Endocrine late effects of childhood cancer therapy.

S pecialized medical care for childhood cancer survivors is a growing field within pediatric oncology. One in a thousand young adults in the United States is a survivor of childhood cancer, as the result of the incredible cure rates oncologists are able to achieve. As cure rates continue to increase and new oncology protocols are modified to maximize cure, we must ask the question, “cure but at what cost?” Accurate assessment of true benefit of a small increase in cure rate requires information and understanding of the medical and psychosocial consequences of cancer therapy. From this premise, we bring focus to the late effects of cancer therapy, through descriptive, etiologic, and interventional studies. Late effects can be predicted by knowing the anticancer modalities used, the age of the child at the time of treatment, and the amount of time elapsed since the end of treatment. In many cancer survivorship programs, medical summaries are generated that require a thorough review of the medical record and a detailed analysis of chemotherapy and radiation therapy used to treat the child. Cumulative doses of certain antineoplastic agents and cumulative and fractional radiation doses to specific areas in the body are calculated. On the basis of this information as well as the dosing schedule, the risk for specific late effects can be predicted. For example, a child who has received 2400 cGy of cranial irradiation to the area of the hypothalamus is highly likely to have growth hormone deficiency by 2 years after treatment, with risk rising as time from treatment increases. It is by understanding the cancer therapies used and their side effects that a clinician can anticipate the long-term medical problems that the survivor may need to have addressed. Nearly two thirds of all cancer survivors will have some form of late effects. The most common late effects are endocrine disorders. In a study by Sklar of 650 cancer survivors, the most common late effects were endocrine, with 40% of his population having a diagnosed endocrine disorder. Endocrine problems can be acute, transient, chronic, or late in onset. An example of an acute endocrine disorder would be diabetes insipidus, which can occur after surgery, after the removal of a suprastellar tumor. A transient endocrine disorder would be diabetes mellitus, caused by decreased insulin release as a consequence of Lasparginase therapy. Growth hormone deficiency is a chronic endocrine disorder that is not reversible or time-limited. Premature menopause after gonadotoxic therapy is an example of an endocrine disorder that is late in onset. As might be expected, the numerous components of the endocrine systems have different vulnerabilities to the various forms of cancer therapy. For example, the hypothalamus is much more sensitive to radiation damage than is the pituitary gland. When the hypothalamic/pituitary area is irradiated, the different hormonal axes respond with varying levels of sensitivity to damage. The GH axis is most sensitive to disturbance and growth hormone insufficiency can be seen after doses of 1200 to 1800 cGy; however, disruption of prolactin inhibition does not occur until hypothalamic doses of radiation exceed 5000 cGy. Likewise, many chemotherapeutic agents cause no disruption of gonadal function, whereas others, such as alkylators, are very toxic to the ovaries and testes. To fully asses endocrine function in the cancer survivor, the clinician must know the modalities used to treat the condition, the cumulative dose of those agents given, the potential for that therapy to alter normal physiology, the age of the patient at the time of exposure to the agent and the role of age in toxicity, From Children’s Healthcare of Atlanta, Emory University, Atlanta, GA, USA. Curr Probl Pediatr Adolesc Health Care 2003;33:217-242. © 2003 Mosby, Inc. All rights reserved. 1538-5442/2003 $30.00 0 doi:10.1016/S1538-5442(03)00053-1