Late Effects to the Thyroid Gland

By Nancy Keene and Kevin Oeffinger MD
Source: Spring 2001 CCCF Newsletter

Treatment for childhood cancer sometimes damages the thyroid gland. Fortunately, late effects to the thyroid are usually very easy to treat. It is therefore important to find out if you are at risk and ensure that you get the appropriate tests so that any problems are identified early and treated appropriately.

What is the thyroid gland?

The thyroid is a small butterfly-shaped gland located in front of the trachea in the lower part of the neck. An exquisitely sensitive gland, it enlarges and becomes more active during puberty, pregnancy, or times of great stress. It also alters its size and shape during women's menstrual cycles.

Some glands produce substances called hormones, a term derived from the Greek word hormaein which means "to excite." Hormones are released in tiny amounts but they travel throughout the body to orchestrate complicated processes like growth, puberty, reaction to stress, temperature regulation, and urine output. Disruptions in the balance of these chemical messengers can profoundly affect both health and quality of life.

Two hormones secreted by the thyroid gland, thyroxine (T4) and triiodothyronine (T3), have far-reaching effects on almost all tissues in the body and are intimately involved in physical growth, metabolism, and mental development. Simplistically, the thyroid hormones, T3 and T4, can be thought of as regulators of our metabolism. Thus, when the thyroid hormones are low, the body's metabolism slows, resulting in fatigue, a lowered heart rate and blood pressure, slowing of the intestines leading to constipation, and a constant feeling of being cold. Conversely, when one or both of the thyroid hormones is high, the body's metabolism is increased, resulting in an increased heart rate and blood pressure, increased activity of the intestines leading to diarrhea, and a constant feeling of being hot.

The pituitary, a gland in the brain, makes a chemical called thyroid-stimulating hormone (TSH) which travels in the blood stream to the thyroid. As you might guess from the name, thyroid-stimulating hormone stimulates the thyroid gland to make the thyroid hormones, T3 and T4. When levels of T3 and T4 are low, then the brain increases the production of TSH which in turn tries to make the thyroid gland produce more T3 and T4. Conversely, if the level of either T3 or T4 is too high, the brain senses this and decreases the production of TSH which leads to less production of T3 and T4.

The possible late effects

The thyroid is generally not affected by chemotherapy. If damage occurs, radiation is usually the culprit. Several types of thyroid problems can develop after radiation.

Primary hypothyroidism. (primary = damage at the thyroid gland; hypo = low; thyroidism = disease of the thyroid) can occur from damage to the thyroid gland caused by radiation. In this type of hypothyroidism, the TSH is elevated because the brain is trying to make the thyroid produce more T3 and T4. If you received more than 1500 cGy of radiation to the neck or more than 750 cGy total body irradiation (TBI), you are at risk. This includes survivors of Hodgkin's disease, non-Hodgkin's lymphoma, head and neck tumors, or those who had TBI prior to a bone marrow transplant. Hypothyroidism sometimes occurs in patients treated with cranial or craniospinal radiation for leukemia.

While less than one percent of children with leukemia treated with 1800 cGy of cranial radiation develop hypothyroidism, 40 to 90 percent of Hodgkin's patients who receive mantle radiation and up to 50 percent of bone marrow transplant patients do. Treatment at a young age may also increase the likelihood of developing a thyroid problem.

Thyroid dysfunction (dys = abnormal) can occur soon after radiation, but generally does not occur until several years later.

Secondary hypothyroidism. (secondary = damage in the pituitary gland/brain) is an uncommon late effect caused by radiation damage to the pituitary gland which results in a decreased production of TSH. Thus, in this type of hypothyroidism, the TSH and T4 levels are low.

Compensated hypothyroidism. A mildly elevated TSH and normal T4 may occur if your thyroid is working too hard. There are usually no symptoms. An overstimulated gland is at increased risk for developing tumors, both benign and malignant. Survivors with compensated hypothyroidism are sometimes given supplemental thyroid hormone to allow the gland to rest.

Hyperthyroidism. (hyper = high) occurs when too much T3 or T4 are produced causing the body to use energy faster than it should. This late effect is not well understood but has been found in very small numbers of survivors who were treated with neck radiation.

Thyroid cancer. Radiation to the neck can result in thyroid cancer later in life so all survivors at risk need life-long evaluation of thyroid function.

What are the symptoms of thyroid damage?

Signs and symptoms of an underactive thyroid (hypothyroidism) can include:

Fatigue or lethargy
Hoarseness
Difficulty concentrating
Depression or mood changes
Constipation
Weakness
Intolerance to cold
Swelling around the eyes
Poor growth
Delayed puberty
Puffy face and hands
Weight gain
Dry or rough skin
Brittle hair
Joint or muscle aches
Slow heart rate
Low blood pressure
High cholesterol
Decreased tolerance for exercise

The signs and symptoms of an overactive thyroid (hyperthyroidism) can include:

Nervousness or anxiety
Difficulty concentrating
Fatigue
Muscle weakness or tremor
Rapid or irregular heartbeat
Excessive perspiration
Heat intolerance
Diarrhea
Weight loss
Menstrual irregularities
Protruding eyes
Tenderness in the neck
Decreased tolerance for exercise

Signs and symptoms of thyroid cancer

Thyroid cancer is generally a slow growing cancer without a lot of signs or symptoms. Usually, a painless, hard mass (lump) in the thyroid gland can be felt. One might also experience hoarseness, problems with swallowing, enlarged lymph nodes in the neck and difficulty breathing.

What follow up is needed for those at risk?

Your T4 and TSH levels should be checked every year after radiation to the chest, neck, or head and any time symptoms develop. These are simple blood tests. At your yearly follow-up appointment, your thyroid should be palpated (felt by hand) and your growth (if you are a child or teen) should be plotted on a chart.

In some facilities, radioactive iodine uptake by the thyroid is measured. The benefit of screening with periodic ultrasound of the thyroid every 1 to 3 years is controversial and is currently being studied. Thyroid problems can occur years or decades after treatment for cancer, so a yearly check is necessary for the rest of your life if you are at risk. If any abnormalities are detected during an examination, referral and follow-up by an endocrinologist or surgeon may be necessary.

How is damage to the thyroid treated?

Your healthcare provider should talk to you about the signs and symptoms of thyroid problems so that you will recognize them if they develop. Although thyroid problems are common in survivors who had radiation to the head and neck, treatment generally is easy and effective.

  • Primary hypothyroidism (high TSH, low or normal T4): To make one euthyroid (normal thyroid level), a daily pill of levothyroxine, a synthetic form of thyroxine, is used to replace what the thyroid gland is not making. Common brand names of this medication include Synthroid, Levoxyl, Levothyroid, and L-thyroxine. Treatment is for life!!! Some survivors to want to avoid taking medications, and so get tired of taking a daily pill. Stopping the medication will result in redeveloping the symptoms of hypothyroidism.
  • Compensated hypothyroidism (mildly elevated TSH, normal T4): Daily pill of levothyroxine may be used to suppress excessive gland activity.
  • Thyroid-stimulating hormone deficiency (low TSH, low T4): Daily levothyroxine.
  • Hyperthyroidism (low TSH, high T3 or T4): The overproduction of the thyroid hormones, T3 or T4, can cause life threatening changes to the body, so more aggressive therapies are required to make the thyroid produce less or no thyroid hormone. There are three options to treat hyperthyroidism: (1) surgery to remove most of the thyroid gland; (2) a medication to cause the thyroid to be unable to make as much thyroid hormone (generally only a temporary treatment); and (3) drinking a radioactive liquid called I131 which is taken up by the thyroid gland and causes it to 'scar' over. The goal of treatment of hyperthyroidism is to make the patient either euthyroid (normal thyroid level) or hypothyroid, which can then simply be treated with a daily pill of levothyroxine.
  • Thyroid nodules: Patients with nodules detected by palpation should be further tested. This is generally done with a special type of needle biopsy called a fine needle aspiration (FNA). A thyroid scan and/or an ultrasound of the thyroid is sometimes done as part of the evaluation.
  • Thyroid cancer: Thyroid cancer is usually very treatable. Depending upon the type and stage of thyroid cancer, treatment generally includes a subtotal thyroidectomy (surgery to remove almost all of the thyroid) followed by taking a large dose of I131 intended to ablate (destroy) any of the remaining thyroid tissue and cancer cells. The patient is then placed on levothyroxine and followed on a regular basis.

If you are risk for thyroid problems, and are planning to become pregnant, you should have a blood test done to evaluate your thyroid function. Both the American Association of Clinical Endocrinologists (AACE) and the American College of Endocrinology recommend that all women planning to become pregnant be screened before they conceive because mothers with thyroid disease have a higher risk of having children with neurological defects.

Thyroid problems are common in survivors who had head or neck radiation. However, treatment is generally easy and effective. Make sure to discuss your thyroid gland with your health care provider at your yearly follow up visits.