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Qian Wang Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Jiacheng Wang Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Yunhui Xin Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Ziyang He Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Xiang Zhou Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Xing Liu Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Teng Zhao Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Lihan He Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Hong Shen Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Mulan Jin Department of Pathology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Bojun Wei Department of Thyroid and Neck Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China

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Background

Parathyroid carcinoma (PC), often misdiagnosed as a parathyroid adenoma (PA), is prone to local relapse due to the initial surgery being restricted to parathyroid lesions instead of en bloc resection of parathyroid lesions with negative incision margins. However, it is very challenging to distinguish PC from PA preoperatively; hence, this study investigated an effective biomarker for increasing accuracy in PC diagnosis.

Method

First, the differentially expressed circular RNAs between three PC tissues and three PA tissues were screened by high-throughput circular RNA sequencing, and the expression of hsa_circ_0005729 was verified by qRT-PCR in 14 patients with PC and 40 patients with PA. Secondly, the receiver operating characteristic curve and the area under the curve (AUC) were used to analyze the diagnostic efficiency of hsa_circ_0005729 in PC by combining with laboratory data. Thirdly, RNF138mRNA, the corresponding linear transcript of hsa_circ_0005729, was measured, and the relationship between hsa_circ_0005729 and RNF138 mRNA was analyzed in patients with PA and patients with PC.

Results

Hsa_circ_0005729 expression was significantly higher in patients with PC than in patients with PA. Serum calcium (P  = 0.045), alkaline phosphatase (ALP) (P  = 0.048), and creatinine levels (P  = 0.036) were significantly higher in patients with PC than in patients with PA. The AUC increased to 0.86 when hsa_circ_0005729 combined with serum calcium, creatinine, and ALP. In addition, hsa_circ_0005729 was positively correlated with RNF138 mRNA in patients with PA but not in patients with PC.

Conclusion

The novel circular RNA hsa_circ_0005729 was found to have a higher expression in patients with PC, indicating its usefulness for distinguishing PC from PA.

Open access
Renata C Scalco Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil
Disciplina de Endocrinologia, Faculdade de Ciências Médicas da Santa Casa de São Paulo, São Paulo, São Paulo, Brazil
Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Ericka B Trarbach Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Edoarda V A Albuquerque Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Thais K Homma Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Thais H Inoue-Lima Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Mirian Y Nishi Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Berenice B Mendonca Unidade de Endocrinologia do Desenvolvimento, Laboratorio de Hormonios e Genetica Molecular LIM/42, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Alexander A L Jorge Unidade de Endocrinologia Genetica, Laboratorio de Endocrinologia Celular e Molecular LIM/25, Disciplina de Endocrinologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, São Paulo, Brazil

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Most patients with Turner syndrome (TS) need hormone replacement therapy because of hypergonadotropic hypogonadism; individual outcomes, however, are highly variable. Our objective was to assess the influence of five estrogen receptor 1 gene (ESR1) polymorphisms (rs543650, rs1038304, rs2046210, rs2234693 and rs9340799) on adult height, breast development, uterine volume and bone mineral density (BMD). We studied 91 TS patients from a tertiary hospital using adult estrogen dose. In our group, ESR1 rs2234693 was associated with femoral neck and total hip BMD, and it accounted for around 10% of BMD variability in both sites (P < 0.01). Patients homozygous for C allele in this polymorphism had significantly lower femoral neck BMD (0.699 ± 0.065 g/cm2 vs 0.822 ± 0.113 g/cm2, P = 0.008) and total hip BMD (0.777 ± 0.118 g/cm2 vs 0.903 ± 0.098 g/cm2, P = 0.009) than patients homozygous for T allele. The other four ESR1 polymorphisms were not able to predict any of the above estrogen therapy outcomes in an isolated manner. Patients homozygous for the haplotype GCG formed by polymorphisms rs543650, rs2234693 and rs9340799 had an even more significantly lower femoral neck BMD (0.666 ± 0.049 vs 0.820 ± 0.105 g/cm2, P = 0.0047) and total hip BMD (0.752 ± 0.093 vs 0.908 ± 0.097 g/cm2, P = 0.0029) than patients homozygous for haplotypes with a T allele in rs2234693. In conclusion, homozygosity for C allele in ESR1 rs2234693 and/or for GCG haplotype appears to be associated with lower femoral neck and total hip BMD. We believe that the identification of polymorphisms related to estrogen outcomes may contribute to individualization of treatment in TS.

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Marcus Quinkler Endocrinology in Charlottenburg, Berlin, Germany

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Bertil Ekman Departments of Endocrinology and Medical and Health Sciences, Linköping University, Linköping, Sweden

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Claudio Marelli Shire International GmbH, Zug, Switzerland

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Sharif Uddin Shire, Lexington, Massachusetts, USA

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Pierre Zelissen Department of Internal Medicine and Endocrinology, University Medical Center Utrecht, Utrecht, the Netherlands

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Robert D Murray Department of Endocrinology, Leeds Teaching Hospitals NHS Trust, St James’s University Hospital, Leeds, UK

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on behalf of the EU-AIR Investigators
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Objective

Prednisolone is used as glucocorticoid replacement therapy for adrenal insufficiency (AI). Recent data indicate that its use in AI is associated with low bone mineral density. Data on risk factors for cardiovascular disease in patients with AI treated with prednisolone are scarce, despite this condition being the predominant cause of excess mortality. We aimed to address this question using real-world data from the European Adrenal Insufficiency Registry (EU-AIR).

Design/methods

EU-AIR, comprising of 19 centres across Germany, the Netherlands, Sweden and the UK, commenced enrolling patients with AI in August 2012. Patients receiving prednisolone (3–6 mg/day, n = 50) or hydrocortisone (15–30 mg/day, n = 909) were identified and grouped at a ratio of 1:3 (prednisolone:hydrocortisone) by matching for gender, age, duration and type of disease. Data from baseline and follow-up visits were analysed. Data from patients with congenital adrenal hyperplasia were excluded.

Results

Significantly higher mean ± s.d. total (6.3 ± 1.6 vs 5.4 ± 1.1 mmol/L; P = 0.003) and low-density lipoprotein (LDL) cholesterol levels (3.9 ± 1.4 vs 3.2 ± 1.0 mmol/L; P = 0.013) were identified in 47 patients on prednisolone vs 141 receiving hydrocortisone at baseline and at follow-up (P = 0.005 and P = 0.006, respectively). HbA1c, high-density lipoprotein and triglyceride levels, body mass index, systolic and diastolic blood pressure and waist circumference were not significantly different.

Conclusions

This is the first matched analysis of its kind. Significantly higher LDL levels in patients receiving prednisolone relative to hydrocortisone could predict a higher relative risk of cardiovascular disease in the former group.

Open access
Mirjana Doknic Neuroendocrine Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Belgrade, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Marko Stojanovic Neuroendocrine Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Belgrade, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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

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Tatjana Milenkovic Mother and Child Health Care Institute of Serbia ‘Dr Vukan Cupic’, Belgrade, Serbia

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Vera Zdravkovic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
University Children’s Clinic, Belgrade, Serbia

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Maja Jesic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
University Children’s Clinic, Belgrade, Serbia

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Sladjana Todorovic Mother and Child Health Care Institute of Serbia ‘Dr Vukan Cupic’, Belgrade, Serbia

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Katarina Mitrovic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Mother and Child Health Care Institute of Serbia ‘Dr Vukan Cupic’, Belgrade, Serbia

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Rade Vukovic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Mother and Child Health Care Institute of Serbia ‘Dr Vukan Cupic’, Belgrade, Serbia

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Dragana Miljic Neuroendocrine Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Belgrade, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Dragan Savic Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia

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Mihajlo Milicevic Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia

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Aleksandar Stanimirovic Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia

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Vojislav Bogosavljevic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia

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Sandra Pekic Neuroendocrine Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Belgrade, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Emilija Manojlovic-Gacic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Institute of Pathology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Aleksandar Djukic Department of Pathophysiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia

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Danica Grujicic Faculty of Medicine, University of Belgrade, Belgrade, Serbia
Clinic for Neurosurgery, University Clinical Center of Serbia, Belgrade, Serbia

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Milan Petakov Neuroendocrine Department, Clinic for Endocrinology, Diabetes and Metabolic Diseases, University Clinical Center of Serbia, Belgrade, Serbia
Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Objective

To analyze metabolic parameters, body composition (BC), and bone mineral density (BMD) in childhood-onset GH deficiency (COGHD) patients during the transition period (TP).

Design

Single- center, retrospective study was performed on 170 consecutive COGHD patients (age 19.2 ± 2.0 years, range 16–25) transferred after growth completion from two pediatric clinics to the adult endocrine unit. Two separate analyses were performed: (i) cross-sectional analysis of hormonal status, metabolic parameters, BC, and BMD at first evaluation after transfer from pediatrics to the adult department; (ii) longitudinal analysis of BC and BMD dynamics after 3 years of GH replacement therapy (rhGH) in TP.

Results

COGHD was of a congenital cause (CONG) in 50.6% subjects, tumor-related (TUMC) in 23.5%, and idiopathic (IDOP) in 25.9%. TUMC patients had increased insulin and lipids levels (P < 0.01) and lower Z score at L-spine (P < 0.05) compared to CONG and IDOP groups. Patients treated with rhGH in childhood demonstrated lower fat mass and increased BMD compared to the rhGH-untreated group (P < 0.01). Three years of rhGH after growth completion resulted in a significant increase in lean body mass (12.1%) and BMD at L-spine (6.9%), parallel with a decrease in FM (5.2%).

Conclusion

The effect of rhGH in childhood is invaluable for metabolic status, BC, and BMD in transition to adulthood. Tumor-related COGHD subjects are at higher risk for metabolic abnormalities, alteration of body composition, and decreased BMD, compared to those with COGHD of other causes. Continuation of rhGH in transition is important for improving BC and BMD in patients with persistent COGHD.

Open access
Unni Syversen Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Department of Endocrinology, Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway

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Mats Peder Mosti Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Medical Clinic, Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway

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Ida Maria Mynarek Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

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Trude Seselie Jahr Vedal Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

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Kristin Aasarød Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Department of Gastroenterology, Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway

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Trude Basso Department of Orthopedics, Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway

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Janne E Reseland Department of Biomaterials, University of Oslo, Oslo, Norway

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Per Medbøe Thorsby Hormone Laboratory, Department of Medical Biochemistry, Oslo University Hospital, Aker, Oslo, Norway

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Bjorn O Asvold Department of Endocrinology, Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway
K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Trondheim, Norway

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Erik Fink Eriksen Department of Biomaterials, University of Oslo, Oslo, Norway

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Astrid Kamilla Stunes Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
Medical Clinic, Trondheim University Hospital (St Olavs Hospital), Trondheim, Norway

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Objective

Type 1 diabetes (T1D) is associated with substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have not been uncovered. Men with T1D seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D.

Design and Methods

In this cross-sectional study, men with T1D and healthy male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body) and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) was measured by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed.

Results

Altogether, 33 men with T1D (43 ± 12 years) and 28 healthy male controls (42 ± 12 years) were included. Subjects with T1D exhibited lower whole-body BMD than controls (P = 0.04). TBS and BMSi were attenuated in men with T1D vs controls (P = 0.016 and P = 0.004, respectively), and T1D subjects also had a lower bone turnover. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD but not with TBS or BMSi.

Conclusions

This study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, our data confirm previous studies which found a modest decrease in BMD and low bone turnover in subjects with T1D. Accordingly, bone should be recognized as a target of diabetic complications.

Open access
Miranda Scharff Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands

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Chantal Maria Wiepjes Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands

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Maartje Klaver Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands

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Thomas Schreiner Department of Endocrinology, Oslo University Hospital, Oslo, Norway

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Guy T’Sjoen Department of Endocrinology & Center for Sexology and Gender, Ghent University Hospital, Ghent, Belgium

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Martin den Heijer Department of Endocrinology and Center of Expertise on Gender Dysphoria, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, the Netherlands

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Objective

Gender-affirming hormonal treatment (HT) in trans people changes physical appearance. Muscle mass and strength are important aspects of physical appearance, but few data exist on the effect of HT on grip strength and muscle mass. This study aimed to investigate the change in grip strength in trans people during the first year of HT and to study the possible determinants of this change and the associations between changes in grip strength, lean body mass and bone mineral density (BMD).

Design and methods

A multicenter, prospective study was performed, including 249 transwomen and 278 transmen. Grip strength, lean body mass and BMD were measured at baseline and after 1 year.

Results

After 1 year of HT, grip strength decreased with −1.8 kg (95% CI −2.6; −1.0) in transwomen and increased with +6.1 kg (95% CI +5.5; +6.7) in transmen. No differences in grip strength change was found between age groups, BMI groups, hormonal administration routes or hormone concentrations. In transmen, increase in grip strength was associated with increase in lean body mass (per kg increase in grip strength: +0.010 kg, 95% CI +0.003; +0.017), while this was not found in transwomen (per kg increase in grip strength: +0.004 kg, 95% CI −0.000; +0.009). Change in grip strength was not associated with change in BMD in transwomen and transmen.

Conclusions

After 1 year of HT, grip strength decreased in transwomen, and increased in transmen. In transmen only, change in grip strength was associated with change in lean body mass.

Open access
Wolfgang Högler Department of Paediatrics and Adolescent Medicine, Johannes Kepler University Linz, Linz, Austria
Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

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Agnès Linglart AP-HP, Hôpital Bicêtre Paris Saclay, service d’endocrinologie et diabète de l’enfant, DMU 3 SEA, centre de référence des maladies rares du métabolisme du calcium et du phosphate, filière OSCAR; Université de Paris-Saclay INSERM U1185, Hôpital Bicêtre, Le Kremlin-Bicêtre, France

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Anna Petryk Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA

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Priya S Kishnani Duke University Medical Center, Durham, North Carolina, USA

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Lothar Seefried University of Würzburg, Würzburg, Germany

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Shona Fang Alexion, AstraZeneca Rare Disease, Boston, Massachusetts, USA

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Cheryl Rockman-Greenberg University of Manitoba, Winnipeg, Manitoba, Canada

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Keiichi Ozono Osaka University, Suita, Osaka, Japan

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Kathryn Dahir Vanderbilt University Medical Center, Nashville, Tennessee, USA

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Gabriel Ángel Martos-Moreno Departments of Pediatrics and Pediatric Endocrinology Hospital Infantil Universitario Niño Jesús, IIS La Princesa, Universidad Autónoma de Madrid, CIBERobn, ISCIII, Madrid, Spain

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Objective

Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineralization, can affect growth. This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children.

Design

Data from children (aged <18 years) with hypophosphatasia were analyzed from the observational Global Hypophosphatasia Registry.

Methods

Anthropometric parameters were evaluated by age group (<2 years and ≥2 years) at assessment. The frequency of hypophosphatasia manifestations was compared between children with short stature (< percentile) and those with normal stature.

Results

This analysis included 215 children (54.4% girls). Short stature presented in 16.1% of children aged <2 years and 20.4% of those aged ≥2 years at assessment. Among those with available data (n = 62), height was below the target height (mean: −0.66 standard deviations). Substantial worsening of growth (mean delta height z score: −1.45; delta weight z score: −0.68) occurred before 2 years of age, while in those aged ≥2 years, anthropometric trajectories were maintained (delta height z score: 0.08; delta weight z score: 0.13). Broad-ranging hypophosphatasia manifestations (beyond dental) were observed in most children.

Conclusions

Short stature was not a consistent characteristic of children with hypophosphatasia, but growth impairment was observed in those aged <2 years, indicating that hypophosphatasia might affect growth plate activity during infancy. In addition, a broad range of clinical manifestations occurred in those above and below the third percentile for height, suggesting that height alone may not accurately reflect hypophosphatasia disease burden and that weight is less affected than longitudinal growth.

Open access
Maria Angela D'amico Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Barbara Ghinassi Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Pascal Izzicupo Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Lamberto Manzoli Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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A Di Baldassarre Section of Human Morphology, Department of Medicine and Aging Sciences, G. d'Annunzio University of Chieti–Pescara, Via Dei Vestini 31, 66013 Chieti, Italy

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Chromogranin A (CgA (CHGA)) is the major soluble protein co-stored and co-released with catecholamines and can function as a pro-hormone by giving rise to several bioactive peptides. This review summarizes the physiological functions, the pathogenic implications, and the recent use of these molecules as biomarkers in several pathological conditions. A thorough literature review of the electronic healthcare databases MEDLINE, from January 1985 to September 2013, was conducted to identify articles and studies concerned with CgA and its processing. The search strategies utilized keywords such as chromogranin A, vasostatins 1 and 2, chromofungin, chromacin, pancreastatin, catestatin, WE14, chromostatin, GE25, parastatin, and serpinin and was supplemented by the screening of references from included papers and review articles. A total of 209 English-language, peer-reviewed original articles or reviews were examined. The analysis of the retrospective literature suggested that CgA and its several bioactive fragments exert a broad spectrum of regulatory activities by influencing the endocrine, the cardiovascular, and the immune systems and by affecting the glucose or calcium homeostasis. As some peptides exert similar effects, but others elicit opposite responses, the regulation of the CgA processing is critical to maintain homeostasis, whereas an unbalanced production of peptides that exert opposing effects can have a pathogenic role in several diseases. These clinical implications entail that CgA and its derived peptides are now used as diagnostic and prognostic markers or to monitor the response to pharmacological intervention not only in endocrine tumors, but also in cardiovascular, inflammatory, and neuropsychiatric diseases.

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Victor Jing-Wei Kang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Bo-Ching Lee Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Jia-Zheng Huang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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Vin-Cent Wu Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Yen-Hung Lin Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

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Chin-Chen Chang Departments of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan

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TAIPAI group
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Primary aldosteronism (PA) is associated with urolithiasis as it causes hypercalciuria and hypocitraturia. However, the influence of different subtypes of PA on urinary stone formation remains unclear. This study aimed to evaluate the association between aldosterone-producing adenoma (APA) and the burden of urolithiasis in patients with PA. In the present study, we enrolled 312 patients with PA from a prospectively maintained database, of whom 179 had APA. Clinical, biochemical, and imaging data (including the presence, volume, and density of urinary stones on abdominal computed tomography) were compared between groups, with employment of propensity score matching (PSM) analysis to balance possible confounding factors. Kaplan–Meier analysis was used to estimate the acute renal colic event during follow-up. After PSM for age, sex, serum calcium, phosphate, blood urea nitrogen, creatinine, and uric acid, the APA and non-APA groups had 106 patients each. Patients with APA had higher serum intact parathyroid hormone (iPTH) (79.1 ± 45.0 vs 56.1 ± 30.3, P < 0.001) and a higher prevalence of urolithiasis (27.4% vs 12.3%, P = 0.006) than non-APA patients. During follow-up, a higher incidence of acute renal colic events was noted in the APA group than the non-APA group (P = 0.011); this association remained significant (P = 0.038) after adjustment for age and sex in Cox-regression analysis. Our data suggest that APA is associated with a heavier burden of urolithiasis and higher incidence of renal colic events compared to the non-APA subtype of PA.

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Charissa van Zwol-Janssens Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Aglaia Hage Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Kim van der Ham Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Birgitta K Velthuis Department of Radiology, University Medical Center Utrecht, University of Utrecht, Utrecht, the Netherlands

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Ricardo P J Budde Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands

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Maria P H Koster Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Arie Franx Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Bart C J M Fauser Department of Reproductive Medicine and Gynaecology, University Medical Center Utrecht & University of Utrecht, Utrecht, the Netherlands

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Eric Boersma Department of Cardiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Daniel Bos Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Joop S E Laven Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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Yvonne V Louwers Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynaecology, Erasmus University Medical Center, Rotterdam, the Netherlands

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the CREW consortium
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the CREW consortium

Besides age, estrogen exposure plays a crucial role in changes in bone density (BD) in women. Premature ovarian insufficiency (POI) and polycystic ovary syndrome (PCOS) are conditions in reproductive-aged women in which the exposure to estrogen is substantially different. Women with a history of preeclampsia (PE) are expected to have normal estrogen exposure. Within the CREw-IMAGO study, we investigated if trabecular BD is different in these women because of differences in the duration of estrogen exposure. Trabecular BD was measured in thoracic vertebrae on coronary CT scans. Women with a reduced estrogen exposure (POI) have a lower BD compared to women with an intermediate exposure (PE) (mean difference (MD) −26.8, 95% CI −37.2 to −16.3). Women with a prolonged estrogen exposure (PCOS) have the highest BD (MD 15.0, 95% CI 4.3–25.7). These results support the hypothesis that the duration of estrogen exposure in these women is associated with trabecular BD.

Significance statement

Our results suggest that middle-aged women with PCOS have a higher BD and women with POI have a lower BD. We hypothesized that this is due to either a prolonged estrogen exposure, as seen in women with PCOS, or a reduced estrogen exposure, as in women with POI. In the counseling of women with reproductive disorders on long-term health issues, coronary CT provides a unique opportunity to assess both coronary artery calcium score for cardiovascular screening as well as trabecular BD.

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