European Journal of Endocrinology (EUR J ENDOCRINOL)

Publisher: European Federation of Endocrine Societies, BioScientifica

Journal description

The journal publishes original research papers, reviews, short communications and case reports within clinical and experimental endocrinology.

Current impact factor: 3.69

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 3.686
2012 Impact Factor 3.136
2011 Impact Factor 3.423
2010 Impact Factor 3.482
2009 Impact Factor 3.539
2008 Impact Factor 3.791
2007 Impact Factor 3.239
2006 Impact Factor 3.145
2005 Impact Factor 2.962
2004 Impact Factor 3.14
2003 Impact Factor 2.941
2002 Impact Factor 2.56
2001 Impact Factor 2.133
2000 Impact Factor 2.315
1999 Impact Factor 2.421
1998 Impact Factor 2.101
1997 Impact Factor 1.968
1996 Impact Factor 1.695
1995 Impact Factor 1.234

Impact factor over time

Impact factor

Additional details

5-year impact 3.58
Cited half-life 6.30
Immediacy index 0.74
Eigenfactor 0.02
Article influence 1.11
Website European Journal of Endocrinology website
Other titles European journal of endocrinology
ISSN 0804-4643
OCLC 29970781
Material type Periodical, Internet resource
Document type Journal / Magazine / Newspaper, Internet Resource

Publisher details


  • Pre-print
    • Author cannot archive a pre-print version
  • Post-print
    • Author cannot archive a post-print version
  • Restrictions
    • 12 months embargo
  • Conditions
    • In any repository
    • Publisher's version/PDF cannot be used
    • Set statement to accompany deposit (see policy)
    • Publisher last contacted on 18/04/2013
  • Classification
    ​ white

Publications in this journal

  • European Journal of Endocrinology 05/2015; DOI:10.1530/EJE-15-0048
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    ABSTRACT: OBJECTIVE: This study aimed at investigating the role of IGF-I and IGF binding protein 3 (IGFBP-3) in the development of β-cell autoimmunity. METHODS: Five hundred sixty-three subjects with HLA-conferred susceptibility to type 1 diabetes were monitored for signs of seroconversion to positivity for insulin and/or GAD, IA-2, and ZnT8 autoantibodies by the age of 3 years. In 40 subjects who developed at least one autoantibody, IGF-I and IGFBP-3 plasma concentrations were measured and compared with 80 control subjects who remained negative for autoantibodies, and were matched for age, sex, country of origin, and HLA genotype. The increment of IGF-I, IGFBP-3 and IGF-I/IGFBP-3 molar ratio before and after seroconverison was compared with corresponding time intervals in controls. RESULTS: The IGF-I concentrations at the age of 12 months, and the IGF-I/IGFBP-3 ratio at the age of 24 months were lower in the autoantibody-positive children (P <0.05). The increase in circulating IGFBP-3 was significantly higher in the autoantibody-positive children before seroconversion than in the corresponding time-intervals in controls (0.43 mg/l; 95% CI 0.29-0.56 vs. 0.22 mg/l; 95% CI 0.10-0.34 mg/l; P <0.01). Children carrying the high-risk HLA genotype had lower plasma IGF-I and IGFBP-3 concentrations at the age of 24 months than those with low-risk genotypes (P < 0.05 and < 0.01, respectively). CONCLUSIONS: Circulating IGF-I and IGFBP-3 appear to have a role in early development of β-cell autoimmunity. The decreased IGF-I concentrations in children with the high-risk HLA genotype may contribute to the reduced growth previously described in such children.
    European Journal of Endocrinology 05/2015; DOI:10.1530/EJE-14-1078
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    ABSTRACT: Reduced circulating omentin levels have been reported in obesity and type 2 diabetes, but data were mostly derived from univariate analyses in small study samples. This study aimed to investigate the relationship between omentin, abnormal glucose tolerance and related metabolic factors in a large population-based cross-sectional study. Serum omentin was measured by ELISA in 1092 participants of the German KORA F4 survey (2006-2008). Associations between omentin serum levels, glucose tolerance (assessed with an oral glucose tolerance test) and diabetes-related factors were estimated using logistic and linear regression models respectively. Serum levels of omentin were not related to categories of glucose tolerance. However, serum omentin was positively associated with whole-body insulin sensitivity index (ISI (composite)) and HDL cholesterol and showed inverse associations with 2-h post-load glucose, fasting insulin, homeostasis model assessment-estimated insulin resistance, BMI and triglycerides (all P≤0.03 after adjustment for age, sex and lifestyle factors). Further adjustment for BMI and/or serum lipids attenuated the associations with parameters of glucose metabolism, whereas adjustment for serum adiponectin virtually abolished all aforementioned associations. In contrast, adjustment for omentin had no effect on the positive association between adiponectin levels and ISI (composite). The data from this large population-based cohort show that circulating omentin levels are associated with insulin sensitivity. Our observations further suggest that omentin acts via upregulation of adiponectin, which in turn affects lipid metabolism and thereby also indirectly enhances insulin sensitivity, but mechanistic studies are required to corroborate this hypothesis. © 2015 European Society of Endocrinology.
    European Journal of Endocrinology 04/2015; 172(4):423-32. DOI:10.1530/EJE-14-0879
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    ABSTRACT: The aim of this systematic review and meta-analysis was to investigate whether mortality is increased in patients biochemically cured after initial treatment for Cushing's disease. This is a systematic review and meta-analysis of follow-up studies in patients cured from Cushing's disease after initial treatment was performed. Eight electronic databases were searched from 1975 to March 2014 to identify potentially relevant articles. Original articles reporting the standardized mortality ratio (SMR) for patients cured of Cushing's disease were eligible for inclusion. SMRs were pooled in a random effects model. I(2) statistics was used for quantification of heterogeneity. Eight cohort studies with a total of 766 patients were included. Out of eight studies, seven showed an SMR above 1.0 for cured patients. The pooled SMR was 2.5 (95% CI 1.4-4.2). The I(2) statistics showed evidence for statistical heterogeneity (78%, Q-statistics P<0.001), which was largely explained by two outliers. This meta-analysis reveals that mortality remains increased in patients with Cushing's disease even after initial biochemical cure remission, suggesting that cure does not directly reverse the metabolic consequences of long-term overexposure to cortisol. Other conditions such as hypopituitarism, including persistent adrenocortical insufficiency after surgery, may also contribute to the increased mortality risk. © 2015 European Society of Endocrinology.
    European Journal of Endocrinology 04/2015; 172(4):R143-R149. DOI:10.1530/EJE-14-0556
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    ABSTRACT: Pituitary incidentalomas (PIs) are commonly encountered in clinical practice. The management of these asymptomatic pituitary lesions is still controversial. Systematic screening for subclinical or mild ACTH-dependent hypercortisolism (AH) is not presently recommended, due to the limited data available thus far on the epidemiological and clinical relevance of this condition in patients with PIs. As subclinical hypercortisolism (SH) was considered to be associated with chronic complications of overt cortisol excess, such as hypertension, diabetes, and osteoporosis, this disorder should be diagnosed at the early stage. The objective of this study was to evaluate the prevalence of hypercortisolism in a population of subjects with PIs. A total of 68 consecutive patients (48 females and 20 males, aged 18-82 years) without clinically overt hypercortisolism, who were referred for evaluation of PIs between January 2010 and March 2013, were prospectively investigated for AH. Pituitary hypercortisolism was diagnosed in the presence of cortisol >50 nmol/l after 1 mg dexamethasone suppression test, non-suppressed ACTH, and the additional finding of one of the following: urinary free cortisol (UFC) >193 nmol/24 h, and midnight serum and salivary cortisol levels >207 and 2.8 nmol/l respectively. Among patients with PIs, we found a 7.3% rate of pituitary hypercortisolism diagnosed with biochemical criteria and a 4.4% rate of histologically confirmed AH. Subclinical or mild hypercortisolism may be more common than generally perceived in patients with PIs. © 2015 European Society of Endocrinology.
    European Journal of Endocrinology 04/2015; 172(4):363-9. DOI:10.1530/EJE-14-0599
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    ABSTRACT: Idiopathic early-onset central diabetes insipidus (CDI) might be due to mutations of arginine vasopressin-neurophysin II (AVP-NPII (AVP)) or wolframin (WFS1) genes. Sequencing of AVP and WFS1 genes was performed in nine children with CDI, aged between 9 and 68 months, and negative family history for polyuria and polydipsia. Two patients carried a mutation in the AVP gene: a heterozygous G-to-T transition at nucleotide position 322 of exon 2 (c.322G>T) resulting in a stop codon at position 108 (p.Glu108X), and a novel deletion from nucleotide 52 to 54 (c.52_54delTCC) producing a deletion of a serine at position 18 (p.Ser18del) of the AVP pre-prohormone signal peptide. A third patient carried two heterozygous mutations in the WFS1 gene localized on different alleles. The first change was A-to-G transition at nucleotide 997 in exon 8 (c.997A>G), resulting in a valine residue at position 333 in place of isoleucine (p.Ile333Val). The second novel mutation was a 3 bp insertion in exon 8, c.2392_2393insACG causing the addition of an aspartate residue at position 797 and the maintenance of the correct open reading frame (p. Asp797_Val798insAsp). While similar WFS1 protein levels were detected in fibroblasts from healthy subjects and from the patient and his parents, a major sensitivity to staurosporine-induced apoptosis was observed in the patient fibroblasts as well as in patients with Wolfram syndrome. Early-onset CDI is associated with de novo mutations of the AVP gene and with hereditary WFS1 gene changes. These findings have valuable implications for management and genetic counseling. © 2015 European Society of Endocrinology.
    European Journal of Endocrinology 04/2015; 172(4):461-72. DOI:10.1530/EJE-14-0942
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    ABSTRACT: Objective To assess, in a pediatric population, the clinical characteristics and management of triiodothyronine-predominant Graves' disease (T3-P-GD), a rare condition well known in adults, but not previously described in children. Design We conducted a university hospital-based observational study. Methods All patients with GD followed for more than one year between 2003 and 2013 (n=60) were included. T3-P-GD (group I) was defined as high fT3 concentration (>8.0 pmol/l) associated with a normal fT4 concentration and undetectable TSH more than one month after the initiation of antithyroid drug (ATD) treatment. Group II contained patients with classical GD without T3-P-GD. Results Eight (13%) of the patients were found to have T3-P-GD, a median of 6.3 (3.0-10.5) months after initial diagnosis (n=4) or 2.8 (2.0-11.9) months after the first relapse after treatment discontinuation (n=4). At GD diagnosis, group I patients were more likely to be younger [6.8 (4.3-11.0) vs. 10.7 (7.2-13.7) years] and had more severe disease than group II patients, with higher serum TRAb levels: 40 (31-69) vs. 17 (8-25) IU/l, p<0.04 and with slightly higher serum fT4 [92 (64-99) vs. 63 (44-83) pmol/l] and fT3 [31 (30-46) vs. 25 (17-31) pmol/l] concentrations. During the three years following T3-P-GD diagnosis, a double dose of ATD was required and median serum fT4/fT3 ratio remained lower in group I than in group II. Conclusion Severe hyperthyroidism, with particularly high TRAb concentrations at diagnosis, may facilitate the identification of patients requiring regular serum fT3 determinations and potentially needing higher doses of ATD dosage during follow-up.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-0959
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    ABSTRACT: Posttraumatic pituitary hormone deficiency is often suggested. The impact of these predominantly mild and often irreproducible deficiencies on outcome is less clear. The study aim was to describe patient reported outcome in a national a-priori unselected cohort of patients with traumatic brain injury (TBI) in relation to deficiencies identified upon pituitary assessment. We conducted a nationwide population-based cohort study. Participants were Danish patients with a head trauma diagnosis recorded in the Danish Board of Health diagnostic code registry; 439 patients (and 124 healthy controls) underwent assessment of anterior pituitary function 2.5 years (median) after TBI. Questionnaires on health related quality of life (QoL)(SF36, EQ5D, QoLAGHDA) and fatigue (MFI-20) were completed in parallel to pituitary assessment. Patients with TBI had significant detriments in QoL. Impairment (mainly physical scales) related to pituitary deficiency, though only partially confirmed after adjustment for demographic differences. Hypogonadotrophic hypogonadism related to several QoL scores. Increasing impairments were observed with declining total-testosterone (men), but not free-testosterone or any other hormone concentrations. Total-testosterone was not independently related to impaired QoL and fatigue, after adjustment for demographics, and treatment with antidiabetics, opioids, antidepressants and anticonvulsants. Only a very limited relationship between pituitary hormone deficiencies and QoL/fatigue was demonstrated. Due to the dominating influence of concurrent comorbidities, pituitary deficiencies were not independently related to QoL/fatigue. Causality is still to be shown, and whether substitution therapy could be of additional relevance in selected patients needs to be proven.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-1069
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    ABSTRACT: Unilateral adrenalectomy is the first-line treatment for aldosterone-producing adenomas (APA). Hyperkalemia after adrenalectomy because of contralateral zona glomerulosa insufficiency has been reported. We investigated clinical risk factors to predict postoperative hyperkalemia in patients with APA undergoing adrenalectomy. The study was conducted by retrospective review of medical records from 2000-2012 at Seoul National University Hospital and two other tertiary centers. Data from 124 patients who underwent adrenalectomy were included. Hyperkalemia was defined as serum potassium >5.5 mmol/l. Clinical preoperative risk factors included age, blood pressure, plasma renin activity (PRA), plasma aldosterone concentration (PAC), serum potassium, serum creatinine, glomerular filtration rate (GFR), the mass size on pathology and mineralocorticoid receptor (MR) antagonist use. Thirteen of 124 patients (10.5%) developed postoperative hyperkalemia. The incidences of transient and persistent hyperkalemia were 3.2% and 7.3%, respectively. Preoperative PRA and PAC were not significantly different in postoperative hyperkalemic patients compared with normokalemic patients. Patients with persistent hyperkalemia were older, had a longer duration of hypertension, larger mass size on pathology, and lower GFR (all P <0.05). The incidence of postoperative hyperkalemia was not different between MR antagonist users and non-users. Older age (≥53 years), longer duration of hypertension (≥9.5 years), larger mass size on pathology (≥1.95 cm), and impaired preoperative renal function (GFR <58.2 ml/min) were associated with prolonged postoperative hyperkalemia in patients with APA. MR antagonist use did not prevent postoperative hyperkalemia. .
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-15-0074
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    ABSTRACT: Background: Neonatal diabetes mellitus (NDM), is a rare form of monogenic diabetes, and usually presents in the first 6 months of life. We aimed to describe the clinical characteristics and molecular genetics of a large Turkish cohort of NDM patients from a single centre and estimate an annual incidence rate of NDM in South-Eastern Anatolian region of Turkey. Design and Methods: NDM patients presenting to Diyarbakir Children State Hospital between 2010 and 2013, and patients under follow up with presumed type 1 diabetes mellitus, with onset before 6 months of age were recruited. Molecular genetic analysis performed. Results: Twenty-two patients(59% males) were diagnosed with NDM(TNDM-5;PNDM-17). Molecular genetic analysis identified a mutation in 20(95%) patients who a mutation analysis was undertaken. In TNDM patients, the genetic cause included chromosome 6q24 abnormalities(n=3), ABCC8(n=1) and homozygous INS(n=1). In PNDM patients, homozygous GCK(n=6), EIF2AK3(n=3), PTF1A(n=3), and INS(n=1) and heterozygous KCNJ11(n=2) mutations were identified. Pancreatic exocrine dysfunction was observed in patients with mutations in the distal PTF1A enhancer. Both patients with a KCNJ11 mutation responded to oral sulfonylurea. A variable phenotype was associated with the homozygous c.-331C>A INS mutation, which was identified in both a PNDM and TNDM patient. The annual incidence of PNDM in South-East Anatolian region of Turkey was 1 in 48,000 live births. Conclusions: Homozygous mutations in GCK, EIF2AK3 and the distal enhancer region of PTF1A were the commonest causes of NDM in our cohort. The high rate of detection a mutation likely reflects the contribution of new genetic techniques (targeted next generation sequencing) and increased consanguinity within our cohort.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-0852
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    ABSTRACT: Background: The association between coffee intake and type 2 diabetes may be modulated by common genetic variation. Objective: The purpose of this study was to examine the association between habitual coffee intake and the risk of type 2 diabetes and to determine whether this association varies by genetic polymorphisms related to type 2 diabetes in Korean adults. Design and Methods: A population-based cohort study over a follow-up of 4 years was conducted. A total of 4,077 Korean men and women aged 40-69 years with a normal glucose level at baseline were included. Coffee intake was assessed using a validated food frequency questionnaire and incident type 2 diabetes or pre-diabetes was defined by oral glucose tolerance test or fasting blood glucose test. The genomic DNA samples were genotyped with the Affymetrix Genome-Wide Human SNP Array 5.0 and 9 single nucleotide polymorphisms related to type 2 diabetes in East Asian populations were extracted. Results: A total of 120 cases of type 2 diabetes and 1,128 cases of pre-diabetes were identified. After adjustment for potential confounding factors, we observed an inverse association, but without any clear linear trend, between coffee intake and the combined risk of type 2 diabetes and pre-diabetes. We found that inverse associations between habitual coffee intake and the combined risk of type 2 diabetes and pre-diabetes were limited to those with the T-allele (GT/TT) of rs4402960 in IGF2BP2, those with the G-allele (GG/GC) of rs7754840 in CDKAL1, or those with CC of rs5215 in KCNJ11. Conclusion: We found a lower risk of pre-diabetes and type 2 diabetes combined with coffee intake among individuals with the GT/TT of IGF2BP2 rs4402960, GG/GC of CDKAL1 rs7754840, or CC of KCNJ11 rs5215 which are known to be related to type 2 diabetes in East Asians.
    European Journal of Endocrinology 03/2015; DOI:10.1530/EJE-14-0805
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    ABSTRACT: Objective: Cortisol excess due to adrenal adenomas or hyperplasia causes Cushing's syndrome. Recent genetic studies have identified a somatic PRKACA(L206R) mutation as a cause of cortisol-producing adenomas. We aimed to compare the clinical features of lesions with PRKACA mutations to those with CTNNB1 mutations and to search for similar mutations in unilateral hyperplasia or tumors co-secreting aldosterone. Design, patients and methods: 60 patients with cortisol excess who had adrenalectomies at our institution between 1992 and 2013 were assessed, and somatic mutations were determined by Sanger sequencing. 36 patients had overt Cushing's syndrome, the remainder were subclinical. 59 cases were adenomas (three bilateral), one was classified as hyperplasia. Four tumors had proven co-secretion of aldosterone. Results: Among cortisol-secreting unilateral lesions without evidence of co-secretion (n=52), we identified somatic mutations in PRKACA (L206R) in 23.1%, CTNNB1 (S45P, S45F) in 23.1%, GNAS (R201C) in 5.8% and CTNNB1 plus GNAS (S45P, R201H) in 1.9%. PRKACA and GNAS mutations were mutually exclusive. Of the co-secreting tumors, two (50%) had mutations in KCNJ5 (G151R and L168R). The hyperplastic gland showed a PRKACA(L206R) mutation, while patients with bilateral adenomas did not have known somatic mutations. PRKACA-mutant lesions were associated with younger age, overt Cushing's syndrome and higher cortisol levels versus non-PRKACA-mutant or CTNNB1-mutant lesions. CTNNB1 mutations were more significantly associated with right than left lesions. Conclusions: PRKACA(L206R) is present not only in adenomas, but also in unilateral hyperplasia and is associated with more severe autonomous cortisol secretion. Bilateral adenomas may be caused by yet-unknown germline mutations.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-1113
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    ABSTRACT: Objective: To explore differences between Europeans and South Asians in BMI, subcutaneous fat and serum leptin (s-leptin) during and after pregnancy, and their relationship with gestational diabetes (GDM). Design: Multi-ethnic population-based cohort study, whereof 353 Europeans (93.1 % of the included) and 190 South Asians (95.0 % of the included). Methods: S-leptin, BMI and subcutaneous fat (sum of triceps, subscapular and suprailiac skinfolds) were measured at 14 and 28 weeks' gestation, and 14 weeks after delivery. GDM diagnosed with the WHO criteria 2013. Results: South Asians had similar thickness of the triceps and suprailiac skinfolds, thicker subscapular skinfold and higher s-leptin than Europeans in early pregnancy, despite lower BMI. South Asians retained more subcutaneous fat (mean (95% CI) 10.0 (7.4-12.7) mm vs. 3.8 (1.9-5.8) mm) and BMI (1.5 (1.2-1.8) kg/m² vs. 0.1 (-0.1-0.3) kg/m²) than Europeans 14 weeks after delivery and s-leptin decreased less in South Asians than Europeans (-0.13 (-0.27 to -0.00) µg/L vs. -0.47 (-0.57 to -0.37) µg/L, P < 0.001 for all). The prevalence of GDM was 23.8% (n = 84) in Europeans and 42.6% (n = 81) in South Asians. BMI, subcutaneous fat and s-leptin were all positively associated with GDM, also after adjustment for covariates. Conclusions: The relatively high amounts of subcutaneous fat and s-leptin in South Asians in early pregnancy contributed to their increased risk of GDM. South Asians retained more weight and subcutaneous fat after delivery, potentially increasing their risk of adiposity and GDM in future pregnancies.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-15-0060
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    ABSTRACT: Objective: Although an inhibin B assay may be useful in the assessment of testicular function in a number of genital conditions, reliable reference ranges are still lacking. This study sought to establish the reference range for serum inhibin B by applying the updated Gen II assay. Design: This prospective study included 818 men referred for semen analysis: 377 were normozoospermic (reference group) and 441 presented at least one abnormal semen parameter (case group). Methods: Semen parameters were interpreted according to the 2010 WHO manual and David's modified classification for normal morphology. The inhibin B concentration was determined with the currently enzyme-linked immunosorbent assay. Results: In the reference group, the 2.5th percentile for inhibin B was 92 pg/mL and the 97.5th percentile for FSH was 7.8 IU/L. In the overall population, an inhibin B level <92 pg/ml was associated with increased odds ratio [95% Confidence Interval] for oligozoospermia (16.93 [9.82-29.18], p<0.0001), asthenozoospermia (4.87 [2.88-8.10], p<0.0001) and teratozoospermia (2.20 [1.31-3.68]. The combination of a FSH >7.8 IU/L and an inhibin B <92 pg/ml was associated with greater odds ratio for oligozoospermia (98.74 [23.99-406.35], p<0.0001) than for each hormone considered separately. Conclusion(s): A new reference range for serum inhibin B was established by the use of updated immunoassay. The correlations between hormone levels and semen parameters highlighted the importance of establishing these values with respect to the spermogram. When combined with FSH assay, the inhibin B range may be of value in the evaluation of spermatogenesis in a number of male genital conditions.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-0932
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    ABSTRACT: Objective: Selenium is present in the active site of proteins important for thyroid hormone synthesis and metabolism. The objective of this study is to investigate the effect of selenium supplementation in different doses on thyroid function, under conditions of suboptimal dietary selenium intake. Design: The Danish PREvention of Cancer by Intervention with SElenium pilot study (DK-PRECISE) is a randomised, double-blinded, placebo-controlled trial. 491 males and females aged 60-74 years were randomised to 100 μg (N=124), 200 μg (N=122) or 300 μg (N=119) selenium-enriched yeast or matching yeast-based placebo tablets (N=126). 361 participants, equally distributed across treatment groups, completed the five-year intervention period. Methods: Plasma samples were analyzed for selenium and serum samples for thyrotropin (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) at baseline, and after six months and five years of supplementation. Results: Plasma selenium concentrations increased significantly and dose-dependently in treatment groups receiving selenium (P < 0.001). Serum TSH and FT4 concentrations decreased significantly and dose-dependently by 0.066 mIU/L (P = 0.010) and 0.11 pmol/L (P = 0.015), respectively, per 100 μg/day increase) with insignificant differences between six months and five years. No significant effects were found for FT3 and FT3:FT4 ratio. Conclusions: In euthyroid subjects, selenium supplementation minutely and dose-dependently affected thyroid function, when compared to placebo, by decreasing serum TSH and FT4 concentrations. Based on these findings, selenium supplementation is not warranted under conditions of marginal selenium deficiency. However, a role for selenium supplementation in the treatment of autoimmune thyroid diseases is still unresolved.
    European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-15-0069
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    ABSTRACT: Intravenous glucocorticoid (i.v.GC) pulse therapy for Graves' ophthalmopathy (GO) can be associated with acute liver damage (ALD), which was roughly estimated to occur in ∼1% of patients, with an overall mortality of 0.4%. The aim of this study was to evaluate the frequency of ALD after the introduction of a series of exclusion criteria and preventive measures. Retrospective evaluation of all consecutive patients candidate to i.v.GC over a period of 5 years. The study includes 376 GO patients candidate to i.v.GC. Several liver tests were performed before, during, and after i.v.GC. To prevent ALD morbidity and mortality, the following measures were applied: i) exclusion of patients with active viral hepatitis and/or severe liver steatosis; ii) reduction in the GC dose, frequency, and number of pulses; and iii) administration of oral GC after i.v.GC, and also during i.v.GC in patients positive for nonorgan-specific autoantibodies (to prevent autoimmune hepatitis due to immune rebound). ALD was defined as an increase in alanine aminotransferase ≥300 U/l. A total of 353 patients were given i.v.GC and 23 were excluded for various conditions. ALD was detected in 4/376 patients candidate to i.v.GC, resulting in a morbidity of 1.06%. One patient recovered spontaneously and three after additional treatment with oral GC, given to re-establish immune suppression in the suspect of an autoimmune hepatitis. ALD related to i.v.GC is a relatively rare adverse event. Provided an accurate selection of patients and a series of preventive measures are applied, i.v.GC is a safe treatment for the liver. © 2015 European Society of Endocrinology.
    European Journal of Endocrinology 03/2015; 172(3):269-76. DOI:10.1530/EJE-14-0712
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    ABSTRACT: Objective: Chromosomal rearrangements of the RET proto-oncogene is one of the most common molecular events in papillary thyroid carcinoma (PTC). However, their pathogenic role and clinical significance are still debated. This study aimed to investigate the prevalence of RET/PTC rearrangement in a cohort of BRAF-wild type PTCs by fluorescence in situ hybridization (FISH) and to search a reliable cut-off level in order to distinguish clonal or non-clonal RET changes. Design: Forty BRAF wild-type PTCs were analyzed by FISH for RET rearrangements. As controls, 6 BRAFV600E mutated PTCs, 13 follicular adenomas (FA) and 10 normal thyroid parenchyma (NTP) were also analyzed. Methods: We performed FISH analysis on formalin-fixed paraffin-embedded (FFPE) tissue using a commercially available RET Break-apart probe. A cut-off level equivalent to 10.2% of aberrant cells was accepted as significant. To validate FISH results, we analyzed the study cohort by qRT-PCR. Results: Split RET signals above the cut-off level were observed in 25% (10/40) of PTCs, harboring a percentage of positive cells ranging from 12% to 50%, and in 1 spontaneous FA (1/13, 7.7%). Overall, the data obtained by FISH matched well with qRT-PCR results. Challenging findings were observed in 5 cases showing a frequency of rearrangement very close to the cut-off. Conclusions: FISH approach represents a powerful tool to estimate the ratio between broken and non-broken RET tumor cells. Establishing a precise FISH cut-off may be useful in the interpretation of the presence of RET rearrangement, primarily when this strategy is used for cytological evaluation or for targeted therapy.
    European Journal of Endocrinology 02/2015; DOI:10.1530/EJE-14-0930
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    ABSTRACT: Objectives: Pituitary stem cells play a role in the oncogenesis of human adamantinomatous craniopharyngiomas (aCPs). We hypothesized that crosstalk between the Wnt/beta-catenin and Sonic Hedgehog (SHH) pathways, both of which are important in normal pituitary development, would contribute to the pathogenesis of aCPs. Design: To explore the mRNA and protein expression of components of the SHH signaling pathway in aCPs and their relationship with the identification of CTNNB1/beta-catenin mutations and patients outcomes. Patients & Methods: In 18 aCP samples, CTNNB1 was sequenced, and the mRNA expression levels of SHH pathway members (SHH, PTCH1, SMO, GLI1, GLI2, GLI3 and SUFU) and SMO, GLI1, GLI3, SUFU, beta-catenin, and Ki67 proteins were evaluated by qPCR and immunohistochemistry, respectively. Anterior normal pituitaries were used as controls. Associations between molecular findings and clinical data were analyzed. Results: The aCPs presented higher mRNA expression of SHH (+400-fold change [FC]; P<0.01), GLI1 (+102-FC; P<0.001) and GLI3 (+5.1-FC; P<0.01) than normal anterior pituitaries. Longer disease-free survival was associated with low SMO and SUFU mRNA expression (P<0.01 and P=0.02, respectively). CTNNB1/beta-catenin mutations were found in 47% of the samples. aCPs with identified mutations presented with higher mRNA expression of SMO and GLI1 (+4.3-FC; P=0.02 and +10.2-FC; P=0.03, respectively). SMO, GLI1, GLI3, and SUFU staining was found in 85%, 67%, 93%, and 64% of the samples, respectively. Strong GLI1 and GLI3 staining was detected in palisade cells, which also labeled Ki67, a marker of cell proliferation. Conclusions: The upregulation of SHH signaling occurs in aCPs. Thus, activation of Wnt/beta-catenin and SHH pathways, both of which are important in pituitary embryogenesis, appears to contribute to the pathogenesis of aCP.
    European Journal of Endocrinology 02/2015; DOI:10.1530/EJE-14-0934