Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The GH response to provocative stimuli in obese is often as low as in panhypopituitaric patients with severe GHD; however, IGF-I levels are normal or slightly reduced. In 53 patients with simple obesity (11 M and 42 F, age: 40.3+/-1.6 yr, BMI: 39.1+/-1.0 Kg/m2), we evaluated the GH response to GHRH (1 microg/kg iv)+arginine (ARG, 0.5 g/kg iv), and total IGF-I levels. The mean (+/-SE) GH peak after GHRH+ARG was markedly lower (74% reduction, p<0.0001) in obese (16.8+/-2.0 microg/l) than in normal subjects (62.7+/-4.3 microg/l). IGF-I levels in obese patients (134.0+/-7.6 microg/l) were lower (33% reduction, p<0.001) than in normal subjects (200.8+/-5.7 microg/l). Taking into account the 3rd centile limit of normal response, the GH response to GHRH+ARG was reduced in 62.3% (33/53) of the obese patients, and 21.2% (7/33) of them had low IGF-I levels. Assuming the 1st centile limit, it was reduced in 33.9% (18/53) obese subjects, and 22% (4/18) of them had low IGF-I levels. Considering 3.0 microg/L as arbitrary cut-off, the GH response was reduced in 5.7% (3/53) of the obese patients, and still one of them had low IGF-I levels. Our findings: a) confirm that the secretory capacity of somatotroph cells is often deeply impaired in obesity; b) demonstrate that IGF-I assay generally rules out severe impairment of GH/IGF-I axis in obese patients with marked reduction of the GH secretion; c) indicate that the percentage of obese patients with concomitant reduction of GH secretion and IGF-I levels is not negligible. Thus, IGF-I assay should be routinely performed in obese patients; those presenting with low IGF-I levels should undergo further evaluation of their hypothalamo-pituitary function and morphology, particularly in the presence of empty sella.
 ...
PMID:Assessment of GH/IGF-I axis in obesity by evaluation of IGF-I levels and the GH response to GHRH+arginine test. 1043 51

Growth hormone (GH) deficiency in adults is characterized by central obesity, dyslipidemia, coagulopathy and glucose intolerance, all features of the "metabolic syndrome", explaining the increased cardiovascular morbidity and mortality associated with GH deficiency in adults. Employing the 2-step euglycemic-hyperinsulinemic clamp, we have demonstrated severe insulin resistance in GH-deficient adults, with a reduction in insulin-mediated glucose utilization of -50%. Basal glucose turnover and partitioning of whole body glucose utilization into glycolytic flux (GF) and glycogen synthesis/glucose storage (GS) pathways are normal, but insulin activation of these 2 pathways is reduced, predominantly in the GS pathway. Activation of muscle glycogen synthase by insulin is markedly decreased, as is glycogen content of muscle. Insulin-induced muscle hexokinase activity appears also to be attenuated in GH-deficient adults with raised intramuscular cellular glucose and normal-reduced concentrations of glucose-6-phosphate. Beta-cell function is not excessive in GH-deficient adults and is inappropriately low for the insulin resistance. Following treatment of GH-deficient adults with recombinant GH (rhGH), the insulin resistance is either unchanged or more pronounced by 3, 6 or 24 months of treatment, despite the significant reduction in general and central obesity. The GF and GS pathways and muscle glycogen synthase and hexokinase activities remain severely impaired. Abnormalities in free fatty acid (FFA) metabolism are present in rhGH-treated GH-deficient adults and correlate significantly with the degree of insulin resistance as do the concentrations of rhGH-induced insulin-like growth factor (IGF)-I, the post-basal insulinemia and the duration of the GHD, but is independent of obesity. In conclusion, long-term rhGH treatment in GH-deficient adults results in persistent insulin resistance and abnormalities in the GF and GS pathways due to reduced glycogen synthase and hexokinase activities, in the presence of an ongoing reduction of central obesity. We postulate that the insulin resistance is due to chronic rhGH-induced alterations in FFA metabolism, non-physiological levels of IGF-I and chronic basal hyperinsulinemia.
 ...
PMID:Insulin sensitivity in growth hormone (GH)-deficient adults and effect of GH replacement therapy. 1044 67

Growth hormone deficiency (GHD) in adults results in alterations of body composition and metabolism associated with a lowered insulin sensitivity and an increased cardiovascular risk. Since hemorheologic disturbances (putative factors of vascular risk) are found in the insulin-resistance syndrome, we investigated blood rheology in 9 adults GHDs (5 men, 4 women; age 37.9+/-4.7 years; body mass index 30.23+/-3.2 kg/m2) compared with 23 lean controls and 37 controls matched for sex, age and body mass index. While this sample of GHDs exhibits the typical metabolic picture of this syndrome (upper body overweight with a waist-to-hip ratio at 0.91+/-0.07; low HDL cholesterol at 1.07+/-0.09 mmol x l(-1); low insulin sensitivity with the minimal model technique at 3.3+/-1.29 min(-1)/(microU/ml) x 10(-4)) they have similar values of blood viscosity at either native or corrected hematocrit, similar hematocrit, similar red cell rigidity viscometric index, similar red cell aggregation parameters than overweight matched controls. There is only a nonsignificant tendency for plasma viscosity to be higher in GHDs: this tendency becomes significant when women are considered alone (GHDs: 1.44+/-0.04 mPa.s; controls: 1.31+/-0.04 mPa.s, p<0.05) while it is no longer found in men. This study suggests that GHDs exhibit the classical hemorheological disturbances of non-GHD individuals with the same degree of obesity. There is no evidence for a further impairment of blood rheology associated with the specific metabolic and endocrine pattern of GHDs that may be involved in their increased vascular risk.
 ...
PMID:Hemorheology of growth hormone-deficient adults. 1046 40

The discovery of a new class of compounds that stimulate the release of growth hormone (GH) in a manner distinctly different from growth hormone-releasing hormone (GHRH) is advancing the understanding of the mechanisms that control GH secretion. These compounds, the GH secretagogues, act at both pituitary and hypothalamic levels, and might even elicit effects in the CNS and peripheral systems. A receptor with high affinity for the GH secretagogues has been identified and several observations suggest the presence of additional receptors. The existence of these specific endogenous receptors could indicate that the mechanism of GH release is not yet fully understood. Several potential indications have been explored clinically and, as some of these compounds are orally active, they could offer attractive alternatives to recombinant human growth hormone (hGH) in treating GH disorders such as growth hormone deficiency (GHD), age-related conditions, obesity and catabolic conditions.
 ...
PMID:Growth hormone secretagogues: recent advances and applications. 1052 67

The long-term effects of radiotherapy and chemotherapy are becoming increasingly recognized as the cure rates of certain childhood malignancies improve. The endocrine system is particularly sensitive to cancer therapies. Long-term survivors of childhood cancer who received cranial irradiation have been shown to have lower than predicted height, an increased prevalence of obesity and reductions in strength, exercise tolerance, bone mineral density, quality of life and academic achievement. Growth hormone deficiency (GHD) is the most frequent endocrine deficiency observed following cranial irradiation. Adults with GHD resulting from primary hypothalamic-pituitary disease during childhood have been shown to exhibit a clinical picture similar to that described in long-term survivors of childhood cancer: increased fat mass and reduced lean mass, strength, exercise tolerance, bone mineral density and quality of life. This review considers the possible contribution of GHD to the adverse sequelae observed in long-term survivors of childhood malignancy and includes our preliminary experience in treating 14 adults with GHD resulting from the treatment of childhood malignancies.
 ...
PMID:Survivors of childhood cancer: long-term endocrine and metabolic problems dwarf the growth disturbance. 1062 38

A female child with peculiar facies, obesity, cleft lip and palate, growth hormone deficiency and mental retardation is described. The present case does not appear to fit any of the known syndromes.
 ...
PMID:Peculiar facies, obesity, cleft lip and palate, growth hormone deficiency and mental retardation: a new syndrome? 1082 35

Prader-Labhart-Willi syndrome (PWS) is the most frequent form of syndromal obesity. Its main features are associated with hypothalamic dysfunction, which has not yet been comprehensively described. The aim of this review is to present arguments to define the presence of genuine growth hormone (GH) deficiency (GHD) in these patients. Decreasing growth velocity despite the onset of obesity, reduced lean body mass in the presence of adiposity, small hands and feet, relatively low insulin-like growth factor-I and low insulin levels, as well as the dramatic effect of GH treatment on growth, support the presence of hypothalamic GHD in PWS. Even though it might be difficult to ultimately prove GHD in PWS because of the obesity-induced counterregulation, the hormonal situation differs from that in simple obesity. The effects of long-term therapies with GH on body composition in these patients are summarized. GH therapy dramatically changes the phenotype of PWS in childhood: height and weight become normal and there is a sustained impact on the net loss of body fat. We conclude that GHD may account for several features of PWS.
 ...
PMID:Is there growth hormone deficiency in prader-willi Syndrome? Six arguments to support the presence of hypothalamic growth hormone deficiency in Prader-Willi syndrome. 1097 Nov 4

Prader-Willi syndrome is characterized by a typical clinical phenotype and by a complex genetic basis that includes large deletions, uniparental disomy and imprinting mutations of chromosome region 15q11-q13. This report delineates the clinical characteristics, morbidity and growth hormone secretory status of 19 adults with Prader-Willi syndrome. The patients were 18-34 years of age. Morbidity included marked obesity with body mass index in excess of 30 kg/m2 (grade 1-3 according to WHO), metabolic diseases, sleep apnoea and lipolymphoedema. Severe growth hormone deficiency (GHD) was seen in 38% of the patients, and levels of insulin-like growth factor I were decreased in 87%. Thus, GHD is seen, not only in children with Prader-Willi syndrome, but also in adults with the syndrome.
 ...
PMID:Adult patients with Prader-Willi syndrome: clinical characteristics, life circumstances and growth hormone secretion. 1098 59

It is now evident that an increased amount of intra-abdominal (visceral) adipose tissue is associated with an impaired metabolic profile, increasing the risk of CVD and NIDDM. Visceral obesity also appears to be associated with impaired GH action. GH replacement therapy in patients with GHD, or GH treatment of viscerally obese individuals, is able to induce a profound reduction in the amount of visceral adipose tissue and to improve the metabolic profile.
 ...
PMID:Effects of growth hormone treatment on visceral adipose tissue. 1099 Jan 32

The diagnosis of growth hormone deficiency (GHD) in adulthood has become increasingly important because of the approved indication for growth hormone (GH) substitution therapy in such patients. While GH stimulation tests are superior to single measurements of other growth factors or spontaneous GH secretion in the diagnosis in adults, the reproducibility and specificity of GH stimulatory tests are often described to be low. This is also the case with the insulin tolerance test. Many external factors, such as fasting, physical activity, heat exposure and sleep, are known to influence GH secretion. The stimulatory or inhibitory effect of these factors on GH secretion might, therefore, influence the GH provocative test and contribute to the variability in response. Age and body composition are also known to influence GH secretion, and these factors must be considered when evaluating GH test responses. However, age-related cut-off levels for GHD have not been defined. Obesity is still a complicating factor in the diagnosis of GHD, even though some GH tests have been able to distinguish between obesity and true GHD. Based on these complicating factors, the parameters of GH stimulatory tests are recommended to be defined and standardized to optimize reproducibility and specificity. Furthermore, such tests should be performed only in patients with firm evidence of pituitary disease.
 ...
PMID:Variability in growth hormone stimulation tests. 1099 88


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>