bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone mineral density, bone metabolism and body composition of children with chronic renal failure, with and without growth hormone treatment
Authors: Boot Annemieke M. , Nauta Jeroen , De Jong Maria C. J. W , Groothoff Jaap W. , Lilien Marc R. , Van Wijk J. Ans E. , Kist‐van Holthe Joana E. , S. Hokken‐Koelega Anita C. , Pols Huibert A. P. , De Muinck Keizer‐Schrama Sabine M. P. F. 
Published: March 2003

OBJECTIVEOsteopenia has been reported in adult patients with chronic renal failure (CRF). Only a few studies have been performed in children. The objective of this study was to evaluate bone mineral density (BMD), bone turnover, body composition in children with CRF and to study the effect of GH on these variables.DESIGNTwo groups were identified: patients with growth retardation who received GH (GH‐group) and patients most of whom were not growth retarded who did not receive GH (no‐GH‐group). After an observation period of 6 months, the patients in the GH‐group started GH treatment. Patients were studied every 6 months during 18 months.PATIENTSThirty‐six prepubertal patients (27 boys and 9 girls), mean age 7.9 years, with CRF participated in the study. The GH‐group consisted of 17 patients of whom 14 completed one year treatment. The no‐GH‐group consisted of 19 patients, of whom 16 were followed for 6 months, 14 for 12 months and 13 for 18 months.MEASUREMENTSLumbar spine BMD, total body BMD and body composition were assessed by dual energy X‐ray absorptiometry, compared to age‐and sex‐matched reference values of the same population and expressed as standard deviation scores (SDS). BMD of appendicular bone was measured by quantitative microdensitometry (QMD). Blood samples were obtained to assess bone metabolism and growth factors.RESULTSBaseline mean lumbar spine and total body BMD SDS of all patients were not significantly different from normal. Mean lumbar spine and total body BMD SDS did not change significantly in the GH‐group during GH treatment. The change of QMD at the midshaft during the first 6 months of GH treatment was significantly smaller than during the observation period (P < 0.01). Height SDS and biochemical markers of both bone formation and bone resorption increased significantly during GH treatment; 1,25‐dihydroxyvitamin D remained stable. Lean tissue mass increased (P < 0.001) and percentage body fat decreased (P < 0.01) during GH treatment. BMD, the biochemical markers of bone turnover which are independent of renal function, and body composition remained stable in the no‐GH‐group.CONCLUSIONSMean lumbar spine and total body BMD of children with chronic renal failure did not differ from healthy controls. The lack of a GH‐induced increase in 1,25‐dihydroxyvitamin D levels, probably due to treatment with alpha‐calcidol, might be linked to the absence of a response in BMD during GH treatment in children with chronic renal failure.
Endothelial dysfunction in hypopituitary adults with growth hormone deficiency
Authors: M Evans  , Davies  , Goodfellow  , Rees  , Scanlon  
Published: March 2003

OBJECTIVESAdult hypopituitarism with growth hormone deficiency (GHD) results in reduced exercise capacity, detrimental changes in body composition and lipid profiles and may be associated with an excess cardiovascular mortality. Endothelial dysfunction is an early event in the pathogenesis of atherosclerosis and predisposes to the deposition of unstable atherosclerotic plaques. We have used a noninvasive method to assess endothelial function in the brachial arteries of a group of treated hypopituitary adults with GHD, and a group of healthy age‐and sex‐matched controls.PATIENTSSeventeen hypopituitary adults with GHD (13 male, 4 female) aged 26–54 years were studied. Each patient was receiving standard replacement therapy for all other hormonal deficiencies such that all target hormones were maintained in the normal reference range. All observations obtained were compared with those made in age‐ and sex‐matched control subjects. All study subjects had no identifiable risk factors for endothelial dysfunction.MEASUREMENTSUsing an ultrasound vessel wall tracking system, the diameter of the left brachial artery was measured at rest, in response to reactive hyperaemia (endothelium‐dependent dilation) and following sublingual glyceryl trinitrate (GTN) (endothelium‐independent vasodilatation). We also measured fasting lipids, insulin, plasma glucose, glycated haemoglobin (HbA1c) and IGF‐1, and studied the relationship of these parameters to endothelial function.RESULTSFlow mediated endothelium‐dependent dilatation (FMD), expressed as a percentage change from resting base‐line diameter, was significantly impaired in the GHD group (3.70 ± 2.36% vs. 7.30 ± 2.42%, P < 0.001). In contrast, GTN‐mediated dilatation was similar in both groups. There were no differences in total cholesterol, HDL cholesterol, LDL cholesterol or plasma triglyceride between the groups. Both fasting insulin (27.1 ± 18.1 vs. 15.89 ± 6.65 mU/l, P < 0.05) and glycated haemoglobin (HbA1c) levels (5.29 ± 0.43 vs. 4.91 ± 0.43%, P < 0.05) were significantly higher in the GHD group. FMD in both groups showed an inverse relationship with total cholesterol (r = − 0.58, P < 0.05, GHD and r = − 0.55, P < 0.05 controls). However, in the GHD subjects, there was a strong inverse relationship between FMD and LDL‐cholesterol (r = − 0.81, P < 0.0001). No other relationships were noted between FMD and any other metabolic parameters, or characteristics of GHD.CONCLUSIONSEndothelial dysfunction is present in GH deficient adults prior to the onset of overt atherosclerotic disease. The similar glucose yet elevated fasting insulin levels imply a state of relative insulin insensitivity. The strong inverse correlation between endothelial dysfunction and LDL‐cholesterol suggests a possible aetiological role for LDL‐cholesterol in the pathogenesis of any excess cardiovascular risk associated with adult hypopituitarism.
Relationships between dehydroepiandrosterone‐sulphate and anthropometric, metabolic and hormonal variables in a large cohort of obese women
Authors: Maccario Mauro , Mazza Enrico , Ramunni Josefina , Oleandri Salvatore E. , Savio Paola , Grottoli Silvia , Rossetto Ruth , Procopio Massimo , Gauna Carlotta , Ghigo Ezio 
Published: March 2003

OBJECTIVEThe aim of the present study was to measure dehydroepiandrosterone‐sulphate (DHEA‐S) levels in obesity and assess the relationships between DHEA‐S and anthropometric, metabolic and hormonal variables.SUBJECTS AND METHODSWe evaluated the serum DHEA‐S levels in 217 obese but otherwise normal female subjects (age (mean ± SEM): 39.4 ± 0.9, range 18–67 years, body mass index (BMI) = 36.1 ± 0.4, range 27.1–57.1 kg/m2).RESULTSDHEA‐S levels showed an age‐dependent fall similar to that observed in normal women (n = 156, age 46.2 ± 1.2, range 22–69 years, BMI < 25 kg/m2). Adjusting for age, obese women had mean DHEA‐S levels higher than the control group (P < 0.02). In obese patients, DHEA‐S levels were directly associated with serum testosterone, androstendione, IGF‐I, fT3 levels and 24 h‐urinary cortisol. On the other hand, DHEA‐S levels were negatively associated with age, total cholesterol, triglycerides levels and systolic blood pressure. No correlation was found with BMI, waist:hip ratio, basal and post‐OGTT insulin and glucose, free fatty acids, GH, PRL, fT4, TSH, SHBG levels or diastolic blood pressure. Multiple regression analysis indicated that in obese women, DHEA‐S levels were associated negatively to age and positively to testosterone, androstendione and IGF‐I levels and daily urinary cortisol. In a subgroup of 20 obese women, DHEA‐S levels significantly (P < 0.001) fell after OGTT without any correlation with the insulin response.CONCLUSIONSThe present results show that dehydroepiandrosterone‐sulphate levels are not reduced in obesity, being slightly increased, particularly in young adulthood. Dehydroepiandrosterone‐sulphate levels are positively and independently associated with androgen, 24‐h urinary cortisol and IGF‐I levels but do not seem associated with insulin levels or cardiovascular risk indices.
The continuous 7‐hour intravenous dexamethasone suppression test in the differential diagnosis of ACTH‐dependent Cushing's syndrome
Authors: Van Den Bogaert Debby P. M. , De Herder Wouter W. , De Jong Frank H. , Biemond Piet , Van Der Lely Aart‐Jan , Lamberts Steven W. J. 
Published: March 2003

OBJECTIVEA recent report showing disappointingly low sensitivity and specificity for the oral high dose dexamethasone test in the differential diagnosis of Cushing's syndrome prompted us to re‐evaluate the results obtained in our centre using the continuous 7‐hour intravenous dexamethasone suppression test for this purpose.PATIENTS105 patients with ACTH–dependent Cushing's syndrome were included in this study; 78 with Cushing's disease, 8 with ectopic ACTH‐secreting tumours and 19 were classified as ‘of unknown aetiology’.RESULTSIn 74/78 (94.9%) of patients with Cushing's disease and in 3/8 (37.5%) patients with the ectopic ACTH syndrome, a plasma cortisol decrease > 190 nmol/l at 7 h as compared to baseline values was achieved in the continuous 7‐hour intravenous dexamethasone suppression test. Using a plasma cortisol decrease > 190 nmol/l at 7 h as compared to baseline values as the cut‐off value, the sensitivity and specificity of the continuous 7‐hour intravenous dexamethasone suppression test for the diagnosis of Cushing's disease in patients with ACTH–dependent Cushing's syndrome were 94.9% and 62.5%, respectively.CONCLUSIONSIn patients with ACTH–dependent Cushing's syndrome with a plasma cortisol decrease > 190 nmol/l at 7 h in the continuous 7‐hour intravenous dexamethasone suppression test, additional localizing investigations such as bilateral simultaneous inferior petrosal sinus sampling and/or pentetreotide scintigraphy should be performed when no clearly discernible pituitary adenoma is observed on MRI studies. Patients with ACTH–dependent Cushing's syndrome with a plasma cortisol decrease < 190 nmol/l at 7 h in the continuous 7‐hour intravenous dexamethasone suppression test should also undergo bilateral simultaneous inferior petrosal sinus sampling and/or pentetreotide scintigraphy to demonstrate the presence of a nonpituitary source of ACTH overproduction.
The relationship among circulating insulin‐like growth factor components, biochemical markers of bone turnover and bone mineral density in postmenopausal women under the age of 60
Authors: Kim  , Shin  , Choi  , Moon  , Kim  , Lee  
Published: March 2003

OBJECTIVESThe changes in circulating IGF components after the menopause and the potential role of new markers of bone turnover and circulating IGF components in predicting bone mass in postmenopausal women are still controversial and the relationship between these two systems has not been investigated. The aims of this study were to investigate the changes in circulating IGF components after the menopause, to evaluate whether new markers of bone turnover and circulating IGF components reflect bone mass in postmenopausal women under the age of 60 and to study the relationship between these two systems.DESIGN, PATIENTS AND MEASUREMENTSSerum IGF‐I, IGF‐II, IGFBP‐1, IGFBP‐2, IGFBP‐3, osteocalcin (OST), bone specific alkaline phosphatase (BAP), urinary deoxypyridinoline (DPYD) and N‐telopeptide of type I collagen (NTX) were measured in 31 premenopausal women aged 31–43 and 65 postmenopausal women aged 47–60: this latter group comprised 30 normal healthy women and 35 osteoporotic women.RESULTSCompared with premenopausal women or normal postmenopausal women, serum IGF‐1 and IGFBP‐3 levels were significantly lower in osteoporotic postmenopausal women while no significant differences in serum levels of IGF‐II, IGFBP‐1 and IGFBP‐2 were observed. The correlations between bone turnover markers and circulating IGF components (except between serum BAP and IGF‐II), and between bone turnover markers and bone mineral density (BMD) in postmenopausal women were not significant. However, serum IGF‐I and IGFBP‐3 correlated positively with BMD of the lumbar spine and/or Ward's triangle even if age, BMI and menopause duration were taken into account in a multiple regression analysis model.CONCLUSIONSCirculating IGF‐I and IGFBP‐3 may be involved in the mechanism of bone loss in postmenopausal women under the age of 60. They may also provide indirect information on the current bone microenvironment different from that provided by new markers of bone turnover.
Splanchnic exchange of insulin‐like growth factor binding protein‐1 (IGFBP‐1), IGF‐I and acid‐labile subunit (ALS) during normo‐ and hyper‐insulinaemia in healthy subjects
Authors: Fernqvist‐Forbes Eva , Ekberg Karin , Lindgren Björn F. , Brismar Kerstin 
Published: March 2003

OBJECTIVEThe main source of circulating IGF‐I, insulin like growth factor binding protein‐1 (IGFBP‐1) and acid‐labile subunit (ALS) is considered to be the liver, but their production rates have not been determined in healthy individuals. Thus, the splanchnic exchange of IGFBP‐1, IGF‐I, ALS and glucose were studied.STUDY DESIGNIn five overnight fasting healthy, normal weight men (mean age 29 ± 1 years) blood samples were taken from a hepatic vein, a brachial artery and a peripheral vein in the basal state and during 3 h i.v. infusion of insulin (1.0 mU/kg/min). Normoglycaemia was maintained with a variable glucose infusion and splanchnic blood flow was determined using a constant rate indicator infusion technique.RESULTSThe basal net splanchnic glucose output amounted 0.96 ± 0.09 mmol/min and the splanchnic production of IGFBP‐1 was 7 ± 2 μg/min. There was a net splanchnic uptake of IGF‐I (7 ± 2 μg/min) in the basal state, while no significant splanchnic exchange of ALS was found. During the insulin infusion, insulin concentration increased from 78 ± 12 to 660 ± 30 pmol/l, resulting in a complete inhibition of splanchnic glucose production after 40 min of infusion. Splanchnic IGFBP‐1 production rose initially to 13 ± 4 μg/min (P < 0.05) and then gradually decreased and was completely inhibited at 180 min (P < 0.05). Insulin infusion influenced neither ALS nor IGF‐I splanchnic exchange.CONCLUSIONSplanchnic production of IGFBP‐1 in the basal state was demonstrated and it is completely inhibited after 180 min of hyperinsulinaemia. In contrast to what is generally held, there was no net splanchnic production of IGF‐I in the basal state or during insulin stimulation.
The effects of metformin on insulin resistance and ovarian steroidogenesis in women with polycystic ovary syndrome
Authors: Ünlühizarci Kürşad , Keleştimur Fahrettin , Bayram Fahri , Şahin Yilmaz , Tutuş Ahmet 
Published: March 2003

OBJECTIVEPolycystic ovary syndrome (PCOS) is a form of functional ovarian hyperandrogenism and affects approximately 5‐10% of women of reproductive age. Insulin resistance and hyperinsulinaemia appear to be almost universal feature of the polycystic ovary syndrome. Abnormal regulation of cytochrome P450c17α causes the exaggerated secretion of ovarian androgens in PCOS. The aim of the present study was to determine whether reduction of insulin levels by metformin would attenuate FSH, LH, 17‐Hydroxyprogesterone (17‐OHP) and androstenedione hyperresponsiveness to buserelin testing in PCOS women.DESIGNThe presence of hyperinsulinaemia in 16 women with PCOS was demonstrated by an oral glucose tolerance test (OGTT) and results were compared with 13 healthy women. PCOS women were also evaluated with insulin tolerance test (ITT) for the assessment of insulin sensitivity. FSH, LH, 17‐OHP and androstenedione responses to buserelin testing were measured in all the women with PCOS. PCOS patients were given metformin (500 mg, orally, two times daily) for 12 weeks and re‐evaluated at the end of the treatment period.RESULTSWomen with PCOS were hyperinsulinaemic (basal insulin 92.1±14.3 vs. 44.0±4.0 pmol/l ; AUCinsulin 68087.4±8862.3 vs. 13075.5±1327.6 pmol/l×120 min) compared with healthy women. Metformin therapy improved menstrual disturbances in 25% of the women with PCOS and also resulted in some improvement in insulin sensitivity and reduced basal and post glucose load insulin levels. However, FSH, LH, 17‐OHP and androstenedione responses to buserelin testing were unaltered in response to metformin.CONCLUSIONIt is clear that PCOS is often associated with profound insulin resistance and hyperinsulinaemia. These abnormalities explain the increased prevalence of glucose intolerance in women with PCOS and metformin has beneficial effects on insulin sensitivity in women with PCOS. Amelioration of hyperinsulinaemia has no significant effect on ovarian cytochrome P450c17α enzyme activity. However, it can be used in obese women with PCOS as an adjuvant therapy and long term studies should be performed to evaluate the endocrine effects of metformin in women with PCOS.
A comparison of lanreotide and octreotide LAR for treatment of acromegaly
Authors: Turner  , Vadivale  , Keenan  , Wass  
Published: March 2003

BACKGROUND AND OBJECTIVETwo long‐acting depot somatostatin analogues have recently been licensed for the treatment of acromegaly. We wished to assess the effectiveness of both these drugs in suppressing mean GH to a target of < 5 mU/l in patients with acromegaly unselected for responsiveness to octreotide, and also to compare the effects of both drugsMETHODSWe prospectively studied 10 unselected patients with acromegaly who were treated first with lanreotide (LAN) and then octreotide LAR (LAR) following a washout period. The target for therapy was to achieve mean GH less than 5 mU/l.RESULTSFive (50%) patients achieved mean GH < 5 mU/l on lanreotide 30 mg every 10 days, and 7 out of 9 (77.8%) achieved this level when the dose frequency was increased to every 7 days. On 20 mg octreotide LAR, 6 (60%) patients achieved the target mean GH and a further 2 (80%) when the dose was increased to 30 mg. Normalization of IGF‐1 occurred in 5/9 (55.6%) patients who received lanreotide and 7/10 (70%) of those who received octreotide LAR. There was a significant difference in mean GH attained on the 2 drugs. The patients' mean GH was significantly lower when treated with octreotide LAR 20 mg every 4 weeks compared with lanreotide 30 mg every 10 days (P = 0.037). Maximal suppression of mean GH with 30 mg octreotide LAR or 7 day dosing of lanreotide was significantly greater on octreotide LAR (P < 0.02).CONCLUSIONSAt current dose recommendations, lanreotide and octreotide LAR are both effective in lowering mean GH to 'safe’ (< 5 mU/l) levels in 80% patients but octreotide LAR treatment leads to significantly lower mean GH.
Analysis of the intracellular signalling domain of the human growth hormone receptor in children with idiopathic short stature
Authors: Johnston Linda B. , Pashankar Farzana , Camacho‐Hübner Cecilia , Savage Martin O. , Clark Adrian J.L. 
Published: March 2003

SummaryOBJECTIVE To investigate the hypothesis that intracellular, dominant‐negative mutations of the growth hormone receptor (GHR) exist in children with idiopathic short stature (ISS) and partial growth hormone insensitivity (GHI).SUBJECTS We studied 31 children aged 4.55–13.14 years with ISS (height ≤‐1.8 standard deviation scores, UK standards 1990). GH provocation tests (glucagon 15μg kg−1 i.m.) excluded GH deficiency In all subjects. Serum IGF‐I levels were below the 50th centile for age in all subjects and below the 10th centile in 64.5% of cases. GH binding protein levels were normal in the 24 subjects in whom It was measured (mean 25.2%; range 10–42.6%).METHODS Exons 9 and 10 of the GHR were amplified by PCR from leucocyte‐derived DNA. Samples were directly sequenced on the ABI 377 DNA analyser using the −21 M13 dye primer cycle sequencing protocol for optimum heterozygote detection.RESULTS No abnormalities were detected in exon 9 which encodes the proline‐rich box 1 motif. In exon 10 two sequence variants were found; a heterozygous, single base alteration (TCT to TCC) in codon 325 which does not change the amino acid sequence in one patient, and the L5261 variant in 24 subjects. L5261 is a conservative amino acid change and had an allele frequency of 0.53 in our patients, which is similar to that reported in a control population.CONCLUSIONS The apparent partial growth hormone insensitivity in this group of idiopathic short‐stature subjects is not related to heterozygous, dominant‐negative variants of the intracellular signalling domain of the GHR. Hence it is likely that other genetic and environmental factors may be involved.
Clinical features of multiple endocrine neoplasia type 1 (MEN1) phenocopy without germline MEN1 gene mutations: analysis of 20 Japanese sporadic cases with MEN1
Authors: Hai Noritaka , Aoki Norihiko , Shlmatsu Akira , Mod Toru , Kosugi Shinjl 
Published: March 2003

SummaryOBJECTIVE Multiple endocrine neoplasia type 1 (MEN1) is a familial tumour syndrome of endocrine tumours involving parathyroids, anterior pituitary and enteropancreatic neuroendocrine tissues, and is inherited in an autosomal dominant manner with high penetrance. Recently, the gene responsible for this syndrome, MEN1, was positionally cloned from chromosome 11q13.PATIENTS To characterize sporadic MEN1 patients, we analysed the MEN1 gene by direct sequencing of the entire open reading frame from 20 individuals. RESULTS We identified heterozygous germline mutations of the MEN1 gene in 8 of 20 (40%) cases. Seven were novel MEN1 germline mutations. Three mutations were splicing abnormalities, and all were confirmed to be splicing defects by RT‐PCR. The clinical significance of detecting germline MEN1 mutations, not only in familial MEN1 but also in sporadic MEN1, was confirmed by the finding of asymptomatic mutant carriers among family members of the sporadic MEN1 patients. Seven of 8 cases with MEN1 mutations had enteropancreatic lesions in contrast to 4 of 12 (P<0.018) in those cases with no mutation. Ten of the 12 cases without MEN1 mutation were more than 50–year‐old. Six of these 10 cases had the same clinical features; primary hyperparathyroidism and a GH‐secreting pituitary tumour.CONCLUSIONS It Is likely that the six cases without mutations were MEN1 phenocopies due to (i) two kinds of tumours with high natural incidence in older subjects developed by chance (ii) another familial tumour syndrome with low penetrance, e.g. familial acromegaly with primary hyperparathyroidism by mutation of another gene, or (iil) somatic mutation during early embryonic stages.