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 (H PT) 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 controv ersal. DESIGN We measured plasma levels of total T3 (T3), total T4 (T4) and TSH be fore stimulation with TRH and plasma levels of TSH, 30 and 150 minutes afte r stimulation with TRH in 95 patients in first continuous remission of chil dhood ALL. PATIENTS Patients diagnosed with ALL before the age of 15 years between 197 0 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 be tween 1.2 and 18.3 years (median: 7.6) after completion of therapy. MEASUREMENTS We measured T4 levels before, and compared TSH levels before a nd after, stimulation with TRH in patients who were treated with prophylact ic 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 (excl uding 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 T SH 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 significan tly 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, iri the CIR group, the T4 le vel decreased significantly over time with -1.5% per year (P = 0.025), whil e toe difference in the non-CIR group was not significant. There was no cor relation between T4 and TSH levels and sex, age at diagnosis, age at the en d 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-pitultary-thyroid function within a media n follow-up time of 8 years.