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: 3.35

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 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 3.26
Cited half-life 7.40
Immediacy index 0.87
Eigenfactor 0.02
Article influence 0.99
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
    • Author can archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • Some journals have separate policies, please check with each journal directly
    • On author's personal website, institutional repositories, arXiv, AgEcon, PhilPapers, PubMed Central, RePEc or Social Science Research Network
    • Author's pre-print may not be updated with Publisher's Version/PDF
    • Author's pre-print must acknowledge acceptance for publication
    • On a non-profit server
    • Publisher's version/PDF cannot be used
    • Publisher source must be acknowledged with citation
    • 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
    ​ yellow

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Although the fundamental significance of both LH and FSH for adequate ovarian folliculogenesis and steroidgenesis has been extensively discussed, the clinical implication of recombinant (r) LH to rFSH for ovarian stimulation employing the GnRH antagonist protocol remains to be elucidated. The aim of this prospective randomized controlled study was to explore whether rLH supplementation to rFSH following GnRH antagonist has an added value to the late follicular ovarian steroidogenesis in the advanced reproductive aged women. Sixty three consecutive infertile women above 35 years of age and/or with a previous low ovarian response admitted for IVF/ICSI treatment were prospectively randomized. Women in the study and control groups were similarly treated employing the rFSH 300 IU/day and the flexible GnRH antagonist 0.25 mg/day protocol. On the day of antagonist initiation, r-LH 150 IU/day was added only to the study group and continued till the hCG day. Serum E2 level on hCG day did not significantly differ between the study and control groups, corresponding to 1,268±1006 and 1,113±669 pg/mL, respectively (P=0.9). In the study group the duration of GnRH antagonist administration was significantly lower than the control group corresponding to 5.0±1.5 to 4.0±1.5 days, respectively (P<0.05). The total dosage of rFSH administration did not differ between the two groups. rLH supplementation to rFSH following GnRH antagonist administration employing the flexible protocol does not seem to significantly augment serum E2 level on the day of hCG administration in the advanced reproductive aging women. This suggests that endogenous serum LH levels following GnRH antagonist initiation are sufficient for adequate late follicular ovarian steroidogensis in this setting. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12886
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    ABSTRACT: Turner's syndrome is a rare genetic condition, affecting 1/2500 live female births, caused by complete or partial absence of an X chromosome (1). The diagnosis is confirmed by the demonstration of X chromosome monosomy or mosaicism on karyotype analysis. Turner's syndrome is almost always characterized by short stature and ovarian failure with infertility. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12885
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    ABSTRACT: Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs) are rare, chromaffin cell derived tumors of the adrenal medulla and extra-adrenal paraganglia respectively. Approximately 40% of these tumors carry a somatic or constitutional mutation in one or several susceptibility gene(s), and based on gene expression studies, mutations in these genes have been found to alter either the kinase signaling pathway or the pseudo-hypoxia response pathway. Although the majority of PCCs and PGLs are benign, a significant subset of PGLs is malignant. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12884
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    ABSTRACT: To evaluate the effects of β-adrenoreceptor antagonists (β-blockers) on the aldosterone renin ratio (ARR) in the context of anti-hypertensive polypharmacy in chronic hypertension. To determine the optimal duration of β-blocker withdrawal required to normalise the ARR. A prospective, longitudinal study design was employed investigating two groups whom either remained on or withdrew from β-blocker therapy. Hypertensive individuals taking β-blockers, and a combination of thiazide diuretics, α1 -blockers, calcium channel antagonists and ACEi/ARB were recruited and followed over 8 weeks. β blockers were withdrawn at the first visit. BP was measured at each visit and blood drawn serially for measurement of plasma renin activity (PRA), direct renin concentration (DRC) and aldosterone. BP was optimised by maximising non-renin-suppressing antihypertensives. Main outcomes were ARR, DRC, PRA and aldosterone. PRA was calculated from angiotensin I measured using radioimmunoassay (RIA), DRC was measured using chemilluminescent immunoassay assay (CLIA) and aldosterone was measured using both RIA and CIL. False positive ARR for primary aldosteronism (PA) occurred in 31% of patients taking β-blockers. ARR returned to normal following β-blocker withdrawal resulting from an increase in the DRC and PRA without affecting aldosterone. The optimum time for β-blocker withdrawal was two weeks when using DRC and 3 weeks for PRA. β-blocker withdrawal did not adversely affect blood pressure. Raised ARR consequent to β-blocker therapy causes false positive screening for PA. Where β-blockers can be safely withdrawn this effect is reversed within 2-3 weeks depending on whether DRC or PRA is used to calculate ARR. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12882
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    ABSTRACT: To investigate the prevalence of endocrine disturbances in a group of HIV positive (HIV+) women, and to identify factors affecting presence of these disorders. To examine specifically if cellular aging, as measured by leukocyte telomere length (LTL) is correlated with presence of endocrine disturbance. A cross-sectional retrospective sub-study of an ongoing prospective cohort study. HIV+ adult (≥19 years) women enrolled in the CARMA (Children and Women: AntiRetrovirals and Markers of Aging) cohort study (N=192). Prevalence of T2DM, glucose intolerance, dyslipidemia, thyroid disorders, adrenal insufficiency, hypogonadism, primary ovarian insufficiency (POI), demographics, HIV and hepatitis C virus (HCV) infection status, baseline LTL, combined antiretroviral therapy (cART) and substance exposures were collected. Statistical analysis included univariable followed by multivariable Poisson regression, and step-wise reduction to refine the multivariable model. Prevalence of any endocrine abnormality was 58% (dyslipidemia 43%, glucose intolerance/T2DM 13%, thyroid disorders 15%). In multivariable analysis, age was associated with number and type (any, glucose, lipid) of abnormality, while increasing body mass index (BMI) was associated with number of diagnoses and with glucose metabolism disorders. Interestingly, peak HIV pVL ≥100, 000 copies/mL was associated with any abnormality, total number of disorders and presence of a thyroid disorder, while any disorder, glucose abnormalities and dyslipidemia were negatively associated with alcohol use. LTL was not associated with number or type of endocrine abnormalities in this study. Further studies examining the relationship between duration and extent of exposure to HIV viremia in relation to developing abnormal endocrine function are warranted. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12881
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    ABSTRACT: The optimal management of non-functioning pituitary adenomas presenting without symptomatic mass effect remains uncertain. The objective of this study was to elucidate the natural history of non-functioning pituitary adenomas managed conservatively. Volumetric evaluation of tumour growth in serial pituitary MRI scans by a single observer and retrospective review of changes in pituitary function. Patients with non-functioning pituitary adenomas who underwent at least 2 serial pituitary MRI scans over ≥6 months between 2003 and 2013 prior to any intervention. Primary endpoint was a ≥20% increase in volume or surgery. Secondary endpoints were rate of pituitary dysfunction and pituitary apoplexy. 50 non-functioning pituitary adenomas (23 macroadenomas and 27 microadenomas, mean age 49, range 17-85 years) were identified. Mean follow up was 36 months (range 6-79). An increase in volume occurred in macroadenomas (P<0.01) but not microadenomas (P=0.44). A ≥20% increase in volume occurred in 9/23 macroadenomas compared with 2/27 microadenomas (P<0.05). Five macroadenomas (1 with new visual field defect) and 1 microadenoma proceeded to surgery (P=0.08). Hormone deficiency was present in 4/24 macroadenomas versus 0/27 microadenomas (P<0.05) at baseline, while new hormone deficiency developed in only two macroadenomas during follow-up. Pituitary apoplexy occurred in one microadenoma. A growth rate of >10 mm(3) /month assessed at approximately 2 years of follow-up among the macroadenoma group was highly predictive (sensitivity and specificity of 90%) of a ≥20% increase in volume or surgery. Non-functioning pituitary macroadenomas have a greater tendency to grow and require surgical intervention while microadenomas rarely progress. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12879
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    ABSTRACT: BRAFV600E mutation is the most common activating mutation associated with aggressive behaviors in human tumors including conventional papillary thyroid carcinoma (cPTC). P-cadherin and cadherin 6 have been shown to be mesenchymal-associated cadherins and promote cancer cell invasion and metastasis. The purpose of this study was to examine BRAFV600E, P-cadherin and cadherin 6 expression in cPTC and to assess the association of their expression with clinicopathological indicators. BRAFV600E, P-cadherin and cadherin 6 protein expression in 80 cPTCs, 61 nodular hyperplasia and 76 normal thyroid tissues were examined by immunohistochemistry. The correlation of their protein expression with clinicopathological indicators of cPTC was statistically analyzed. rotein expression of BRAFV600E, P-cadherin and cadherin 6 was upregulated in cPTC. High protein expression of BRAFV600E, P-cadherin and cadherin 6 was significantly correlated with high TNM stage and lymph node metastasis (LNM) (P < 0.001). Furthermore, BRAFV600E, P-cadherin and cadherin 6 protein expression were correlated with one another. BRAFV600E high expression combined with both P-cadherin and cadherin-6 high expression had stronger correlation with high TNM stage and LNM when compared with BRAFV600E high expression combined with either P-cadherin or cadherin-6 high expression (P = 0.042, 0.017 for TNM stage and P = 0.003, 0.006 for LNM, respectively) and only BRAFV600E high expression (P < 0.001 for both TNM stage and LNM). Concomitant high expression of BRAFV600E, P-cadherin and cadherin 6 is strongly associated with high TNM stage and LNM in cPTC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12878
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    ABSTRACT: The results of longitudinal studies on the association between thyroid function and blood pressure (BP) are divided. This study aimed to investigate this association in cross-sectional and longitudinal settings in a nationwide, random sample representative of the Finnish adult population aged 30 and over. The study sample was randomly drawn from the population register. 5655 participants were included in the baseline analyses and 3453 in the 11-year prospective analyses. The associations between baseline TSH and 1) BP and BP change over time; and 2) prevalent and incident hypertension were assessed using linear and logistic models, adjusted for age, gender, smoking and body mass index. A positive association (β±standard error) was observed between TSH and diastolic (0.36±0.12, p=0.003) but not systolic BP (0.16±0.21, p=0.45) at baseline. TSH was negatively associated with 11-year BP change in men (systolic: -0.92±0.41, p=0.03; diastolic: -0.66±0.26, p=0.01) but not in women (p≥0.09 for systolic and diastolic BP change). Participants in the highest TSH tertile within the TSH reference interval (0.4-3.4 mU/L), as compared with the lowest, had increased odds of prevalent (odds ratio 1.22, 95% confidence interval 1.05-1.43, p=0.01) but not incident hypertension (odds ratio 0.93, 95% confidence interval 0.73-1.19, p=0.58). A modest association was found between increasing TSH and prevalent but not incident hypertension. TSH was inversely associated with BP change in men in our study. These findings contest an independent role of thyroid function at normal to near-normal levels in the pathogenesis of hypertension. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12876
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    ABSTRACT: The management of a benign thyroid nodule includes follow-up until its size requires a surgical or alternative treatment. To date, it is difficult or impossible to predict the size changes of a benign nodule in a given patient because no specific growth parameters exist. RAS mutations have been described in thyroid adenomas and hyperplastic benign nodules. The aim of this study was to establish whether the volume changes of benign nodules are associated withthe presence of RAS mutation. Genomic DNA obtained by fine-needle aspiration of 78 thyroid noduleswith benign cytologywasanalyzed by pyrosequencing for the presence of NRAS(61) and KRAS(13) mutations.Ultrasonographic features were obtained. The volume of nodules at baseline and their changes after a mean follow-up of 25 months were evaluated according to the presence of RAS mutation. A RAS mutation was found in 24 thyroid aspirates (30.8%, 8 NRAS(61) and 16 KRAS(13) ). RAS mutation was not associated with ultrasonographic features, butwas significantly associated with a larger size at baseline (p = 0.017). After a 25 months mean follow-up, RAS mutation positive nodules displayed faster growth (RAS mutation positive vs. negative % annual growth 27.6% +/- 32.2% vs. 1.0% +/- 17.0%, p <0.001). Benign thyroid nodules bearing RAS mutation grow more rapidly than those with wild type RAS. Searching for RAS mutations in thyroid nodules with benign cytology might be useful to the clinician in choosing a more appropriate and timely surgical management. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12875
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    ABSTRACT: We thank Pacifico and Chiesa who have contributed to this very pleasant debate on our manuscript entitled "Non-alcoholic fatty pancreas disease and Non-alcoholic fatty liver disease: more than ectopic fat", recently published on Clinical Endocrinology. In our manuscript, we stated that our study is the first aiming to clarify the possible link between fatty pancreas and hepato-metabolic features in obese children affected by NAFLD, evaluating the correlation between NAFPD and NAFLD/NASH (fatty liver associated to inflammation and fibrosis) and between NAFPD and β-cell function. As recently reported in the Position Paper of Hepatology Committee of ESPGHAN on diagnosis of NAFLD (1), liver biopsy remains the only method to make a definite diagnosis of NASH and to evaluate liver fibrosis. In fact, the major aim of our study was to investigate the possible correlation between fatty pancreas and severity of liver damage, with particular regards to liver fibrosis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12877
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    ABSTRACT: Aldosterone-producing adenomas (APAs) and bilateral adrenal hyperplasia are important causes of secondary hypertension. Somatic mutations in KCNJ5, CACNA1D, ATP1A1, ATP2B3 and CTNNB1 have been described in APAs. To characterize clinical-pathological features in APAs and unilateral adrenal hyperplasia, and correlate them with genotypes. Retrospective study. Clinical and pathological characteristics of 90 APAs and 7 diffusely or focally hyperplastic adrenal glands were reviewed, and samples were examined for mutations in known disease genes by Sanger or exome sequencing. Mutation frequencies were: KCNJ5, 37.1%; CACNA1D, 10.3%; ATP1A1, 8.2%; ATP2B3, 3.1%; CTNNB1, 2.1%. Previously unidentified mutations included I157K, F154C and 2 insertions (I150_G151insM and I144_E145insAI) in KCNJ5, all close to the selectivity filter, V426G_V427E_A428_L433del in ATP2B3, and A39Efs*3 in CTNNB1. Mutations in KCNJ5 were associated with female, and other mutations with male gender (p=0.007). On computed tomography, KCNJ5-mutant tumors displayed significantly greater diameter (p=0.023), calculated area (p=0.002) and lower pre-contrast Hounsfield Units (p=0.0002) vs. tumors with mutations in other genes. Accordingly, KCNJ5-mutant tumors were predominantly comprised of lipid-rich fasciculata-like clear cells, whereas other tumors were heterogeneous (p=5x10(-6) vs. non-KCNJ5 mutant and p=0.0003 vs. wild type tumors, respectively). CACNA1D mutations were present in two samples with hyperplasia without adenoma. KCNJ5 mutant tumors appear to be associated with fasciculata-like clear cell predominant histology and tend to be larger with a characteristic imaging phenotype. Novel somatic KCNJ5 variants likely cause adenomas by loss of potassium selectivity, similar to previously described mutations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12873
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    ABSTRACT: Graves' disease (GD) is an autoimmune disease characterized by the presence of circulating autoantibodies against thyroid stimulating hormone (TSH) receptor. Despite extensive research, the pathogenic mechanisms remain unclear. Immune responses associated with the disease may lead to cell activation/apoptosis and the release of microvesicles (MVs) into the circulation. MVs can display biological activities which may aggravate GD further. We studied immune mechanisms in GD by investigating the numbers and phenotype of circulating MVs in patients before and after antithyroid therapy with thiamazole. Samples were obtained from 15 patients with GD in the acute phase of hyperthyroidism and following 17-26 months treatment and 14 healthy controls. MVs from platelets, endothelial cells and monocytes exposing inflammation/activation markers (P-selectin, CD40 ligand, E-selectin and HMGB1) and MVs containing nuclear molecules were measured with flow cytometry. Patients had elevated baseline values of MVs (p<0.001 for all types of MVs), while the levels decreased during thiamazole treatment (p<0.05 for all types of MVs). The majority of MV populations remained, however, significantly higher in patients after treatment compared to levels in controls. GD patients have elevated levels of MVs that carry molecules with potential biological activities. MVs are significantly reduced after antithyroid treatment with thiamazole but still higher compared to levels in healthy controls. Assessment of MV levels and pattern may therefore provide additional information on underlying immune disturbances not obtained by measurements of hormone levels alone. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12872
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    ABSTRACT: The treatment options in the young patient with Graves' disease are the same as in adults, namely anti-thyroid drug (ATD), surgery (partial or total thyroidectomy) and radio-iodine. However the emphasis and expectation is different in the young person, reflecting a range of considerations including age, pubertal status, disease natural history, likely impact of ATD on disease course and the implications of radiation exposure. New therapeutic strategies that could increase the likelihood of long term remission are being explored. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12871
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    ABSTRACT: Life expectancy of cancer survivors has doubled in the past four decades; however, death due to cardiovascular disease is more prevalent in survivors than the general population. We evaluated novel and traditional cardiometabolic risk factors in young male cancer survivors in a cross-sectional study of male cancer survivors aged 25-45 years compared with age-matched non-cancer controls. Demographic and anthropometric data were recorded and biochemical and hormonal parameters assayed from fasting blood samples in 176 survivors and 213 controls (lipids were measured in all survivors and 97 controls). Compared with controls, survivors had significantly higher body mass index, adipocytokines, insulin resistance, total cholesterol and triglyceride levels and lower free androgen index (FAI). Handgrip strength, smoking, alcohol consumption, free estrogen index, insulin-like growth factor 1 and high-density lipoprotein cholesterol levels did not differ between cancer survivors and controls. Risk factors were analysed simultaneously using stepwise multi-variable logistic regression, and this showed that high leptin:adiponectin ratio (odds ratio=2.63; 95% confidence interval 1.34-5.15; P=0.005), hypercholesterolaemia (odds ratio=1.85; 95%CI 1.08-3.17; P=0.025) and low FAI (odds ratio=2.01; 95% confidence interval 1.07-3.79; P=0.030) were independently more common in survivors. The odds ratio in survivors for having at least two of these three risk factors rose to 6.58 (95% confidence interval 3.30-13.12; P<0.001). Among survivors, risk factors were not different between cancer therapies but worse in survivors who had radiotherapy involving the testes (hyperleptinaemia and insulin resistance) or age at diagnosis above group median (hypertriglyceridaemia and hypercholesterolaemia). A high leptin:adiponectin ratio, hypercholesterolaemia and low FAI are observed in young male cancer survivors, especially those who received radiotherapy involving the testes or were diagnosed at a later age. In view of their youth and known increased risk of cardiovascular death, treatment strategies are required to address this cardiovascular risk. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 08/2015; DOI:10.1111/cen.12869
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    ABSTRACT: Mitotane, a steroidogenesis inhibitor with adrenolytic properties used to treat adrenal cortical cancer (ACC), can affect thyroid function. A reduction of FT4 levels with normal FT3 and TSH has been described in these patients. Using an in vitro murine model, the secretory capacity of thyrotrophic cells has been shown to be inhibited by mitotane. To investigate the pathogenesis of thyroid abnormalities in mitotane-treated ACC patients. In five female ACC patients (median age 47; range 31-65) treated with mitotane (dosage 1.5 g/day; 1.0-3.0) we analysed the pattern of TSH and thyroid function index (FT4, FT3 and FT3/FT4 ratio) compared to an age- and gender-matched control group. The in vivo secretory activity of the thyrotrophic cells was evaluated using a standard TRH test (200 μg) and the response was compared to both a group of age-matched female controls (n=10) and central hypothyroid patients (n=10). Basal TSH (median 1.54 mU/l; range 1.20-2.17) was normal and scattered around our median reference value, FT3 levels (median 3.80 pmol/l; 3.30-4.29) were normal but below the median reference value of 4.37 pmol/l, and FT4 levels were below the normal range in all patients (median 8.40 pmol/l; 7.6-9.9). FT3/FT4 ratio was in the upper range in 4 patients and higher than normal in one patient. A blunted TSH response to TRH was observed in mitotane-treated patients. ΔTSH (absolute TSH response, peak TSH minus basal TSH) was 3.65 (range 3.53-5.26), 12.37 (range 7.55-19.97) and 1.32 mU/l (range 0.52-4.66) in mitotane-treated patients, controls and central hypothyroid patients, respectively. PRL secretion was normal. Mitotane-treated ACC patients showed low FT4, normal FT3 and TSH and impaired TSH response to TRH, characteristic of central hypothyroidism. Furthermore, the elevated FT3/FT4 ratio of these subjects reflects an enhanced T4 to T3 conversion rate, a compensatory mechanism characteristic of thyroid function changes observed in hypothyroid conditions. This finding thus confirms in vitro studies and may have a therapeutic implication for treatment with thyroid hormones, as suggested by current guidelines for this specific condition. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2015; DOI:10.1111/cen.12868
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    ABSTRACT: Idiopathic short stature (ISS) has a strong familial component but genetics explains only part of it. Indeed, environmental factors act on human growth either directly or through epigenetic factors that remain to be determined. Given the importance of the GH/IGF1 axis for child growth, we suspected that such epigenetic factors could involve the CG methylation at the IGF1 gene P2 promoter, which was recently shown to be a transcriptional regulator for IGF1 gene and a major contributor to GH sensitivity. Explore if the methylation of the two IGF1 low-CG rich promoters (P1 and P2) is associated with ISS. 94 children with ISS were compared with 119 age-matched children of normal height for the methylation of CGs located within the IGF1 promoters measured with bisulfite-PCR-pyrosequencing. The methylation of 5 CGs of the P2 promoter was higher in ISS children, notably CG-137 (49 ± 4% in ISS versus 46 ± 4% in control children, P= 9x10(-5) ). This was also true for CG-611 of the P1 promoter (93 ± 3% vs 91 ± 3% P=10(-4) ). The CG methylation of the IGF1 promoters thus takes place among the multifactorial factors that are associated with ISS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2015; DOI:10.1111/cen.12867
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    ABSTRACT: An adrenal crisis (AC) is a potential life threatening event in patients with adrenal insufficiency (AI). This study aims to determine the incidence, causes and risk factors of AC in AI. Patients with AI diagnosed and treated at the University Medical Center Utrecht for the past 30 years were identified and all medical records were assessed by two independent investigators. The observed frequency of AC was determined as incidence rate, calculated as the number of AC divided by person years (PY). In addition precipitating factors and risk factors were assessed. We observed an incidence rate of 5.2 AC (95% CI 4.3-6.3) per 100 PY in primary adrenal insufficiency (PAI, a total of 111 patients), and 3.6 AC (95% CI 3.1-4.1) per 100 PY in secondary adrenal insufficiency (SAI a total of 319 patients). Patients with an established diagnosis of tertiary (glucocorticoid-induced) adrenal insufficiency (a total of 28 patients) had 15.1 AC (95% CI 11.0-19.9) per 100 PY. The most important risk factor was the existence of comorbidity. Gastro-enteritis and other infections were the most common precipitating factors for AC. AC still occurs relatively frequent in patients with AI, mostly precipitated by infections and particularly in patients with high co-morbidity. This should be taken into account in the education and follow up of patients with AI. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2015; DOI:10.1111/cen.12865
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    ABSTRACT: Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome (HFRS) caused by Puumala hantavirus (PUUV). Pituitary hemorrhage and hypopituitarism may complicate recovery from acute NE. Forty-seven of our recent cohort of 58 NE patients volunteered to be re-examined in order to estimate the burden of hormonal deficiency 4 to 8 years after the acute illness. Two patients had suffered from pituitary hemorrhage but many others exhibited pituitary oedema during their acute infection. In this study, we searched for symptoms of hormonal deficiency, performed hormonal laboratory screening, and most patients underwent pituitary MRI examination. The pituitary size had diminished in all patients in whom MRI was performed (p<0.001). One patient with acute phase hemorrhage had made a complete recovery while the other continued to require hormonal substitution. In addition, hormonal laboratory abnormalities were observed in nine other patients; these being attributable to several reasons e.g. independent peripheral hormonal diseases, side effects of medication or other secondary causes such as obesity. None of them had signs of late-onset pituitary insufficiency caused by their previous NE. Health-related quality of life (mean and median 15D score) of patients was comparable to that of age-standardized general population. None of our patients had developed obvious late-onset hypopituitarism despite of the fact that pituitary gland can be affected during acute NE. We recommend requesting a history of hantavirus infection whenever the possibility of pituitary dysfunction is suspected at least in patients originating from regions with high NE infection rate. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2015; DOI:10.1111/cen.12863