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Long-term neuro-endocrine sequelae after treatment for childhood medulloblastoma
J Heikens1, E M Michiels, H Behrendt
1Department of Internal Medicine, Emma Kinderziekenhuis, Amsterdam, The Netherlands.
Abstract:
The occurrence of neuro-endocrine deficiencies following craniospinal irradiation for medulloblastoma is well known, but data concerning the spectrum and prevalence of endocrine abnormalities in adulthood are scarce. We studied endocrine function in 20 (median age 25 years) adult subjects, 8-25 years (median 16 years) after therapy. The radiation dose to the whole cranium and spinal axis was 35 +/- 2.6 Gray (mean +/- standard deviation) with a boost to the posterior fossa of 18 +/- 3.7 Gray. 13 subjects had received additional chemotherapy. In 15 of 20 (75%) subjects, endocrine abnormalities were observed. In 14 (70%), growth hormone (GH) secretion was impaired; 7 (35%) subjects had an absolute GH deficiency, while 7 (35%) showed subnormal responses to insulin-induced hypoglycaemia. In contrast, only 20% (4) of these subjects showed impairment of the hypothalamus-pituitary-thyroid (HPT) axis, while 15% (3) showed central impairment of hypothalamus-pituitary-gonadal (HPG) function. Central impairment of the HPG axis was associated with impaired GH secretion in all cases. Central adrenal insufficiency was not observed. Basal levels of prolactin were normal in all subjects. Young age at treatment was a determinant of GH deficiency in adulthood (P = 0.014). Neither post-treatment interval, nor the use of chemotherapy were determinants of central endocrine impairment in adulthood. In long-term survivors of medulloblastoma, GH deficiency has a high prevalence. In contrast, impairment of the HPG and HPT axis is less common, while central adrenal insufficiency was not observed.
Insights
Adult survivors of medulloblastoma often experience neuro-endocrine deficiencies, particularly impaired growth hormone (GH) secretion, even years after treatment. Early age at therapy is linked to higher GH deficiency risk in adulthood.
Area of Science:
- Pediatric Oncology
- Endocrinology
- Radiation Oncology
Background:
- Craniospinal irradiation for medulloblastoma can cause neuro-endocrine deficiencies.
- Data on adult endocrine abnormalities post-treatment are limited.
Purpose of the Study:
- To investigate the spectrum and prevalence of endocrine dysfunction in adult medulloblastoma survivors.
- To identify factors associated with endocrine impairment in adulthood.
Main Methods:
- Evaluated endocrine function in 20 adult survivors (median age 25 years) 8-25 years post-therapy.
- Assessed growth hormone (GH), hypothalamus-pituitary-thyroid (HPT), and hypothalamus-pituitary-gonadal (HPG) axes.
- Correlated endocrine outcomes with age at treatment, time since therapy, and chemotherapy use.
Main Results:
- 75% of subjects had endocrine abnormalities.
- 70% exhibited impaired GH secretion (35% absolute deficiency, 35% subnormal response).
- 20% had HPT axis impairment, 15% had HPG axis impairment; no central adrenal insufficiency observed.
Conclusions:
- GH deficiency is highly prevalent in adult medulloblastoma survivors.
- HPG and HPT axis impairment are less common; central adrenal insufficiency was not observed.
- Younger age at treatment is a significant predictor of adult GH deficiency.