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Biomedical subjects

Jürgen Kratzsch

Publications and source records attributed to Jürgen Kratzsch.

At least 19 recordsLinked to original sources
PubMed2006

Resistin and adiponectin in major depression: the association with free cortisol and effects of antidepressant treatment.

Major depression is associated with an increased risk for myocardial infarction. Adipokines have been shown to link obesity with metabolic disturbances. Based on this finding the present study was designed to investigate the effect of antidepressive treatment with either amitriptyline or paroxetine on circulating concentrations of resistin and adiponectin in depressed patients, and to establish, whether these adipokines are associated with the activation of the hypothalamic-pituitary-adrenal (HPA)-system. Thirty-seven depressed in-patients were treated in a double-blind, randomized protocol with either amitriptyline or paroxetine over a period of five weeks. After six drug free days blood was drawn on day 1 and again 36 days after antidepressive treatment for the measurement of resistin and adiponectin, fasting glucose and insulin concentrations. For quantification of free cortisol levels saliva was obtained daily at 0800 hours during weeks 1 and 5. While resistin concentrations decreased in patients remitting under amitriptyline and paroxetine (p<0.03), no changes were observed in non-remitters. At baseline, though not during treatment, circulating resistin concentrations correlated positively with free cortisol levels and with BMI (p<0.01). Adiponectin levels, however, did not change during treatment and were not associated with free cortisol concentrations but were instead positively related to QUICKI (p<0.03). In conclusion, the present data revealed resistin but not adiponectin to be related to free cortisol concentrations and to decline in remitters to antidepressive treatment.

Adiponectin↗
PubMed2006

Effect of a 4 week physical training program on plasma concentrations of inflammatory markers in patients with abnormal glucose tolerance.

OBJECTIVE: Subclinical chronic inflammation could be a unifying factor linking type 2 diabetes (T2D) and atherosclerosis. The beneficial effects of physical activity on a reduced risk of coronary heart disease could at least in part be mediated by improved markers of inflammation. RESEARCH DESIGN AND METHODS: The aim of this study was to determine the effect of 4 weeks of physical training on plasma concentrations of interleukin (IL)-6, C-reactive protein (CRP), adiponectin and IL-10 in 60 individuals with normal glucose tolerance, impaired glucose tolerance (IGT) or T2D. RESULTS: In patients with IGT and T2D, significant improvement in body fat, fitness level, glucose metabolism and insulin sensitivity after 4 weeks of physical training was associated with significantly improved plasma concentrations of adiponectin and CRP, but not IL-6. Regression analysis demonstrated only for the anti-inflammatory parameters adiponectin and IL-10 a significant relationship with the decrease in fasting plasma glucose, whereas changes in IL-6 and CRP were not significantly related to changes in fasting plasma glucose, body fat, maximal oxygen uptake, or insulin sensitivity. In a multivariate linear regression analysis, only changes in circulating adiponectin, fasting plasma glucose and percentage body fat were determinants of changes in insulin sensitivity. CONCLUSIONS: Physical training was associated with a near normalization of adiponectin and CRP plasma concentrations in subjects with IGT and T2D. Increased insulin sensitivity after training was most strongly related to changes in adiponectin plasma concentrations, in fasting plasma glucose and percentage body fat, whereas changes in IL-6, IL-10 and CRP plasma concentrations did not significantly contribute to improved insulin sensitivity.

Adiponectin↗
PubMed2005

Physical activity and restlessness correlate with leptin levels in patients with adolescent anorexia nervosa.

BACKGROUND: In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia nervosa (AN). METHODS: Serum leptin, body mass index (BMI), % body fat, and self- and expert-ratings of qualities of physical activity and restlessness were assessed in 26 inpatients with acute AN. Accelerometry was also performed. Regression analyses were used to predict activity and restlessness using BMI, % body fat, and leptin levels as predictor variables. RESULTS: Leptin levels significantly contributed to the prediction of all measures of activity and restlessness. CONCLUSIONS: This is the first study linking hypoleptinemia in AN patients to subjective and objective measures of higher physical activity and motor and inner restlessness. Leptin may directly or indirectly (or both) influence behaviors and cognitions contributing to hyperactivity and motor restlessness.

Adolescent↗
PubMed2005

Adiponectin expression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight.

Adiponectin is an adipocytokine with profound anti-diabetic and anti-atherogenic effects. Even though adiponectin expression is restricted to adipocytes, serum levels are paradoxically decreased in obesity. We characterized how adiponectin expression and regulation relates to adipocyte differentiation in a human adipocyte cell culture model. Adiponectin was not expressed by human preadipocytes. Differentiation into adipocytes was necessary to induce an increasing expression of adiponectin (359 +/- 64-fold, P < 0.001) in parallel to an increasing expression of adipocyte differentiation markers. Adiponectin protein synthesis and secretion occurred specifically in mature adipocytes and may thus serve as a distinctive marker of adipocyte differentiation. Addition of serum during the course of differentiation as well as acutely to mature adipocytes significantly and concentration-dependently suppressed adiponectin to almost non-detectable levels (to 9.8 +/- 0.03%, P = 0.0043), suggesting a strong humoral serum component of adiponectin down-regulation. This serum component is present in both obese and lean individuals with a tendency to a stronger effect in obese men and women. Separation by molecular size suggests that higher molecular weight (>30 kDa) fractions exert inhibition of adiponectin. Withdrawal of adipogenic ingredients from the culture medium also resulted in a decrease of adiponectin expression and secretion to 62.01 +/- 0.09% and 70.86 +/- 0.05%, respectively. We identified insulin as a critical component to maintain adiponectin expression with a down-regulation to 61.6 +/- 0.1% (P = 0.0011) in the absence of insulin. These dynamic changes of adiponectin expression and regulation with adipocyte differentiation are of physiological interest in the light of the paradoxical decrease of adiponectin levels and the continuous recruitment of preadipocytes for differentiation in obesity.

Adipocytes↗
PubMed2005

Circulating resistin concentrations in children depend on renal function.

BACKGROUND: Resistin is a newly discovered peptide hormone that inhibits adipogenesis. Furthermore, it may be involved in regulative processes taking place in insulin resistance and inflammation. In human beings as well as in rodents, the exact physiological role of resistin is unknown. The objective of this study was to examine whether resistin serum concentrations in childhood are regulated by renal function. METHODS: Fifteen patients with end stage renal disease treated by haemodialysis (HD) (6m, 9f; age (median (25-75% percentile)) 16.1 (14.2-16.9) years; body mass index (BMI) 17.8 (17.6-20.6) kg/m2; glomerular filtration rate (GFR)<10 ml/min/1.73 m2), 11 patients with chronic renal failure (CRF) (4m, 7f; age 11.3 (9.2-16.9) years; BMI 17.9 (15.4-22.1) kg/m2; GFR 21.2 (19.8-39.4) ml/min/1.73 m2) and 23 healthy children (13m, 10f; age 7.8 (4.7-14.5) years; BMI 16.5 (14.9-18.1) kg/m2; GFR 168.5 (154.0-197.2) ml/min/1.73 m2) were included. Resistin concentration in serum was measured by ELISA, leptin by RIA. RESULTS: Resistin concentrations were significantly elevated in HD (6.6 (5.7-8.7) ng/ml) and CRF (4.8 (4.1-6.2) ng/ml) compared to healthy controls [2.7 (2.0-3.6) ng/ml; P<0.0001 by multiple regression analysis]. Furthermore, resistin concentrations showed a tendency to be higher in children below the age of 5.5 years (youngest tertile) and above 12.5 years of age (oldest tertile), compared to children aged between 5.5 and 12.5 years (P=0.053 and P=0.043, respectively). Gender (P=0.686) and BMI (P =0.663) did not have a significant influence on resistin concentrations. Resistin and leptin serum concentrations correlated in HD patients only (r=0.62, P=0.013 by Spearman correlation). Haemodialysis did not eliminate resistin. CONCLUSIONS: With decreasing renal function, resistin concentration in serum increases in our small paediatric cohort. Age possibly influences circulating resistin concentration. The hypothesis that elevated serum resistin in children with chronic renal failure or end stage renal disease may add to malnutrition and reduced BMI needs further investigation and is not supported by our data.

Adolescent↗
PubMed2005

Evidence against a direct effect of leptin on insulin-like growth factor-I (IGF-I), IGFBP-2 and IGF-I receptor expression in human SK-N-MC neuroepithelioma cells.

The ob gene product, leptin, is synthesized by adipocytes. In rodents, its main role is to regulate energy expenditure and food intake. The growth hormone (GH)-insulin-like growth factor (IGF) system is also ubiquitously expressed, is also involved in energy homeostasis and shares some of the signaling molecules of leptin and its receptors. Therefore, we have asked whether or not leptin interacts with the GH-IGF system in an in vitro model. SK-N-MC cells were chosen for further investigation since they express IGF-I, IGF-I receptor and IGFBP-2 mRNA and secrete IGF-I and IGFBP-2 protein. Specific leptin receptor mRNA, both short and long isoform transcripts, were identified in SK-N-MC cells by RT-PCR. Secondly and most importantly, when SK-N-MC cells were cultured in the presence of leptin, neither IGF-I, nor IGF-I receptor or IGFBP-2 mRNA expression was different than in the absence of leptin. In addition, an increase in leptin did not alter secretion of immunoreactive IGF-I or IGFBP-2 protein into cell culture medium. In conclusion, (1) human SK-N-MC neuroepithelioma cells express ob and leptin receptor mRNA and secrete leptin. (2) Added exogenous leptin does not affect IGF-I, IGFBP-2 or IGF-I receptor mRNA expression and IGF-I and IGFBP-2 secretion by SK-N-MC cells in vitro under the conditions studied. We hypothesize that leptin and the IGF system do not interact directly in a cell culture model of neuroepithelioma cells.

Animals↗
PubMed2005

Leptin as a new diagnostic tool in chronic heart failure.

Leptin, the product of the ob-gene, regulates cellular homeostasis and glycemic control. While initially described as an adipocyte-derived protein with expression and secretion restricted to adipose tissue, recent reports have shown local expression of leptin in several tissues including the skeletal muscle, heart, vessels and brain. Leptin acts through the different isoforms of its receptor which are ubiquitously expressed and can be detected in endothelium, vascular smooth muscle and myocardium. In addition to its metabolic effects, leptin has distinct effects in the cardiovascular system leading to increased production of proinflammatory cytokines and oxidative stress, vascular remodeling and neointima formation as well as cardiomyocyte hypertrophy. Notably, recent clinical studies have linked serum levels of leptin to the occurrence of cardiovascular events such as myocardial infarction and stroke suggesting that leptin promotes pro-atherogenic vascular mechanisms. In contrast, less is known about the role and effects of leptin in the setting of chronic heart failure. We here review the current knowledge on cardiovascular effects of leptin and discuss its potential as a new therapeutic tool in chronic heart failure.

Animals↗
PubMed2005

Adipocytokines: leptin--the classical, resistin--the controversical, adiponectin--the promising, and more to come.

With the growing prevalence of obesity, scientific interest in the biology of adipose tissue has been extended to the secretory products of adipocytes, since they are increasingly shown to affect several aspects in the pathogenesis of obesity-related diseases. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centred in the hypothalamus. In recent years, a number of additional signalling molecules secreted by adipose tissue have been discovered, commonly referred to as 'adipocytokines'. Among these, adiponectin is perhaps the most interesting and promising compound for the clinician since it has profound protective actions in the pathogenesis of diabetes and cardiovascular disease. Adiponectin is low in obese subjects and, in particular, insulin-resistant patients. In contrast, resistin seems to be of greater relevance in relation to the immune stress response than in the regulation of glucose homeostasis. However, inflammatory processes have recently been connected with the development of atherosclerosis. Finally, little is known regarding the clinical relevance of visfatin. Recent research has revealed many functions of adipocytokines extending far beyond metabolism, such as immunity, cancer and bone formation. This report aims to review some of the recent topics of adipocytokine research that may be of particular importance.

Adiponectin↗
PubMed2005

Insulin-like growth factor I, growth hormone and insulin in white adipose tissue.

Maturation of adipose tissue results from both the expansion of mature adipocytes and the formation of new adipocytes from adipocyte precursor cells. A variety of hormones related to adipogenesis have been identified recently. Both growth hormone (GH) and insulin-like growth factor I (IGF-I) are of major significance in adipocyte differentiation. IGF-I has been suggested to be a major regulator of cell proliferation, differentiation and metabolism, thus regulating, among other biological processes, adipose tissue growth and differentiation of pre-adipocytes into adipocytes. GH exerts its effects by increasing the pool of adipocyte precursor cells capable of differentiating into mature adipocytes. In addition, GH seems to have the potential to reduce the volume of mature adipocytes, thus inhibiting the expansion of adipose tissue and reducing body fat. This chapter gives an overview of studies that have investigated the roles of insulin, GH and IGF-I in adipogenesis.

Adipocytes↗
PubMed2005

Association of plasma resistin levels with coronary heart disease in women.

OBJECTIVE: To examine the association between plasma resistin levels and the presence of coronary heart disease (CHD) in women. RESEARCH METHODS AND PROCEDURES: Plasma resistin levels were measured in a case-control study including 185 women with angiographically confirmed CHD and 227 population-based female controls from the Coronary Risk Factors for Atherosclerosis in Women (CORA) study. RESULTS: After adjustment for age, smoking, family history of myocardial infarction, retirement, education, physical activity, menopausal status, hormone replacement use, BMI, hypertension, diabetes, and dyslipidemia, the odds ratio for CHD for women in the highest compared with lowest quintile of plasma resistin levels was 3.19 (95% confidence interval, 1.44 to 7.10; p log trend, 0.001). After additional adjustment for plasma C-reactive protein levels, this association was substantially attenuated and no longer significant (odds ratio, 1.80; 95% confidence interval, 0.69 ti 4.69; p trend = 0.23). DISCUSSION: These results suggest that plasma resistin levels are significantly associated with the presence of CHD in women; however, this association can largely be explained by concomitant inflammatory processes. Further studies are needed to determine the causal role of resistin in the development of CHD in humans.

Adult↗
PubMed2005

Effects of exercise training on insulin-like growth factor-I expression in the skeletal muscle of non-cachectic patients with chronic heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with progressive muscle atrophy and reduced local expression of insulin-like growth factor I (IGF-I). DESIGN: The present study was designed to test the hypothesis that the local deficiency of IGF-I in the skeletal muscle of patients with CHF would respond to a 6-months aerobic training intervention. Therefore, 18 patients [mean age 52.4 (SD 4.8) years, left ventricular ejection function (LVEF) 27 (SD 6)%] were prospectively randomized to either 6 months of training or sedentary lifestyle. METHODS: Serum levels of growth hormone (GH) were measured by immunofluorometric assay, IGF-I by competitive solid phase immunoassay. IGF-I expression was assessed in vastus lateralis biopsies by real-time PCR. RESULTS: Exercise training led to a significant increase in peak oxygen uptake by 26% [from 20.3 (SD 3.3) ml/kg per min to 25.5 (SD 5.7) ml/kg per min, P=0.003 versus control]. Local expression of IGF-I increased significantly after exercise training by 81% [from 6.3 (SE 0.8) to 11.4 (SE 1.4) relative units, P=0.007 versus control] while IGF-I receptor expression was reduced by 33% [from 20.0 (SE 2.1) to 13.8 (SE 1.7) relative units, P=0.008 versus control]. Serum growth hormone (GH) rose modestly from 0.12 (SE 0.07) to 0.65 (SE 0.37) ng/ml in the training group (P=0.043 versus baseline), however, this change was not significant compared to the control group (P=0.848). IGF-I serum levels remained virtually unchanged. CONCLUSIONS: Exercise training improves local IGF-I expression without significant changes of systemic parameters of the GH/IGF-I axis. These findings indicate that exercise training has the therapeutic potential to attenuate peripheral skeletal muscle alterations in particular with respect to local IGF-I expression in patients with moderate CHF.

Adult↗
PubMed2005

Comparison of adrenal function tests in children--the glucagon stimulation test allows the simultaneous assessment of adrenal function and growth hormone response in children.

The accurate assessment of adrenal function is necessary in many children with suspicion of pituitary insufficiency. The objective of this study was to evaluate the adrenal response during the glucagon stimulation test (GST) and its diagnostic utility in children. A total of 290 children, aged 10.1 +/- 5.0 years, were evaluated for adrenal function using the corticotrophin releasing hormone (CRH) test, the GST, and/or the insulin tolerance test (ITT). Glucagon stimulation provoked a substantial rise in cortisol and adrenocorticotropin (ACTH) that was independent of gender, age, or underlying growth hormone deficiency. There were no differences in peak cortisol levels in the GST compared to the CRH test in pair-wise intra-individual analyses in children with both tests performed within one year (615.4 +/- 30.5 vs 602.8 +/- 22.4 nmol/l, n=52). Similarly, there were no differences in the cortisol response between the ITT and CRH test. Peak cortisol levels in the CRH test correlated with the GST and the ITT. The magnitude of ACTH response, in contrast, was highest in the ITT with a 9.8-fold increase over baseline, while the increase in the GST (3.1-fold) and CRH test (1.6-fold) were more subtle. Since there is controversy concerning reliable cut-off values for adrenal function tests in children, we analyzed cut off levels in 186 children, including 26 children with adrenal insufficiency, using the CRH test. A peak cortisol level of 450 nmol/l provided the best balance of sensitivity (88.5%) and specificity (86.8%), while higher cut-off levels did not increase sensitivity but lost in specificity. In summary, the GST constitutes an1 equally sensitive test for the assessment of adrenal function in children that is not confounded by anthropometric parameters and is generally not accompanied by major side effects. It allows the simultaneous assessment of corticotroph and somatotroph function and may thus constitute a valuable alternative to the ITT.

Adolescent↗
PubMed2004

Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels.

Adiponectin is an adipocytokine with profound antidiabetic and antiatherogenic effects that is decreased in obesity. With the increasing prevalence of obesity and the emergence of related disorders, including type 2 diabetes in children, the regulation of adiponectin and its relationship to childhood obesity is of great interest. In this study we aimed to elucidate the impact of gender, pubertal development, and obesity on adiponectin levels in children. We investigated two phenotypically characterized cohorts of 200 normal weight and 135 obese children and adolescents covering a wide range of age (3.4-17.9 yr) and body mass index (-2.1 to +4.8 sd score). In healthy lean boys, adiponectin levels significantly declined in parallel with physical and pubertal development, subsequently leading to significantly reduced adiponectin levels in adolescent boys compared with girls (5.6 +/- 0.5 vs. 7.1 +/- 0.5 mg/liter; P = 0.03). This decline was inversely related to testosterone (r = -0.42; P < 0.0001) and dehydroepiandrosterone sulfate (r = -0.20; P = 0.0068) serum concentrations and may account for the gender differences seen in adults. Using a stepwise forward multiple regression model, pubertal stage was the strongest independent predictor of adiponectin (r(2) = 0.206; P < 0.0001), with additional influences of body mass index sd score and testosterone. Adiponectin levels were decreased in obese children and adolescents compared with lean peers of corresponding age and pubertal stage (5.18 vs. 7.13 mg/liter; P = 0.015). In obese children, adiponectin levels were closely associated with parameters related to the metabolic syndrome, such as insulin resistance, hyperinsulinemia, blood pressure, and uric acid, in univariate and multivariate analyses, with the insulin sensitivity index being the strongest independent parameter identified by stepwise forward multiple regression (r(2) = 0.226; P < 0.0001). Hence, there is a strong association of adiponectin serum concentrations with obesity, pubertal development, and metabolic parameters in children indicating epidemiological and pathophysiological relevance already in childhood.

Adiponectin↗
PubMed2004

PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.

Mutations in the PROP1 gene are the most frequent genetic defects in patients with combined pituitary hormone insufficiency. However, controversy exists about the timing and extent of pituitary insufficiency, and it remains unclear whether adrenal failure is a typical feature of this condition. We performed a retrospective longitudinal analysis of nine patients with PROP1 mutations who were under medical supervision at our clinic for 15.7 +/- 3.4 yr. All patients initially presented with growth failure (height sd score, -3.7 +/- 0.3) at a mean age of 4.9 +/- 0.8 yr. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 yr, respectively. All seven patients who reached pubertal age required sex hormone substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency, with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 +/- 3.5 yr. It is concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence.

Adolescent↗
PubMed2003

IGF-I receptor mutations resulting in intrauterine and postnatal growth retardation.

BACKGROUND: Approximately 10 percent of infants with intrauterine growth retardation remain small, and the causes of their growth deficits are often unclear. We postulated that mutations in the gene for the insulin-like growth factor I receptor (IGF-IR) might underlie some cases of prenatal and postnatal growth failure. METHODS: We screened two groups of children for abnormalities in the IGF-IR gene. In one group of 42 patients with unexplained intrauterine growth retardation and subsequent short stature, we used single-strand conformation polymorphism analysis, followed by direct DNA sequencing of any abnormalities found. A second cohort consisted of 50 children with short stature who had elevated circulating IGF-I concentrations. Complete sequencing of the IGF-IR gene was performed with DNA from nine children. We also studied a control group of 43 children with normal birth weights. RESULTS: In the first cohort, we identified one girl who was a compound heterozygote for point mutations in exon 2 of the IGF-IR gene that altered the amino acid sequence to Arg108Gln in one allele and Lys115Asn in the other. Fibroblasts cultured from the patient had decreased IGF-I-receptor function, as compared with that in control fibroblasts. No such mutations were found in the 43 controls. In the second group, we identified one boy with a nonsense mutation (Arg59stop) that reduced the number of IGF-I receptors on fibroblasts. Both children had intrauterine growth retardation and poor postnatal growth. CONCLUSIONS: Mutations in the IGF-IR gene that lead to abnormalities in the function or number of IGF-I receptors may also retard intrauterine and subsequent growth in humans.

Amino Acid Sequence↗
PubMed2003

Muscular levels of proinflammatory cytokines correlate with a reduced expression of insulinlike growth factor-I in chronic heart failure.

OBJECTIVE: Chronic heart failure (CHF) is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. To assess the role of proinflammatory cytokines for the local expression of insulin-like growth factor-I (IGF-I) in this process, muscular and systemic levels of interleukin-1 beta (IL-1beta), tumor necrosis factor alpha (TNFalpha) and IGF-I were analyzed in an animal model of CHF. METHODS: Ligation of the left coronary artery or sham operation was performed in adult Wistar Kyoto rats. After 12 weeks, all animals were assessed by echocardiography and cardiac catheterization. Serum levels of IGF-I, IL-1beta, TNFalpha and IL-6 were determined by ELISA. In the quadriceps muscle, the expression of IGF-I, IGF-I receptor, IL-1beta and TNFalpha were assessed by RT-PCR and quantitative immunohistochemistry. Alterations in muscle fiber morphology were analyzed microscopically. RESULTS: The local expression of IGF-I decreased significantly in animals with CHF (0.47 +/- 0.07 versus 0.77 +/- 0.09; p < 0.01). This reduction correlated with a decreased muscle fiber cross-sectional area (r = 0.62; p < 0.01) and inversely with the local expression of IL-1beta (r = -0.49; p < 0.05). IGF-I serum levels showed no significant differences between the two groups. CONCLUSIONS: In CHF, the local IGF-I expression is reduced in the presence of normal serum levels of IGF-I. Both elevated proinflammatory cytokines and reduced local IGF-I expression contribute to a catabolic metabolism that may finally result in skeletal muscle atrophy and cardiac cachexia.

Animals↗
PubMed2003

Re-assessment of growth hormone secretion in young adult patients with childhood-onset growth hormone deficiency.

OBJECTIVE: Patients with childhood-onset GH deficiency (coGHD) need retesting in late adolescence or young adulthood to verify whether they need to continue GH treatment. For this purpose the Growth Hormone Research Society (GRS) recommends the insulin tolerance test (ITT), or as an alternative the arginine + growth hormone releasing hormone test (ARG + GHRH test) as a diagnostic tool in adolescents and adults. However, there are no standardized cut-off levels based on normal GH secretion for determining GHD vs. GH sufficiency in young adults for the ITT, the ARG + GHRH test or the pyridostigmine + GHRH (PD + GHRH) test, a further new GH stimulation test. PATIENTS AND MEASUREMENTS: We studied 43 patients (28 with organic coGHD, 15 with idiopathic coGHD; 30 males, 13 females; aged 20.4 years, range 16.2-25.4; body mass index 23.5, range 16.3-35.8) using the ARG [0.5 g/kg intravenously (i.v.)] + GHRH (1 micro g/kg i.v.) test, the PD (120 mg orally) + GHRH (1 micro g/kg i.v.) test and the ITT (0.1 IU/kg i.v.) and compared these data with the results of 40 healthy age- and weight-matched volunteers. RESULTS: The GH response in patients was significantly lower than in healthy controls: ARG + GHRH test, 0.8 micro g/l (interquartile range 0.3-2.6) vs. 51.8 micro g/l (32.6-71.2) in controls (P < 0.0001); PD + GHRH test, 0.9 micro g/l (0.3-1.9) vs. 40.4 micro g/l (27.1-54.4) in controls (P < 0.0001); ITT, 0.1 micro g/l (0.0-0.8) vs. 20.3 micro g/l (14.7-31.7) in controls (P < 0.0001). In the ARG + GHRH test we found a diagnostic sensitivity of 100% and a specificity of 97.5% for a cut-off range from 15.1 to 20.3 micro g/l, in the PD + GHRH test a sensitivity of 100% and a specificity of 97% (cut-off range 9.1-13.1 micro g/l) and in the ITT a sensitivity and specificity of 100% each within a cut-off range from 2.7 to 8.8 micro g/l. CONCLUSION: There were no marked differences in sensitivity and specificity in young adults among ARG + GHRH test, PD + GHRH test and the ITT in assessing GH secretion. Because of the lack of side-effects, the ARG + GHRH test is the recommended method for re-evaluation of coGHD in young adults when pituitary GHD is suspected. Furthermore, in adult patient groups where organic pituitary coGHD is common, the ITT may be completely replaced by the ARG + GHRH test. Because of the predominance of hypothalamic GHD in childhood, the ITT is commonly performed for the re-evaluation of patients with childhood-onset GHD because of its mechanism of GH stimulation. The present results confirm the high discriminatory capability of the ITT in young adults.

Adolescent↗