Clinical Endocrinology Journal Impact Factor & Information

Publisher: Wiley

Journal description

Clinical Endocrinology publishes papers and reviews which focus on the practical aspects of clinical endocrinology, such as protocols for investigation of endocrine disorders, imaging in endocrinology and the clinical application of molecular endocrinology. It also features reviews, current therapy papers and cases of the month. Clinical Endocrinology is essential reading not only for those engaged in endocrinological research but also for those involved primarily in clinical practice.

Current impact factor: 3.46

Impact Factor Rankings

2015 Impact Factor Available summer 2016
2014 Impact Factor 3.457
2013 Impact Factor 3.353
2012 Impact Factor 3.396
2011 Impact Factor 3.168
2010 Impact Factor 3.323
2009 Impact Factor 3.201
2008 Impact Factor 3.398
2007 Impact Factor 3.37
2006 Impact Factor 3.358
2005 Impact Factor 3.412
2004 Impact Factor 3.023
2003 Impact Factor 2.767
2002 Impact Factor 2.674
2001 Impact Factor 2.465
2000 Impact Factor 2.922
1999 Impact Factor 2.833
1998 Impact Factor 3.101
1997 Impact Factor 2.447
1996 Impact Factor 2.414
1995 Impact Factor 2.279
1994 Impact Factor 2.657
1993 Impact Factor 2.642
1992 Impact Factor 2.211

Impact factor over time

Impact factor

Additional details

5-year impact 3.41
Cited half-life 8.00
Immediacy index 0.92
Eigenfactor 0.02
Article influence 1.07
Website Clinical Endocrinology website
Other titles Clinical endocrinology (Oxford, England: Online)
ISSN 1365-2265
OCLC 46569692
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publisher details


  • Pre-print
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    • 12 months embargo
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    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
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    • Non-Commercial
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    • Must link to publisher version with set statement (see policy)
    • If OnlineOpen is available, BBSRC, EPSRC, MRC, NERC and STFC authors, may self-archive after 12 months
    • If OnlineOpen is available, AHRC and ESRC authors, may self-archive after 24 months
    • Publisher last contacted on 07/08/2014
    • This policy is an exception to the default policies of 'Wiley'
  • Classification

Publications in this journal

  • Clinical Endocrinology 01/2016;
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    ABSTRACT: Objective: Chromogranin-A (CgA) and -B (CgB) are markers for monitoring disease status in patients with gastroenteropancreatic neuroendocrine tumours (NETs). These are specialised diagnostic tests often necessitating referral of specimens to a supra-regional assay service (SAS) laboratory for analysis. The aim of this audit was to assess if measurement of either plasma CgA or CgB alone provides sufficient clinical information in comparison to the current practice of measuring both markers together. Design: A retrospective analysis was undertaken for all chromogranin tests requested for patients with a known NET diagnosis. Results were categorised based on whether plasma concentrations were elevated for one or both CgA and CgB. Results: 325 sequential patients with a NET diagnosis had plasma chromogranin levels measured during the period of review. Baseline CgA was elevated in 60.9% of patients. Isolated elevations in CgA (with normal CgB) were found in 44.9% of patients, whilst combined elevations in both CgA and CgB were found in 16% of patients. Combined CgA and CgB concentrations within the normal range were observed for 38.5% of patients. Only 2 patients (0.6%) had an isolated elevation in CgB at baseline. Both patients had a diagnosis of pancreatic NET and were radiologically stable. Plasma CgA and CgB corresponded with disease stage (localised vs. metastatic). CgB in addition to CgA did not provide any significant improvement in diagnostic performance for identification of metastatic disease compared to CgA alone. Conclusions: Based on this NET population and specific assay performance characteristics, CgA alone provides sufficient information for the management of NET patients; the routine estimation of CgB in all patients is not informative in clinical practice. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12985
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    ABSTRACT: Objective: Although menstrual cycle length is one of the main concerns of women and may have important health consequences, little is known about its predictors. The aim of this study was to identify predictors of menstrual cycle length variability in healthy women. Design: Prospective cross-sectional study. Patients: 200 healthy women aged 21-45. Measurements: A questionnaire was administered to determine lifestyle factors. Ovarian parameters, metabolic parameters, pituitary hormones, sex steroids, and anti- müllerian hormone (AMH) were measured. Results: Women with long (≥35 days) and normal (25-34 days) menstrual cycles had >5-fold and >2-fold higher serum AMH levels, respectively, compared to those with short cycles (<25 days). Menstrual cycle length was associated with age but not lifestyle factors. Only one factor group (-AMH, antral follicle count [AFC], ovarian volume, testosterone and LH) was significantly associated with menstrual cycle length. Within this factor group, only the ovarian parameters (AMH, AFC, ovarian volume) predicted menstrual cycle length. Each SD increase in AMH (32.9 pmol/L) and ovarian volume (2.29 cm(3) ) was associated with 2.80-fold (95% CI: 1.67-4.69) and 1.62-fold (95% CI: 1.08-2.43) increased risks, respectively, for longer menstrual cycles. Conclusions: AMH, AFC, and ovarian volume are positively associated with menstrual cycle length in healthy women. Our identification of AMH as an independent predictor of menstrual cycle length puts forth a new notion of utilizing menstrual cycle length to predict possible AMH-dependent/associated outcomes. In addition, this novel relationship may facilitate the interpretation of AMH levels and its clinico-pathological significance across different centres. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12984
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    ABSTRACT: Objective: Polycystic ovarian syndrome (PCOS) is estimated to affect up to 20% of women. PCOS is associated with insulin resistance and cardiovascular (CV) risk factors. We aimed to evaluate the impact of race/ethnicity on the prevalence of CV risk factors and subclinical predictors of CV events. Design: Cross-sectional analysis of data collected by the Dallas Heart Study, an urban, population-based cohort oversampled for blacks. Patients: A previously described cohort of women with PCOS and control subjects of the same racial/ethnic group, matched for age and body mass index. Measurements: Hormonal and clinical measures associated with PCOS and CV risk factors. Results: The study included 117 women with PCOS and 204 controls. Women with PCOS had significant differences across racial/ethnic groups in the prevalence of hypertension, hypercholesterolemia, hypertriglyceridemia, and impaired fasting glucose (P<.05). Controls showed significant racial/ethnic differences in the prevalence of hypertension and impaired fasting glucose (P<.05). The odds of hypertension were significantly greater among women with PCOS than controls after adjusting for race/ethnicity (odds ratio, 1.50 [95% CI, 1.03-2.30]; P=.04). However, we did not see an interaction of race/ethnicity that significantly changed CV risk factor prevalence between PCOS and controls. In addition, subclinical measures of CV disease were not different between women with PCOS vs controls, even among hypertensive women. Conclusions: Race/ethnicity affects the prevalence of CV risk factors for women with and without PCOS. However, race/ethnicity does not interact with PCOS to additionally increase CV risk factor prevalence or subclinical CV disease. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12986
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    ABSTRACT: Objective: We have previously reported a new luteal-phase ovarian stimulation (LPS) strategy for infertility treatment. The purpose of this study was to systematically assess the efficiency and safety of this strategy by comparing it with conventional ovarian stimulation protocols. Design: Retrospective cohort study. Subjects: Patients with normal ovarian reserve undergoing ovum pick-up (OPU) cycles between April 2012 and September 2013 were enrolled: 708 patients underwent the LPS protocol compared with 745 patients who underwent the mild treatment protocol and 1287 patients who underwent the short-term protocol. Measurements: Number of mature oocytes retrieved and top-quality embryos obtained, implantation rate, pregnancy rate, live birth and ongoing pregnancy rate, and neonatal outcomes. Results: The numbers of mature oocytes retrieved and top-quality embryos obtained per OPU cycle were significantly increased in the LPS group (10.9±7.6 and 4.6±4.3, respectively) compared with the mild treatment group (3.7±3.0 and 1.8±1.8, respectively, both p<0.001) or the short-term group (9.1±5.5 and 3.7±3.1, respectively, both p<0.001). Moreover, the total gonadotrophin used was also the highest in the LPS group. No significant differences were identified in the implantation rate (35.5% vs. 34.8%, p>0.05), pregnancy rate (46.2% vs. 43.7%, p>0.05), or live birth and ongoing pregnancy rate (44.4% vs. 41.7%, p>0.05) per frozen-thawed embryo transfer (FET) cycle in the LPS and mild treatment groups, respectively. However, the LPS protocol achieved a higher implantation rate (35.5% vs. 31.8%, p=0.012), pregnancy rate (46.2% vs. 41.9%, p=0.041), and live birth and ongoing pregnancy rate (44.4% vs. 39.2%, p=0.012) compared with the short-term protocol. Neonatal outcomes in the LPS group were similar to the other two groups. Conclusions: The available data suggest that LPS is a feasible strategy for infertility treatment and complements the available follicular-phase ovarian stimulation strategies. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12983
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    ABSTRACT: Objective: Recombinant human leptin (metreleptin) improves glycemia and hypertriglyceridemia in patients with generalized lipodystrophy; antibody development with in vitro neutralizing activity has been reported. We aimed to characterize anti-metreleptin antibody development, including in vitro neutralizing activity. Design: Two randomized controlled studies in patients with obesity (twice-daily metreleptin ± pramlintide for 20-52 weeks; 2006-2009); two long-term, open-label studies in patients with lipodystrophy (once-daily or twice-daily metreleptin for 2 months to 12.3 years; 2000-2014). Patients: 579 metreleptin-treated patients with obesity, 134 metreleptin-treated patients with lipodystrophy (antibody/neutralizing activity data: n=105). Measurements: Anti-metreleptin antibodies, in vitro neutralizing activity. Results: Anti-metreleptin antibodies developed in most patients (obese: 96-100%; lipodystrophy: 86-92%). Peak antibody titers (~1:125 to 1:3125) generally occurred within 4-6 months and decreased with continued therapy (lipodystrophy). Antibody development did not adversely impact efficacy or safety (patients with obesity), except for inflammatory injection site reactions, but was associated with elevated leptin concentrations. Three patients with obesity developed in vitro neutralizing activity coincident with weight gain. Weight later returned to baseline in one patient despite persistent neutralizing activity. Four patients with generalized lipodystrophy developed in vitro neutralizing activity concurrent with worsened metabolic control; two with confounding comorbidities had sepsis. One patient with lipodystrophy had resolution of neutralizing activity on metreleptin. Conclusions: Development of in vitro neutralizing activity could be associated with loss of efficacy but has not been consistently associated with adverse clinical consequences. Whether neutralization of endogenous leptin with clinical consequences occurs remains unclear. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12980
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    ABSTRACT: Background: Recent studies have found that mild secondary hyperparathyroidism might be another clinical feature of patients with primary aldosteronims (PA), but whether serum parathyroid hormone level (PTH) is correlated with subtypes of PA and what contributes to the elevated PTH level remains unclear. Objective: To illustrate the changes of PTH in PA and to partly explain the mechanism of how the effects of aldosterone regulating the secretion of PTH in PA. Methods: We enrolled a total of 120 patients with primary hypertension(PH)and 242 patients with PA, which included 89 APAs (aldosterone-producing adenoma), 119 IHAs (idiopathic hyperaldosteronism) and 34 UAHs(unilateral adrenal hyperplasia). The plasma levels of aldosterone, renin activity, parathyroid hormone and markers associated with calcium metabolism were measured. Results: We found serum PTH level was significantly elevated in patients with PA compared with primary hypertension [9.0(6.6,11.7).vs. 5.7(4.4,7.0)] pmol/L, p<0.001]. However, no difference was found between the three PA subtypes (p>0.05). Stepwise multiple regression analysis showed that in patients with PA, serum levels of K(+) and Ca(2+) were independently associated with serum PTH level. More importantly, elevated PTH level could be corrected either by unilateral adrenalectomy [9.9(7.5,12.8).vs. 5.2(4.4,7.0) pmol/L, p<0.001] or mineralocorticoid receptor (MR) antagonists treatment [11.7(9.1,13.4).vs. 6.3(5.1,7.8) pmol/L, p<0.001]. Conclusions: PTH level is elevated in PA patients and irrelevant with subtypes of PA. Serum K(+) and serum Ca(2+) level are main factors influence the plasma PTH level in PA patients. After medical or surgical treatment, PTH levels return to normal. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12981
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    ABSTRACT: Objective: Lipodystrophy (LD) is characterized by loss of adipose tissue, dysregulation of adipokines, and severe metabolic complications. Regulation of the insulin resistance-inducing and proinflammatory adipokine chemerin has not been assessed in LD. Therefore, we determined chemerin serum levels in LD, chemerin mRNA expression in insulin-sensitive tissues of LD mice, as well as the impact of metreleptin treatment on circulating chemerin in LD patients. Research design and methods: Serum chemerin, as well as clinical and biochemical parameters of glucose metabolism, lipid metabolism, and inflammation, were measured in 37 LD patients and 37 age-, gender- and body mass index-matched controls. Furthermore, chemerin mRNA expression was determined in LD mice and controls. Moreover, circulating chemerin was assessed at five different time points in 10 LD patients treated with metreleptin over 1 year. Results: Median serum chemerin levels were significantly higher in 37 subjects with LD (234.3 μg/l) as compared to controls (204.0 μg/l) (p=0.002). Multiple linear regression analysis showed that circulating chemerin was independently and positively associated with glycosylated hemoglobin A1c (HbA1c) and C reactive protein (CRP). Chemerin mRNA expression was significantly increased 2.5-fold in visceral adipose tissue (VAT) and 5.3-fold in brown adipose tissue (BAT) of LD mice as compared to controls (p<0.01). Circulating chemerin was not significantly altered by metreleptin treatment. Conclusions: Circulating levels of the adipokine chemerin are elevated in LD, as well as independently and positively associated with HbA1c and CRP. Increased chemerin might originate from VAT and BAT. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12976
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    ABSTRACT: Objective: Controversy surrounds the importance of the different amino acids substituting for cysteine in REarranged during Transfection (RET) codon 634 for multiple endocrine neoplasia 2A (MEN 2A). This study aimed to clarify the relevance of these amino acid substitutions for the development of MEN 2A. Design: Cross-sectional study at surgical referral centres in Germany. Patients: Included were 184 carriers of RET mutations in codon 634. Measurements: Arginine (79 carriers) and tyrosine (50 carriers) substitutions in codon 634 were compared with each other and, for the first time, gauged against a common reference standard comprising all other amino acid substitutions (phenylalanine, 35 carriers; serine, 12 carriers; glycine, 7 carriers; tryptophan, 1 carrier). Results: Arginine substitutions in codon 634 were associated with higher penetrance of medullary thyroid cancer (MTC; 82 vs. 62%; P=0.010), any phaeochromocytoma (44 vs. 15%, P<0.001), bilateral phaeochromocytoma (32 vs. 5%; P<0.001), and primary hyperparathyroidism (18 vs. 5%; P=0.039) relative to the reference standard. The penetrance rates of any phaeochromocytoma (44 vs. 26%; P=0.041) and bilateral phaeochromocytoma (32 vs. 14%; P=0.035) were also higher with arginine than with tyrosine substitutions. Corrected for multiple testing, the associations of arginine with any phaeochromocytoma and bilateral phaeochromocytoma remained statistically significant. Progression of MTC, evidenced by largest primary tumour diameter, nodal status, distant metastasis and biochemical cure, did not differ by amino acid substitution. Conclusions: In codon 634, arginine substitutions for cysteine may cause slightly higher penetrance rates of MEN 2A which, overall, are too small to treat carriers differently. The mode of action by which arginine exerts these subtle effects warrants further research. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12978
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    ABSTRACT: Patients with multiple endocrine neoplasia type 1 (MEN1) are commonly evaluated for clinical manifestations of this syndrome with the rationale that early diagnosis and adequate treatment will result in improved survival and quality of life. Thymic and bronchial carcinoid tumors are uncommon but important manifestation of MEN1. Current practice guidelines recommend evaluation with computed tomography or magnetic resonance imaging scan of the chest every 2-3 years to detect these neoplasms. However, the certainty that patients will be better off (increased survival or quality of life) as a result of this case detection strategy is based on evidence at moderate-high risk of bias that yields only imprecise results of indirect relevance to these patients. In order to improve the care that patients with MEN1 receive, coordinated efforts from different stakeholders are required so that large, prospective, multicenter studies evaluating patient important outcomes are carried out. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12972
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    ABSTRACT: Objective: Obesity is associated with alterations in thyroid hormone (TH) levels in obese, pregnant individuals. The maintenance of TH levels throughout gestation is important for proper fetal development. The aim of this study was to measure levels of fT3, fT4 and TSH in maternal and matched cord blood serum from normal weight, overweight and obese gravidae to determine alterations in maternal and neonatal TH levels by virtue of maternal obesity. Design, setting, subjects, outcome measures: ELISA was utilized to measure fT3, fT4 and TSH levels from banked, matched maternal and neonatal (cord blood) serum (N=205 matched pairs). Data was stratified according to pre-pregnancy or first trimester BMI. Results: Both maternal and neonatal fT3 levels consistently increased with increasing maternal obesity, and maternal and neonatal fT3 were significantly correlated (r =0.422, p<0.001). Maternal and neonatal fT3 were also significantly associated with birthweight (□=0.155, p=0.027 and □=0.171, p=0.018 respectively). Both the maternal and neonatal fT3 to fT4 ratio significantly increased with increasing maternal obesity. We further found that excess gestational weight gain was associated with a decrease in maternal fT4 compared with gravidae who had insufficient gestational weight gain (0.86±0.17 vs. 0.95±0.22, p<0.01). Conclusion: Maternal obesity is not only associated with maternal alterations in TH, but with accompanying neonatal changes. Because both maternal obesity and alterations in TH levels are associated with childhood obesity, based on these findings and our prior analyses in a non-human primate model we propose that changes in fT3 levels in the offspring of obese mothers may be a potential molecular mediator of fetal overgrowth and childhood obesity. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12974
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    ABSTRACT: A 49 year old female presented to our Neuroendocrine Tumour (NET) centre with recurrent severe and disabling hypoglycaemia. She had previously been extensively investigated with a clinical and biochemical diagnosis of endogenous hyperinsulinemic hypoglycaemia although the source of hormonal hypersecretion could not be localised with MRI, EUS and (111) In-Octreotide scans. After extensive discussion the patient opted for blind surgical resection undergoing a pylorus-preserving pancreaticoduodenectomy in December 2010. Histological examination of the resected operative specimen demonstrated a normal pancreas with no evidence of neuroendocrine tumour. Consistent with this, post-surgery her hypoglycaemic symptoms persisted with fasting capillary blood glucose of 2.1-6.0 mmol/l with increasing hypoglycaemia unawareness. Consequently she sought alternative clinical opinions from two European Neuroendocrine Tumour Society (ENETS) Centres of Excellence who investigated her collaboratively. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12973
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    ABSTRACT: Objective: Patients with type 2 diabetes mellitus (T2DM) have a high risk of fracture although they have slightly higher bone mineral density (BMD). There is no evidence that dipeptidyl peptidase-4 (DPP-4) is involved in the bone fragility of the patients. The aim of this study is to investigate the association between serum DPP-4 levels and vertebral fractures (VFs) in men with T2DM. Design: We conducted a cross-sectional study and investigated the relationships between serum DPP-4 levels versus BMD at lumbar spine, femoral neck and radius, bone turnover markers, and presence of VFs in 204 Japanese male patients. Results: Multiple regression analyses adjusted for confounders such as age, duration of diabetes, body mass index, serum creatinine, HbA1c, serum albumin, log(alanine transaminase), and log(C-reactive protein) showed that serum DPP-4 was positively associated with bone formation markers (bone-specific alkaline phosphatase and osteocalcin) as well as a bone resorption marker [tartrate-resistant acid phosphatase 5b (TRACP5b)] (β=0.25, p<0.01; β=0.17, p<0.05; and β=0.30, p<0.01, respectively), but not BMD at each site. Multivariate logistic regression analyses adjusted for the confounders described above revealed that serum DPP-4 levels were associated with the presence of multiple VFs (odds ratio 1.61, 95% confidential interval 1.05-2.49 per SD increase, p<0.05). This association was still significant after additional adjustment for any sites of BMD or bone turnover markers except for TRACP-5b. Conclusions: We firstly showed that high level of serum DPP-4 is associated with prevalent multiple VFs independently of BMD and bone formation in men with T2DM. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12971
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    ABSTRACT: Context: Thyroid stimulating hormone (TSH) levels within populations do not follow Gaussian distribution and normal limits are derived after mathematical normalization. The clinical relevance of these limits is unknown. The objective of this study was to compare upper and lower TSH limits by four data-normalization methods with non-normalized data and assess their clinical relevance. Design, patients and measurements: Results of blood samples taken by community physicians and stored in a computerized data base were analyzed after removing samples from patients with evidence of thyroid illness. TSH values were normalized by the Hoffmann and Tukey methods and each method with natural log transformation. Non-normalized data for TSH in the uppermost and lowermost percentile were also calculated. Clinical relevance was determined by alterations in thyroid hormone levels at, below and above the limits for each method. Results: The maximal reduction from non-normalized data for the upper normal limit (UNL) was by the Hoffman method (up to 43%=3.1mIU/L). The maximal increase for the lower normal limit (LNL) was also by the Hoffman method (708%= 0.81mIU/L). There was very limited difference in average FT3 and FT4 between patients with TSH within, below or above the normal range for all methods. Conclusions: Different normalization methods alter the normal limits greatly. However, in individuals without thyroid illness, thyroid hormone values are stable over a wide range of TSH levels including beyond the UNL for all methods. Indeed there may be no true universal upper TSH cutoff level and clinical decision-making cannot rely on these calculated limits. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12970
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    ABSTRACT: Background and objective: Kisspeptin stimulates hypothalamic GnRH secretion resulting in gonadotrophin release and has potential as a future therapeutic. Chronic subcutaneous infusion of kisspeptin via a pump (similar to an insulin pump) may provide an alternative route of administration in the future. We investigated for the first time in humans, the gonadotrophin response to subcutaneous (SC) infusions of kisspeptin-54 in healthy women. Women are markedly more responsive to exogenous kisspeptin in the late follicular phase pre-ovulation when oestradiol levels are naturally high. Therefore we further investigated whether there was a correlation between baseline oestradiol levels and LH response to kisspeptin. Design and patients: A prospective, single-blinded placebo-controlled study. Healthy women (n=4) received an 8 hour SC infusion of kisspeptin-54 0.1, 0.3 or 1.0nmol/kg/h or saline in the early follicular phase of 4 separate menstrual cycles. Gonadotrophins and oestradiol were measured every 10 minutes during the infusions. Results: SC infusion of kisspeptin-54 increased LH and FSH. The LH response to SC infusion of kisspeptin-54 (0.3 and 1.0nmol/kg/h) positively correlated with baseline oestradiol levels (p<0.001). Further statistical analyses showed that in the 1.0nmol/kg/h group a 100pmol/L rise in baseline oestradiol was associated with a 1.0 IU/L increase in LH. Conclusions: Kisspeptin administered via a SC infusion could be a viable future therapeutic route of administration for patients with infertility. Baseline oestradiol levels may be an important determinant of the gonadotropin response to kisspeptin treatment in women and should be taken into consideration when evaluating gonadotrophin response. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 11/2015; DOI:10.1111/cen.12977
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    ABSTRACT: Objective: In Europe, growth hormone (GH) treatment for children born small for gestational age (SGA) can only be initiated after 4 years of age. However, younger age at treatment initiation is a predictor of favourable response. To assess the effect of GH treatment on early growth and cognitive functioning in very young (<30 months), short-stature children born SGA. Design: 2-year, randomized controlled, multicentre study (NCT00627523; EGN study), in which patients received either GH treatment or no treatment for 24 months. Patients: Children aged 19-29 months diagnosed as SGA at birth, and for whom sufficient early growth data were available, were eligible. Patients were randomized (1:1) to GH treatment (Genotropin(®) , Pfizer Inc.) at a dose of 0·035 mg/kg/day by subcutaneous injection, or no treatment. Measurements: The primary objective was change from baseline in height standard deviation score (SDS) after 24 months of GH treatment. Results: Change from baseline in height SDS was significantly greater in the GH treatment versus control group at both month 12 (1·03 vs 0·14) and month 24 (1·63 vs 0·43; both P < 0·001). Growth velocity SDS was significantly higher in the GH treatment versus control group at 12 months (P < 0·001), but not at 24 months. There was no significant difference in mental or psychomotor development indices between the two groups. Conclusions: GH treatment for 24 months in very young short-stature children born SGA resulted in a significant increase in height SDS compared with no treatment. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 10/2015; DOI:10.1111/cen.12968
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    ABSTRACT: Objective: There are limited data concerning the evolution of radiation-induced hypopituitarism in adult-onset brain tumour (AO-BT) survivors; in part the consequence of the limited survival of many of these individuals. We aim to characterise the pituitary-related outcomes following cranial radiotherapy (cXRT) for adult-onset primary non-pituitary brain tumours. Design: We retrospectively analyzed longitudinal data of patients with AO-BT who received cXRT within a tertiary cancer referral center. Patients: 107 adults (age 40.0±13.1 years) followed for a median duration of eight years following cXRT. Measurements: Prevalence of radiotherapy-induced hypopituitarism. Results: 94.4% received fractionated photon radiotherapy (median dose 54Gy), while the remaining patients received proton beam or stereotactic radiotherapy. 88.8% of patients developed hypopituitarism during follow-up. The frequency of GH, gonadotropin, ACTH and TSH deficiencies was 86.9% (severe GHD 64.5%, partial GHD 22.4%), 34.6%, 23.4% and 11.2% respectively. ACTH deficiency was clinically significant, necessitating glucocorticoid replacement, in only 10.3% of cases. Hyperprolactinaemia developed in 15% of patients, which was persistent in only 50% of cases. Multiple pituitary hormone deficiencies were present in 47.7% of patients; encountered more frequently in patients with tumours in proximity to the sella. Longitudinal data analysis revealed accumulation of hormone deficits throughout the follow-up period, with incidence of all pituitary hormone deficiencies almost doubling between years 2 and 7 of follow-up. Conclusions: Pituitary dysfunction in AO-BT survivors following cXRT is a common, evolving, time-dependent phenomenon. It is important deficits are identified early and replacement therapies introduced to optimize quality of life in these individuals, where prognosis is often guarded. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 10/2015; DOI:10.1111/cen.12969
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    ABSTRACT: Objective: Postprandial hyperglycaemia is associated with increased arterial stiffness and cardiovascular events. Low-dose prednisolone causes insulin resistance that typically manifests as postprandial hyperglycaemia. We investigated whether prednisolone causes postprandial vascular dysfunction in a cohort of patients with rheumatoid arthritis. Design: An open interventional and cross-sectional study were undertaken. Patients and measurements: Eighteen subjects with rheumatoid arthritis who had not taken oral glucocorticoids for ≥6 months were studied before and after prednisolone 6 mg/day for 7 days to determine the acute effects of prednisolone. Pre-prednisolone data were compared to 18 subjects with rheumatoid arthritis taking long-term (>6 months) prednisolone (6.5±1.8 mg/day) to assess the chronic effects of prednisolone. Augmentation index (by applanation tonometry) and reactive hyperaemia index (by peripheral artery tonometry) were measured before and after a mixed meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). Insulin sensitivity was estimated by the Matsuda index and sympathetic nervous system activity from urinary noradrenaline excretion. Results: Matsuda index was lower after acute (2.0±1.0 vs 3.6±1.1, p=0.01) and chronic (1.9±1.0 vs 3.6±1.1, p=0.04) prednisolone. Postprandial augmentation index was lower after acute prednisolone (2551±197 vs 2690±272%*min, p≤0.001), but not chronic prednisolone. There were no significant differences in reactive hyperaemia index with acute or chronic prednisolone. Noradrenaline excretion was lower after acute (54±8 vs 93±23 nmol/6h, p=0.02), but not chronic, prednisolone. Conclusions: Prednisolone-induced insulin resistance is not associated with postprandial vascular dysfunction in patients with rheumatoid arthritis. Reduced sympathetic activity may contribute to the reduction in postprandial arterial stiffness with acute prednisolone. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 10/2015; DOI:10.1111/cen.12966