Short-term effects of GH treatment on coagulation, fibrinolysis, inflammation biomarkers, and insulin resistance status in prepubertal children with GH deficiency

Cañete, Ramón; Valle, Miguel; Martos, Rosario; Sánchez-Carrión, Adela; Cañete, María Dolores; Donkelaar, Eva L. van

doi:10.1530/eje-12-0214

Cited by 24 publications

(27 citation statements)

References 30 publications

(34 reference statements)

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“…Other studies have reported even increased insulin sensitivity in young pre- or early pubertal children, and that there is progressive deterioration in this insulin sensitivity with advancing age and pubertal development. [2930]…”

Section: Discussionmentioning

confidence: 99%

Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

Metwalley

Farghaly

El-Hafeez

2013

Indian J Endocr Metab

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Background:Growth hormone deficiency (GHD) in adults is associated with a cluster of cardiovascular risk factors that may contribute to an increased mortality for cardiovascular disease. In children, relatively few studies have investigated the effect of GHD and replacement therapy on cardiac performance and metabolic abnormalities that may place them at a higher risk of cardiovascular disease (CVD) at an early age.Aim:This study was aimed to assess the left ventricular function, lipid profile, and degree of insulin resistance in Egyptian children with GHD before and after 1 year of GH replacement therapy.Settings and Design:Prospective case-control study, single-center study.Materials and Methods:Thirty children with short stature due to GHD were studied in comparison to 20 healthy age- and sex-matched children. All subjects were subjected to history, clinical examination, auxological assessment, and echocardiography to assess the left ventricular function. Blood samples were collected for measuring IGF-1, lipid profile (Total, LDL, HDL cholesterol, triglyceride, and atherogenic index (AI), fasting blood sugar, and fasting insulin levels. In addition, basal and stimulated GH levels were measured in children with suspected GHD.Statistical Analysis Used:Student's t-test was used for parametric data, and the Mann-Whitney U-test was used for non-parametric data.Results:Total, LDL cholesterol, triglyceride, AI, and insulin were significantly higher in children with GHD than in healthy controls at baseline. After 12 months of GH replacement therapy, total, LDL cholesterol, triglyceride, AI and insulin were significantly decreased, while homeostatic model assessment for insulin resistance index (HOMA-IR) was significantly increased compared to both pre-treatment and control values. At baseline, the left ventricular mass (LVM) and left ventricular mass index (LVMi) were significantly lower in GHD children than in controls. After 12 months of GH replacement therapy, LVM and LVMi in GHD patients were significantly increased compared to pre-treatment values.Conclusions:GHD in children is associated with a significantly reduced cardiac mass and impairment of lipid profile. GH replacement therapy exerts beneficial effects both on cardiac mass and lipid metabolism by normalizing cardiac size and improving the lipid profile. On the contrary, an increase in insulin resistance is observed after 12 months GH treatment. The study suggests that children with GH deficiency should have echocardiography and lipid profile monitoring before and during treatment with GH.

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Section: Discussionmentioning

confidence: 99%

Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

Metwalley

Farghaly

El-Hafeez

2013

Indian J Endocr Metab

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“…Data derived from a cohort of 36 prepubertal children with GHD showed higher levels of fibrinogen and activated PAI‐1 compared with controls. Reduction in PAI‐1 concentrations, but not in fibrinogen and vWF levels, was observed after 6 months of GH replacement therapy …”

Section: Pituitary Disordersmentioning

confidence: 95%

The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications

Kyriakakis

Lynch

Ajjan

et al. 2015

Clinical Endocrinology

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Disturbances of coagulation and fibrinolysis are usually multifactorial and growing evidence suggests that endocrinopathies modulate the haemostatic balance. The thrombotic alterations in endocrine disorders range from mild laboratory clotting abnormalities with little clinical significance to serious thrombotic and bleeding disorders directly related to hormonal disturbances. This literature review focuses on presenting the current data on the effects of thyroid and pituitary disorders on various parameters of the haemostatic system. With the exception of overt hypothyroidism which appears to cause a bleeding tendency, the rest of the endocrinopathies discussed in this review (subclinical hypothyroidism, hyperthyroidism, endogenous hypercortisolaemia, growth hormone deficiency, acromegaly, prolactinoma/hyperprolactinaemia and hypogonadotrophic hypogonadism) are associated with a hypercoagulable and hypofibrinolytic state, increasing the overall cardiovascular risk and thromboembolic potential in these patients. In most studies, the haemostatic abnormalities seen in endocrine disorders are usually reversible with successful treatment of the underlying condition and biochemical disease remission. High-quality studies on larger patient cohorts are needed to produce robust evidence on the effects of endocrine disorders and their therapeutic interventions on coagulation and fibrinolysis, as well as on the long-term mortality and morbidity outcomes in association with endocrine-related haemostatic imbalance. Given the rarity of some of the endocrine disorders, multicentre studies are required to achieve this target.

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“…A number of serum circulating markers, including C-reactive protein (CRP), fibrinogen, active plasminogen activator inhibitor type-1 and homocysteine have been proposed as potential risk factors for atherothrombotic vascular disease [17,18]. …”

Section: Biochemical Alterations and The Effect Of R-hgh Therapymentioning

confidence: 99%

“…In the pediatric population, a few studies have been reported, some in adolescents with GHD, finding elevated CRP and fibrinogen levels [16,22,23,24]; however, less studies were conducted in prepubertal children with the identification of high levels of fibrinogen, CRP and homocysteine [11,16,17,25]. Of note, in all these studies, the biochemical parameters were reversed by short-term r-hGH therapy.…”

Section: Biochemical Alterations and The Effect Of R-hgh Therapymentioning

confidence: 99%

Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease

Leonibus¹,

Marco²,

Stevens³

et al. 2016

Horm Res Paediatr

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Background: Cardiovascular (CV) risk factors have been identified in adults with untreated growth hormone deficiency (GHD). Existing evidence suggests that the development of the atheromatous plaque begins early in childhood. Previous reports have shown that GHD children are prone to increased CV risks including impaired cardiac function, dyslipidemia and abnormalities in body composition. Recent studies in epigenetics and metabolomics have defined specific fingerprints that might be associated with an increased risk of CV disease. Aim: The aim of this review is to point out the most significant biochemical and clinical predictive markers of CV disease in prepubertal children and to evaluate the effect of recombinant human growth hormone therapy on most of these alterations. The novel findings in epigenetics and metabolomics are also reviewed, with a particular focus on translating them into clinical practice.

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Short-term effects of GH treatment on coagulation, fibrinolysis, inflammation biomarkers, and insulin resistance status in prepubertal children with GH deficiency

Abstract: At early ages, GH therapy appears to exert beneficial effects on the amount of aPAI-1. At the same time, it increases the state of insulin resistance (HOMA-IR index) without modifying the levels of fibrinogen, vWF, CRP, and IL6.

Cited by 24 publications

References 30 publications

Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

Evaluation of left ventricular mass and function, lipid profile, and insulin resistance in Egyptian children with growth hormone deficiency: A single-center prospective case-control study

The effects of pituitary and thyroid disorders on haemostasis: potential clinical implications

Growth Hormone Deficiency in Prepubertal Children: Predictive Markers of Cardiovascular Disease

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