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Growth and growth hormone status after a bone marrow transplant
1Department of Endocrinology, Christie Hospital, Manchester, UK. stephen.m.shalet@man.ac.uk
Insights
Pediatric cancer survivors treated with radiotherapy may develop growth hormone deficiency (GHD). Early diagnosis and treatment decisions for GHD are crucial for optimizing growth outcomes in these young patients.
Area of Science:
- Pediatric oncology
- Endocrinology
- Radiation oncology
Background:
- Children treated for cancer, particularly brain tumors, acute lymphoblastic leukemia, and other malignancies requiring irradiation, face significant risks of endocrine dysfunction.
- Radiotherapy (XRT) targeting the hypothalamic-pituitary axis can lead to growth hormone deficiency (GHD), impacting growth and final height.
- Specific XRT doses and treatment modalities (e.g., cranial XRT, total body irradiation) are associated with varying risks of GHD.
Purpose of the Study:
- To outline diagnostic and therapeutic challenges in managing growth hormone deficiency (GHD) in pediatric cancer survivors.
- To provide guidance on the timing and decision-making process for growth hormone (GH) replacement therapy.
- To emphasize the importance of a multidisciplinary approach involving pediatric oncologists and endocrinologists.
Main Methods:
- Review of clinical situations involving pediatric cancer patients treated with radiotherapy (XRT) and potential for GHD.
- Analysis of diagnostic tools, including Insulin-like Growth Factor 1 standard deviation score (IGF-1 SDS) and provocative GH testing.
- Consideration of auxological (growth) data and pubertal status in assessing GH status and guiding treatment.
Main Results:
- High risk (>50%) of GHD two years after XRT doses >= 30 Gy to the hypothalamic-pituitary axis.
- IGF-1 SDS is a valuable diagnostic tool, especially in severe XRT-induced GHD.
- Auxology plays a key role in assessing GH status for patients receiving lower cranial or total body irradiation.
Conclusions:
- Collaborative decisions between oncologists and endocrinologists are essential for managing GHD in pediatric cancer survivors.
- Therapeutic strategies for GH replacement require careful consideration of biochemical evidence, auxology, and prognosis.
- Early intervention for precocious puberty may be necessary to preserve final height in irradiated children.
Abstract:
The three most common clinical situations which have given rise to diagnostic and therapeutic issues involve the child treated for: (1) a brain tumour or extracranial tumour with radiotherapy (XRT) which includes an XRT dose of > or =30 Gy to the hypothalamic-pituitary axis; (2) acute lymphoblastic leukaemia with a cranial XRT dose of 18-24 Gy, and (3) haematological malignancy or solid tumour requiring total body irradiation (dose 10-14 Gy) and BMT. The decision about the intent to treat and the timing of GH replacement needs to be taken in collaboration with the paediatric oncologist who will provide guidance about overall prognosis and the risk of relapse. After a dose of > or =30 Gy to the hypothalamic pituitary axis the risk of GH deficiency (GHD) 2 years later is very high (>50%) and therefore there is 'solid' epidemiological evidence, which predicts outcome. Therapeutically the choice is whether or not to offer GH replacement at 2 years in the presence of biochemical evidence of GHD but independent of auxology, or wait until the growth rate declines. Diagnostically the IGF-1 SDS is more useful than previously thought, particularly if XRT-induced GHD is severe; there may, however, be systematic discordancy between the GH responses to different pharmacological stimuli (ITT vs. arginine). For irradiated children in categories 2 and 3, greater emphasis is placed on auxology in determining the need for assessment of GH status. Early rather than very precocious puberty is a real issue and needs to be actively treated with a GnRH analogue if final height appears to be significantly compromised.