IGF-I, IGF-II and IGFBPs in children with subclinical hypothyroidism

Abstract

Congenital hypothyroidism (CH) results from an inadequate production of thyroid hormones during childhood. Primary CH is the most severe form of the disease and can lead to permanent sequels if untreated. By the other hand no signs or symptoms is observed in subclinical hypothyroidism (SH), a condition where normal free T4 is associated with marginally elevated TSH. Thyroid hormones regulate IGF-I (insulin-like growth factor-I) production and IGF-I deficiency is associated with impaired growth. IGF-1 acts on cell proliferation, growth and differentiation at autocrine, paracrine and endocrine levels and it has also metabolic actions. Recent reports suggest that even small changes in thyroid function can be associated with changes in IGF-1 levels. The impact of SH on growth is poorly studied and there are lot of discussions regarding treating or not patients with TSH between 5 and 10 mUI/L. The present study aims to answer if SH affect IGFs and IGFBPs levels and in this way growth rate in children. AIM: The aim of this study is to evaluate IGF-I, IGF-II and IGFBPs concentrations in children with SH and to correlate these data with anthropometric parameters used to evaluate growth. Subjects and Study Design Seventy children under 2 years of age will be enrolled in the study. They will be divided in 2 age-groups: A. Subjects under 3 months of chronologiacal age Thirty children aged less than 3 months evaluated due to a screening test where TSH > 5 mU/ml will be studied. They will be further grouped in 3 minors subgroups according to serum TSH levels in the time of the reassessment as described: Group I: TSH < 5 mU/ml (Control Group 1) Group II: 5 < TSH < 10 mU/mlGroup III: TSH > 10 mU/mlB. Group aged between 3 months and 2 years Twenty children with SH (TSH between 5 and 10 µUI/ml and normal levels of free and total T4 : 1-2 ng/ml and 8-10 ug/ml, respectively) will be studied. Another group of 20 children with TSH < 5,0 mU/ml will form the Control Group 2. Length, weight, head circumference, BMI will be checked every 3 months during 1 year. Data regarding the period before the enrolment will be collected from medical files. Children bearing chronic diseases or those undernourished will be excluded. Blood sample (1 ml) for IGF-I, IGF-II and IGFBPs determination will be obtained from each patient at the same moment they collect blood for routine TSH/T4 determinations. Assays TSH, total and free T4 levels will be determined by specific immunoassays. IGF-I, IGF-II and IGFBP-3 concentrations will be determined by imunoenzimometric assays (ELISA). Concentrations of IGFBP-1, IGFBP-2 and IGFBP-4 will be analyzed by Western ligand blotting. (AU)