To determine the late effects of treatment on thyroid function in children who survive acute lymphoblastic leukemia, we assessed plasma levels of thyroid hormones in 24 children (15 girls and 9 boys) who had received combination of chemotherapy along with 18-24 Gy of irradiation to the cranium. The children were aged between 1 and 10.5 years (mean 3.1) at diagnosis and thyroid status was investigated between 1.3 and 13 years (mean 6.8) after completion of therapy. Six children showed a low peak of plasma thyroid stimulating hormone (TSH), after stimulation with thyrotrophin-releasing hormone (TRH). Three children showed a low basal plasma TSH concentration. Serum levels of thyroxine (T4, fT4) and triiodothyronine (T3, fT3) were normal in all patients. The frequency of thyroid hypofunction (low peak response of TSH to TRH) was more common in children receiving 24 compared to 18 Gy cranial irradiation (50% vs 14%; odds ratio = 7) and those who had completed therapy more than 5 years ago (31.3% vs 12.5%, odds ratio 3.18) although no significant association could be found (95% IC: 0.27-65.8 and 0.24-90 respectively). Because of the low mean age at diagnosis of our population no significant association could be found between children younger than 3 years of age at diagnosis and thyroid hypofunction (odds ratio = 0.14; 95% IC: 0.01-1.48). We conclude that treatment for acute lymphoblastic leukemia including cranial irradiation may lead to TRH/TSH dysfunction and therefore long term survivors should be followed for a long period after completion of therapy.
Euthyroid sick syndrome is related to profound changes in thyroid metabolism induced by nonthyroidal diseases. To determine whether children with newly diagnosed Hodgkin disease might present thyroid abnormalities and to establish their predictive value, the authors performed regular thyroid function testing. Seven children (5 M, 2 F) with a mean age of 10.4 years (range: 4.6-15 years) at diagnosis were studied for a period of 6.9 years (4.2-10.5 years). Five patients presented at diagnosis with euthyroid sick syndrome characterized by borderline low thyroxine circulating levels (T3 0.8-1.3 ng/mL, FT3 1.5-1.7 pg/mL) and mildly raised TSH (4.6-5 microU/mL). Thyroid function turned normal within 6 months of therapy. Subsequently, 3 children developed overt hypothyroidism (T4 35-40 ng/mL, FT4 2-7 pg/mL, TSH 5.5-11 microU/mL) requiring substitution therapy. Euthyroid sick syndrome was not associated with a poorer outcome in terms of survival or long-term thyroid consequences. Thyroid function testing should be performed routinely at diagnosis and thereafter in children with Hodgkin disease to detect subtle abnormalities.
The tractographic reconstruction of anatomical and microstructural features provided by Magnetic Resonance (MR) Diffusion Tensor Imaging (DTI) gives essential information of brain damage in several pathological animal models. The optimization of a tractographic protocol is undertaken in normal rats for the future construction of a reference atlas, as prerequisite for preclinical pathological in-vivo studies. High field, preclinical in-vivo DTI faces important difficulties relevant to Signal-to-Noise Ratio (SNR), distortion, high required resolution, movement sensitivity. Given a pixel-size of 0.17 mm and TE/TR = 29/6500 ms, b value and slice thickness were fixed at 700 s/mm(2) and 0.58 mm, respectively, on preventive ex-vivo studies. In-vivo studies led to the choice of 30 diffusion directions, averaged on 16 runs. The final protocol required 51 min scanning and permitted a reliable reconstruction of main rat brain bundles. Tract reconstruction stopping rules required proper setting. In conclusion, the viability of DTI tractography on in-vivo rat studies was shown, towards the construction of a normal reference atlas.
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