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Medical Late Effects

Originally published on November 10, 2009
Most recently updated on April 10, 2013

Late effects span a spectrum from mild and easily treatable problems (such as an underactive thyroid) to, on rare occasions, serious and life-threatening problems (a second, new cancer).  One way to determine your risk for late effects is through the Oncolink Web site.  On the site, a person can create a survivorship care plan based on medical history.

Fortunately, many late effects can be treated and controlled. For many of these problems, outcome is best when the problem is detected early, often before any symptoms or signs are evident. The following are the most common delayed complications that have been observed in childhood brain tumor survivors.

Physical Growth and Endocrine or Hormone Problems

The endocrine (or hormone-producing) system consists of several organs or glands (the thyroid, adrenals, testicles, and ovaries) that are under the control of the pituitary gland, which is located in the brain, just behind the eyes. Each of these organs produces one or more substances or hormones that can affect many important body functions. These endocrine organs can be damaged as a result of a tumor, surgery, radiation therapy, and, less often, by chemotherapy. For the endocrine glands that come in pairs (the adrenals, testicles, and ovaries), removal of just one gland does not usually cause a problem.

Endocrine problems may not develop until several years after the treatments have ended; in fact, some hormone disorders have been known to appear as long as 25 or more years after the completion of cancer treatment. Most problems can be easily diagnosed with routine blood tests and are treatable.

Pituitary Problems

The pituitary gland makes at least five different hormones, all of which can be affected by radiation therapy and surgery. Pituitary problems are most often seen in individuals who have been treated with radiation to the head and those whose pituitary has been damaged by a tumor and/or surgery for a tumor. although most of the time the problems are due to underproduction or deficiency of a hormone, accelerated production or overproduction of certain hormones can also occur.

Growth Hormone Deficiency

Loss of the ability to make normal amounts of growth hormone is the most common pituitary problem seen after radiation therapy to the brain. It occurs after radiation with doses as low as 1,800 cGy (centigray). After radiation doses of 3,500 cGy or more to the area of the pituitary, 75% to 100% of children will develop growth hormone deficiency. As its name suggests, growth hormone is essential for normal physical growth; children who are deficient in growth hormone grow slowly and are short when they reach adulthood. Growth hormone also affects bone strength, cholesterol levels, amount of body fat, and stamina. Treatment is available for children who are deficient in growth hormone and for selected adults with severe growth hormone deficiency. Children who also receive radiation to the spine may experience severe growth problems. However, even though growth hormone therapy may improve growth, it can’t overcome damage to the spine caused by radiation treatments.

Early Sexual Maturation

Young children treated with radiation to the brain tend to start their pubertal develop at a younger age than the general population. This problem is seen more often in girls than boys. Early puberty, though not a serious medical condition, can lead to a shorter final height; specific drugs are available that can temporarily postpone puberty.

Obesity

Young adult survivors of childhood brain tumors may be at increased risk of becoming overweight. Radiation to the brain appears to be an important risk factor, especially for girls treated at a young age. Young adult survivors who have a tendency to gain weight need to pay careful attention to their dietary habits and to incorporate a sensible exercise regimen into their regular routine.

Other Pituitary Problems

Deficiencies of the pituitary hormones that regulate the thyroid, testicles, ovaries, and adrenal glands occur less frequently. These problems are usually noted several years after high doses of radiation (more than 4,000 cGy) to the pituitary region. Young adult survivors who have received high-dose radiation to the pituitary should have long-term monitoring by an endocrinologist to ensure that appropriate testing takes place.

Thyroid Problems

The thyroid gland, a butterfly-shaped organ situated in the neck just above the collarbone, is often damaged by radiation to the neck, spine, or upper chest. The most common condition is hypothyroidism, which is an underactive thyroid. Symptoms of hypothyroidism can be subtle and often go unnoticed. Moreover, it may take more than 20 years after treatment for the problem to develop. Hypothyroidism can be easily treated with a thyroid pill taken daily.

In addition to an underactive thyroid gland, prior therapy with radiation increases the chance of tumors of the thyroid. Fortunately, most of these tumors are benign and easily cured. A complete examination of the thyroid should be part of the yearly checkup for anyone who has received radiation to the neck region.

Testicles and Ovaries

The testicles perform two separate functions: (1) producing the male hormone testosterone, which is needed for sexual development (beard growth, muscle growth, and maturation of the sex organs) and (2) producing sperm. These two functions are affected very differently by cancer therapy. The male hormone–producing cells are rarely damaged by the treatments, except in males who have received high doses of radiation directly to the testicles. For men who produce low levels of testosterone, treatment with testosterone (injections or daily skin application of a gel) are available. The sperm-producing cells, however, are often damaged by a variety of chemotherapy drugs (such as cyclophosphamide, busulfan, thiotepa, CCNU) and low doses of radiation. A sperm analysis is required to determine if a male survivor is fertile.

The ovaries also perform two separate functions: (1) producing female hormones (estrogen and progesterone) and (2) producing eggs. However, in females, these two functions are affected equally by the treatments. Thus, when the ovaries are damaged, there is loss of both hormone production and egg production (fertility). This usually results in lack of menstruation. The ovaries are most often damaged when the treatments are given in late adolescence and after radiation to the pelvic area and high-dose chemotherapy. For women with loss of normal ovarian function, treatment with estrogen and progesterone is usually recommended. Some women who continue to have regular periods after cancer therapy are at risk of entering menopause at a younger age than the general population. This is especially true of women who received radiation to the whole spine and those who were treated with the class of chemotherapy drugs known as alkylating agents (which includes cyclophosphamide, procarbazine, and thiotepa).

Many new techniques are now available to assist cancer survivors who experience infertility. All studies to date suggest that the children of cancer survivors are no more likely to have major problems than the children of people in the general population.

Other Late Effects

A small number of survivors can develop other disorders such as heart, lung, kidney, or skeletal problems (such as curvature of the spine). New tumors can also develop, but the overall risk is quite small, on the order of 1% to 3% of survivors at 20 years from diagnosis. Your child's risk of developing these problems will depend, in large part, on the treatments he received and his age at the time of the treatments.

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