T4) normal.
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Particularly if none of the above are present (the person does not have symptoms, the TSH is not significantly elevated, and the antibodies are normal/negative), regular monitoring is a reasonable approach. More frequent monitoring (every 3 to 6 months) may initially be considered, but if the thyroid normalizes or remains stable with borderline hypothyroidism, annual monitoring may again be appropriate. However, if the symptoms of hypothyroidism do occur, a repeat blood test should be considered at that time.
Hyperthyroidism
Hyperthyroidism (overactive thyroid) is a little more common in people with Down syndrome than in people without Down syndrome, but nowhere near as common as hypothyroidism. In our practice, about 2.5% of the individuals have been diagnosed with hyperthyroidism.
In the early stages of Hashimoto’s thyroiditis, the thyroid may be overactive initially. Sometimes it later “burns out” and becomes underactive (hypothyroidism). Grave’s disease, another autoimmune disorder, can also cause hyperthyroidism.
Symptoms and signs
Symptoms of hyperthyroidism include:
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Nervousness, anxiety
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Increased sweating
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Heat intolerance
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Palpitations (a sense of an abnormal or fast heart rate - usually noted as above 100 beats per minute or higher than usual for the person)
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Fatigue and weakness
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Weight loss
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Increased appetite
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Tremor
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Emotional lability (frequent mood swings)
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Sleep disturbance (often sleeping less or more restlessly)
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Thyroid eye disease
Diagnosis
Diagnosis of hyperthyroidism is made based on blood tests (a low TSH level and high T4 and/or T3). Additional diagnostic testing may include an I-123 thyroid scan. This test involves injecting a small amount of radioactive iodine into the bloodstream and then doing a scan. This is a painless test, except for the IV used to inject the iodine. This scan can help look for abnormal nodules and assess thyroid function. If any suspicious nodules are found on the thyroid during the physical exam or on the scan, an ultrasound and a fine needle aspiration (biopsy) may be recommended to assess for cancer in the nodule. If necessary, the skin can be “numbed” with local anesthetic. In some cases, the person may need to be sedated to allow this test to be done.
Treatment
Treatment for hyperthyroidism may include medications to treat symptoms and/or medication or other modalities to reduce thyroid hormone (T4 and T3).
Medications known as beta blockers are used to treat symptoms. Propranolol (Inderal) is recommended most often. It does not reduce the thyroid function, but it does reduce the symptoms. It is usually used temporarily while another treatment is being implemented to reduce thyroid hormone.
Medications to reduce thyroid hormone (and function) include methimazole (Tapazole) and propylthiouracil (also referred to as PTU).
People taking these medications should have complete blood count (CBC) and liver blood tests done to monitor for side effects. Possible side effects include a decrease in red and white blood cells and platelets and toxicity (damage) to the liver.
Some individuals develop thyroid eye disease due to hyperthyroidism causing inflammation behind the eye that pushes the eyeball forward (proptosis). In addition to treating the overactive thyroid function, additional treatments include steroids (e.g., prednisone) and teprotumumab-trbw (Tepezza).
If medications alone cannot control the thyroid hormone, other treatments include:
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Ablating (destroying) the thyroid gland with an injection of radioactive (I-131) iodine.
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Surgically removing the thyroid. This would be the choice if the thyroid was enlarged and causing serious symptoms, such as compressing the airway.
If the thyroid is removed or destroyed, the person will have to take medication for hypothyroidism (levothyroxine, Levoxyl, Synthroid).
In many of the individuals we have treated for hyperthyroidism, the thyroid eventually “burns out” and the thyroid becomes underactive (hypothyroidism). Therefore, for many, the treatment for hyperthyroidism has been temporary, although it may need to continue for months to even years. Eventually, many have developed hypothyroidism.
Conditions that change thyroid hormone requirements
Advanced age and malnourishment
As a person with Down syndrome ages, often the medication dose can be decreased because of changes associated with the aging process. Another important consideration for people with Down syndrome is the risk of malnourishment. Certain conditions can increase the chances of a person with Down syndrome developing malnourishment including uncontrolled celiac disease, gastroesophageal reflux disease (GERD), and loss of appetite due to Alzheimer’s disease. All these conditions can decrease the dose of thyroid medication that the individual needs.
Medication side effects
Some medications decrease the availability of thyroid hormone for use by the body, while others cause the hormone to be used more quickly.
Medications that may decrease the hormone level (larger dose of thyroid medication may be needed):
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Lithium
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Iodine-containing medications
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Amiodarone (Cordarone)
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Sucralfate (Carafate)
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Iron supplements
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Cholestyramine (Questran)
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Colestipol (Colestid)
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Antacids with aluminum
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Calcium supplements
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Rifampin (Rifaidin)
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Phenobarbital
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Carbamazepine (Tegratol)
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Warfarin (Coumadin)
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Oral anti-diabetic medications
Medications that may increase the hormone level (smaller dose of thyroid medication may be needed):
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Furosemide (Lasix)
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Mefenamic acid (Ponstel)
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Aspirin
Additionally, some substances do not affect the thyroid hormone function but alter the tests. An example is the vitamin biotin that can affect the TSH, T4, and/or T3 levels.
Additional information
Does TSH Tell the Whole Story? (article)
Prevalence of Endocrine Disorders Among 6078 Individuals with Down Syndrome (medical journal article)
Taking My Thyroid Medication (visual)
Thyroid, Weight, and Metabolism (article)
Original article written by Ima V. Jonkheer, DO, in July 2017. Article updated by Brian Chicoine, MD, in April 2024.