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Radiotherapy that reaches the pituitary stops the growth hormone signal, and radiotherapy to the spine stops the spine growing. In a Dutch cohort of 573 survivors, 8.9 per cent ended up more than two standard deviations below mean adult height, the largest losses after total body irradiation and craniospinal radiotherapy. Replacement restores some height.
Three separate things take height from a child treated for cancer, and they need separating because the answers differ.
The pituitary. Growth hormone deficiency is the commonest and earliest of the anterior pituitary deficits after cranial radiotherapy. In the St Jude Lifetime Cohort's study of 748 survivors treated with cranial radiotherapy, mean age 34.2, observed for a mean of 27.3 years, the estimated point prevalence of growth hormone deficiency was 46.5 per cent, and doses of 22 to 29.9 gray were already significantly associated with it compared with doses below 22 gray. The same analysis found that growth hormone deficiency was not treated in 99.7 per cent of affected adults, and that untreated deficiency was significantly associated with decreased muscle mass and exercise tolerance.
The spine. Radiotherapy to the vertebral bodies stops them growing, which shortens the trunk without affecting the legs, so a survivor of craniospinal irradiation may sit short and stand less short. Total body irradiation before transplant does the same to the whole skeleton. In a cohort of 573 Dutch survivors with height recorded both at diagnosis and in adulthood, height was normal at diagnosis but 8.9 per cent had an adult height two or more standard deviations below the mean, and the largest treatment effects were total body irradiation (minus 1.56 standard deviation scores) and craniospinal radiation (minus 1.37). Younger age at diagnosis contributed negatively.
Early puberty. A child whose puberty starts early finishes growing early, so the growth that is lost is at the end. This is covered in the pituitary and puberty record alongside this one, and it is the reason a child who is growing fast can still be heading for a short adult height.
What to do about it. Height is measured at every follow-up visit and plotted; a falling height velocity is the signal, not a single measurement. Growth hormone replacement is given by paediatric endocrinologists where deficiency is confirmed and the child is still growing. The safety question was asked directly in the Childhood Cancer Survivor Study. Among 361 growth-hormone-treated survivors in a cohort of 13,539, the relative risk of disease recurrence was 0.83 (95 per cent confidence interval 0.37 to 1.86, P = 0.65), the risk of death was not associated with growth hormone use (P = 0.43), but there were 15 second neoplasms, all solid tumours with no secondary leukaemias, a relative risk of 3.21 (1.88 to 5.46, P < 0.0001), mainly from a small excess in survivors of acute leukaemia. After a further 32 months of follow-up the relative risk had fallen to 2.15 (1.3 to 3.5, P < 0.002) across 20 second neoplasms, nine of them meningiomas, and the authors wrote that "the elevation of risk due to GH use appears to diminish with increasing length of follow-up. Continued surveillance is essential." Both analyses rest on small numbers of events and the International Guideline Harmonization Group still lists growth hormone treatment among its topics in development.
What comes back, and when: growth hormone replacement adds height while the growth plates are open and does nothing once they have fused, which is why the referral is urgent in a child and not in an adult. Spinal shortening from radiotherapy does not respond to growth hormone at all, because the bone itself was irradiated. In adults, growth hormone replacement is given for the metabolic and body-composition consequences rather than for height, and in this cohort almost nobody received it.
Somatotroph cells of the anterior pituitary are the most radiosensitive of the hormone-producing cell types, so growth hormone secretion fails at lower doses and sooner than the other axes. Vertebral growth depends on the epiphyseal plates of the vertebral bodies, which irradiation damages directly, producing a deficit that no hormone can correct. Recombinant growth hormone acts on open growth plates, so its effect is bounded by the time remaining before epiphyseal fusion.
Query for this technology: (TITLE:"Growth and final height after treatment in childhood, and growth hormone" OR ABSTRACT:"Growth and final height after treatment in childhood, and growth hormone") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Growth and final height after treatment in childhood, and growth hormone, not a curated reading list.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age, Childhood Cancer Survivor Study (CCSS), Radiotherapy and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), Childhood Cancer Survivor Study (CCSS), Paediatric low-grade glioma and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares Total body and total marrow irradiation, International Guideline Harmonization Group for late effects of childhood cancer, The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood, The Children's Oncology Group Long-Term Follow-Up Guidelines and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares Total body and total marrow irradiation, International Guideline Harmonization Group for late effects of childhood cancer, The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood, St Jude Lifetime Cohort Study (SJLIFE) and the tags rejuvenation, survivorship, paediatric, late-effects.