bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low‐dose GH replacement improves the adverse lipid profile associated with the adult GH deficiency syndrome
Authors: Murray R. D. , Wieringa G. E. , Lissett C. A. , Darzy K. H. , Smethurst L. E. , Shalet S. M. 
Published: March 2003

Summaryobjective Adult growth hormone deficiency (AGHD) is associated with an adverse lipid profile. The majority of previous studies of GH replacement have used supraphysiological doses and reported favourable changes in the lipid profile. Whether this beneficial effect is the result of pharmacological GH therapy, or occurs in response to low‐dose GH replacement aimed at normalization of the serum IGF‐I, has not been fully elucidated.study design We studied 67 patients with GH deficiency using a low‐dose individualized GH replacement regimen. GH was commenced at a dose of 0·27 mg/day and the GH dose titrated until the serum IGF‐I was normalized. Serum lipids were assessed at baseline, 12 and 24 months.results A reduction in total cholesterol (TC) was observed at 12 (6·01 vs. 5·77 mmol, P = 0·04) and 24 months (6·01 vs. 5·56, P = 0·09). The reduction in LDLC failed to reach significance at 12 months (3·97 vs. 3·8, P = 0·09), but was significant at 24 months (3·97 vs. 3·50, P = 0·02). Levels of HDLC did not change significantly at 12 or 24 months. Significant improvements in the TC/HDLC ratio were observed at both 12 (5·68 vs. 5·29, P = 0·01) and 24 months (5·68 vs. 4·86, P = 0·007). A significant fall in triglycerides (TG) was present at 12 months (2·07 vs. 1·83, P = 0·01), and was maintained at 24 months, but was no longer significant (2·07 vs. 1·89, P = 0·28). At 12 months there was no correlation between improvements in lipid parameters and either the change in IGF‐I SD score or the GH dose. Using multivariate analysis the change in TC, LDLC and the TC/HDLC ratio with 12 months GH replacement were determined by the baseline TC, LDLC and TC/HDLC levels (R2 = 0·18, P = 0·004; R2 = 0·20, P = 0·006; and R2 = 0·33, P < 0·0001), respectively.conclusions Low‐dose individualized GH replacement aimed at normalization of the serum IGF‐I is associated with significant improvements in TC, LDLC, TGs and the TC/HDLC ratio. The greatest improvements are observed in patients with the most adverse lipid profiles at baseline. Improvements are independent of changes in the IGF‐I SDS and GH dose.
Changes in adiposity and excess body weight correlate with growth responses but not with decreases in low‐density lipoprotein cholesterol levels during GH treatment in GH‐deficient children
Authors: Kuromaru Ryuichi , Kohno Hitoshi , Hara Toshiro 
Published: March 2003

Summarybackground and aims GH has profound effects on body composition and lipid metabolism in children as well as in adults. The relationship between such metabolic effects and the growth‐promoting effects of GH has not been studied thoroughly in children with GH deficiency. This prospective study was designed to determine the relationship between growth and lipid metabolism during long‐term GH treatment.patients and methods Twenty‐two boys with idiopathic GH deficiency were studied. Height, per cent overweight (%OW), per cent body fat (%BF) and serum low‐density lipoprotein (LDL) cholesterol levels were determined every 6 months during 3 years of GH treatment.results After 3 years of GH treatment, the mean height SD score had increased significantly from −2·70 SD to −1·59 SD (P < 0·0001), while the mean %OW and LDL cholesterol level had decreased significantly from 7·0% to 1·3% (P < 0·0001) and from 2·69 mmol/l to 2·04 mmol/l (P < 0·0001), respectively. The mean %BF fell significantly from 15·5% to 11·1% during the first 6 months of GH treatment (P < 0·0001). The 6‐month reduction in %BF correlated significantly with the 3‐year increase in height SD score (r = −0·58, P = 0·008). The decrease in %OW also correlated negatively with the change in height SD score (r = −0·48, P = 0·03). However, there was no correlation between the changes in LDL cholesterol levels and those in %BF, %OW or height SD score.conclusion We conclude that the growth‐promoting effects of GH correlate significantly with the reductions in %BF and %OW but not with the decrease in LDL cholesterol level in children with GH deficiency. The changes in LDL cholesterol did not correlate with any of the changes in body composition parameters, suggesting that the various actions of GH may have different mechanisms of regulation.
Combination therapy for postmenopausal osteoporosis
Authors: Compston Juliet E. , Watts Nelson B. 
Published: March 2003

SummaryA number of agents have been shown to reduce the risk of fractures in patients with postmenopausal osteoporosis. However, the additional benefits of combination therapy as opposed to monotherapy are uncertain. We performed a MEDLINE search and reviewed the published randomized trials of agents used in combination. Combination therapy results in greater gains in bone mineral density than monotherapy and possibly greater effects on bone turnover. However, none of these studies are large enough or of sufficient duration to determine whether a greater reduction in fracture is achieved. Combination therapy has important cost implications and is likely to be associated with an increased prevalence of adverse events, reduced tolerability and a reduction in adherence. Furthermore, over‐suppression of bone turnover as a result of combination antiresorptive therapy might have adverse effects on bone strength, particularly with long‐term treatment. Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence.
The influence of human leucocyte antigen (HLA) genes on autoimmune thyroid disease (AITD): results of studies in HLA‐DR3 positive AITD families
Authors: Ban Yoshiyuki , Davies Terry F. , Greenberg David A. , Concepcion Erlinda S. , Tomer Yaron 
Published: March 2003

Summaryobjective Population‐based, case–control studies have consistently shown association of Graves’ disease (GD) with human leucocyte antigen (HLA)‐DR3 in Caucasian populations. HLA association studies in Hashimoto's thyroiditis (HT) have also suggested an association with DR3, as well as with other HLA alleles. In contrast, HLA linkage studies in autoimmune thyroid disease (AITD) have been largely negative. The aim of the present study was to investigate the role of HLA in AITD and to explain the observed associations, but lack of linkage, by examining only AITD families with the associated allele, DR3.patients We studied 99 probands (60 with GD and 39 with HT) from 99 multiplex, multigenerational Caucasian AITD families, and 135 age‐ and sex‐matched Caucasian controls in association studies. In addition, a dataset of 34 Caucasian AITD families (out of the 99 families) with HLA‐DR3 positive probands were analysed in linkage studies.design HLA typing was performed using the technique of group‐specific polymerase chain reaction‐amplification with restriction enzyme digestion. Whole genome screening was performed using the ABI microsatellite panels. For fine mapping of the HLA region, we used the following markers: D6S276, D6S464, D6S439, D6S273, tumour necrosis factor α and D6S1610. LOD scores were calculated using the LIPED and GeneHunter programs.results Case–control association analyses using the probands from our 99 Caucasian families showed an association of GD with DRB1*03 [P = 0·00032, relative risk (RR) = 3·4]. Linkage analysis for the HLA region in the 34 DR3 positive AITD families showed negative LOD scores throughout the region. The two‐point LOD score at marker D6S273 (the closest to HLA‐DRB1) was −3·0, and the multipoint LOD score was −7·6, demonstrating strong evidence against linkage to the HLA region in the subset of DR3 positive families. Whole genome screening in the subset of 34 DR3 positive families revealed one locus showing evidence for linkage to AITD: D3S1580 on chromosome 3q27 with a maximum two‐point LOD score of 2·1.conclusions The HLA locus did not cosegregate with disease in DR3 positive families, suggesting that HLA genes are not major genes for AITD expression even within DR3 positive families; Hence, although HLA‐DR3 was associated with GD in the probands, it was most likely a modulating gene and not causative; and, as the DR3 positive families showed evidence for linkage with D3S1580, it may imply that the DR3 gene modulated the effect of a susceptibility gene within the D3S1580 locus.
Endocrine consequences of premature pubarche in post‐pubertal Caucasian girls
Authors: Meas Taly , Chevenne Didier , Thibaud Elisabeth , Léger Juliane , Cabrol Sylvie , Czernichow Paul , Lévy‐Marchal Claire 
Published: March 2003

Summarybackground It has been postulated that intrauterine undernutrition may predispose to serious endocrine consequences, including precocious pubarche (PP), functional ovarian hyperandrogenism and insulin resistance syndrome.objective The aim of this study was to determine whether a history of PP was associated with the development of hyperandrogenism and/or metabolic consequences and to evaluate the effect of birth weight on this association.patients The study population comprised 27 Caucasian girls with a history of PP and 25 healthy girls of similar age (17·4 ± 1·3 vs. 17·7 ± 0·9 years).results Gynecological age, irregular menses and oral contraceptive use were similar in the two groups. PP girls showed an increased Ferriman‐Gallway Score [median (range) 8 (4–17) vs. 6 (2–10), P = 0·02] and tended to have more previous history of acne. No statistical differences were found between the groups for mean testosterone (1·7 ± 0·7 vs. 1·4 ± 0·7 nmol/l, P = 0·49) and dehydroepiandrosterone sulphate concentrations (7·2 ± 3·7 vs. 5·8 ± 2·0 µmol/l, P = 0·15), but mean Δ4‐androstenedione concentrations (7·3 ± 2·4 vs. 4·9 ± 2·1 nmol/l, P = 0·007) and free androgen index (8·5 ± 9·7 vs. 3·6 ± 3·9 IU, P = 0·003) were significantly increased in the PP group. All girls showed normal glucose tolerance with an oral glucose tolerance test. Derived insulin resistance parameters were not statistically different between the two groups and fasting lipids were comparable in both groups. There was no significant effect of birth weight on androgen levels in the PP girls. Moreover, none of the PP girls demonstrated the above‐described association.conclusions Precocious pubarche could be the first sign of future functional ovarian hyperandrogenism but a link between this condition and intrauterine undernutrition or insulin resistance could not be demonstrated in this study.
Effects of a growth hormone receptor antagonist on bone markers in acromegaly
Authors: Fairfield W. P. , Sesmilo G. , Katznelson L. , Pulaski K. , Freda P. U. , Stavrou S. , Kleinberg D. , Klibanski A. 
Published: March 2003

Summaryobjective Excess GH secretion, as occurs in acromegaly, is associated with abnormalities in bone turnover markers and bone mineral density (BMD). GH administration in GH deficient patients causes an increase in bone turnover. IGF‐I mediates many of the metabolic actions of GH, although GH may have direct effects upon bone. In patients with acromegaly who are treated with a GH receptor antagonist, selective blockade of the GH receptor results in a decrease in circulating IGF‐I levels in the majority of cases. We hypothesized that, in acromegaly, antagonism of GH receptors would result in a decrease in serum markers of bone turnover, including serum procollagen I carboxy‐terminal propeptide (PICP), osteocalcin and N‐telopeptide (NTx).design and subjects Twenty‐seven patients with acromegaly were enrolled as part of a multicentre 12‐week trial of a GH receptor antagonist and were randomized to placebo (n = 7) or 10, 15 or 20 mg of pegvisomant (n = 20).measurements Serum markers of bone turnover were determined at baseline and 12 weeks.results Baseline bone turnover markers were above the upper limit of normal in 23%, 19% and 32% of subjects for osteocalcin, PICP and NTx, respectively. During the 12‐week placebo‐controlled period, there were significant decreases in serum markers of bone formation, osteocalcin (−2·2 ± 0·44 vs. placebo +0·01 ± 0·39 nmol/l, P = 0·009) and PICP (−23·6 ± 9·6 vs. placebo +18·1 ± 12·8 µg/l, P = 0·022) and a serum marker of bone resorption, NTx (−4·4 ± 1·4, placebo +1·0 ± 0·3 nm, P = 0·024).conclusions Using a specific GH receptor antagonist, we found that normalization of IGF‐I is associated with rapid reductions in markers of both bone formation and resorption, and that these processes remain coupled. These data confirm the highly significant effects of GH and IGF‐I in modulating bone turnover. The independent contributions of GH and IGF‐I to these effects and the long‐term effects on BMD in this population remain to be determined.
Intraoperative gamma probe detection of insulinoma in an elderly patient with pancreatic cystic lesions
Authors: Rosière Alain , Ernst Yves J. , Roelants Véronique , Vander Borght Thierry , Michel Luc , Donckier Julian E. 
Published: March 2003

SummaryInsulinoma is a rare endocrine tumour in the elderly. We report the case of an 81‐year‐old woman suffering from grand mal seizures. Insulinoma was suspected because plasma glucose and insulin levels were 1·5 mmol/l and 80·4 pmol/l, respectively. A pancreatic computerized tomography (CT) scan, magnetic resonance imaging (MRI) and arteriography were normal but 111In‐DTPA‐octreotide scintigraphy detected a hotspot in the pancreatic tail. Intraoperative pancreatic ultrasonography and palpation were non‐contributory due to multiple pancreatic cysts and nodular lesions. However, a gamma‐detecting probe localized a small tumour, labelled preoperatively with 111In‐DTPA‐octreotide. Intraoperative insulin measurements in portal venous blood confirmed the successful removal of an insulinoma that was 6 mm in diameter histologically. Pancreatic cystic lesions increase with age and make the intraoperative localization of the insulinoma difficult. Intraoperative gamma probe detection of the tumour labelled with 111In‐DTPA‐octreotide might therefore constitute a useful surgical tool.
Neck circumference a good predictor of raised insulin and free androgen index in obese premenopausal women: changes with weight loss
Authors: Dixon John B. , O'Brien Paul E. 
Published: March 2003

SummaryObjective Severe obesity can be associated with evidence of androgen excess and insulin resistance, which are features of the metabolic and polycystic ovary syndromes (PCOS). In this study, we examined the association between clinical and biochemical features of these syndromes and assess changes with weight loss.Design A consecutive series of 107 severely obese premenopausal women presenting for obesity surgery.Measurements Pre‐operative assessment included details of clinical comorbidity, anthropometric measures and biochemical measures, including fasting insulin, glucose, lipid profile and sex hormone analysis. Changes in these measures for 42 of 52 (81%) patients at 1 year post surgery are reported.Results Neck circumference and younger age were independent predictors of higher free androgen index (FAI) (combined r2 = 0·36). If neck circumference is not included, then younger age, higher body mass index and raised fasting insulin levels were all independent predictors of FAI (r2 = 0·29). Waist to hip ratio showed no predictive value (r = 0·14). Neck circumference was also a good clinical predictor of menstrual irregularity, hirsutism, infertility, insulin resistance and the PCOS. Neck circumference of less than 39, 39–42 and greater than 42 cm reflect a low, intermediate and high risk of the metabolic and PCOS syndromes in obese premenopausal women. For 42 patients who were followed for 1 year after surgery, the weight loss was associated with reduction of FAI, less insulin resistance and improved menstrual regularity and resolution of the PCOS in 11 of 12 cases.Conclusions Neck circumference is a good predictive measure of hyperinsulinaemia and raised androgens in obese premenopausal women. Weight loss following surgery improves ovarian function and vasculopathic risk.
Increased serum leptin concentrations correlate with soluble tumour necrosis factor receptor levels in patients with cirrhosis
Authors: Lin Shih Yi , Wang Ya Yu , Sheu Wayne Huey‐Herng 
Published: March 2003

SummaryObjective Several reports have documented the involvement of hyerleptinaemia in malnutrition associated with liver cirrhosis. However, the mechanisms of elevated leptin levels remains unclear. Serum concentrations of tumour necrosis factor‐α (TNF‐α), and two soluble TNF receptors (sTNF‐RI and sTNF–RII) are increased in patients with liver cirrhosis. In rodents, administration of TNF‐α has been shown to stimulate plasma leptin concentration, suggesting that a cytokine–leptin link may mediate anorexia and weight loss during chronic inflammation. In this study, we investigate the potential interaction of the TNF‐α system with leptin in the development of malnutrition in liver cirrhosis.Study Design A total of 26 male patients with liver cirrhosis and 25 healthy people were recruited at an outpatient clinic at the Veterans General Hospital in Taiwan. Serum biochemistry and anthropometric measurement by bioelectrical impedance analysis were used to assess nutrition status, and immunoassay was used to determine serum leptin, TNF‐α sTNF‐RI and sTNF‐RII concentrations.Results In cirrhotic patients, the body fat mass (FM) and serum albumin levels were both lower than control subjects [15·8 (13·2–19·5) kg vs. 18·9 (16·2–20·1) kg; 35 (33–41) g/l vs. 43 (41–45) g/l, respectively; P < 0·05]. Serum TNF‐α sTNF‐RI and sTNF‐RII were significantly elevated in cirrhotic patients compared to healthy controls [9·8 (7·2–13·5) ng/l vs. 4·3 (3·4–7·3) ng/l; 1682·1 (1344·8–2179·4) ng/l vs. 1319·6 (1037·7–1632·1) ng/l; 4462·2 (3748·5–5159·4) ng/l vs. 3559·8 (2506·9–3988·9 ng/l, respectively; P < 0·01] and correlated with disease severity (graded by Pugh–Child's scores). An inverse correlation was observed between circulating sTNF‐RI and sTNF‐RII to serum albumin levels (r =−0·42, r = −0·398; P < 0·05). The serum leptin levels in cirrhotic patients were significantly higher [6·0 (3·6–7·7) (g/l vs. 3·4 (2·9–4·3) (g/l; P < 0·01) and correlated with body FM (r = 0·52; P < 0·01]. Using a multiple linear regression analysis with leptin as dependent variable and FM and TNF‐α, sTNF‐R as independent variables, FM and serum sTNF‐RI concentrations were found to predict independently the leptin levels in cirrhotic patients.Conclusion Our study demonstrated that serum levels of TNF‐α, sTNF‐RI, sTNF‐RII and leptin were all elevated in cirrhotic patients. The severity of liver cirrhosis was an important factor for the activation of TNF‐α system. The activated TNF‐α system conjointly with hyperleptinaemia might mediate malnutrition in patients with liver cirrhosis.
Demonstration of human telomerase reverse transcriptase (hTERT) in human parathyroid tumours by in situ hybridization with a new oligonucleotide probe
Authors: Kammori Makoto , Nakamura Ken‐Ichi , Ogawa Toshihisa , Mafune Ken‐Ichi , Tatutomi Yusuke , Obara Takao , Onoda Naoyoshi , Fujiwara Mutsunori , Izumiyama‐Shimomura Naotaka , Mori Masaki , Kaminishi Michio , Takubo Kaiyo 
Published: March 2003

Summarybackground and objective Telomerase activity is present in most malignant tumours and might provide a mechanism for unlimited replication of neoplastic cells. Expression of the gene encoding human telomerase reverse transcriptase (hTERT), the telomerase catalytic subunit gene, is associated with telomerase activity, and it is overexpressed in most parathyroid carcinomas. We have therefore studied hTERT expression in parathyroid tumours.methods In the present study, we assayed telomerase activity by the telomeric repeat amplification protocol (TRAP) and used in situ hybridization (ISH) to study hTERT mRNA expression in four parathyroid metastatic cancers, six adenomas and two parathyroid hyperplasia tissue specimens.results Telomerase activity was detected by the TRAP assay in all of the parathyroid cancers (100%) but in none of the eight parathyroid benign lesions. hTERT gene expression was detected in the nuclei of the parathyroid cancer cells in all of the lesions (100%) but in none of the eight parathyroid benign lesions.conclusions Our results demonstrate a correlation between telomerase activity and hTERT gene expression measured by ISH (P < 0·001) in parathyroid tumours. We succeeded in very clearly and sensitively demonstrating hTERT mRNA in parathyroid tissues by using a new probe.
Significant ethnic variation in total and free testosterone concentration
Authors: Heald Adrian H. , Ivison Fiona , Anderson Simon G. , Cruickshank Kennedy , Laing Ian , Gibson J. Martin 
Published: March 2003

Summaryobjective Measurement of serum testosterone is an integral part of the assessment of men presenting to endocrine clinics. Little is known about the variation of total bound or bioavailable testosterone by ethnic group. The principal determinant of testosterone bioavailability is SHBG, which itself is a marker for insulin sensitivity. Our aim was to examine variations in testosterone and SHBG levels across three ethnic groups in relation to ethnic differences in insulin sensitivity.design Men of three ethnic groups living in Manchester, UK, were sampled randomly from population registers being of white European (n = 55), Pakistani (n = 50) and African‐Caribbean (AfC) origin (n = 75). Circulating serum testosterone and SHBG concentrations were measured and free testosterone calculated. Insulin sensitivity (HOMA‐S) and insulin secretory capacity (HOMA‐B) were determined from fasting plasma intact insulin and glucose values.results Testosterone levels were lower in Pakistani men (mean 14·6 nmol/l, 95% confidence interval 12·6–16·6 nmol/l) than in Europeans (18·7, 16·8–20·6 nmol/l) or AfCs (18·0, 16·4–19·6 nmol/l) (F = 4·8, P = 0·009). Despite SHBG levels also being lower in Pakistani men (22·9, 19·4–26·5 nmol/l) compared with Europeans (28·7, 25·7–31·8 nmol/l) and AfCs (26·9, 23·9–30·0 nmol/l) (F = 3·0, P < 0·05), circulating free testosterone was significantly lower in the Pakistani group (367, 326–408 pmol/l) than in Europeans (455, 416–494 pmol/l) or AfCs (458, 424–492 pmol/l) (F = 6·8, P = 0·001).Pakistani men were on average 4 cm shorter than other groups. However, the lower free testosterone persisted even when adjusted for height or waist–hip ratio. The lower SHBG in the Pakistani men was paralleled by a lower HOMA‐S (0·40, 0·25–0·56) compared with Europeans (0·77, 0·61–0·93) and AfCs (0·80, 0·66–0·93) (F = 8·2, P < 0·0001). SHBG correlated positively with HOMA‐S (ρ = 0·28, P < 0·001) and strongly with total testosterone (ρ = 0·54, P < 0·001). There was no difference in insulin secretory capacity (HOMA‐B) in Pakistani men compared with Europeans and AfCs.Multiple linear regression analysis showed that total testosterone was independently and negatively related to ln fasting insulin (β = −0·28, P < 0·001) and age (β =−0·17, P = 0·02) and positively to ln SHBG (β = 0·23, P < 0·001) and height (β = 0·22, P = 0·001). There was no relationship with ethnicity or waist–hip ratio.conclusion Both total bound and calculated free testosterone were lower in Pakistani men. SHBG levels were also lower in Pakistani men, in keeping with poorer insulin sensitivity. We propose that further work is necessary to establish ethnic‐specific ranges for the interpretation of total circulating and free testosterone levels in men.