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1. Congenital Hypothyroidism due to a Low Level of Maternal Thyrotropin Receptor-Blocking Antibodies

Author

Véronique Raverot, Juliette Abeillon, Patricia Bretones, Myriam Moret, Solène Castellnou, Karim Chikh, Pauline Perrin, Fédération d’Endocrinologie, Maladies Métaboliques, Diabète et Nutrition [Bron] (FEMMDN/Hôpital Louis Pradel ), Hospices Civils de Lyon (HCL)-Groupement Hospitalier Est [Bron], Service d'endocrinologie pédiatrique [CHU Lyon-Hospices Civils de Lyon], Hospices Civils de Lyon (HCL), Service de Biochimie et Biologie Moléculaire Grand Est [HCL, Lyon] (Centre de Biologie et de Pathologie), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Biologie et de Pathologie Sud [HCL, Lyon], and CarMeN, laboratoire

Subjects
medicine.medical_specialty, TBAb, endocrine system, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], 030209 endocrinology & metabolism, Reference range, Thyrotropin receptor, 03 medical and health sciences, 0302 clinical medicine, Maternal hypothyroidism, TSHR Ab, Internal medicine, medicine, Thyrotropin receptor-blocking antibodies, business.industry, Thyroid, medicine.disease, Thyroid disorder, 3. Good health, Congenital hypothyroidism, [SDV] Life Sciences [q-bio], TRAb, medicine.anatomical_structure, Endocrinology, 030220 oncology & carcinogenesis, Clinical Thyroidology / Case Report, Thyroglobulin, Thyroid function, business, hormones, hormone substitutes, and hormone antagonists
Abstract

Introduction: Maternal TSH receptor antibodies (TRAbs) can cross the placenta and affect fetal and neonatal thyroid function. Maternal TSH receptor-blocking antibodies (TBAbs) are a rare cause of congenital hypothyroidism. Case Report: Following the discovery of a highly elevated TSH on her neonatal screening test, a 10-day-old girl with no familial history of thyroid disorder was referred to the pediatric endocrinology unit. Hypothyroidism was confirmed with a highly elevated TSH (817 mIU/L, reference range 0.4–3.1) and very low levels of FT4 (1.8 pmol/L, reference range 12–22). Anti-TPO antibodies were at 81 IU/mL (reference range Conclusion: We report herein a case of transient congenital hypothyroidism with a normal neonatal TRAbs level. In case of maternal TBAbs, similar activity of maternal TBAbs must be expected in the neonate, independently of the neonatal level of TRAbs.

Published
2020
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2. Growth curves for congenital adrenal hyperplasia from a national retrospective cohort

Author

Patricia Bretones, Benjamin Riche, Emmanuel Pichot, Michel David, Pascal Roy, Véronique Tardy, Behrouz Kassai, Ségolène Gaillard, Delphine Bernoux, Yves Morel, Pierre Chatelain, Marc Nicolino, Catherine Cornu, null for the French Collaborative CAH Gr, Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Evaluation et modélisation des effets thérapeutiques, Service de Biostatistiques [Lyon], and Hospices Civils de Lyon (HCL)

Subjects
Adult, Male, medicine.medical_specialty, Pediatrics, Adolescent, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Population, 030209 endocrinology & metabolism, Logistic regression, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, 030225 pediatrics, Internal medicine, medicine, Humans, Congenital adrenal hyperplasia, Sexual Maturation, Growth Charts, Young adult, Child, education, ComputingMilieux_MISCELLANEOUS, Retrospective Studies, education.field_of_study, Bone Development, Adrenal Hyperplasia, Congenital, business.industry, Infant, Newborn, Infant, Retrospective cohort study, Bone age, medicine.disease, Body Height, Child, Preschool, Pediatrics, Perinatology and Child Health, Bone maturation, Female, business, Follow-Up Studies, Cohort study
Abstract

Background: In congenital adrenal hyperplasia (CAH), adjusting hydrocortisone dose during childhood avoids reduced adult height. However, there are currently no CAH-specific charts to monitor growth during treatment. Our objective was to elaborate growth reference charts and bone maturation data for CAH patients. Methods: We conducted a retrospective observational cohort study, in 34 French CAH centers. Patients were 496 children born 1970–1991 with genetically proven 21-hydroxylase deficiency. Their growth and bone maturation data were collected until age 18 together with adult height, puberty onset, parental height, and treatment. The mean (SD) heights were modeled from birth to adulthood. The median±1 SD and ±2 SDs model-generated curves were compared with the French references. A linear model for bone maturation and a logistic regression model for the probability of short adult height were built. Results: Growth charts were built by sex for salt wasting (SW) and simple virilizing (SV) children treated before 1 year of age. In girls and boys, growth was close to that of the general French population up to puberty onset. There was almost no pubertal spurt and the mean adult height was shorter than that of the general population in girls (−1.2 SD, 156.7 cm) and boys (−1.0 SD, 168.8 cm). Advanced bone age at 8 years had a strong impact on the risk of short adult height (OR: 4.5 per year advance). Conclusions: The 8-year bone age is a strong predictor of adult height. It will help monitoring the growth of CAH-affected children.

Published
2016
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3. Predictive value of maternal second-generation thyroid-binding inhibitory immunoglobulin assay for neonatal autoimmune hyperthyroidism

Author

Karim Chikh, Jacques Orgiazzi, Juliette Abeillon-du Payrat, Véronique Raverot, Pascal Gaucherand, Anne Charrié, Claire Bournaud, O Claris, Patricia Bretones, Nadine Bossard, Françoise Borson-Chazot, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Biostatistiques santé, Département biostatistiques et modélisation pour la santé et l'environnement [LBBE], Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Pediatrics, endocrine system diseases, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Thyroid Gland, Disease, Infant, Newborn, Diseases, 0302 clinical medicine, Endocrinology, Prenatal Exposure Delayed Effects/*immunology, Pregnancy, Pregnancy Complications/*immunology, biology, Thyroid, General Medicine, Graves Disease, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Predictive value of tests, Prenatal Exposure Delayed Effects, Female, France, Antibody, hormones, hormone substitutes, and hormone antagonists, Immunoglobulins, Thyroid-Stimulating, Diseases/*immunology, Adult, medicine.medical_specialty, endocrine system, Thyroid Gland/*immunology, Immunoglobulins, 030209 endocrinology & metabolism, Context (language use), Graves Disease/*immunology, Thyroid-Stimulating/*blood, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Humans, Retrospective Studies, Fetus, business.industry, Infant, Newborn, Infant, Retrospective cohort study, medicine.disease, Newborn, Pregnancy Complications, biology.protein, business, Biomarkers, Biomarkers/blood
Abstract

ContextHyperthyroidism occurs in 1% of neonates born to mothers with active or past Graves' disease (GD). Current guidelines for the management of GD during pregnancy were based on studies conducted with first-generation thyroid-binding inhibitory immunoglobulin (TBII) assays.ObjectiveThis retrospective study was conducted in order to specify the second-generation TBII threshold predictive of fetal and neonatal hyperthyroidism, and to identify other factors that may be helpful in predicting neonatal hyperthyroidism.MethodsWe included 47 neonates born in the Lyon area to 42 mothers harboring measurable levels of TBII during pregnancy. TBII measurements were carried out in all mothers; bioassays were carried out in 20 cases.ResultsNine neonates were born with hyperthyroidism, including five with severe hyperthyroidism requiring treatment. Three neonates were born with hypothyroidism. All hyperthyroid neonates were born to mothers with TBII levels >5 IU/l in the second trimester (sensitivity, 100% and specificity, 43%). No mother with TSH receptor-stimulating antibodies (TSAb measured by bioassay) below 400% gave birth to a hyperthyroid neonate. Among mothers of hyperthyroid neonates, who required antithyroid drugs during pregnancy, none could stop treatment before delivery. Analysis of TBII evolution showed six unexpected cases of increasing TBII values during pregnancy.ConclusionMaternal TBII value over 5 IU/l indicates a risk of neonatal hyperthyroidism. Among these mothers, a TSAb measurement contributes to identify more specifically those who require a close fetal thyroid ultrasound follow-up. These results should be confirmed in a larger series.

Published
2014
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4. Late prenatal dexamethasone and phenotype variations in 46,XX CAH: concerns about current protocols and benefits for surgical procedures

Author

Daniela Gorduza, Véronique Tardy-Guidollet, Elsa Robert, Claire-Lise Gay, Pierre Chatelain, Michel David, Patricia Bretones, Anne Lienhardt-Roussie, Aude Brac de la Perriere, Yves Morel, and Pierre Mouriquand

Subjects
Pediatrics, medicine.medical_specialty, Urology, Gestational Age, Dexamethasone, Drug Administration Schedule, Pregnancy, Medicine, Humans, Sex organ, Congenital adrenal hyperplasia, Genital tubercle, Glucocorticoids, Retrospective Studies, Fetal Therapies, Adrenal Hyperplasia, Congenital, business.industry, Infant, Surgical procedures, medicine.disease, Virilism, Large cohort, Phenotype, Pediatrics, Perinatology and Child Health, Gestation, Female, business, medicine.drug
Abstract

Objective To describe the action of prenatal dexamethasone (PreDex) on the anatomy of female congenital adrenal hyperplasia (CAH) genitalia when started at later stages of gestation. Materials and methods Our group follows a large cohort of French CAH patients who underwent PreDex therapy, of whom 258 were recently reported. Four 46,XX patients with a delayed PreDex treatment presented with a virilized genitalia and required surgical reconstruction. This is a retrospective report on genital phenotyping at the time of surgery of these four patients who began PreDex therapy at 8, 12, 20, and 28 weeks of gestation. Results Although this series is limited in number, the anatomical description of the length of the genital tubercle, the height of the urethra–vaginal confluence, and the degree of fusion of the genital folds seems to be dependent upon the starting date of PreDex. Most PreDex treatments prescribed up to now have covered the full duration of gestation. Conclusions Our findings suggest that PreDex therapy could be limited to the period of the partitioning window. It is hoped that further prospective multicentric clinical studies will obtain ethical approval in order to elucidate the place and protocols of PreDex therapy in the management of CAH.

Published
2013

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