Search Results

You are looking at 1 - 10 of 10 items for

  • Author: A S Paul van Trotsenburg x
Clear All Modify Search
Christiaan F. Mooij Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Christiaan F. Mooij in
Google Scholar
PubMed
Close
,
Nitash Zwaveling-Soonawala Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
, and
A.S. Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Close
Open access
Annabel S. Zaat Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Annabel S. Zaat in
Google Scholar
PubMed
Close
,
Joep P.M. Derikx Department of Pediatric Surgery, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam and Vrije Universiteit, Amsterdam, The Netherlands

Search for other papers by Joep P.M. Derikx in
Google Scholar
PubMed
Close
,
Nitash Zwaveling-Soonawala Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Close
,
A.S. Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Close
, and
Christiaan F. Mooij Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Christiaan F. Mooij in
Google Scholar
PubMed
Close

Background: Graves’ disease (GD) is the most common cause of hyperthyroidism. In children, the overall relapse frequency after treatment with antithyroid drugs is high. Therefore, many pediatric GD patients eventually require thyroidectomy as definitive treatment. However, the postoperative complications of thyroidectomy in pediatric GD patients are poorly reported. Objective: To identify the frequency of short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients. Methods: A systematic review of the literature (PubMed and Embase) was performed to identify studies reporting short- and long-term postoperative morbidities after thyroidectomy in pediatric GD patients according to the PRISMA guidelines. Results: Twenty-two mainly retrospective cohort studies were included in this review evaluating short- and long-term morbidities in 1,424 children and adolescents. The frequency of transient hypocalcemia was 22.2% (269/1,210), with a range of 5.0–50.0%. The frequency of permanent hypocalcemia was 2.5% (36/1,424), with a range of 0–20.0%. Two studies reported high frequencies of permanent hypocalcemia, 20.0 (6/30) and 17.4% (9/52), respectively. The 20% frequency could be explained by low-volume surgeons in poorly controlled GD patients. Only 21 cases of permanent hypocalcemia were reported in the 1,342 patients included in the other 20 studies (1.6%). Transient and permanent recurrent laryngeal nerve injury were reported less frequently, with frequencies between 0–20.0 and 0–7.1%, respectively. Infection, hemorrhage/hematoma, and keloid development were only rarely reported as postoperative complications. Conclusion: The results of this systematic review suggest that thyroidectomy is a safe treatment option for pediatric GD patients. The minority of patients will experience transient and benign morbidities, with hypocalcemia being the most common transient postoperative morbidity. Permanent postoperative morbidities are relatively rare.

Open access
Christiaan F Mooij Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Christiaan F Mooij in
Google Scholar
PubMed
Close
,
Timothy D Cheetham Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
Department of Pediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK

Search for other papers by Timothy D Cheetham in
Google Scholar
PubMed
Close
,
Frederik A Verburg Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands

Search for other papers by Frederik A Verburg in
Google Scholar
PubMed
Close
,
Anja Eckstein Department of Ophthalmology, University Duisburg Essen, Essen, Germany

Search for other papers by Anja Eckstein in
Google Scholar
PubMed
Close
,
Simon H Pearce Translational and Clinical Research Institute, Newcastle University, Newcastle-upon-Tyne, UK
Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK

Search for other papers by Simon H Pearce in
Google Scholar
PubMed
Close
,
Juliane Léger Department of Pediatric Endocrinology and Diabetes, Reference Center for Rare Endocrine Growth and Development Diseases, Endo-ERN HCP, Assistance Publique-Hôpitaux de Paris, Robert Debré University Hospital, University of Paris, NeuroDiderot Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, France

Search for other papers by Juliane Léger in
Google Scholar
PubMed
Close
, and
A S Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Close

Hyperthyroidism caused by Graves’ disease (GD) is a relatively rare disease in children. Treatment options are the same as in adults – antithyroid drugs (ATD), radioactive iodine (RAI) or thyroid surgery, but the risks and benefits of each modality are different. The European Thyroid Association guideline provides new recommendations for the management of pediatric GD with and without orbitopathy. Clinicians should be alert that GD may present with behavioral changes or declining academic performance in children. Measurement of serum TSH receptor antibodies is recommended for all pediatric patients with hyperthyroidism. Management recommendations include the first-line use of a prolonged course of methimazole/carbimazole ATD treatment (3 years or more), a preference for dose titration instead of block and replace ATD, and to avoid propylthiouracil use. Where definitive treatment is required either total thyroidectomy or RAI is recommended, aiming for complete thyroid ablation with a personalized RAI activity. We recommend avoiding RAI in children under 10 years of age but favor surgery in patients with large goiter. Pediatric endocrinologists should be involved in all cases.

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

Search for other papers by Sarah L. Lutterman in
Google Scholar
PubMed
Close
,
Nitash Zwaveling-Soonawala Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Close
,
Hein J. Verberne Department of Radiology and Nuclear Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Hein J. Verberne in
Google Scholar
PubMed
Close
,
Frederik A. Verburg Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

Search for other papers by Frederik A. Verburg in
Google Scholar
PubMed
Close
,
A.S. Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Close
, and
Christiaan F. Mooij Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Christiaan F. Mooij in
Google Scholar
PubMed
Close

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.

Open access
Anita Boelen Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close
,
Nitash Zwaveling-Soonawala Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Close
,
Annemieke C Heijboer Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands
Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands
Endocrine Laboratory, Department of Laboratory Medicine, Amsterdam UMC, location Vrije Universiteit Amsterdam, Amsterdam, The Netherlands

Search for other papers by Annemieke C Heijboer in
Google Scholar
PubMed
Close
, and
A S Paul van Trotsenburg Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, The Netherlands
Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Close

Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2–3 years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage.

Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterized by low TH concentrations, while TSH is normal, low or slightly elevated.

Most newborn screening (NBS) programs for CH are primarily TSH based and thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4–TSH–thyroxine-binding globulin (TBG) NBS algorithm for CH, which enables the detection of primary and central CH.

Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild and that early detection of central CH by NBS probably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Open access
Yalan Hu Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands

Search for other papers by Yalan Hu in
Google Scholar
PubMed
Close
,
Kim Falize Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Kim Falize in
Google Scholar
PubMed
Close
,
A S Paul van Trotsenburg Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Department of Pediatric Endocrinology, Emma Children’s Hospital, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Close
,
Raoul Hennekam Department of Pediatrics, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Raoul Hennekam in
Google Scholar
PubMed
Close
,
Eric Fliers Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
,
Eveline Bruinstroop Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands

Search for other papers by Eveline Bruinstroop in
Google Scholar
PubMed
Close
, and
Anita Boelen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close

Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is a WD40 repeat-containing protein and part of the corepressor complex SMRT/NCoR that binds to the thyroid hormone receptor (TR). We recently described a mutation in TBL1XR1 in patients with Pierpont syndrome. A mouse model bearing this Tbl1xr1 mutation (Tbl1xr1Y446C/Y446C ) displays several aspects of the Pierpont phenotype. Although serum thyroid hormone (TH) concentrations were unremarkable in these mice, tissue TH action might be affected due to the role of TBL1XR1 in the SMRT/NCoR corepressor complex. The aim of the present study was to evaluate tissue TH metabolism and action in a variety of tissues of Tbl1xr1Y446C/Y446C mice. We studied the expression of genes involved in TH metabolism and action in tissues of naïve Tbl1xr1Y446C/Y446C mice and wild type (WT) mice. In addition, we measured deiodinase activity in liver (Dio1 and Dio3), kidney (Dio1 and Dio3) and BAT (Dio2). No striking differences were observed in the liver, hypothalamus, muscle and BAT between Tbl1xr1Y446C/Y446C and WT mice. Pituitary TRα1 mRNA expression was lower in Tbl1xr1Y446C/Y446C mice compared to WT, while the mRNA expression of Tshβ and the positively T3-regulated gene Nmb were significantly increased in mutant mice. Interestingly, Mct8 expression was markedly higher in WAT and kidney of mutants, resulting in (subtle) changes in T3-regulated gene expression in both WAT and kidney. In conclusion, mice harboring a mutation in TBL1XR1 display minor changes in cellular TH metabolism and action. TH transport via MCT8 might be affected as the expression is increased in WAT and kidney. The mechanisms involved need to be clarified.

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

Search for other papers by Kevin Stroek in
Google Scholar
PubMed
Close
,
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

Search for other papers by Annemieke C. Heijboer in
Google Scholar
PubMed
Close
,
Marja van Veen-Sijne Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Marja van Veen-Sijne in
Google Scholar
PubMed
Close
,
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

Search for other papers by Annet M. Bosch in
Google Scholar
PubMed
Close
,
Catharina P.B. van der Ploeg Department of Child Health, Netherlands Organization for Applied Scientific Research TNO, Leiden, The Netherlands

Search for other papers by Catharina P.B. van der Ploeg in
Google Scholar
PubMed
Close
,
Nitash Zwaveling-Soonawala Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Close
,
Robert de Jonge Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit & University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Robert de Jonge in
Google Scholar
PubMed
Close
,
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

Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Close
, and
Anita Boelen Endocrine Laboratory, Department of Clinical Chemistry, Amsterdam Gastroenterology, Endocrinology & Metabolism, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close

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.

Open access
Luca Persani Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

Search for other papers by Luca Persani in
Google Scholar
PubMed
Close
,
Georg Brabant Experimental and Clinical Endocrinology Medical Clinic I – University of Lübeck, Lübeck, Germany

Search for other papers by Georg Brabant in
Google Scholar
PubMed
Close
,
Mehul Dattani Genetics and Genomic Medicine Programme, UCL GOS Institute of Child Health, London, United Kingdom

Search for other papers by Mehul Dattani in
Google Scholar
PubMed
Close
,
Marco Bonomi Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

Search for other papers by Marco Bonomi in
Google Scholar
PubMed
Close
,
Ulla Feldt-Rasmussen Department of Medical Endocrinology and Metabolism, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark

Search for other papers by Ulla Feldt-Rasmussen in
Google Scholar
PubMed
Close
,
Eric Fliers Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by Eric Fliers in
Google Scholar
PubMed
Close
,
Annette Gruters Department for Pediatric Endocrinology and Diabetes, Charité University Medicine, Berlin, Germany
University Hospital Heidelberg, Heidelberg, Germany

Search for other papers by Annette Gruters in
Google Scholar
PubMed
Close
,
Dominique Maiter Department of Endocrinology and Nutrition, UCL Cliniques Saint-Luc, Brussels, Belgium

Search for other papers by Dominique Maiter in
Google Scholar
PubMed
Close
,
Nadia Schoenmakers University of Cambridge Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, Addenbrooke’s Hospital and National Institute for Health Research Cambridge Biomedical Research Centre, Addenbrooke’s Hospital, Cambridge, United Kingdom

Search for other papers by Nadia Schoenmakers in
Google Scholar
PubMed
Close
, and
A.S. Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Close

Objectives: Central hypothyroidism (CeH) is a rare form of hypothyroidism characterized by insufficient thyroid stimulation due to disturbed pituitary and/or hypothalamic functioning. Due to its origin and the whole clinical context, CeH represents a challenging condition in clinical practice as it is characterized by suboptimal accuracy of clinical and biochemical parameters for diagnosis and management. Since no expert consensus or guidance for this condition is currently available, a task force of experts received the commitment from the European Thyroid Association (ETA) to prepare this document based on the principles of clinical evidence. Study Design: The task force started to work in February 2017 and after a careful selection of appropriate references (cohort studies, case reports, expert opinions), a preliminary presentation and live discussion during the 2017 ETA meeting, and several revision rounds, has prepared a list of recommendations to support the diagnosis and management of patients with CeH. Results: Due to the particular challenges of this rare condition in the different ages, the target users of this guidance are pediatric and adult endocrinologists. Experts agreed on the need to recognize and treat overt CeH at all ages, whereas treatment of milder forms may be dispensable in the elderly (> 75 years). Conclusions: Despite the lack of randomized controlled clinical trials, the experts provide 34 recommendations supported by variable levels of strength that should improve the quality of life of the affected patients and reduce the metabolic and hormonal consequences of inadequate management.

Free access
Heleen I Jansen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

Search for other papers by Heleen I Jansen in
Google Scholar
PubMed
Close
,
Marije van Haeringen Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands

Search for other papers by Marije van Haeringen in
Google Scholar
PubMed
Close
,
Marelle J Bouva Reference Laboratory Neonatal Screening, Center for Health protection, National Institute for Public Health and the Environment, Bilthoven, The Netherlands

Search for other papers by Marelle J Bouva in
Google Scholar
PubMed
Close
,
Wendy P J den Elzen Department of Laboratory Medicine, Laboratory Specialized Diagnostics & Research, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Public Health, Amsterdam, The Netherlands

Search for other papers by Wendy P J den Elzen in
Google Scholar
PubMed
Close
,
Eveline Bruinstroop Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Endocrinology and Metabolism, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

Search for other papers by Eveline Bruinstroop in
Google Scholar
PubMed
Close
,
Catharina P B van der Ploeg TNO - Child Health, Sylviusweg, Leiden, The Netherlands

Search for other papers by Catharina P B van der Ploeg in
Google Scholar
PubMed
Close
,
A S Paul van Trotsenburg Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Close
,
Nitash Zwaveling-Soonawala Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Paediatric Endocrinology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Close
,
Annemieke C Heijboer Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location Vrije Universiteit Amsterdam, Boelelaan, Amsterdam, The Netherlands
Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

Search for other papers by Annemieke C Heijboer in
Google Scholar
PubMed
Close
,
Annet M Bosch Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Pediatrics, Division of Metabolic Disorders, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

Search for other papers by Annet M Bosch in
Google Scholar
PubMed
Close
,
Robert de Jonge Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Amsterdam UMC, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands
Department of Laboratory Medicine, Amsterdam UMC, University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands

Search for other papers by Robert de Jonge in
Google Scholar
PubMed
Close
,
Mark Hoogendoorn Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands

Search for other papers by Mark Hoogendoorn in
Google Scholar
PubMed
Close
, and
Anita Boelen Amsterdam Gastroenterology, Endocrinology and Metabolism, Amsterdam, The Netherlands
Department of Laboratory Medicine, Endocrine Laboratory, Amsterdam UMC location University of Amsterdam, Meibergdreef, Amsterdam, The Netherlands
Amsterdam Reproduction & Development Research Institute, Amsterdam, The Netherlands

Search for other papers by Anita Boelen in
Google Scholar
PubMed
Close

Objective

Congenital hypothyroidism (CH) is an inborn thyroid hormone (TH) deficiency mostly caused by thyroidal (primary CH) or hypothalamic/pituitary (central CH) disturbances. Most CH newborn screening (NBS) programs are thyroid-stimulating-hormone (TSH) based, thereby only detecting primary CH. The Dutch NBS is based on measuring total thyroxine (T4) from dried blood spots, aiming to detect primary and central CH at the cost of more false-positive referrals (FPRs) (positive predictive value (PPV) of 21% in 2007–2017). An artificial PPV of 26% was yielded when using a machine learning-based model on the adjusted dataset described based on the Dutch CH NBS. Recently, amino acids (AAs) and acylcarnitines (ACs) have been shown to be associated with TH concentration. We therefore aimed to investigate whether AAs and ACs measured during NBS can contribute to better performance of the CH screening in the Netherlands by using a revised machine learning-based model.

Methods

Dutch NBS data between 2007 and 2017 (CH screening results, AAs and ACs) from 1079 FPRs, 515 newborns with primary (431) and central CH (84) and data from 1842 healthy controls were used. A random forest model including these data was developed.

Results

The random forest model with an artificial sensitivity of 100% yielded a PPV of 48% and AUROC of 0.99. Besides T4 and TSH, tyrosine, and succinylacetone were the main parameters contributing to the model’s performance.

Conclusions

The PPV improved significantly (26–48%) by adding several AAs and ACs to our machine learning-based model, suggesting that adding these parameters benefits the current algorithm.

Open access
Chantal A Lebbink Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, The Netherlands

Search for other papers by Chantal A Lebbink in
Google Scholar
PubMed
Close
,
Thera P Links Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Search for other papers by Thera P Links in
Google Scholar
PubMed
Close
,
Agnieszka Czarniecka The Oncologic and Reconstructive Surgery Clinic, M. Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Gliwice, Poland

Search for other papers by Agnieszka Czarniecka in
Google Scholar
PubMed
Close
,
Renuka P Dias Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, United Kingdom

Search for other papers by Renuka P Dias in
Google Scholar
PubMed
Close
,
Rossella Elisei Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

Search for other papers by Rossella Elisei in
Google Scholar
PubMed
Close
,
Louise Izatt Department of Clinical Genetics, Guy's and St Thomas’ NHS Foundation Trust, London, United Kingdom

Search for other papers by Louise Izatt in
Google Scholar
PubMed
Close
,
Heiko Krude Institute of Experimental Pediatric Endocrinology, Charité - Universitätsmedizin, Berlin, Germany

Search for other papers by Heiko Krude in
Google Scholar
PubMed
Close
,
Kerstin Lorenz Department of Visceral, Vascular and Endocrine Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany

Search for other papers by Kerstin Lorenz in
Google Scholar
PubMed
Close
,
Markus Luster Department of Nuclear Medicine, University Hospital Marburg, Marburg, Germany

Search for other papers by Markus Luster in
Google Scholar
PubMed
Close
,
Kate Newbold Thyroid Therapy Unit, The Royal Marsden NHS Foundation Trust, London, United Kingdom

Search for other papers by Kate Newbold in
Google Scholar
PubMed
Close
,
Arnoldo Piccardo Department of Nuclear Medicine, EO Ospedali Galliera, Genoa, Italy

Search for other papers by Arnoldo Piccardo in
Google Scholar
PubMed
Close
,
Manuel Sobrinho-Simões University Hospital of São João, Medical Faculty and Institute of Molecular Pathology and Immunology, University of Porto, Porto, Portugal

Search for other papers by Manuel Sobrinho-Simões in
Google Scholar
PubMed
Close
,
Toru Takano Thyroid Center, Rinku General Medical Center, Osaka, Japan

Search for other papers by Toru Takano in
Google Scholar
PubMed
Close
,
A S Paul van Trotsenburg Department of Pediatric Endocrinology, Emma Children's Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands

Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Close
,
Frederik A Verburg Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

Search for other papers by Frederik A Verburg in
Google Scholar
PubMed
Close
, and
Hanneke M van Santen Wilhelmina Children’s Hospital and Princess Máxima Center, Utrecht, The Netherlands

Search for other papers by Hanneke M van Santen in
Google Scholar
PubMed
Close

At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.

Open access