Circulating asymmetric dimethylarginine and lipid profile in pre-pubertal children with growth hormone deficiency: Effect of 12-month growth hormone replacement therapy
Introduction
Adults with growth hormone deficiency (GHD) are known to have reduced life expectancy because of increased cardiovascular and cerebrovascular events [1].
Previous studies have reported that adults as well as adolescents with severe GHD have a cluster of cardiovascular risk factors, including abnormal lipid profile, abdominal obesity, insulin resistance, hypertension, reduced exercise capacity, increased carotid intima-media thickness, and impaired cardiac morphology and function [2], [3], [4].
Impaired vascular reactivity, reduced bioavailability of nitric oxide (NO) and impaired oxidant-antioxidant status are all alterations detected in subjects with GHD, where they contribute to endothelial dysfunction, which in turn is one of the first events leading to cardiovascular disease [5], [6], [7].
During the last years there has been an increasing interest in a circulating marker of endothelial dysfunction, asymmetric dimethylarginine (ADMA), which is a naturally occurring l-arginine analogue found in plasma and various tissues [8]. ADMA is an endogenous inhibitor of endothelial NO synthase and in this way it contributes to the pathogenesis of endothelial dysfunction [9]. ADMA is considered as an emerging cardiovascular marker and its levels have been found to be increased in patients with hypercholesterolemia, hypertension, coronary artery disease, diabetes mellitus, chronic renal failure and hypopituitarism [10]. Interestingly, adult studies have shown that growth hormone (GH) replacement can decrease ADMA levels [11].
Increased levels of ADMA have also been reported in children and adolescents with pathological conditions, where they have been associated with early markers of atherosclerosis, such as increased carotid artery intima-media thickness [12]. However, up to now there are no studies on ADMA in GHD children. Limited are also pediatric studies [13], [14], [15] assessing other cardiovascular risk factors in children with GHD, and the potential beneficial effect of GH treatment on the cardiovascular profile of young people with this condition.
The aim of the present study was to evaluate ADMA levels along with other cardiovascular risk factors in pre-pubertal children with idiopathic GHD and to test whether 12-month GH replacement therapy could improve their cardiovascular profile.
Section snippets
Study population
We recruited 20 Caucasian pre-pubertal children (6 boys and 14 girls, mean age (± SD): 9.5 ± 1.8 years), who had been referred to the Endocrine Clinic of the Department of Pediatrics, University of Chieti, Italy, between May 2010 and July 2012, for short stature and in whom a diagnosis of GHD was made. These children were a subgroup of patients with a diagnosis of GHD made during that time period and who consecutively agreed to take part in the study.
These patients were matched for sex and age with
General characteristics of the study population at baseline
The baseline clinical and biochemical characteristics of the whole study population are reported in Table 1.
At baseline, GHD and control children were similar for age, sex distribution, weight, BMI and BMI SDS, whereas, as expected, a significant difference was found in height SDS. GHD patients also showed significantly lower IGF-1 SDS than control children (Table 1).
No significant difference between the two groups was found in parameters related to glucose metabolism, such as fasting glucose,
Discussion
In the present study we found elevated ADMA levels and an alteration in lipid profile in pre-pubertal children with GHD compared to age and sex-matched healthy controls. Interestingly, GH treatment was associated with an improvement in cardiovascular profile, as documented by decreased ADMA levels, total cholesterol and LDL-cholesterol, which reached values comparable to those in healthy children.
In adults, GHD is associated with an increased prevalence of premature atherosclerosis [20], [21]
Conflict of interest
None to declare.
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2016, Best Practice and Research: Clinical Endocrinology and MetabolismCitation Excerpt :These findings point towards a prothrombotic state in untreated GHD but further studies are necessary. Children with GHD were shown to have an impaired oxidant-antioxidant status with a reduced nitric oxide (NO) bioavailability and vascular reactivity, which in turn led to endothelial dysfunction and CVD [8,66]. Asymmetric dimethylarginine (ADMA) is an endogenous plasmatic inhibitor of endothelial NO synthase and is considered as a cardiovascular marker.
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