Thyroid function in survivors of childhood acute lymphoblastic leukaemia: the significance of prophylactic cranial irradiation.
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.


METHODS
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.


METHODS
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.


METHODS
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.
Lando
A
A
Department of Growth and Reproduction, The Juliane Marie Centre, Rigshospitalet, 9 Blegdamsvej, DK-2100 Copenhagen, Denmark.
Holm
K
K
Nysom
K
K
Rasmussen AK
Feldt-Rasmussen
U
U
Petersen
J H
JH
Müller
J
J
D000293:Adolescent; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016371:Cranial Irradiation / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D017254:Leukemic Infiltration / Q000517:prevention & control*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000473:pathology*; D013961:Thyroid Gland / Q000503:physiopathology / Q000528:radiation effects*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine