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Imane Benabbad Endocrinology and Diabetes Unit, Eli Lilly, Neuilly-sur-Seine, France

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Myriam Rosilio Endocrinology and Diabetes Unit, Eli Lilly, Neuilly-sur-Seine, France

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Maité Tauber Department Endocrine, Bone Diseases, Genetics, Obesity, and Gynecology Unit, Children’s Hospital, University Hospital, Toulouse, France

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Emmanuel Paris BioClinica, Lyon, France

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Anne Paulsen Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France

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Lovisa Berggren Eli Lilly and Company, Bad Homburg, Germany

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Hiren Patel Eli Lilly and Company, Indianapolis, Indiana, USA

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Jean-Claude Carel Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France
Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Universitaire Robert-Debré, Department of Pediatric Endocrinology and Diabetology, and Centre de Référence des Maladies Endocriniennes Rares de la Croissance, Paris, France

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the Phoenix Study Group
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Objective

There is a scarcity of data from randomised controlled trials on the association of growth hormone (GH) with gonadotrophin-releasing hormone agonists in idiopathic short stature (ISS), although this off-label use is common. We aimed to test whether delaying pubertal progression could increase near-adult height (NAH) in GH-treated patients with ISS.

Methods

Patients with ISS at puberty onset were randomised to GH with leuprorelin (combination, n = 46) or GH alone (n = 45). NAH standard deviation score (SDS) was the primary outcome measure. The French regulatory authority requested premature discontinuation of study treatments after approximately 2.4 years; patients from France were followed for safety.

Results

Mean (s.d.) baseline height SDS was −2.5 (0.5) in both groups, increasing at 2 years to −2.3 (0.6) with combination and −1.8 (0.7) with GH alone. NAH SDS was −1.8 (0.5) with combination (n = 19) and −1.9 (0.8) with GH alone (n = 16). Treatment-emergent adverse events and bone fractures occurred more frequently with combination than GH alone.

Conclusion

Due to premature discontinuation of treatments, statistical comparison of NAH SDS between the two cohorts was not possible. During the first 2–3 years of treatment, patients treated with the combination grew more slowly than those receiving GH alone. However, mean NAH SDS was similar in the two groups. No new GH-related safety concerns were revealed. A potentially deleterious effect of combined treatment on bone fracture incidence was identified.

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Elena Galazzi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Paolo Duminuco IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Mirella Moro IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Fabiana Guizzardi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy

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Nicoletta Marazzi IRCSS Istituto Auxologico Italiano, Laboratory for Auxo-Endocrinological Research, Milan, Italy

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Alessandro Sartorio IRCSS Istituto Auxologico Italiano, Laboratory for Auxo-Endocrinological Research, Milan, Italy
Division of Auxology and Metabolic Diseases, IRCSS Istituto Auxologico Italiano, Piancavallo (VB), Italy

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Sabrina Avignone Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico di Milano, U.O.C Neuroradiologia, Milan, Italy

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Marco Bonomi IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Luca Persani IRCSS Istituto Auxologico Italiano, Laboratory of Endocrine and Metabolic Research and Division of Endocrine and Metabolic Diseases, Milan, Italy
Department of Clinical Sciences and Community Health, Università degli Studi, Milan, Italy

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Maria Teresa Bonati IRCCS Istituto Auxologico Italiano, Service of Medical Genetics, Milan, Italy

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Ulnar-mammary syndrome (UMS) is characterized by ulnar defects, and nipple or apocrine gland hypoplasia, caused by TBX3 haploinsufficiency. Signs of hypogonadism were repeatedly reported, but the mechanisms remain elusive. We aim to assess the origin of hypogonadism in two families with UMS. UMS was suspected in two unrelated probands referred to an academic center with delayed puberty because of the evident ulnar ray and breast defects in their parents. Clinical, biochemical and genetic investigations proved the existence of congenital normosmic IHH (nIHH) associated with pituitary hypoplasia in the two probands who were heterozygous for novel TBX3 pathogenic variants. The mutations co-segregated with delayed puberty, midline defects (nose, teeth and tongue anomalies) and other variable features of UMS in the two families (absent axillary hairs and nipple hypoplasia, asymmetrical features including unilateral ulnar or renal abnormalities). The combined analysis of these findings and of the previous UMS reports showed delayed puberty and other signs of hypogonadism in 79 and 37% of UMS males, respectively. Proband 1 was followed up to adulthood with persistence of nIHH. In conclusion, UMS should be suspected in patients with delayed puberty and midline defects, including pituitary hypoplasia, in the presence of mild cues for TBX3 mutation, even in the absence of limb malformations. In addition, TBX3 should be included among candidate genes for congenital nIHH.

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Sharmin Jahan Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia
Department of Endocrinology and Metabolism, BSMMU, Dhaka, Bangladesh

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Jun Yang Department of Medicine, Monash University, Melbourne, Victoria, Australia
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia

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Jinbo Hu Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Qifu Li Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

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Peter J Fuller Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Victoria, Australia

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Primary aldosteronism (PA) is the most common cause of endocrine hypertension and is often underdiagnosed. This condition is associated with increased cardiovascular morbidity and mortality in comparison to age and blood pressure matched individuals with essential hypertension (EH). The diagnostic pathway for PA consists of three phases: screening, confirmatory testing, and subtyping. The lack of specificity in the screening step, which relies on the aldosterone to renin ratio, necessitates confirmatory testing. The Endocrine Society’s clinical practice guideline suggests four confirmatory tests, including the fludrocortisone suppression test (FST), saline suppression test (SST), captopril challenge test (CCT), and oral sodium loading test (SLT). There is no universally accepted choice of confirmatory test, with practices varying among centers. The SST and FST are commonly used, but they can be resource-intensive, carry risks such as volume overload or hypokalemia, and are contraindicated in severe/uncontrolled HTN as well as in cardiac and renal impairment. In contrast, CCT is a safe and inexpensive alternative that can be performed in an outpatient setting and can be applied when other tests are contraindicated. Despite its simplicity and convenience, the variability in captopril dose, testing posture, and diagnostic threshold limit its widespread use. This narrative review evaluates the diagnostic accuracy of the CCT across different populations, addresses controversies in its usage, and proposes recommendations for its use in the diagnosis of PA. Furthermore, suggestions for future research aimed at promoting the wider utilization of the CCT as a simpler, safer, and more cost-effective diagnostic test are discussed.

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Amalie Carlsson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

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Kaspar Sørensen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
The Child and Youth Clinic, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark

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Anna-Maria Andersson Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

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Hanne Frederiksen Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

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Anders Juul Department of Growth and Reproduction, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
International Research and Research Training Center in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen, Denmark

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Introduction

Bisphenol A and several of the most commonly used phthalates have been associated with adverse metabolic health effects such as obesity and diabetes. Therefore, we analyzed these man-made chemicals in first morning urine samples from 107 healthy normal-weight Danish children and adolescents.

Method

This was a cross-sectional study. Participants were recruited as part of the Copenhagen Puberty Study. The subjects were evaluated by an oral glucose tolerance test (OGTT), a dual-energy X-ray absorptiometry (DXA) scan, direct oxygen uptake measurement during cycle ergometry and fasting blood samples. First morning urine was collected and phthalate metabolites and BPA were measured by liquid chromatography-tandem mass spectrometry (LC–MS/MS) with prior enzymatic deconjugation. Individual chemical concentrations were divided into tertiles and analyzed in relation to biological outcome.

Results

Children in the lowest tertile of urinary BPA had significantly higher peak insulin levels during OGTT (P = 0.01), lower insulin sensitivity index (P < 0.01), higher leptin (P = 0.03), triglyceride (P < 0.01) and total cholesterol levels (P = 0.04), lower aerobic fitness (P = 0.02) and a tendency toward higher fat mass index (P = 0.1) compared with children in the highest tertile for uBPA. No significant differences in anthropometrics, body composition or glucose metabolism were associated with any of the phthalate metabolites measured.

Conclusion

This pilot study on healthy normal-weight children suggests an inverse association between BPA and insulin resistance. Our findings contrast other cross-sectional studies showing a positive association for BPA, which may be due to confounding or reverse causation because diet is an important source of both BPA exposure and obesity.

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Thomas Reinehr Pediatric Endocrinology, Diabetes and Nutrition Medicine, Vestische Children’s Hospital, University of Witten/Herdecke, Datteln, Germany

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Martin Carlsson Endocrine Care, Pfizer Inc, New York, New York, USA

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Dionisios Chrysis Division of Pediatric Endocrinology, University of Patras, Patras, Greece

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Cecilia Camacho-Hübner Endocrine Care, Pfizer Inc, New York, New York, USA

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Background

The precision of adult height prediction by bone age determination in children with idiopathic growth hormone deficiency (IGHD) is unknown.

Methods

The near adult height (NAH) of patients with IGHD in the KIGS database was compared retrospectively to adult height prediction calculated by the Bayley–Pinneau (BP) prediction based on bone age by Greulich–Pyle (GP) in 315 children and based on the Tanner-Whitehouse 2 (TW2) method in 121 children. Multiple linear regression analyses adjusted for age at GH start, age at puberty, mean dose and years of of GH treatment, and maximum GH peak in stimulation test were calculated.

Results

The mean underestimation of adult height based on the BP method was at baseline 4.1 ± 0.7 cm in girls and 6.1 ± 0.6 cm in boys, at 1 year of GH treatment 2.5 ± 0.5 cm in girls and 0.9 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 0.4 ± 0.6 cm in girls and 3.8 ± 0.5 cm in boys. The mean underestimation of adult height based on the TW2 method was at baseline 5.3 ± 2.0 cm in girls and 7.9 ± 0.8 cm in boys, at 1 year of GH treatment adult height was overestimated in girls 0.1 ± 0.6 cm in girls and underestimated 4.1 ± 0.4 cm in boys, while at last bone age determination adult height was overestimated in mean by 3.1 ± 1.5 cm in girls and 3.6 ± 0.8 cm in boys.

Conclusions

Height prediction by BP and TW2 at onset of GH treatment underestimates adult height in prepubertal IGHD children, while in mean 6 years after onset of GH treatment these prediction methods overestimated adult height.

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Rebeca Esquivel-Zuniga Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

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Alan D Rogol Department of Pediatrics, University of Virginia, Charlottesville, Virginia, USA

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Hypogonadism is a clinical syndrome resulting from failure to produce physiological concentrations of sex steroid hormones with accompanying symptoms, such as slowed growth and delayed pubertal maturation. Hypogonadism may arise from gonadal disease (primary hypogonadism), dysfunction of the hypothalamic–pituitary axis (secondary hypogonadism) or functional hypogonadism. Disrupted puberty (delayed or absent) leading to hypogonadism can have a significant impact on both the physical and psychosocial well-being of adolescents with lasting effects. The diagnosis of hypogonadism in teenagers can be challenging as the most common cause of delayed puberty in both sexes is self-limited, also known as constitutional delay of growth and puberty (CDGP). Although an underlying congenital cause should always be considered in a teenager with hypogonadism, acquired conditions such as obesity, diabetes mellitus, other chronic diseases and medications have all been associated with low sex steroid hormone levels. In this review, we highlight some forms of functional hypogonadism in adolescents and the clinical challenges to differentiate normal variants from pathological states.

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Marko Stojanovic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Zida Wu Department of Medicine for Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin, Campus Mitte, Berlin, Germany

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Craig E Stiles Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Dragana Miljic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Ivan Soldatovic University of Belgrade, Medical Faculty, Belgrade, Serbia
Insitute of Medical Statistics and Informatics, Belgrade, Serbia

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Sandra Pekic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Mirjana Doknic Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Milan Petakov Neuroendocrinology Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, Clinical Centre of Serbia, Belgrade, Serbia
University of Belgrade, Medical Faculty, Belgrade, Serbia

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Vera Popovic University of Belgrade, Medical Faculty, Belgrade, Serbia

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Christian Strasburger Department of Medicine for Endocrinology, Diabetes and Nutritional Medicine, Charité Universitätsmedizin, Campus Mitte, Berlin, Germany

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Márta Korbonits Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK

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Background

Aryl hydrocarbon receptor-interacting protein (AIP) is evolutionarily conserved and expressed widely throughout the organism. Loss-of-function AIP mutations predispose to young-onset pituitary adenomas. AIP co-localizes with growth hormone in normal and tumorous somatotroph secretory vesicles. AIP protein is detectable in circulation. We aimed to investigate possible AIP and GH co-secretion, by studying serum AIP and GH levels at baseline and after GH stimulation or suppression, in GH deficiency (GHD) and in acromegaly patients.

Subjects and methods

Insulin tolerance test (ITT) was performed in GHD patients (n = 13) and age-BMI-matched normal GH axis control patients (n = 31). Oral glucose tolerance test (OGTT) was performed in active acromegaly patients (n = 26) and age-BMI-matched normal GH axis control patients (n = 18). In-house immunometric assay was developed for measuring circulating AIP.

Results

Serum AIP levels were in the 0.1 ng/mL range independently of gender, age or BMI. Baseline AIP did not differ between GHD and non-GHD or between acromegaly and patients with no acromegaly. There was no change in peak, trough or area under the curve during OGTT or ITT. Serum AIP did not correlate with GH during ITT or OGTT.

Conclusions

Human circulating serum AIP in vivo was assessed by a novel immunometric assay. AIP levels were independent of age, sex or BMI and unaffected by hypoglycaemia or hyperglycaemia. Despite co-localization in secretory vesicles, AIP and GH did not correlate at baseline or during GH stimulation or suppression tests. A platform of reliable serum AIP measurement is established for further research of its circulatory source, role and impact.

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Weidi Wang Department of Emergency, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

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Lingjun Kong Department of Thyroid and Breast, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

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Hongkun Guo Department of Emergency, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

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Xiangjin Chen Department of Thyroid and Breast, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

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Abstract

Background

The presence of clinically negative nodules on the contralateral lobe is common in patients with unilateral papillary thyroid microcarcinoma (PTMC). The appropriate operational strategies of contralateral thyroid nodules remain controversial. In this study, we analyzed clinical features that could be predictors for malignancy of contralateral thyroid nodules coexisting with diagnosed unilateral PTMC.

Methods

The literatures published from January 2000 to December 2019 were searched in PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wan Fang database. Odds ratio (OR) with 95% CI was used to describe categorical variables. Heterogeneity among studies was examined by the Q test and I2 test; potential publication bias was detected by Harbord test and ‘trim and fill’ method.

Results

In this meta-analysis, 2541 studies were searched and 8 studies were finally included. The results showed that the rate of carcinoma in contralateral nodules was 23% (OR = 0.23, 95% CI = 0.18–0.29). The pooled data indicated that contralateral malignancy was not associated with age, gender, primary lesion size, ipsilateral central lymph node metastasis and multifocality of contralateral lesion. The following variables have correlations with an increased risk of contralateral malignancy: multifocality of primary carcinomas (OR = 3.93, 95% CI = 2.70–5.73, P < 0.0001), capsular invasion (OR = 1.61, 95% CI = 1.10–2.36, P = 0.01), and Hashimoto's thyroiditis (OR = 1.57, 95% CI = 1.13–2.20, P = 0.008).

Conclusions

Based on our meta-analysis, the rate at which contralateral malignancies are preoperatively misdiagnosed as benign is 23%. The risk factors for contralateral malignancy in unilateral PTMC patients with contralateral clinical negative nodules include multifocality of primary carcinomas, capsular invasion, and Hashimoto's thyroiditis.

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Shuang Ye Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

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Yuanyuan Xu Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

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Jiehao Li Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

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Shuhui Zheng Research Center for Translational Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China

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Peng Sun Department of Pathology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China

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Tinghuai Wang Department of Physiology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou, China

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The role of G protein-coupled estrogen receptor 1 (GPER) signaling, including promotion of Ezrin phosphorylation (which could be activated by estrogen), has not yet been clearly identified in triple-negative breast cancer (TNBC). This study aimed to evaluate the prognostic value of GPER and Ezrin in TNBC patients. Clinicopathologic features including age, menopausal status, tumor size, nuclear grade, lymph node metastasis, AJCC TNM stage, and ER, PR and HER-2 expression were evaluated from 249 TNBC cases. Immunohistochemical staining of GPER and Ezrin was performed on TNBC pathological sections. Kaplan–Meier analyses, as well as logistic regressive and Cox regression model tests were applied to evaluate the prognostic significance between different subgroups. Compared to the GPER-low group, the GPER-high group exhibited higher TNM staging (P = 0.021), more death (P < 0.001), relapse (P < 0.001) and distant events (P < 0.001). Kaplan–Meier analysis showed that GPER-high patients had a decreased OS (P < 0.001), PFS (P < 0.001), LRFS (P < 0.001) and DDFS (P < 0.001) than GPER-low patients. However, these differences in prognosis were not statistically significant in post-menopausal patients (OS, P = 0.8617; PFS, P = 0.1905; LRFS, P = 0.4378; DDFS, P = 0.2538). There was a significant positive correlation between GPER and Ezrin expression level (R = 0.508, P < 0.001) and the effect of Ezrin on survival prognosis corresponded with GPER. Moreover, a multivariable analysis confirmed that GPER and Ezrin level were both significantly associated with poor DDFS (HR: 0.346, 95% CI 0.182–0.658, P = 0.001; HR: 0.320, 95% CI 0.162–0.631, P = 0.001). Thus, overexpression of GPER and Ezrin may contribute to aggressive behavior and indicate unfavorable prognosis in TNBC; this may correspond to an individual’s estrogen levels.

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Luca Boeri Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Paolo Capogrosso Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Walter Cazzaniga Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Edoardo Pozzi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Luigi Candela Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Federico Belladelli Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Davide Oreggia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Eugenio Ventimiglia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Nicolò Schifano Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Giuseppe Fallara Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Marina Pontillo Laboratory Medicine Service, IRCCS Ospedale San Raffaele, Milan, Italy

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Costantino Abbate Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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Emanuele Montanari Department of Urology, Foundation IRCCS Ca’ Granda – Ospedale Maggiore Policlinico, University of Milan, Milan, Italy

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Francesco Montorsi Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Andrea Salonia Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy
University Vita-Salute San Raffaele, Milan, Italy

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Objective:

We aimed to test the association between age, BMI and sex-hormone–binding globulin (SHBG) in a homogenous cohort of white-European men presenting for primary couple’s infertility.

Design:

Retrospective study.

Methods:

Data from 1547 infertile men were analysed. Health-significant comorbidities were scored with the Charlson comorbidity index (CCI). Fasting serum hormones were measured in every patient. Age was considered according to quartile groups (<33, 33-41, >41 years) and BMI as normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obesity (>30 kg/m2). Descriptive statistics and linear regression analysis tested the associations between age, BMI and SHBG.

Results:

Median SHBG levels increased across quartiles of age and decreased along with BMI increases (all P < 0.001). For each year increase in age, SHBG increased 0.32 nmol/L; conversely, for each unit increase in BMI, SHBG decreased by 1.1 nmol/L (all P < 0.001). SHBG levels decline with increasing BMI was greater than SHBG progressive increase with age. Overall, BMI explained 3.0 times more of the variability in SHBG than did ageing. At multivariate linear model, age and BMI were the most significant factors influencing SHBG concentration (all P < 0.001), after accounting for CCI, albumin levels and smoking status.

Conclusions:

We found a wide distribution of SHBG concentrations across age and BMI values in primary infertile men. The association between BMI and lowered SHBG levels seems to be greater than the association of ageing with increased SHBG.

Open access