Effect of oxidative stress on major plasma carotenoid content and composition in prepubertal children with growth hormone deficiency

Objective and hypotheses. This study aimed at examining the effect of oxidative stress on amount and composition of major plasma carotenoids in prepubertal children with growth hormone deficiency (GHD).Material and methods. Thirteen prepubertal treatment-naive children (2 girls, 11 boys; aged 3.5—12.0 yr, median 8.0 years; bone age 1.5—8.0 yr; median 6.0 years,) with GHD and 7 prepubertal health children (7 boys; aged 6—11 years; median 9.3 years) were included in the study. The levels and composition of carotenoids (lutein with zeaxanthin, lycopene isomers, β-cryptoxanthin, β- and α-carotene and ketocarotenoids) were measured using reverse phase HPLC. Activity of the antioxidant system was assayed via thiobarbituric acid reactive substances (TBARS), ceruloplasmin (CP) levels and total antioxidant capacity (TAC) of plasma. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were also measured.Results. The levels of TBARS, TC and LDL-C in the GHD children were higher than in healthy children (median 5.6 vs 3.8 µM/L, 4.00 vs 4.37 and 2.40 vs 2.70 mM/L, respectively). Total carotenoid level did not significantly differ between control and the GHD groups. However, contents of lutein and β-cryptoxanthin were significantly lower in the GHD children in comparison with control group (21.34 vs 6.97 and 25.23 vs 10.08 mg/l, respectively). In contrast, levels of lycopene, α- and β-carotene did not significantly differ in the GHD and control groups. At the same time, the level of ketocarotenoids in the GHD children increases (35.67 vs 114.9 mg/l).Conclusions. We observed that the presence of mild oxidative stress leads to a changes in carotenoid profile of GHD children.

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Psycho-Emotional and Behavioral Problems in Children With Growth Hormone Deficiency

Frontiers in Pediatrics ◽

10.3389/fped.2021.707648 ◽

2021 ◽

Vol 9 ◽

Author(s):

Mykola Aryayev ◽

Liudmyla Senkivska ◽

John B. Lowe

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Internalizing Problems ◽

Psychosocial Functioning ◽

Emotional Problem ◽

Self Esteem ◽

Hormone Deficiency ◽

Control Group ◽

Healthy Children ◽

Sociodemographic Determinants

Objective: To identify psychosocial problems and self-esteem in children with growth hormone deficiency (GHD) and define the role of some clinical and sociodemographic determinants in the conceptualization of internalizing and externalizing problems as criteria for psychosocial functioning.Materials and Methods: A GHD sample (46 prepubescent children) was selected and compared to a matched control group (80 healthy children). Psychosocial functioning in children with GHD was investigated using Goodman's “Strengths and Difficulties Questionnaire (SDQ).” The study of children's self-esteem was carried out by the Dembo–Rubinstein method.Results: This study reveals that the GHD sample has more internalizing problems and lower self-esteem. Higher score and frequency of assessment in the abnormal score for “total difficulties,” “emotional problem,” and “peer problem” were found in children with GHD. The SDQ score and the frequency of assessment in the abnormal score for all SDQ scales in children with more pronounced growth deficit (height SDS < −3) did not exceed the same indicators in children with less growth retardation (−3 < height SDS < −2). A comparison of psychosocial features in children with isolated growth hormone deficiency and multiple pituitary hormones deficiency did not reveal differences in SDQ score and the frequency of assessment in the abnormal score for all SDQ scales. It was found that children with GHD have a reduced level of assertions, low self-esteem, and a weak discrepancy between the level of assertions and self-esteem. Some sociodemographic determinants (male gender, age < 9 years, and low family income) and clinical determinants (low compliance and suboptimal growth response after 1 year of rGHh therapy) have an impact on the overall assessment of psychological problems in children with GHD. The internalizing difficulties are associated with certain clinical determinants (growth status and treatment status) and sociodemographic determinants (female gender, age < 9 years).Conclusions: The identification of low self-esteem and the high SDQ score for scales “total difficulties,” “emotional problems,” and “peer problems” indicates psychosocial maladjustment and conceptualization of internalizing problems in children with GHD.

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The associations between the growth hormone/insulin-like growth factor-1 axis, adiponectin, resistin and metabolic profile in children with growth hormone deficiency before and during growth hormone treatment

Acta Biochimica Polonica ◽

10.18388/abp.2018_2601 ◽

2018 ◽

Vol 65 (2) ◽

pp. 333-340 ◽

Cited By ~ 2

Author(s):

Ewelina Witkowska-Sędek ◽

Małgorzata Rumińska ◽

Anna Stelmaszczyk-Emmel ◽

Anna Majcher ◽

Beata Pyrżak

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Growth Hormone Deficiency ◽

Total Cholesterol ◽

Metabolic Profile ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Hormone Deficiency ◽

Gh Therapy ◽

Gh Treatment

The study investigated the associations between the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis, adiponectin, resistin and metabolic profile in 47 GH-deficient children before and during 12 months of GH treatment. 23 short age-matched children without growth hormone deficiency (GHD) or any genetic or chronic disorders were recruited as controls at baseline. Metabolic evaluation included measurements of adiponectin, resistin, IGF-1, total cholesterol (total-C), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glucose, insulin, glycated hemoglobin (HbA1c), thyroid stimulating hormone (TSH) and free thyroxine (free T4) concentrations. The GH-deficient children had significantly higher adiponectin (p<0.05) and total cholesterol (p<0.05) and significantly lower resistin (p<0.05) than the controls. Resistin at 6 months of GH treatment correlated significantly with changes in height SDSin that period (r=0.35) and with fasting insulin (r=0.50), the HOMA-IR (r=0.56) and the QUICKI (r= - 0.53) at 12 months of therapy. Adiponectin at 12 months of GH treatment was significantly associated with changes in HDL-C within the first 6 months (r=0.73) and also within 12 months (r=0.56) of therapy, while resistin correlated significantly with an increment in IGF-1 within 12 months of treatment (r=0.49) and with total-C at 12 months (r=0.56). Untreated GH-deficient children had higher adiponectin and lower resistin than healthy short children without GHD. Adiponectin and resistin did not change significantly during the first 12 months of GH therapy. Good responders to GH treatment had a tendency for higher resistin during GH therapy, which correlates positively with insulin resistance parameters.

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Circadian variation of plasma cortisol in prepubertal children with normal stature, short stature and growth hormone deficiency

Clinical Endocrinology ◽

10.1046/j.1365-2265.1999.00674.x ◽

1999 ◽

Vol 50 (4) ◽

pp. 473-479 ◽

Cited By ~ 2

Author(s):

Ramón C. Hermida ◽

Leopoldo García ◽

Diana E. Ayala ◽

José R. Fernández

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Plasma Cortisol ◽

Circadian Variation ◽

Hormone Deficiency ◽

Prepubertal Children ◽

Normal Stature

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Effects of human recombinant growth hormone on exercise capacity, cardiac structure, and cardiac function in patients with adult-onset growth hormone deficiency

Journal of International Medical Research ◽

10.1177/0300060517723798 ◽

2017 ◽

Vol 45 (6) ◽

pp. 1708-1719 ◽

Cited By ~ 4

Author(s):

S Gonzalez ◽

JD Windram ◽

T Sathyapalan ◽

Z Javed ◽

AL Clark ◽

...

Keyword(s):

Growth Hormone ◽

Cardiac Function ◽

Growth Hormone Deficiency ◽

Exercise Capacity ◽

Left Ventricular ◽

Hormone Deficiency ◽

Control Group ◽

Cardiac Structure ◽

Adult Onset ◽

Risk Of Death

Objective Epidemiological studies suggest that adult-onset growth hormone deficiency (AGHD) might increase the risk of death from cardiovascular causes. Methods This was a 6-month double-blind, placebo-controlled, randomised, cross-over trial followed by a 6-month open-label phase. Seventeen patients with AGHD received either recombinant human growth hormone (rGH) (0.4 mg injection daily) or placebo for 12 weeks, underwent washout for 2 weeks, and were then crossed over to the alternative treatment for a further 12 weeks. Cardiac magnetic resonance imaging, echocardiography, and cardiopulmonary exercise testing were performed at baseline, 12 weeks, 26 weeks, and the end of the open phase (12 months). The results were compared with those of 16 age- and sex-matched control subjects. Results At baseline, patients with AGHD had a significantly higher systolic blood pressure, ejection fraction, and left ventricular mass than the control group, even when corrected for body surface area. Treatment with rGH normalised the insulin-like growth factor 1 concentration without an effect on exercise capacity, cardiac structure, or cardiac function. Conclusion Administration of rGH therapy for 6 to 9 months failed to normalise the functional and structural cardiac differences observed in patients with AGHD when compared with a control group.

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Relationship between 1 Month Biomarker Changes and 1 Year Growth Response in Prepubertal Children with Growth Hormone Deficiency (GHD) or Turner Syndrome (TS) Treated for 1 Year with GH: The PREDICT Multicentre, Observational Follow-Up Study.

10.1210/endo-meetings.2010.part1.p14.p1-677 ◽

2010 ◽

pp. P1-677-P1-677

Author(s):

P Chatelain ◽

L Tato ◽

V Peterkova ◽

A Belgorosky ◽

R Reynaud ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Turner Syndrome ◽

Growth Response ◽

Hormone Deficiency ◽

Prepubertal Children ◽

Follow Up Study

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Can plasma antioxidants prevent DNA damage in oxidative stress condition induced by growth hormone deficiency? A pilot study

PLoS ONE ◽

10.1371/journal.pone.0248971 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0248971

Author(s):

Antonio Mancini ◽

Francesco Guidi ◽

Carmine Bruno ◽

Flavia Angelini ◽

Edoardo Vergani ◽

...

Keyword(s):

Oxidative Stress ◽

Growth Hormone ◽

Pilot Study ◽

Oxidative Damage ◽

Growth Hormone Deficiency ◽

Hormone Deficiency ◽

Serum Samples ◽

Adult Growth ◽

Significant Difference ◽

Thymidine Glycol

Adult growth hormone deficiency (GHD), a condition characterized by increased oxidative stress, is related to augmented cardiovascular, metabolic and oncological risk. A case-control observational study has been performed to evaluate DNA oxidative damage analysing the production of thymidine-glycol in lymphocytes and its correlation with plasma antioxidant levels, evaluated as Total Antioxidant Capacity (TAC). GHD was diagnosed using GHRH 50μg iv+arginine 0,5 g/Kg test, with peak GH response <9 μg/L when BMI was <30 kg/m2 or <4 μg/L when BMI was >30 kg/m2. Three groups were identified: total GHD (n = 16), partial GHD (n = 11), and controls (n = 12). Thymidine-glycol, TAC and IGF-1 have been determined respectively in lymphocytes, plasma and serum samples. When considering thymidine-glycol, we found a significant difference between total vs partial GHD and controls. Unexpectedly thymidine-glycol was lower in total GHD, also accompanied with a significant increase in plasmatic TAC. Our results showed that in adult GHD condition, the production of antioxidant species, in response to increased oxidative stress, could exert a protective effect on thymidine-glycol formation, and consequently on DNA intracellular damages. This pilot study could be inserted in the complex scenario of oxidative damage of GHD, a subtle, yet poorly defined condition, worthy of further insights.

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Cholesterol Metabolism Is Enhanced in the Liver and Brain of Children With Citrin Deficiency

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2017-02664 ◽

2018 ◽

Vol 103 (7) ◽

pp. 2488-2497 ◽

Cited By ~ 1

Author(s):

Satoshi Hirayama ◽

Hironori Nagasaka ◽

Akira Honda ◽

Haruki Komatsu ◽

Takahiro Kodama ◽

...

Keyword(s):

Cholesterol Synthesis ◽

Cholesterol Metabolism ◽

Density Lipoprotein ◽

Normal Liver ◽

Serum Lipoprotein ◽

Lipoprotein Cholesterol ◽

Control Group ◽

Healthy Children ◽

Citrin Deficiency ◽

Deficient Group

Abstract Context Citrin-deficient infants present neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), which resolves at 12 months. Thereafter, they have normal liver function associated with hypercholesterolemia, and a preference for lipid-rich carbohydrate-restricted diets. However, some develop adult-onset type II citrullinemia, which is associated with metabolic abnormalities. Objectives To identify the causes of hypercholesterolemia in citrin-deficient children post-NICCD. Design and Setting We determined the concentrations of sterol markers of cholesterol synthesis, absorption, and catabolism by liquid chromatography–electrospray ionization–tandem mass spectrometry and evaluated serum lipoprotein profiles. Subjects Twenty citrin-deficient children aged 5 to 13 years and 37 age-matched healthy children. Intervention None. Main Outcome Measures Relationship between serum lipoproteins and sterol markers of cholesterol metabolism. Results The citrin-deficient group had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than did the control group (78 ± 11 mg/dL vs 62 ± 14 mg/dL, P < 0.001), whereas the two groups had similar low-density lipoprotein cholesterol and triglyceride concentrations. The concentrations of markers of cholesterol synthesis (lathosterol and 7-dehydrocholesterol) and bile acids synthesis (7α-hydroxycholesterol and 27-hydroxycholesterol) were 1.5- to 2.8-fold and 1.5- to 3.9-fold, respectively, higher in the citrin-deficient group than in the control group. The concentration of 24S-hydroxycholesterol, a marker of cholesterol catabolism in the brain, was 2.5-fold higher in the citrin-deficient group. In both groups, the HDL-C concentration was significantly positively correlated with that of 27-hydroxycholesterol, the first product of the alternative bile acid synthesis pathway. Conclusions HDL-C and sterol marker concentrations are elevated in citrin-deficient children post-NICCD. Moreover, cholesterol synthesis and elimination are markedly enhanced in the liver and brain of citrin-deficient children.

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Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature

Acta Endocrinologica ◽

10.1530/acta.0.1270351 ◽

1992 ◽

Vol 127 (4) ◽

pp. 351-358 ◽

Cited By ~ 16

Author(s):

Zvi Laron ◽

Anne-Maria Suikkari ◽

Beatrice Klinger ◽

Aviva Silbergeld ◽

Athalia Pertzelan ◽

...

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Hormone Deficiency ◽

Pituitary Hormone ◽

Healthy Children ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Igf I

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p<0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N= 10) or subcutaneous (N=9) administration ofIGF-I (75 μg·kg−1 and 150 μg·kg−1, respectively) in LTD children resulted in a rapid 50–60% fall in serum insulin (p<0.02), a decline in blood glucose and a concomitant 40–60% rise of IGFBP-1 levels (p<0.05). Treatment for seven days with IGF-I (150 μg·kg−1·d−1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p<0.05), in GHD adults by 52% (p<0.02) and in children with constitutional short stature by 17% (p<0.02). IGFBP-1 and insulin concentrations were inversely related in patients with GHD (r= −0.66, p<0.001) or with LTD (r= −0.57, p<0.05). Our data suggest that: (a) increased IGFBP-1 concentration in LTD, GHD and constitutional short children may, at least in part, be accounted for by an IGF-I deficiency; (b) both the rise in IGF-I and a fall in insulin contributed to the rise in IGFBP-1 after acute IGF-I administration; (c) prolonged IGF-I or GH treatment causes a persistent decline in IGFBP-1 concentration. In conclusion, IGF-I and GH may regulate IGFBP-1 secretion either directly or via insulin.

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Total Oxidant and Antioxidant Status in Prepubertal Children with Obesity

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/5621989 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 8

Author(s):

Grażyna Rowicka ◽

Hanna Dyląg ◽

Jadwiga Ambroszkiewicz ◽

Agnieszka Riahi ◽

Halina Weker ◽

...

Keyword(s):

Oxidative Stress ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Significant Negative Correlation ◽

Stress Index ◽

Healthy Children ◽

Obese Children ◽

Free Radical Damage ◽

Prepubertal Children

Aims. Obesity is accompanied by the formation of oxygen free radicals, whose intensified activity without effective defense mechanisms can lead to oxidative stress and related complications. We evaluated the presence of oxidative stress in obese prepubertal children. Methods. The study included 83 healthy children aged 2–10 years (62 with obesity and 21 nonobese controls). Total oxidant capacity (TOC), total antioxidant capacity (TAC), oxidized low-density lipoprotein (ox-LDL), lipid parameters, glucose, and C-reactive protein (CRP) were measured in serum. Oxidative stress index (OSI) was calculated. Results. Serum TOC concentration was significantly higher (p<0.05) and TAC concentration was lower (p<0.05) in obese children. OSI was higher (p<0.01) in obese subjects compared with controls. CRP levels were normal in all children, but median CRP value was higher (p<0.01) and HDL cholesterol levels were lower (p<0.05) in the obese group. We found a significant negative correlation between TAC and ox-LDL concentrations (r=−0.27, p<0.05) in obese children. Furthermore, obesity duration was positively correlated with TOC level (r=0.32, p<0.05) in this group. Conclusions. Obesity-related oxidative stress already occurs in prepubescence. Early obesity diagnosis and the necessary therapeutic activity implementation is a vital strategy for the prophylaxis of free radical damage and related multiorgan complications.

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