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Director, Neuroendocrinology Program
Director, Growth Program
Division of Endocrinology
Boston Children’s Hospital
Associate Professor of Pediatrics
Harvard Medical School
Laurie E. Cohen, MD, has disclosed that she has received funds for research support from Pfizer, speaker fees from Novo Nordisk, and other financial or material support from Sandoz.
In this commentary, I answer questions from a symposium on late endocrine effects in cancer survivors. Slides from the symposium are also available for self-study or to use in your noncommercial presentations.
For a cancer survivor with growth hormone (GH) deficiency, how long should one wait after the completion of therapy before starting GH replacement? Is this interval shorter in children with craniopharyngioma?
Because healthcare professionals have generally waited to treat with GH until a survivor of a malignant neoplasm is disease free for 1-2 years, there are no data about starting GH therapy earlier than 1 year.
Healthcare professionals are becoming less conservative in delaying GH therapy, especially for a craniopharyngioma. For a craniopharyngioma, which is considered a “benign” neoplasm, there are reports in the literature of starting GH therapy as early as approximately 6 months after diagnosis. However, one should wait until there has been recovery from therapy (ie, surgery, radiation, or chemotherapy) because illness, undernutrition, and inflammation can lead to states of GH resistance.
There are also no data on what to do for patients with stable disease, such as low-grade gliomas, but some healthcare professionals are treating these patients as well.
Bottom line: Healthcare professionals should discuss whether or not to initiate GH therapy and its timing with the patient’s oncologist.
Should all cancer survivors with childhood-onset GH deficiency be retested after attaining final height to assess the persistence of this deficiency? If so, what is the best time to retest and which testing protocol (dynamic test) do you use?
If the patient has 3 other confirmed anterior pituitary hormone deficits, testing is not necessary. Testing may also be unnecessary in isolated GH deficiency, if the patient received high-dose cranial radiation.
The first screen is generally an IGF-I level. If the IGF-I level is above 0 SDS, the patient is unlikely to have GH deficiency.
The goal of GH therapy in adults is to treat to an IGF-I level of approximately 0 SDS. In this treatment setting, however, the patient should not be discharged from long-term surveillance. A postpubertal individual produces less GH than someone in a pubertal growth spurt. Because hypothalamic–pituitary axis dysfunction may continue to develop over time and we are not sure if the risk of GH deficiency ever plateaus, monitoring needs to be continued.
If the IGF-I level is low and the risk for adult GH deficiency is less clear (eg, lower dose hypothalamic–pituitary radiation exposure), GH stimulation testing should be performed. If the IGF-I result is between 0 and -2 SDS, I use some clinical discretion as to when I am going to retest, but generally, I retest those with IGF-I levels below -1.5 SDS. However, we still do not have great normative data as to what a peak GH response should be in the transition period.
In the general population, the recommendation is to wait at least 1 month off therapy before retesting. In my practice, I tend to wait to closer to 3 months and sometimes up to 6 months. Often a patient who is truly GH deficient will start to show some of the manifestations of GH deficiency, such as increased abdominal adiposity, giving support to the diagnosis. There is unlikely to be significant morbidity due to untreated GH deficiency over this time.
Along with GH replacement, is there a place for aromatase inhibitors for height enhancement in individuals with early nonprecocious puberty?
There is still debate about the use of aromatase inhibitors in the general population for idiopathic short stature, and by themselves, they may not significantly increase adult final height. Their use is more promising when used in conjunction with GH therapy. However, more data are needed to determine whether or not aromatase inhibitors affect bone turnover, bone architecture, lipids, cognition, or prostate. Many cancer survivors already have risk of impairments in many of these areas, so caution is advised.
Do you think there is enough evidence to support routine use of pharmacotherapies such as oxytocin for hypothalamic obesity, or is this still an active area for research?
Oxytocin is still under investigation. Other pharmacotherapies, such as stimulant medications and/or GLP-1 receptor agonists, may or may not work for individual patients—studies are small and show varying degrees of success.
What are your thoughts on managing hypothalamic–pituitary dysfunction in cancer survivors? Answer the polling question and share your thoughts in the comments box below.