Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation
Abstract
OBJECTIVE: Focus on long-term side-effects after cancer therapy in childhood has become of the utmost importance. The hypothalamic-pituitary thyroid (HPT) axis is exposed to irradiation when some children are treated for acute lymphoblastic leukaemia (ALL) with prophylactic cranial irradiation (CIR). Whether this treatment causes hypofunction of the HPT axis remains controversial. DESIGN: We measured plasma levels of total T3 (T3), total T4 (T4) and TSH before stimulation with TRH and plasma levels of TSH, 30 and 150 minutes after stimulation with TRH in 95 patients in first continuous remission of childhood ALL. PATIENTS: Patients diagnosed with ALL before the age of 15 years between 1970 and 1991 and who were in first continuous remission and off treatment for at least one year were studied. The children were aged between 0.5 and 14.8 years (median: 3.9) at diagnosis of ALL. Thyroid function was assessed between 1.2 and 18.3 years (median: 7.6) after completion of therapy. MEASUREMENTS: We measured T4 levels before, and compared TSH levels before and after, stimulation with TRH in patients who were treated with prophylactic CIR (15-24 Gy) (n = 38) (CIR group) with patients who were treated with chemotherapy only (n = 57) (non-CIR group). RESULTS: We found that T3 and T4 levels were normal in all individuals (excluding the women who were on oral contraceptives). The median time from end of treatment to time at follow-up was 9.1 years in the non-CIR group vs. 4.2 years in the CIR group (P < 0.001), and the effect on follow-up time was significant (P = 0.04). It was estimated that just after irradiation, the TSH levels before and 30 and 150 minutes after TRH stimulation was 49% lower in the CIR group; however, after 4.0 years, TSH levels were not significantly different between the two groups. Although within normal limits, the T4 levels were significantly higher in the CIR group compared to the non-CIR group (P = 0.003). It was estimated that, just after the end of treatment, T4 was 19.9% higher in the CIR group. However, in the CIR group, the T4 level decreased significantly over time with -1.5% per year (P = 0.025), while the difference in the non-CIR group was not significant. There was no correlation between T4 and TSH levels and sex, age at diagnosis, age at the end of treatment or age at follow-up. CONCLUSIONS: We conclude that, in our cohort of survivors of childhood ALL, prophylactic cranial irradiation of the central nervous system did not have an adverse effect on hypothalamo-pituitary-thyroid function within a median follow-up time of 8 years.
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Craniopharyngiomas are the leading cause of acquired central hypothyroidism in children, followed by cranial irradiation for other childhood brain tumours.
“Craniopharyngiomas are the leading cause of acquired central hypothyroidism in children, followed by cranial irradiation for other childhood brain tumours such as dysgerminomas or malignant haematological diseases (Gurney et al., 2003;Lando et al., 2001;Schmiegelow et al., 2003).”
From The hypothalamus-pituitary-thyroid (HPT)-axis and its role in physiology and pathophysiology of other hypothalamus-pituitary functions (2021) · cites this paper as Lando et al., 2001
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Self-citation
- Authors
- Lando, A., Holm, K., Nysom, K., Rasmussen, Å. K., Feldt‐Rasmussen, U., Petersen, J. H., & Müller, J.
- Affiliations
- Rigshospitalet (DK)
- University of Copenhagen (DK)
- Corresponding author
- Müller, Jørn
- Venue
- Clinical Endocrinology
- Publisher
- Wiley
- Published
- 2001-07
- Volume
- 55
- Issue
- 1
- Pages
- 21-25
- ISSN
- 0300-0664 (ISSN-L)
- 1365-2265
- OpenAlex
- W2054863001
- Cited by
- 46
- References
- 15
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 5 · 2017: 2 · 2016: 2 · 2014: 1 · 2013: 2 · 2012: 4
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Kræftens Bekæmpelse
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- childhood acute lymphoblastic leukemia, prophylactic cranial irradiation, thyroid function, hypothalamic-pituitary-thyroid axis, thyroid-stimulating hormone, TRH stimulation test, thyroid hormone levels, thyroxine, hypothyroidism, follow-up duration, oral contraceptives, childhood cancer survivors
- MeSH terms
- Adolescent, Brain, Child, Child, Preschool, Female, Follow-Up Studies, Humans, Infant, Male, Thyroid Gland, Thyrotropin, Thyroxine, Triiodothyronine, Cohort Studies, Cranial Irradiation, Leukemic Infiltration, Precursor Cell Lymphoblastic Leukemia-Lymphoma
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