No thyroid abnormalities in patients submitted to cardiac catheterization in the first eighteen months of life.

BACKGROUND: No data are available about the risk of thyroid disturbance after exposure to low-dose radiation due to the use of cardiac catheterization in the first years of life. AIM: To determine the risk of functional and morphological thyroid abnormalities in a homogeneous cohort of patients who underwent diagnostic low-dose radiation for heart catheterization during the first 18 months of life. SUBJECTS AND METHODS: Fifty-five patients, submitted to cardiac catheterization during the first 18 months of life, underwent evaluation of the thyroid function and structure after a median period of 13 yr since the first radiation exposure. Sixty-eight unexposed controls matched for age and sex, underwent the same protocol. Twenty-two patients were then re-evaluated after a median period of 22 yr. RESULTS: Thyroid function resulted normal in both patients and controls. The prevalence of small thyroid nodules and inhomogeneous structures in ultrasound study was not augmented in irradiated patients compared to controls. No thyroid tumors or reduced thyroid volume were observed. CONCLUSIONS: Neither functional nor morphological disorders of the thyroid gland were demonstrated after a period up to 24 yr in patients exposed to diagnostic ionizing radiation for cardiac catheterization during the first 18 months of life.

Effects of insulin-like growth factor binding proteins in bone -- a matter of cell and site.

The actions of the insulin-like growth factor (IGF)-system are controlled by six IGF-binding proteins (IGFBPs). The IGFBPs are thought to affect local effects of IGF-I and IGF-II due to higher affinity if compared to IGF-I receptors and due to cell-type specific IGFBP expression patterns. It was found in IGFBP knockout models that the IGFBP family is functionally redundant. Thus, functional analysis of potential effects of IGFBPs is dependent on descriptive studies and models of IGFBP overexposure in vitro and in vivo. In the literature, the role of the IGFBPs for bone growth is highly controversial and, to date, no systematic look has been taken at IGFBPs resolving functional aspects of IGFBPs at levels of cell types and specific locations within bones. Since IGFBPs are thought to represent local modulators of the IGF actions and also exert IGF-independent effects, this approach is particularly reasonable on a physiological level. By sorting the huge number of in part controversial results on IGFBP effects in bone present in the literature for distinct cell types and bone sites it is possible to generate a focused, more specific and a less controversial picture of IGFBP functions in bone.

The interaction of glucocorticoids with the growth hormone-insulin-like growth factor axis and its effects on growth plate chondrocytes and bone cells.

Glucocorticosteroids interfere with the growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis at different levels, and while low-dose corticosteroids may have permissive effects, high-dose, long-term treatment with corticosteroids may lead to growth disturbance. The mechanism involved is not clearly understood. The Janus kinase (JAK)-2/signal transducers and activators of transcription (STAT)-5 pathway is the means by which the corticosteroid interacts with the target-cell GH receptors. The production of local IGF-I is lowered by the corticosteroid via IGF-I transcription inhibition, and the rate of apoptosis is also increased, both in growth plate chondrocytes and osteoblast cell lines. GH in vitro and in vivo can partly counterbalance the negative effects of glucocorticoids on growth. GH has been seen to normalize growth rates in corticosteroid-treated rats as well as in children receiving glucocorticoids for immunosuppression following kidney transplantation.

Serum insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 in children with chronic renal failure: relationship to growth and glomerular filtration rate. The European Study Group for Nutritional Treatment of Chronic Renal Failure in Childhood. German Study Group for Growth Hormone Treatment in Chronic Renal Failure.

Growth retardation in children with chronic renal failure (CRF) is partly due to an inhibition of insulin-like growth factor (IGF) activity by an excess of high-affinity IGF-binding proteins (IGFBPs). The aim of this study was to analyze the serum levels and forms of IGFBP-4 and IGFBP-5 in CRF patients using specific, recently developed radioimmunoassays (RIAs) and immunoblot analysis. We examined 89 children [age 11.5 (2.8-19.0) years] with CRF [glomerular filtration rate 26.6 (7.0-67.4) ml/min per 1.73 m2], nine of them with end-stage renal disease undergoing peritoneal dialysis. Serum-immunoreactive IGFBP-4 levels were fourfold increased in CRF (prepubertal 1080+/-268 ng/ml; pubertal 989+/-299 ng/ml) compared to healthy prepubertal controls (265+/-73 ng/ml). In contrast, serum IGFBP-5 levels were not significantly increased neither in prepubertal (361+/-120 ng/ml vs 282+/-75 ng/ml in controls) nor pubertal CRF children (478+/-165 ng/ml vs 491+/-80 ng/ml in controls). Immunoblot analysis showed the presence of intact as well as fragmented IGFBP-4 and IGFBP-5. Serum IGFBP-4, but not IGFBP-5, levels were inversely correlated with GFR (r=-0.39, P<0.001). In prepubertal children, IGFBP-4 levels were inversely correlated with standardized height (r=-0.40; P<0.005). In contrast, IGFBP-5 levels were positively correlated both with standardized height (r=0.32, P<0.02) and baseline height velocity (r=0.45, P<0.005). A 3-month therapy with rhGH stimulated serum IGFBP-5 levels by 43% (P<0.01); there was no consistent effect on IGFBP-4 levels. There was a positive correlation between IGFBP-4 and IGFBP-2 (r=0.46, P<0.001); IGFBP-5 was positively correlated with IGF-I (r=0.59, P<0.001), IGF-II(r=0.42, P<0.001)and IGFBP-3 (r=0.47, P<0.001) and inversely correlated with IGFBP-1 (r=-0.41, P<0.001). In summary, serum IGFBP-4 is fourfold elevated in children with CRF in relation to the degree of renal dysfunction and contributes to the marked increase in IGF-binding capacity in CRF serum. The inverse correlation of serum IGFBP-4 with standardized height is consistent with its role as another inhibitor of the biological action of the IGFs on growth plate cartilage. In contrast, serum IGFBP-5 is not elevated in CRF serum and circulates mainly as proteolysed fragments. The positive correlation of serum IGFBP-5 with growth and its increase during GH therapy indicate that IGFBP-5 is a stimulatory IGFBP in patients with CRF, either by enhancing IGF activity through better presentation of TGF to its receptor or by an IGF-independent effect through activation of a specific, recently described putative IGFBP-5-receptor.