Interview with Dr. Michele Christie, M.D., pediatric endocrinologist for Kaiser Permanente

Colleen Snyder



Colleen Snyder: When a pediatric patient presents with a brain tumor, what does that trigger you to monitor and what concerns does a brain tumor in a child raise from an endocrine standpoint?

Dr. Michele Christie, M.D.: From an endocrine standpoint, a child with a brain tumor or who has been treated with a brain tumor, must be evaluated and followed for any possible deficiency of the hypothalamic-pituitary axis. Specifically, this would mean evaluating for deficiencies of growth hormone, thyroid hormone, cortisol, vasopressin (the hormone that allows the kidney to concentrate urine) and the hormones that control puberty, LH and FSH. The type and location of the tumor and the course of treatment influence the possibility of finding any of the above.

Snyder: As a patient begins to undergo treatment--typically surgery, chemotherapy, and cranial radiation--are there endocrine conditions that may develop which need to be monitored or treated?

Christie: During treatment, the use of high dose corticosteroids (typically prednisone), may lead to glucose intolerance/high blood sugars which may require insulin injections to control. The use of chemotherapy, specifically cyclophosphamide, may be associated with amenorrhea and azoospermia. Estrogen replacement should be considered by age 13 in girls with evidence of ovarian failure to allow normal pubertal progression and to minimize the risk of osteoporosis.

Snyder: Could you please comment on the late effects of cranial radiation on the endocrine system and give a timeline of when these endocrine problems may occur post-radiation.

Christie: The late effects of cranial radiation on the endocrine system include growth hormone deficiency, thyroid hormone deficiency, adrenal insufficiency (through decreased ACTH production) and precocious puberty. Growth hormone deficiency often presents within 3-5 years of radiation. Thyroid deficiency may present at variable times depending on whether there has been radiation to the spine which potentially damages the thyroid gland itself. Adrenal insufficiency is found much less frequently but should be screened for on a regular basis. Precocious puberty also may present at variable times after radiation. Delayed puberty may be seen after spinal radiation.

Snyder: As you mentioned, children with brain tumors are at risk for developing precocious puberty. Could you please define the condition.

Christie: The definition of precocious puberty is currently being modified as a result of recent data better defining current normal ages for onset of puberty. The new guidelines will likely suggest that the appearance of breast development in girls before the age of seven and of testicular enlargement in boys before the age of nine constitutes precocious puberty. Of note, the development of body odor, pubic and axillary hair may develop earlier. This is under the control of the adrenal glands and is not considered, by itself, to be evidence of precocious puberty.

Snyder: How does bone age affect the treatment of precocious puberty?

Christie: The bone age is used to determine how much potential growth a child may have in the future. This is a critical piece of information in determining whether or not to suppress precocious puberty for the purpose of trying to achieve a greater final height. If the bone age is too advanced, there may be no additional height gained by suppressing puberty.

Snyder: Many children receive Lupron to suppress puberty. There is some concern that the shots may affect tumor growth either by stunting the tumor's growth while the child is on Lupron and then causing the tumor to growth once treatment is stopped. Is there any validity to the concern that once a child is taken off Lupron his brain tumor may begin to grow? In addition, is there any indication that injections of growth hormone would cause tumor growth?

Christie: Lupron is a LHRH analog, not a growth hormone analog, so it should not have any impact on brain tumor growth. Growth hormone, theoretically, may have an impact on tumor growth; however, to date there has been no data confirming increased risk of recurrence or second malignancy. For this reason, it should only be prescribed to a patient with GH deficiency when that patient has been in remission for one year. Even then, the patient should be followed carefully with regular CNS scans to rule out recurrence.

Snyder: Children with brain tumors are at risk for developing thyroid problems. What thyroid conditions are typically a problem and how are they treated? If these conditions result from cranial radiation, what is a typical timeline of when they would develop post-radiation?

Christie: The two most likely thyroid condition that may result from radiation are hypothyroidism and thyroid nodules. The former is a result of either decreased TSH production or direct damage to the thyroid gland. This may show up at time within one to several years after diagnosis (typically 1-5 years). It is treated by replacing thyroid hormone in the form of a pill taken once a day (e.g. Synthroid, Levothroid). Thyroid nodules may appear in a patient with a history of spinal radiation if there has been enough secondary exposure to the thyroid gland. These may show up 5-10 or more years after radiation. They require evaluation to be sure they do not represent a secondary cancer. Primary treatment for a malignant thyroid nodule is surgical excision.

Snyder: How does cranial radiation affect the satiety center or other functions of the hypothalamus in children with brain tumors and how it is treated?

Christie: There is little information available about the effect of radiation on the satiety center within the hypothalamus. It is difficult to determine in a patient with a brain tumor near the hypothalamus whether or not any effect on appetite may be a surgical complication or a radiation side-effect. Currently, there is no satisfactory treatment for abnormal satiety other than strict portion control. It is possible that research on the hormone leptin will lead to a better understanding of the mechanisms underlying satiety and hence possible treatment for patients with this complication.

Snyder: Is obesity a problem with these children?

Christie: Obesity may be a problem with these children. Contributors to obesity include unrecognized hypothyroidism, abnormal satiety, stunted linear growth, and decreased activity secondary to other complications such as visual loss.

Snyder: How prevalent is diabetes insipidus in brain tumor children and how is it treated?

Christie: Diabetes insipidus is a potential complication of any tumor involving the hypothalamic-pituitary axis. It is treated by replacing the hormone vasopressin, either by using a nasal spray or, more recently, taking pills generally one to two times a day. Careful attention must be given to fluid intake and output to avoid either dehydration or water excess.



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