Search Results
You are looking at 1 - 10 of 11 items for
- Author: A.S. Paul van Trotsenburg x
Search for other papers by Christiaan F. Mooij in
Google Scholar
PubMed
Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Search for other papers by Eric Fliers in
Google Scholar
PubMed
Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Search for other papers by Annabel S. Zaat in
Google Scholar
PubMed
Search for other papers by Joep P.M. Derikx in
Google Scholar
PubMed
Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Search for other papers by Christiaan F. Mooij in
Google Scholar
PubMed
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.
Search for other papers by Sarah L. Lutterman in
Google Scholar
PubMed
Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Search for other papers by Hein J. Verberne in
Google Scholar
PubMed
Search for other papers by Frederik A. Verburg in
Google Scholar
PubMed
Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Search for other papers by Christiaan F. Mooij in
Google Scholar
PubMed
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.
Search for other papers by Christiaan F Mooij in
Google Scholar
PubMed
Department of Pediatric Endocrinology, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
Search for other papers by Timothy D Cheetham in
Google Scholar
PubMed
Search for other papers by Frederik A Verburg in
Google Scholar
PubMed
Search for other papers by Anja Eckstein in
Google Scholar
PubMed
Endocrine Unit, Royal Victoria Infirmary, Newcastle-upon-Tyne, UK
Search for other papers by Simon H Pearce in
Google Scholar
PubMed
Search for other papers by Juliane Léger in
Google Scholar
PubMed
Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
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.
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
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
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
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
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.
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Search for other papers by Yalan Hu in
Google Scholar
PubMed
Search for other papers by Kim Falize in
Google Scholar
PubMed
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
Search for other papers by Raoul Hennekam in
Google Scholar
PubMed
Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Search for other papers by Eric Fliers in
Google Scholar
PubMed
Department of Endocrinology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Search for other papers by Eveline Bruinstroop in
Google Scholar
PubMed
Amsterdam Gastroenterology, Endocrinology & Metabolism (AGEM) Research Institute, Amsterdam UMC, Amsterdam, the Netherlands
Search for other papers by Anita Boelen in
Google Scholar
PubMed
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.
Search for other papers by Kevin Stroek in
Google Scholar
PubMed
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
Search for other papers by Marja van Veen-Sijne in
Google Scholar
PubMed
Search for other papers by Annet M. Bosch in
Google Scholar
PubMed
Search for other papers by Catharina P.B. van der Ploeg in
Google Scholar
PubMed
Search for other papers by Nitash Zwaveling-Soonawala in
Google Scholar
PubMed
Search for other papers by Robert de Jonge in
Google Scholar
PubMed
Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
Search for other papers by Anita Boelen in
Google Scholar
PubMed
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.
Search for other papers by Yalan Hu in
Google Scholar
PubMed
Search for other papers by Lorraine Soares De Oliveira in
Google Scholar
PubMed
Search for other papers by Kim Falize in
Google Scholar
PubMed
Search for other papers by A S Paul van Trotsenburg in
Google Scholar
PubMed
Search for other papers by Eric Fliers in
Google Scholar
PubMed
Search for other papers by Joseph E Kaserman in
Google Scholar
PubMed
Search for other papers by Andrew A Wilson in
Google Scholar
PubMed
Search for other papers by Anthony N Hollenberg in
Google Scholar
PubMed
Search for other papers by Eveline Bruinstroop in
Google Scholar
PubMed
Search for other papers by Anita Boelen in
Google Scholar
PubMed
Background:
Mutations in TBL1X, part of the NCoR1/SMRT corepressor complex, were identified in patients with hereditary X-linked central congenital hypothyroidism and associated hearing loss. The role of TBL1X in thyroid hormone (TH) action, however, is incompletely understood. The aim of the present study was to investigate the role of TBL1X on T3 regulated gene expression in two human liver cell models.
Methods:
A human hepatoma cell line (HepG2) wherein TBL1X was down regulated using siRNAs, and human-induced pluripotent stem cell-derived hepatocytes (iHeps) generated from individuals with a TBL1X N365Y mutation. Both cell types were treated with increasing concentrations of T3. The expression of T3 regulated genes was measured by qPCR.
Results:
KLF9, CPT1A and PCK1 mRNA expression was higher upon T3 stimulation in the HepG2 cells with decreased TBL1X expression compared to controls, while DIO1 mRNA expression was lower. Hemizygous TBL1X N365Y iHeps exhibited decreased expression of CPT1A, G6PC1, PCK1, FBP1 and ELOVL2 compared to cells with the heterozygous TBL1X N365Y, but KLF9 and HMGCS2 expression was unaltered.
Conclusion:
Downregulation of TBL1X in HepG2 cells and the TBL1X N365Y variant in iHeps have differential effects on T3 regulated gene expression. This suggests that TBL1X may play a gene context role in thyroid hormone TH action.
Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Search for other papers by Luca Persani in
Google Scholar
PubMed
Search for other papers by Georg Brabant in
Google Scholar
PubMed
Search for other papers by Mehul Dattani in
Google Scholar
PubMed
Division of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy
Search for other papers by Marco Bonomi in
Google Scholar
PubMed
Search for other papers by Ulla Feldt-Rasmussen in
Google Scholar
PubMed
Search for other papers by Eric Fliers in
Google Scholar
PubMed
University Hospital Heidelberg, Heidelberg, Germany
Search for other papers by Annette Gruters in
Google Scholar
PubMed
Search for other papers by Dominique Maiter in
Google Scholar
PubMed
Search for other papers by Nadia Schoenmakers in
Google Scholar
PubMed
Search for other papers by A.S. Paul van Trotsenburg in
Google Scholar
PubMed
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.
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
Department of Computer Science, Vrije Universiteit, Boelelaan, Amsterdam, The Netherlands
Search for other papers by Marije van Haeringen in
Google Scholar
PubMed
Search for other papers by Marelle J Bouva in
Google Scholar
PubMed
Amsterdam Public Health, Amsterdam, The Netherlands
Search for other papers by Wendy P J den Elzen in
Google Scholar
PubMed
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
Search for other papers by Catharina P B van der Ploeg in
Google Scholar
PubMed
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
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
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
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
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
Search for other papers by Mark Hoogendoorn in
Google Scholar
PubMed
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
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.
