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Huda M Elsharkasi Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Suet C Chen Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Lewis Steell Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Shuko Joseph Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK
Paediatric Neurosciences Research Group, Royal Hospital for Children, NHS Greater Glasgow & Clyde, Glasgow, UK

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Naiemh Abdalrahaman Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Christie McComb Department of Clinical Physics, NHS Greater Glasgow & Clyde, Glasgow, UK

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Blair Johnston Department of Clinical Physics, NHS Greater Glasgow & Clyde, Glasgow, UK

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John Foster Department of Clinical Physics, NHS Greater Glasgow & Clyde, Glasgow, UK

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Sze Choong Wong Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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S Faisal Ahmed Developmental Endocrinology Research Group, University of Glasgow, Glasgow, UK

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Objective

The aim of this study is to investigate the role of 3T-MRI in assessing musculoskeletal health in children and young people.

Design

Bone, muscle and bone marrow imaging was performed in 161 healthy participants with a median age of 15.0 years (range, 8.0, 30.0).

Methods

Detailed assessment of bone microarchitecture (constructive interference in the steady state (CISS) sequence, voxel size 0.2 × 0.2 × 0.4 mm3), bone geometry (T1-weighted turbo spin echo (TSE) sequence, voxel size 0.4 × 0.4 × 2 mm3) and bone marrow (1H-MRS, point resolved spectroscopy sequence (PRESS) (single voxel size 20 × 20 × 20 mm3) size and muscle adiposity (Dixon, voxel size 1.1 × 1.1 × 2 mm3).

Results

There was an inverse association of apparent bone volume/total volume (appBV/TV) with age (r = −0.5, P < 0.0005). Cortical area, endosteal and periosteal circumferences and muscle cross-sectional area showed a positive association to age (r > 0.49, P < 0.0001). In those over 17 years of age, these parameters were also higher in males than females (P < 0.05). This sex difference was also evident for appBV/TV and bone marrow adiposity (BMA) in the older participants (P < 0.05). AppBV/TV showed a negative correlation with BMA (r = −0.22, P =  0.01) which also showed an association with muscle adiposity (r = 0.24, P = 0.04). Cortical geometric parameters were highly correlated with muscle area (r > 0.57, P < 0.01).

Conclusions

In addition to providing deep insight into the normal relationships between bone, fat and muscle in young people, these novel data emphasize the role of MRI as a non-invasive method for performing a comprehensive and integrated assessment of musculoskeletal health in the growing skeleton.

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Sarantis Livadas Endocrine Unit, Athens Medical Centre, Athens, Greece

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Christina Bothou Department of Endocrinology, Diabetology and Clinical Nutrition, University Hospital of Zurich, Zurich, Switzerland

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Justyna Kuliczkowska-Płaksej Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Ralitsa Robeva Ushate ‘acad. IV. Penchev’, Department of Endocrinology, Faculty of Medicine, Medical University-Sofia, Sofia, Bulgaria

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Andromahi Vryonidou Department of Endocrinology and Diabetes, Hellenic Red Cross Hospital, Athens, Greece

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Jelica Bjekic Macut Department of Endocrinology, UMC Bežanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Ioannis Androulakis Endocrine Unit, Athens Medical Centre, Athens, Greece

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Milica Opalic Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Zadalla Mouslech 1st Medical Propedeutic, Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Andrej Milewicz Department of Endocrinology, Diabetology and Isotope Therapy, University of Medicine, Wrocław, Poland

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Alessandra Gambineri Department of Medical and Surgical Science-DIMEC Endocrinology Unit, University of Bologna – S. Orsola-Mapighi Hospital, Italy

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Dimitrios Panidis Gynaecological Endocrinology Infirmary of the Second Department of Obstetrics and Gynaecology, Aristotle University of Thessaloniki, Thessaloniki, Greece

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Djuro Macut Clinic of Endocrinology, Diabetes and Metabolic Diseases, Faculty of Medicine, University of Belgrade, Belgrade, Serbia

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Background

Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear.

Aim of the study

To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk.

Subjects and methods

The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI.

Results

Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice.

Conclusions

One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

Open access
Andre Madsen Hormone Laboratory, Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway
Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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

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Lise Aksglaede Department of Growth and Reproduction, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health (EDMaRC), Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark

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Objective

Klinefelter syndrome (KS) is the most common sex chromosome disorder and genetic cause of infertility in males. A highly variable phenotype contributes to the fact that a large proportion of cases are never diagnosed. Typical hallmarks in adults include small testes and azoospermia which may prompt biochemical evaluation that typically shows extremely high follicle-stimulating hormone and low/undetectable inhibin B serum concentrations. However, in prepubertal KS individuals, biochemical parameters are largely overlapping those of prepubertal controls. We aimed to characterize clinical profiles of prepubertal boys with KS in relation to controls and to develop a novel biochemical classification model to identify KS before puberty.

Methods

Retrospective, longitudinal data from 15 prepubertal boys with KS and data from 1475 controls were used to calculate age- and sex-adjusted standard deviation scores (SDS) for height and serum concentrations of reproductive hormones and used to infer a decision tree classification model for KS.

Results

Individual reproductive hormones were low but within reference ranges and did not discriminate KS from controls. Clinical and biochemical profiles including age- and sex-adjusted SDS from multiple reference curves provided input data to train a ‘random forest’ machine learning (ML) model for the detection of KS. Applied to unseen data, the ML model achieved a classification accuracy of 78% (95% CI, 61–94%).

Conclusions

Supervised ML applied to clinically relevant variables enabled computational classification of control and KS profiles. The application of age- and sex-adjusted SDS provided robust predictions irrespective of age. Specialized ML models applied to combined reproductive hormone concentrations may be useful diagnostic tools to improve the identification of prepubertal boys with KS.

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Estelle Bonnet Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France

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Mathias Winter Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de psychopathologie du développement, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de biologie et pathologie Est, Service d’hormonologie, d’endocrinologie moléculaire et des maladies rares, Bron, France

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Delphine Mallet Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Centre de biologie et pathologie Est, Service d’hormonologie, d’endocrinologie moléculaire et des maladies rares, Bron, France

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Ingrid Plotton Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service Endocrinologie Moléculaire et Maladies Rares, Bron, France

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Claire Bouvattier Centre Hospitalier Universitaire AP-HP, Hôpital Bicêtre, Service d’endocrinologie pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN Université Paris Saclay, Le Kremlin-Bicêtre, France

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Maryse Cartigny Centre Hospitalier Régional Universitaire Lille, Hôpital Jeanne de Flandre, Unité d’Endocrinologie pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Lille, France

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Laetiti Martinerie Centre Hospitalier Universitaire AP-HP, Hôpital Robert Debré, Service d’Endocrinologie pédiatrique Centre de Référence des Maladies Rares Endocriniennes de la Croissance et du Développement – CRMERC Université de Paris, Paris, France

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Michel Polak Centre Hospitalier Universitaire AP-HP, Hôpital universitaire Necker Enfants malades, Endocrinologie gynécologie diabétologie pédiatriques Centre de référence des maladies endocriniennes rares de la croissance et du développement Inserm U1016, institut Imagine, Paris, France

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Anne Bachelot Centre Hospitalier Universitaire AP-HP, Hôpital Pitié Salpêtrière, Department of Endocrinology and Reproductive Medicine Centre de Référence des Maladies Endocriniennes Rares de la Croissance et du Développement Centre de Référence des pathologies gynécologiques rares IE3M, Paris, France

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Frédéric Huet Centre Hospitalier Universitaire Dijon-Bourgogne, Hôpital d’Enfants, Service de Pédiatrie Multidisciplinaire, Dijon, France

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Sabine Baron Centre Hospitalier universitaire de Nantes, Hôpital Mère-Enfant, Service de Pédiatrie, Nantes, France

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Muriel Houang Centre Hospitalier Universitaire AP-HP, Hôpital Armand Trousseau, Service d'Explorations Fonctionnelles Endocriniennes, Paris, France

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Sylvie Soskin Hôpitaux Universitaires de Strasbourg, CHU Hautepierre, Service de Pédiatrie 1, Strasbourg, France

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Anne Lienhardt Centre hospitalier universitaire Limoges, Hôpital de la Mère et de l’enfant, Service de Pédiatrie, Limoges, France

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Jérôme Bertherat Groupement Hospitalier Universitaire de Paris, AP-HP, Hôpital Cochin, Service d'Endocrinologie, Paris, France

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Cyril Amouroux Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Service de Néphrologie et Endocrinologie Pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Montpellier, France

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Aurore Bouty Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France

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Lise Duranteau AP-HP, Hôpital Bicêtre, Unité de gynécologie de l’adolescente Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN Université Paris Saclay, Le Kremlin-Bicêtre, France

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Rémi Besson Centre Hospitalier Régional Universitaire Lille, Hôpital Jeanne de Flandre, Service de chirurgie pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Lille, France

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Alaa El Ghoneimi Centre Hospitalier Universitaire AP-HP Robert Debré, Service de Chirurgie Viscérale et Urologie pédiatrique Centre de Référence des Maladies Endocriniennes de la croissance et du développement – CRMERC Université de Paris, Paris, France

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Dinane Samara-Boustani Centre Hospitalier Universitaire AP-HP, Hôpital Necker Enfants malades, Endocrinologie gynécologie diabétologie pédiatriques Centre de référence des maladies endocriniennes rares de la croissance et du développement, Paris, France

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François Becmeur Hospitaux Universitaires de Strasbourg, CHU Hautepierre, Service de chirurgie pédiatrique, Strasbourg, France

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Nicolas Kalfa Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Service de Chirurgie Viscérale et Urologie Pédiatrique Centre National de Référence Maladies Rares du Développement Génital Constitutif Sud Institut Debrest de Santé Publique IDESP, UMR INSERM, Université de Montpellier, Montpellier, France

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Françoise Paris Centre Hospitalier Universitaire de Montpellier, Hôpital Lapeyronie, Service de Néphrologie et Endocrinologie Pédiatrique Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Montpellier, France

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François Medjkane Centre Hospitalier Régional Universitaire Lille, Hôpital Jeanne de Flandre, Service de psychiatrie de l’enfant et de l’adolescent Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Lille, France

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Aude Brac de la Perrière Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Groupement Hospitalier Est, Service d’endocrinologie, Bron, France

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Patricia Bretones Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France
Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France

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Hervé Lejeune Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de médecine de la reproduction, Bron, France
Université Claude Bernard, Lyon, France

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Marc Nicolino Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France
Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Université Claude Bernard, Lyon, France

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Pierre Mouriquand Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France
Université Claude Bernard, Lyon, France

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Daniela-Brindusa Gorduza Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France
Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service de chirurgie Uro-viscérale et de Transplantation de l’Enfant, Bron, France

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Claire-Lise Gay Hospices Civils de Lyon, Hôpital Femme-Mère-Enfant, Service d’endocrinologie pédiatrique, Bron, France
Centre National de Référence Maladies Rares du développement génital du fœtus à l’adulte DEV-GEN, Hospices Civils de Lyon, Bron, France

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Objectives

To examine the changes in diagnostic practices and clinical management of patients with 5α-reductase type 2 (SRD5A2) or 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) deficiency since molecular diagnoses became available.

Methods

Clinical, laboratory, and therapeutic data were retrieved from the medical records of 52 patients with a molecular diagnosis of SRD5A2 (n = 31) or HSD17B3 (n = 21) deficiency. Temporal trends regarding age at assessment and initial sex assignment over 1994–2020 were qualitatively analyzed. Age at molecular diagnosis was compared between two subgroups of patients according to their year of birth.

Results

Fifty-eight percent (n = 30) patients were diagnosed during the perinatal period, 33% (n = 17) during infancy, and 9% (n = 5) during adolescence or adulthood. Over the studied period, the patients’ age at initial assessment and diagnosis frankly decreased. The median (range) age at diagnostic confirmation was 10.5 (0–53.2) years for patients born before 2007 and 0.4 (0–9.3) years for those born in 2007 or later (P = 0.029). Genetic testing identified 27 different variants for the SRD5A2 gene (30% novel, n = 8) and 18 for the HSD17B3 gene (44% novel, n = 8). Before 2002, most patients were initially assigned as females (95%, n = 19), but this proportion dropped for those born later (44%, n = 14; P < 0.001). The influence of initial genital appearance on these decisions seemingly decreased in the most recent years. Therapeutic interventions differed according to the sex of rearing. Ten percent (n = 2) patients requested female-to-male reassignment during adulthood.

Conclusion

This study showed, over the past two decades, a clear trend toward earlier diagnosis and assignment of affected newborns as males.

Open access
Teodoro Durá-Travé Department of Pediatrics, School of Medicine, University of Navarra, Pamplona, Spain
Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain
Navarra Institute for Health Research (IdisNA), Pamplona, Spain

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Fidel Gallinas-Victoriano Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain

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María Malumbres-Chacon Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain

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Lotfi Ahmed-Mohamed Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain

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María Jesús Chueca -Guindulain Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain
Navarra Institute for Health Research (IdisNA), Pamplona, Spain

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Sara Berrade-Zubiri Department of Pediatrics, Navarra Hospital Complex, Pamplona, Spain
Navarra Institute for Health Research (IdisNA), Pamplona, Spain

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Objective

The objective of this study was to analyze whether some auxological characteristics or a single basal gonadotropin measurement will be sufficient to distinguish the prepubertal from pubertal status.

Methods

Auxologycal characteristics were recorded and serum LH and FSH were measured by immunochemiluminescence assays before and after GnRH stimulation test in a sample of 241 Caucasian girls with breast budding between 6- and 8-years old. Peak LH levels higher than 5 IU/L were considered a pubertal response. Area under the curve, cut-off points, sensitivity, and specificity for auxologycal variables and basal gonadotropins levels were determined by receiver operating curves.

Results

There were no significant differences in age at onset, weight, height, BMI and height velocity between both groups. Bone age was significantly higher in pubertal girls (P < 0.05), although with limited discriminatory capacity. The sensitivity and specificity for the basal LH levels were 89 and 82%, respectively, for a cut off point of 0.1 IU/L. All girls in the pubertal group had a basal LH higher than 1.0 IU/L (positive predictive value of 100%). There was a wide overlap of basal FSH and LH/FSH ratio between prepubertal and pubertal girls.

Conclusions

Auxologycal characteristics should not be used only in the differential diagnosis between prepubertal from pubertal status in 6- to 8-year-old girls. We found a high specificity of a single basal LH sample and it would be useful for establishing the diagnosis of puberty in this age group, reducing the need for GnRH stimulation testing.

Open access
David Mark Robertson Department of Molecular and Translational Sciences, Hudson Institute of Medical Research, Monash University, Clayton, Victoria, Australia
School of Women’s & Children’s Health, Discipline of Obstetrics and Gynaecology, University of New South Wales, Sydney, Australia

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Chel Hee Lee Clinical Research Support Unit, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

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Angela Baerwald Department of Obstetrics, Gynecology & Reproductive Sciences, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada

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It is recognised that ovarian factors, including steroid and protein hormones, are critical in the feedback regulation of pituitary gonadotropins; however, their individual contributions are less defined. The aim of this study was to explore the reciprocal relationships between ovarian and pituitary hormones across the normal ovulatory menstrual cycle as women age. FSH, LH, oestradiol, progesterone, inhibin A, inhibin B and anti-mullerian hormone (AMH) were measured in serum collected every 1–3 days across one interovulatory interval (IOI) from 26 healthy women aged 18–50 years. The antral follicle count (AFC) for follicles 2–5 mm, >6 mm and 2–10 mm were tabulated across the IOI. Independent associations between ovarian hormones/AFC vs pituitary follicle-stimulating hormone (FSH) and luteinising hormone (LH) were investigated using multivariate regression analysis. The data were sub-grouped based on the presence or absence luteal phase-dominant follicles (LPDF). Serum oestradiol and AMH were inversely correlated with FSH in both follicular and luteal phases. Inhibin B correlated inversely with FSH and LH in the late follicular phase and directly in the luteal phase. AFC, inhibin A and progesterone were not key predictors of either FSH or LH. The strong association between AMH and FSH with age implies that AMH, as well as oestradiol and inhibin B are important regulators of FSH. The change in feedback response of inhibin B with both FSH and LH across the cycle suggests two phases of the negative feedback.

Open access
Andrew R Dismukes Department of Human Development and Family Studies, Iowa State University, Ames, Iowa, USA
Tulane University School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Tulane University, New Orleans, Louisiana, USA

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Vanessa J Meyer Department of Human Development and Family Studies, Iowa State University, Ames, Iowa, USA
Tulane University School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Tulane University, New Orleans, Louisiana, USA

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Elizabeth A Shirtcliff Department of Human Development and Family Studies, Iowa State University, Ames, Iowa, USA

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Katherine P Theall Tulane University School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Tulane University, New Orleans, Louisiana, USA

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Kyle C Esteves Tulane University School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Tulane University, New Orleans, Louisiana, USA

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Stacy S Drury Tulane University School of Medicine, Department of Psychiatry, Division of Child and Adolescent Psychiatry, Tulane University, New Orleans, Louisiana, USA

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The current investigation examined the association between the aging-related biomarkers dehydroepiandrosterone (DHEA) and telomere length (TL) in community-recruited African-American youth. The examination of DHEA included stress reactive, basal and diurnal sampling, in order to elucidate the underlying physiological process that may overlap with TL. One hundred and two participants completed the Trier Social Stressor Test for children (TSST-C). TL was obtained from all youth from buccal swabs on the same day as the TSST-C. Saliva samples from 83 participants were obtained over the course of two additional days to measure waking and diurnal levels of DHEA. DHEA diurnal slope was a robust predictor of TL (B=0.516, P<0.05), while other DHEA values were not significantly associated with TL. This study is one of the first studies to examine basal, diurnal and reactivity measurements of DHEA in youth. Furthermore, this is the first study, to our knowledge, to demonstrate a positive association between DHEA, a putative anti-aging hormone, and TL, an indicator of cellular aging.

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Xi Wang Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

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Qi Yu Department of Obstetrics and Gynaecology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China

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Objective

To evaluate the safety and efficacy of letrozole in girls with progressive precocious puberty (PP) associated with McCune–Albright syndrome (MAS).

Design

Monocentric retrospective cross-sectional and longitudinal study of consecutive patients.

Patients

Ten MAS patients treated at Peking Union Medical College Hospital between September 1999 and December 2017 were retrospectively reviewed; those with complications due to PP were followed.

Results

The mean age at letrozole initiation was 4.5 ± 2.6 years, while the mean duration of treatment was 3.3 ± 2.4 years. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a significant decrease in the bone age-to-chronological age (BA/CA) ratio from 1.9 ± 1.1 pre-treatment to 1.5 ± 1.2 on letrozole treatment (P = 0.016). Moreover, growth velocity Z-scores declined from 0.41 ± 0.5 to −0.2 ± 0.31 with treatment (P < 0.001). Predicted adult height Z-scores increased significantly from −2.03 ± 2.33 at baseline to 1.13 ± 0.84 following treatment initiation (P = 0.029). Moreover, vaginal bleeding declined significantly on letrozole.

Conclusions

Our findings suggest that letrozole may be an effective therapy in some girls with MAS, as treatment results in improved BA/CA ratio, growth velocity and predicted adult height. Possible adverse effects include nettle rash.

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Jing Wang Tianjin Women’s and Children’s Health Center Tianjin, China
Chronic Disease Epidemiology Laboratory Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

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Leishen Wang Tianjin Women’s and Children’s Health Center Tianjin, China

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Huikun Liu Tianjin Women’s and Children’s Health Center Tianjin, China

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Shuang Zhang Tianjin Women’s and Children’s Health Center Tianjin, China

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Junhong Leng Tianjin Women’s and Children’s Health Center Tianjin, China

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Weiqin Li Tianjin Women’s and Children’s Health Center Tianjin, China

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Tao Zhang Tianjin Women’s and Children’s Health Center Tianjin, China

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Nan Li Tianjin Women’s and Children’s Health Center Tianjin, China

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Wei Li Tianjin Women’s and Children’s Health Center Tianjin, China

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Andrea A Baccarelli Department of Environmental Health Sciences Columbia University Mailman School of Public Health, New York, New York, USA

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Lifang Hou Department of Preventive Medicine Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA

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Gang Hu Chronic Disease Epidemiology Laboratory Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA

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Previous studies found conflicting results about the associations between the exposure to hyperglycemia in utero and the later risks of childhood overweight and obesity. The aim of the present study is to compare the children’s BMI growth between offspring exposed to maternal gestational diabetes mellitus (GDM) and those not exposed and assess the associations between maternal GDM and their offspring’s overweight and obesity risk. We performed a large observational study in 1156 women and their offspring (578 GDM and 578 non-GDM mother–child pairs, matched by their offspring’s gender and age). Maternal GDM was diagnosed according to the World Health Organization criteria. Childhood height, weight, waist circumference, body fat and skinfold were measured using standardized methods. After adjustment for maternal and children’s characteristics, children born to mothers with GDM during pregnancy had higher mean values of Z scores for BMI-for-age, Z scores for weight-for-age, waist circumferences, body fat, subscapular skinfold and suprailiac skinfold, in comparison with their counterparts born to mothers with normal glucose during pregnancy (all P values <0.05). Moreover, maternal GDM was associated with a higher risk of childhood overweight and obesity with multivariate-adjusted odds ratios of 1.42 (95% confidence interval (CI): 1.02–1.97) and 1.18 (95% CI: 1.11–1.24), respectively, compared with the children of mothers without GDM during pregnancy. This study demonstrates that maternal GDM is an independent risk factor of childhood overweight and obesity and is associated with higher BMI in the offspring.

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Iulia Soare University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania

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Anca Sirbu University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania

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Mihai Mircea Diculescu University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Gastroenterology, Fundeni Clinical Institute, Bucharest, Romania

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Bogdan Radu Mateescu University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Gastroenterology, Colentina Hospital, Bucharest, Romania

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Cristian Tieranu University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Gastroenterology, Elias Hospital, Bucharest, Romania

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Sorina Martin University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania

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Carmen Gabriela Barbu University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania

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Mirela Ionescu University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Gastroenterology, Elias Hospital, Bucharest, Romania

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Simona Fica University of Medicine and Pharmacy ‘Carol Davila’ Bucharest, Bucharest, Romania
Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania

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Background and aim

Low bone mineral density (BMD) is a common complication in patients with inflammatory bowel disease (IBD). However, debates are ongoing with regard to the other involved factors, especially in younger patients. This study aimed to evaluate the parameters that contribute to decreased BMD, focusing on premenopausal women and men aged <50 years.

Methods

This study included 81 patients with IBD and 81 age-, sex- and BMI-matched controls. Blood tests were conducted on IBD patients, and a dual-energy X-ray absorptiometry (DXA) scan was performed on both groups.

Results

Low BMD and fragility fracture were found to be more prevalent in IBD patients than in healthy subjects (49.3% vs 23.4%, P = 0.001 and 9.8% vs 1.2%, P = 0.01, respectively). Patients with low BMD were older, with a longer disease duration, higher faecal calprotectin (FC) levels and lower magnesium and lean mass (appreciated as appendicular skeletal muscle index (ASMI)). Multiple regression analysis revealed that ASMI, age and use of glucocorticoids were the independent parameters for decreased BMD. Although 91.3% of the patients had a 25-hydroxy vitamin D level of <30 ng/mL, it was not a statistically significant factor for decreased BMD.

Conclusion

In our study, the levels of vitamin D did not seem to have an important impact on BMD. Conversely, FC, magnesium and lean mass are important factors, suggesting that good control of disease, adequate magnesium intake and increased lean mass can have a good impact on bone metabolism in patients with IBD.

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