European Thyroid Journal paediatric thyroidology special collection

 

European Thyroid Journal (ETJ) publishes papers reporting original research in basic, translational and clinical thyroidology. The journal is fully open-access, ensuring the highest impact for authors publishing in ETJ.

There are clear challenges to managing thyroid disorders in children and young people including more aggressive disease and greater concerns about the long-term effects of therapy. This special topic collection on pediatric thyroid disease brings together high quality articles on the management of diverse aspects of paediatric thyroid diseases.

 

Comments from Editor-in-Chief Professor Simon Pearce – University of Newcastle

"The management of thyroid disease in childhood holds special challenges and children cannot be treated as small adults. Europe is home to many of the world’s leading authorities on paediatric thyroidology and this special topic collection from European Thyroid Journal includes some important papers including the recent ETA guidelines on management of paediatric Graves’ disease. I hope you enjoy reading the collection."

 

Explore all European Thyroid Journal Special Collections

 

Paediatric thyroidology

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Paolo Cavarzere Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy

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Laura Palma Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy

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Lara Nicolussi Principe Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy

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Monica Vincenzi Pediatric Section, Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
Regional Center for Newborn Screening, Diagnosis and Treatment of Congenital Metabolic and Endocrinological Diseases, Verona, Italy

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Silvana Lauriola Neonatal Intensive Cure Unit, Department of Pediatrics, University Hospital of Verona, Verona, Italy

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Rossella Gaudino Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy
Pediatric Section, Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy

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Virginia Murri Pediatric Division, Hospital of San Bonifacio, Verona, Italy

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Luigi Lubrano Pediatric Division, Hospital of Legnago, Verona, Italy

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Giuliana Rossi Pediatric Division, Hospital of Mestre, Venezia, Italy

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Alessia Sallemi Pediatric Division, Hospital of Venezia, Venezia, Italy

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Ermanna Fattori Pediatric Division, Hospital of Negrar, Verona, Italy

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Marta Camilot Pediatric Section, Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
Regional Center for Newborn Screening, Diagnosis and Treatment of Congenital Metabolic and Endocrinological Diseases, Verona, Italy

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Franco Antoniazzi Pediatric Division, Department of Pediatrics, University Hospital of Verona, Verona, Italy
Pediatric Section, Department Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy
Regional Center for the Diagnosis and Treatment of Children and Adolescents Rare Skeletal Disorders, Pediatric Clinic, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy

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Introduction

Infants of mothers with autoimmune hypothyroidism (AH) are at risk of developing late-onset hypothyroidism, often escaping at newborn screening. This condition might be caused both by the action of maternal antibodies and/or by maternal treatment.

Objectives

The aim of this study is to evaluate the prevalence of AH in the mothers of children born in Veneto region, Italy, and to define what is the most appropriate management for these newborns.

Methods

Newborns of six different hospitals with a mother suffering from AH and with negative neonatal screening for congenital hypothyroidism (CH) were included in the study. Between 15 and 20 days of life, we collected a serum sample for the evaluation of thyroid function (thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3)) and anti-thyroid antibodies. On the same occasion, a capillary blood sampling was performed for a second screening test.

Results

Maternal AH has a prevalence of 3.5%. A total of 291 newborns were enrolled from November 2019 to May 2021. Whereas the 11.4% of infants had a slight elevated serum TSH (>6 mU/L) and required a follow-up, only 2 children presented an elevated TSH level at the second screening test. One of these, with the gland in situ, showed persistently elevated serum TSH levels and required treatment with levothyroxine.

Conclusions

Maternal AH rarely caused neonatal thyroid dysfunction. We suggest to reassess newborns from mothers with AH 15 days after birth by means of a second neonatal screening test. This procedure avoids false negatives due to maternal thyroid status, is less invasive and cheaper than the serum TSH evaluation, and prevents a long follow-up.

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Zohar Steinberg Ben-Zeev Pediatric Department A, Ha’Emek Medical Center, Afula, Israel

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Marina Peniakov Neonatal Intensive Care Unit, Ha’Emek Medical Center, Afula, Israel

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Clari Felszer Neonatal Intensive Care Unit, Ha’Emek Medical Center, Afula, Israel

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Scott A Weiner Neonatal Intensive Care Unit, Ha’Emek Medical Center, Afula, Israel

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Avishay Lahad Pediatric Department A, Ha’Emek Medical Center, Afula, Israel

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Shlomo Almashanu The National Newborn Screening Program, Ministry of Health, Tel Hashomer, Ramat Gan, Israel

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Yardena Tenenbaum Rakover Consulting Medicine in Pediatric Endocrinology, Clalit Health Services, Afula, Israel
The Rappaport Faculty of Medicine, Technion, Institute of Technology, Haifa, Israel

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Introduction

Maternal thyroid disease is considered as a risk factor for abnormal thyroid function at birth, as well as for long-term morbidity in offspring. The potential harmful effects on the neonate had led to the clinical practice of thyroid function assessment in infants born to mothers with thyroid disease during pregnancy. In this study, we evaluated the usefulness of routine thyroid function tests for every newborn of a mother with thyroid dysfunction.

Methods

Data were collected retrospectively from the medical files of mothers diagnosed with thyroid disease and their infants (496 mother–neonate pairs). All mothers with diagnosed thyroid disease who gave birth in the years 2016–2019 at our medical center were included.

Results

Hypothyroidism was the most common maternal diagnosis (91.4%), among which 48.7% had Hashimoto’s thyroiditis. Hyperthyroidism was diagnosed in 8.6% of the cohort – 71.6% of them with Graves’ disease. None of the newborns was diagnosed with congenital hypothyroidism in the screening program. Thyroid-stimulating hormone was >10 mIU/L in 14.6% and >20 mUI/L in 2.2%; all had free thyroxine within normal range. Serum thyroid function test identified four infants with thyroid disease; two had congenital hypothyroidism not related to maternal thyroid disease, one had transient familial congenital hypothyroidism and one had neonatal Graves’ disease.

Conclusions

Thyroid function testing for all newborns of mothers with thyroid dysfunction seems redundant. However, in cases of congenital hypothyroidism in siblings, thyroid function test, in addition to newborn thyroid screening, is recommended, and more careful follow-up is indicated. In maternal Graves’ disease, thyroid function test on days 2–3 of life is recommended.

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Giorgio Radetti Marienklinik, Bolzano, Italy

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Franco Rigon Department of Paediatrics, University of Padua, Padua, Italy

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Alessandro Salvatoni Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Irene Campi Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Tiziana De Filippis Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Valentina Cirello Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy

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Silvia Longhi Department of Paediatrics, Regional Hospital of Bolzano, Bolzano, Italy

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

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Marco Bonomi Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Luca Persani Division of Endocrine and Metabolic Diseases and Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano, IRCCS, Milan, Italy
Department of Medical Biotechnology and Translational Medicine, University of Milan, Milan, Italy

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Introduction

Patients with congenital hypothyroidism (CH) may transiently show a certain degree of pituitary resistance to levothyroxine (LT4) which, however, normalizes subsequently. However, in some individuals, thyroid-stimulating hormone (TSH) fails to normalize despite adequate LT4 treatment.

Methods

Nine patients with CH followed in three Academic Centre who developed over time resistance to thyroid hormones underwent extensive biochemical and genetic analyses. These latter were performed by Sanger sequence or targeted next-generation sequencing technique including a panel of candidate genes involved in thyroid hormone actions and congenital hypothyroidism (CH): THRA, THRB, DIO1, DIO2, SLC16A2, SECISBP2, DUOX2, DUOXA2, FOXE1, GLIS3, IYD, JAG1, NKX2-1, NKX2- 5, PAX8, SLC26A4, SLC5A5, TG, TPO, TSHR.

Results

All patients displayed a normal sensitivity to thyroid hormone (TH) in the first years of life but developed variable degrees of resistance to LT4 treatment at later stages. In all cases, TSH normalized only in the presence of high free thyroxine levels. Tri-iodothyronine suppression test followed by thyrotrophin-releasing hormone stimulation was performed in two cases and was compatible with central resistance to THs. This biochemical feature was present independently on the cause of CH, being observed either in patients with an ectopic (n = 2) or eutopic gland (n = 3) or in case of athyreosis (n = 1). None of the patients had genetic variants in genes involved in the regulation of TH actions, while in two cases, we found two double heterozygous missense variants in TSHR and GLIS3 or in DUOX2 and SLC26A4 genes, respectively.

Conclusions

We report CH patients who showed an acquired and unexplainable pituitary refractoriness to TH action.

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Aurore Geslot Department of Endocrinology and metabolic diseases, CHU Larrey, Toulouse, France

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Frédérique Savagner Laboratory of Biochemistry, CHU Purpan, Toulouse, France

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Philippe Caron Department of Endocrinology and metabolic diseases, CHU Larrey, Toulouse, France

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Introduction: Iodothyronine deiodinases are selenoproteins with the amino acid selenocysteine (Sec) introduced into the position of a TGA stop codon by a complex machinery involving tRNA<sup>[Ser]Sec</sup> when a cis-acting Sec-insertion sequence element is present in the 3′ end of the mRNA. Recently, a variant in the TRU-TCA1-1 gene encoding for tRNA<sup>[Ser]Sec</sup> was reported, which resulted in reduced expression of stress-related selenoproteins. The proband presented with multisystem symptoms, euthyroid hyperthyroxinemia, and selenium deficiency. Here, we describe 2 new members of a family harboring the same tRNA<sup>[Ser]Sec</sup> variant. Case Presentation: A 13-year-old patient was seen for Hashimoto’s disease with high FT3 (4.6 pg/mL, normal range 2–4.2 pg/mL) and normal FT4 and TSH concentrations. He had no clinical complaints. During a 6-year clinical and hormonal follow-up, the index patient was not treated, FT3 decreased, FT4 increased, and serum TSH stayed in the normal range resulting in a euthyroid hyperthyroxinemia. Reverse T3 concentration was significantly increased at the last visit (19 years and 4 months). At the last evaluation, the total selenium level was low (91 μg/L, normal range 95–125). DNA sequencing identified a germinal homozygous variant (C65G) in the TRU-TCA1-1 gene. During follow-up, no additional clinical symptom was observed in the absence of any treatment. The same germinal tRNA<sup>[Ser]Sec</sup> variant was identified at heterozygous state in his father, who had normal thyroid function tests except a moderately increased reverse T3 concentration, with increased total selenium (143 μg/L) level. In both patients, the expression of stress-related selenoprotein GPX3 was in the low-normal range (168 and 180 IU/L, respectively, normal range: 150–558 IU/L). We did not find any significant biological abnormalities evocative of other selenoprotein deficiencies. Discussion/Conclusion: We report on 2 members of a family with a variant in the TRU-TCA1-1 gene encoding for tRNA<sup>[Ser]Sec</sup>. Our study suggests that this tRNA<sup>[Ser]Sec</sup> variant is not exclusively causative of disruption in selenoprotein synthesis.

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Yuwei Liu Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Shengcai Wang Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Yanzhen Li Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Xuexi Zhang Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Zhiyong Liu Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Qiaoyin Liu Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Nian Sun Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Jie Zhang Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Wentong Ge Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Yongli Guo Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Yuanhu Liu Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Xiaolian Fang Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Tingting Ji Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Jun Tai Children’s Hospital Capital Institute of Pediatrics, Department of Otolaryngology, Head and Neck Surgery, Beijing, China

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Xin Ni Department of Otolaryngology, Head and Neck Surgery, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China
Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health (NCCH), Beijing, China

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Objectives: The objectives of this study were to explore the clinical heterogeneity of differentiated thyroid cancer (DTC) between prepubertal children and adolescents and guide clinical treatment. Methods: A retrospective study included patients with DTC aged ≤19 years in Beijing Children’s Hospital from June 2014 to June 2019. All patients were enrolled and divided into 2 subgroups based on the threshold age of 10 years, namely the childhood group (CG) (≤10 years old); and the adolescent group (AG) (between 10 and 19 years old). The χ<sup>2</sup> test and Fisher’s exact test were used to estimate the effect of risk factors in the 2 age groups. Multivariate binary logistic regression models were conducted to assess the recurrent risk factors. Results: Seventy cases of DTC were included with an average age of 9.94 ± 2.88 years, including 35 in CG and 35 in AG. The most common clinical manifestation was a painless mass in the neck, accounting for 77.1% (54/70) of patients. Compared with the AG, the CG was more likely to have lymph node metastasis (p = 0.022) and distant metastasis (p = 0.041). The CG was more likely to have extrathyroidal extension (p = 0.012) and had a significantly higher recurrence rate than the AG (p = 0.040). Age was an independent variable predictive of recurrence (p = 0.0347). Conclusion: Regional invasiveness, cervical lymph node metastasis, and distant metastasis of DTC were more likely to occur in children ≤10 years old. Meanwhile, children ≤10 years old with DTC were more likely to have recurrence than adolescent’s postsurgical treatment. Thus, children younger than 10 years of age with DTC should be treated more aggressively.

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Sarah L. Lutterman Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Nitash Zwaveling-Soonawala Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Hein J. Verberne Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Frederik A. Verburg Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

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A.S. Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Christiaan F. Mooij Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Background: Graves’s disease (GD) is the most common cause of hyperthyroidism. Maximal 30% of pediatric GD patients achieve remission with antithyroid drugs. The majority of patients therefore require definitive treatment. Both thyroidectomy and radioactive iodine (RAI) are often used as definitive treatment for GD. However, data on efficacy and short- and long-term side effects of RAI treatment for pediatric GD are relatively scarce. Methods: A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting the efficacy or short- and long-term side effects of RAI treatment in pediatric GD. Results: Twenty-three studies evaluating 1,283 children and adolescents treated with RAI for GD were included. The treatment goal of RAI treatment changed over time, from trying to achieve euthyroidism in the past to aiming at complete thyroid destruction and subsequent hypothyroidism in the last 3 decades. The reported efficacy of a first RAI treatment when aiming at hypothyroidism ranged from 42.8 to 97.5%, depending on the activity administered. The efficacy seems to increase with higher RAI activities. When aiming at hypothyroidism, both short- and long-term side effects of treatment are very rare. Long-term side effects were mainly seen in patients in whom treatment aimed at achieving euthyroidism. Conclusion: RAI is a safe definitive treatment option for pediatric GD when aiming at complete thyroid destruction. When aiming at hypothyroidism, the efficacy of treatment seems to increase with a higher RAI activity. Prospective studies are needed to determine the optimal RAI dosing regimen in pediatric GD.

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Tal Almagor Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel
Pediatric Department B, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

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Shoshana Rath Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel

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Dan Nachtigal Department of Otolaryngology, Head and Neck Surgery, Ha’Emek Medical Center, Afula, Israel

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Zohara Sharroni Department of Otolaryngology, Head and Neck Surgery, Ha’Emek Medical Center, Afula, Israel

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Ghadir Elias-Assad Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

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Ora Hess Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel

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Gilad Havazelet Clalit Health Services, North District, Israel

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Yoav Zehavi Pediatric Department B, Ha’Emek Medical Center, Afula, Israel

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Ronen Spiegel Pediatric Department B, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

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Dani Bercovich Faculty of Medical Science, Tel Hai Academic College Upper Galilee, Tel Hai, Israel
GGA – Galil Genetic Analysis Laboratory Ltd., Kazerin, Israel

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Shlomo Almashanu The National Newborn Screening Program, Ministry of Health, Tel-HaShomer, Israel

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Yardena Tenenbaum-Rakover Pediatric Endocrine Institute, Ha’Emek Medical Center, Afula, Israel
Rappaport Faculty of Medicine, Technion – Israel Institute of Technology, Haifa, Israel

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Background: An association between hearing impairment (HI) and congenital hypothyroidism (CH) has been reported previously. However, in general, studies were retrospective and had small sample sizes, and the results were variable and inconclusive. The aim of our study was to assess the prevalence of HI among patients with CH and to examine factors potentially predictive of HI including severity of CH, etiology of CH, and timing of treatment initiation. Methods: Audiometry was undertaken prospectively in 66 patients aged 3–21 years diagnosed with primary CH and 49 healthy matched controls. All patients with HI underwent examination by an otolaryngologist, and in patients with sensorineural loss, brainstem evoked response audiometry was performed. A next-generation sequencing (NGS) panel for genes involved in deafness was performed in patients with sensorineural HI to exclude additional genetic etiologies. Results: HI was found in 19 patients (28.7%). Among them, 5 (7.6%) had moderate to severe bilateral sensorineural impairment and 14 (21.2%) had mild conductive HI. Conductive HI was bilateral in 5 of these patients (36%). None of the controls had HI. No specific etiology was found in patients with HI, and no differences were identified in age at diagnosis, age at initiation of levothyroxine (LT<sub>4</sub>) therapy, gender, or ethnicity between patients with and without HI. A nonsignificant trend toward lower mean screening TT<sub>4</sub> levels was found in patients with HI (compared to those without HI) (3.42 vs. 5.34 μg/dL, p = 0.095). No pathogenic variants in genes attributed to HI were identified by NGS in the 5 patients with sensorineural deafness, indicating that HI in these patients was likely attributable to CH rather than other genetic etiologies. Conclusions: Our findings indicate a high prevalence of HI among patients with CH, predominantly of the conductive type. HI was not associated with the etiology of CH or with delayed initiation of LT<sub>4</sub> therapy. Audiometry is recommended for children diagnosed with CH and repeat monitoring may be warranted to identify acquired HI and to prevent long-term sequelae of undiagnosed deafness.

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Kevin Stroek Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Annemieke C. Heijboer Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands
Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, Vrije Universiteit, Amsterdam, The Netherlands

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Marja van Veen-Sijne Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Annet M. Bosch Division of Metabolic Disorders, Department of Pediatrics, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Catharina P.B. van der Ploeg Department of Child Health, Netherlands Organization for Applied Scientific Research TNO, Leiden, The Netherlands

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Nitash Zwaveling-Soonawala Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Robert de Jonge Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit & University of Amsterdam, Amsterdam, The Netherlands

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A.S. Paul van Trotsenburg Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Anita Boelen Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

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Introduction: Newborn screening (NBS) for congenital hypothyroidism (CH) in the Netherlands consists of thyroxine (T4), thyroid-stimulating hormone (TSH), and T4-binding globulin (TBG) measurements to detect thyroidal CH and central CH (CH-C). CH-C is detected by T4 or a calculated T4/TBG ratio, which serves as an indirect measure of free T4. TSH and TBG are only measured in the lowest 20 and 5% of daily T4 values, respectively. A recent evaluation of the Dutch NBS for CH showed that the T4 and T4/TBG ratio contribute to the detection of CH-C but also lead to a low positive predictive value (PPV). Dried blood spot (DBS) reference intervals (RIs) are currently unknown and may contribute to improvement of our NBS algorithm. Materials and Methods: RIs of T4, TSH, TBG, and the T4/TBG ratio were determined according to Clinical & Laboratory Standards Institute guidelines in heel puncture cards from routine NBS in both sexes and at the common NBS sampling ages. Scatter plots were used to compare the healthy reference population to previously published data of CH-C patients and false positives. Results: Analyses of 1,670 heel puncture cards showed small differences between subgroups and led to the formulation of total sample DBS RIs for T4 (56–118 nmol/L), TSH (<2.6 mIU/L), TBG (116–271 nmol/L), and the T4/TBG ratio (>20). 46% of false-positive referrals based on T4 alone had a TBG below the RI, indicating preventable referral due to partial TBG deficiency. One case of CH-C also had partial TBG deficiency (TBG 59 and T4 12 nmol/L blood). Discussion/Conclusion: Established DBS RIs provided possibilities to improve the PPV of the Dutch CH NBS algorithm. We conclude that by taking partial TBG deficiency into account, approximately half of T4 false-positive referrals may be prevented while maintaining NBS sensitivity at the current level.

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Solène Castellnou Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Bron, France

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Patricia Bretones Service d’Endocrinologie Pédiatrique, Hospices Civils de Lyon, Groupement Hospitalier Est, Bron, France

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Juliette Abeillon Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Bron, France

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Myriam Moret Hospices Civils de Lyon, Groupement Hospitalier Est, Fédération d’Endocrinologie, Bron, France

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Pauline Perrin Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Bron, France

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Karim Chikh Centre de Biologie et de Pathologie Sud, Hospices Civils de Lyon, Groupement Hospitalier Sud, LBMMS, Saint Genis Laval, France

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Véronique Raverot Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, Groupement Hospitalier Est, LBMMS, Bron, France

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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 <34), TRAbs at 1.7 IU/L (reference range <1.75), and thyroglobulin at 9.4 µg/L (reference range 3.5–77). The thyroid appeared normal on ultrasonography, and no radioiodine uptake was seen on the scintigraphy after the perchlorate discharge test. Concomitantly, a severe maternal hypothyroidism was discovered (TSH 224 mIU/L). The maternal ultrasound appeared normal, anti-TPO antibodies were moderately elevated, and TRAbs were at 3.2 IU/L. TBAbs activity was measured in the mother and her daughter, and a very high and similar blocking activity was observed in both patients (TBAbs 89%, reference range <10%). L-thyroxine treatment was introduced in the newborn and was successfully discontinued at 6.5 months of age, as the TBAbs activity decreased. 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.

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Catarina Senra Moniz Department of Endocrinology and Nutrition, Hospital do Divino Espírito Santo de Ponta Delgada, Ponta Delgada, Portugal

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Rita Carvalho Department of Endocrinology and Nutrition, Hospital do Divino Espírito Santo de Ponta Delgada, Ponta Delgada, Portugal

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Susana Prazeres Laboratory of Endocrinology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, Lisboa, Portugal

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Edward Limbert Department of Endocrinology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, Lisboa, Portugal

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Inês Mendes Department of Endocrinology and Nutrition, Hospital do Divino Espírito Santo de Ponta Delgada, Ponta Delgada, Portugal

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Rui César Department of Endocrinology and Nutrition, Hospital do Divino Espírito Santo de Ponta Delgada, Ponta Delgada, Portugal

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Introduction: Iodine is an essential micronutrient and its deficiency can severely impact children’s development. In 2012, the Thyroid Study Group of the Portuguese Society of Endocrinology, Diabetes and Metabolism discovered that the median urinary iodine concentration (mUIC) level in schoolchildren of São Miguel was far too low at 70.9 μg/L. In response, the government implemented a salt iodization program to help normalize levels. This investigation evaluated the efficacy of such an approach. Methods: Urinary iodine concentration (UIC) was evaluated in 362 schoolchildren from São Miguel using the fast colorimetric method. Results: mUIC was 106.7 μg/L, significantly higher than that observed in 2012 (p < 0.001). Over half (55.5%) of the schoolchildren had a UIC >100 μg/L versus 23.0% in 2012 (p < 0.001). 9.4% of schoolchildren had a UIC <50 μg/L, significantly lower than the 30.6% reported in 2012 (p < 0.001). Discussion/Conclusion: Five years after the implementation of the government salt iodization program, the mUIC increased from 70.9 to 106.7 μg/L. This study confirms the efficacy of the adopted measures in schoolchildren population.

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