Carotid Intima-Media Thickness in Children Treated with Growth Hormone: A Follow-Up Study over Three Years

Abstract

Background: There is an ongoing discussion whether high doses of growth hormone (GH) may lead to cardiovascular diseases. Therefore, we studied the longitudinal relationships between GH treatment and carotid intima-media thickness (cIMT), which is predictive of the development of atherosclerosis. Methods: We measured blood pressure, lipids, hemoglobin HbA_1c, IGF-1, IGFBP-3, and cIMT in 28 children treated with supraphysiological doses of GH (mean age 9.8 ± 2.2 years, 39% males) and 36 children suffering from GH deficiency (GHD) and treated with physiological doses of GH (mean age 9.7 ± 2.2 years, 72% males) in a longitudinal study over 3 years. Results: The cIMT values did not change significantly in the observation period in children with GHD (Δmaximum and Δmean cIMT 0.0 ± 0.1 mm). The mean (+0.1 ± 0.1 mm) but not the maximum cIMT (0.0 ± 0.1 mm) increased significantly (p = 0.049) in the children treated with supraphysiological doses of GH. Blood pressure, lipids, and HbA_1c were not related to cIMT, while IGF-1, IGFBP-3, body mass index expressed as a standard deviation score, and treatment duration correlated significantly with cIMT. Conclusions: We did not find any robust evidence that GH treatment is associated with changes in cIMT. Further studies are necessary to analyze the impact of IGF-1 and IGFBP-3 concentrations on cIMT.

Increased Carotid Intima-media Thickness and Its Association with Carbohydrate Metabolism and Adipocytokines in Children Treated with Recombinant Growth Hormone

“…A persistent very low IGF-1 level might have a protective role, whereas a milder decrease, such as in adult-onset GH-deficiency, might be predisposing to CVD risk ( 45 ). Rothermel et al ( 16 ) showed a correlation between cIMT and changes in IGF-1 SDS after rhGH treatment in GHD children, but not with the dose of the rhGH treatment. In our study, there was no association between IGF-1 SDS and cIMT-SDS.…”

“…In a cohort of children and adults consisting of 105 subjects over eight generations with GHD, there was no association between increased cIMT and GHD, but treatment with rhGH led to the appearance of carotid plaques ( 42 ). Rothermel et al ( 16 ) demonstrated cIMT increase in children treated for three years with a supraphysiological rhGH dose but not in those treated with a physiological dose. Another study did not demonstrate any change after four years of rhGH treatment in cIMT levels in a cohort consisting of children and adolescents receiving rhGH for various indications ( 17 ).…”

“…Alterations in body composition, carbohydrate metabolism and lipid profile have long been suspected of being risk factors for CVD in children with GHD ( 46 ), and in children treated with rhGH ( 16 , 17 , 25 ). In GHD children, rhGH therapy reduces insulin sensitivity and causes a compensatory hyperinsulinemia with normal glucose levels ( 26 ).…”

“…Furthermore, there was no difference between the subgroups stratified by IR. Limited studies evaluating the effect of body composition and serum lipid profile on cIMT in children have shown a positive association between cIMT and BMI-SDS ( 17 ) and baseline LDL-cholesterol ( 16 ). In our study, there were no associations between cIMT-SDS and body composition parameters (BMI-SDS at diagnosis and study time, ∆BMI-SDS, and waist-SDS), but lower HDL-cholesterol levels showed an independent association with higher cIMT-SDS.…”

“…The prodromal stage of atheromatous plaque begins very early in life ( 12 , 13 ) and it predicts CVD ( 14 , 15 ). Excessive GH secretion leading to acromegaly is a known cause of increased cIMT ( 4 ), but the results of the various studies which have examined cIMT in GH-deficient children treated with rhGH are controversial ( 16 , 17 , 18 , 19 ). Furthermore, none of these studies used sex- and height-specific normative cIMT values to calculate standard deviation (SD) scores (SDS) to compare with healthy children.…”