Thyroid laboratory

Our research team pursues different lines of research that are interconnected with the clinics of the Erasmus MC Academic for Thyroid Diseases.
Thyroid hormone is essential for development and metabolism. At the cellular level, thyroid hormone bioactivity is governed by plasma membrane transporters, deiodinating enzymes and nuclear receptors. Our group has identified several disorders that result from mutations in either of those key players in local thyroid hormone signaling. Employing established and novel technologies, we investigate normal and abnormal thyroid hormone signaling using different models, including patient-derived induced pluripotent stem cells

Thyroid hormone transport

Our group discovered that mutations in the thyroid hormone transporter MCT8 give rise to a severe disease with intellectual and motor disability and abnormal thyroid function tests in the blood. After preclinical development, we coordinated an international trial that showed beneficial effects in such patients who were treated with the thyroid hormone analog Triac. A second international trial is underway. Patient-derived induced pluripotent stem cells are employed to model this disease.

Thyroid hormone receptor

We and others discovered a novel disease due to mutations in the thyroid hormone receptor alpha, which is associated with a variable phenotype of intellectual and motor disability, delayed growth and abnormal thyroid hormone concentrations. Our group focuses on clinical phenotyping of patients with thyroid hormone resistance and on unravelling the molecular mechanisms behind the disease.

Thyroid and pregnancy

Thyroid hormone is essential for a normal development of virtually all tissues, especially the brain. As a consequence, untreated overt maternal hypothyroidism during pregnancy is associated with an adverse risk of pregnancy and fetal outcomes. In recent years our studies on the consequences of mild changes in thyroid function for clinical outcome, as well as the work on re-defining the reference range for thyroid function have altered clinical practice and international guidelines. Current research focuses on a better understanding of gestational physiology, regulation of thyroid hormone transport across the placenta, the consequences of endocrine disruptors on the thyroid system during pregnancy and improving treatment of patients with thyroid disease during pregnancy. This line of research is closely embedded in the Generation R study, a population-based pregnancy cohort. 

Optimal thyroid function and clinical outcome 

Thyroid hormone plays a crucial role in maintenance of tissue function. Altered thyroid function is associated with an increased prevalence of cardiovascular, neurological and other diseases of older age. In addition, a major part of patients with treated thyroid disease continue to have complaints of (tissue-specific) hypothyroidism. Current research focuses on the optimal timing and threshold for treatment of thyroid disease, as well unravelling the genetic and environmental determinants of the thyroid setpoint. This line of research is closely embedded in the Rotterdam Study (ERGO), a population-based cohort in aging individuals.

• New thyroid hormone transporters: We aim to identify the new thyroid hormone transporters and their role in physiology
• Mechanisms underlying defective thyroid hormone transport: We employ patient-derived cells as ex vivo model to study the underlying mechanisms of disease (collaboration Dept of Molecular Psychiatry)
• International trial with Triac in MCT8 deficiency: Triac Trial II: We coordinate a multicentre international clinical trial in whom young children are treated with the thyroid hormone analog Triac and investigate the effects on neurocognitive outcomes
• New thyroid hormone metabolism pathway: We investigate the functional role of AADAT as a new key player in thyroid hormone metabolism
• Thyroid hormone action in health and disease: We investigate the molecular regulation of thyroid hormone receptors and study the functional consequences of patient-derived mutations in thyroid hormone receptor alpha.
• Unravelling the mechanisms and regulation of transport of thyroid hormone across the placenta: We aim to identify the relevant thyroid hormone transporters in placenta, and study their role in an ex-vivo placenta perfusion model using specific inhibitors 
• Unravelling the role of non-classical thyroid hormone metabolites in (patho)fysiology: We have recently developed (in close collaboration with the Dept of Clinical Chemistry) a novel method to measure a full profile of thyroid hormone metabolites in a single run. Current studies focus on the role of these metabolites in health and disease.
• Unravelling the mechanisms of endocrine disruption on the thyroid system during pregnancy, and its consequences: We aim to study the consequences of several endocrine disruptors on thyroid hormone action as well as pregnancy outcome.

• Friesema, ECH, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ. Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 2003; 278: 40128-40135.
• Friesema ECH, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MHA, Kuiper GGJM, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ. Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor. Lancet 2004; 364: 1435-1437.
• Van Mullem A, van Heerebeek R, Chrysis D, Visser E, Medici M, Andrikoula M, Tsatsoulis A, Peeters R, Visser TJ. Clinical phenotype and mutant TRa1. N Engl J Med 2012; 366: 1451-1453.
• Strømme P, Groeneweg S, Lima de Souza EC, Zevenbergen C, Torgersbråten A, Holmgren A, Gurcan E, Meima ME, Peeters RP, Visser WE, Høneren Johansson L, Babovic A, Zetterberg H, Heuer H10, Frengen E, Misceo D, Visser TJ. Mutated Thyroid Hormone Transporter OATP1C1 Associates with Severe Brain Hypometabolism and Juvenile Neurodegeneration. Thyroid. 2018 Nov;28(11):1406-1415.
• Groeneweg S, Peeters RP, Moran C, Stoupa A, Auriol F, Tonduti D, Dica A, Paone L, Rozenkova K, Malikova J, Van der Walt A, De Coo IF, McGowan A, Lyons G, Aarsen FK, Barca D, Van Beynum IM, Van der Knoop MM, Jansen J, Manshande M, Lunsing RJ, Nowak S, Den Uil C, Zillikens MC, VIssesr FE, Vrijmoeth P, De Wit MCY, Wolf NI, Zandstra A, Ambegaonkar G, Singh Y, De Rijke Y, Medici M, Bertini ES, Depoorter S, Lebl J, Cappa M, De MEirleir L, Krude H, Craio D, Zibordi F, Oliver Petit I, Polak M, Chatterjee K, Visser TJ, Visser WE. Effectiveness and safety of Triac in children and adults with MCT8 deficiency: an international, multicentre, single group, open-label, phase 2 trial. Lancet Diabetes Endocrinol 2019 (accepted) 
• Chaker L, Bianco AC, Jonklaas J, Peeters RP. Hypothyroidism.
  Lancet. 2017 Sep 23;390(10101):1550-1562. doi: 10.1016/S0140-6736(17)30703-1. 
• Chaker L, Cappola AR, Mooijaart SP, Peeters RP. Clinical aspects of thyroid function during ageing. Lancet Diabetes Endocrinol. 2018 Sep;6(9):733-742.
• Chaker L, van den Berg ME, Niemeijer MN, Franco OH, Dehghan A, Hofman A, Rijnbeek PR, Deckers JW, Eijgelsheim M, Stricker BH, Peeters RP. Thyroid Function and Sudden Cardiac Death: A Prospective Population-Based Cohort Study. Circulation. 2016 Sep 6;134(10):713-22.
• Korevaar TIM, Medici M, Visser TJ, Peeters RP. Thyroid disease in pregnancy: new insights in diagnosis and clinical management. Nat Rev Endocrinol. 2017 Oct;13(10):610-622.
• Korevaar TI, Muetzel R, Medici M, Chaker L, Jaddoe VW, de Rijke YB, Steegers EA, Visser TJ, White T, Tiemeier H, Peeters RP. Association of maternal thyroid function during early pregnancy with offspring IQ and brain morphology in childhood: a population-based prospective cohort study. Lancet Diabetes Endocrinol. 2016 Jan;4(1):35-43.
• Teumer A, Chaker L, Groeneweg S, Li Y, Di Munno C, Barbieri C, Schultheiss UT, Traglia M, Ahluwalia TS, Akiyama M, Appel EVR, Arking DE, Arnold A, Astrup A, Beekman M, Beilby JP, Bekaert S, Boerwinkle E, Brown SJ, De Buyzere M, Campbell PJ, Ceresini G, Cerqueira C, Cucca F, Deary IJ, Deelen J, Eckardt KU, Ekici AB, Eriksson JG, Ferrrucci L, Fiers T, Fiorillo E, Ford I, Fox CS, Fuchsberger C, Galesloot TE, Gieger C, Gögele M, De Grandi A, Grarup N, Greiser KH, Haljas K, Hansen T, Harris SE, van Heemst D, den Heijer M, Hicks AA, den Hollander W, Homuth G, Hui J, Ikram MA, Ittermann T, Jensen RA, Jing J, Jukema JW, Kajantie E, Kamatani Y, Kasbohm E, Kaufman JM, Kiemeney LA, Kloppenburg M, Kronenberg F, Kubo M, Lahti J, Lapauw B, Li S, Liewald DCM; Lifelines Cohort Study, Lim EM, Linneberg A, Marina M, Mascalzoni D, Matsuda K, Medenwald D, Meisinger C, Meulenbelt I, De Meyer T, Meyer Zu Schwabedissen HE, Mikolajczyk R, Moed M, Netea-Maier RT, Nolte IM, Okada Y, Pala M, Pattaro C, Pedersen O, Petersmann A, Porcu E, Postmus I, Pramstaller PP, Psaty BM, Ramos YFM, Rawal R, Redmond P, Richards JB, Rietzschel ER, Rivadeneira F, Roef G, Rotter JI, Sala CF, Schlessinger D, Selvin E, Slagboom PE, Soranzo N, Sørensen TIA, Spector TD, Starr JM, Stott DJ, Taes Y, Taliun D, Tanaka T, Thuesen B, Tiller D, Toniolo D, Uitterlinden AG, Visser WE, Walsh JP, Wilson SG, Wolffenbuttel BHR, Yang Q, Zheng HF, Cappola A, Peeters RP, Naitza S, Völzke H, Sanna S, Köttgen A, Visser TJ, Medici M. Genome-wide analyses identify a role for SLC17A4 and AADAT in thyroid hormone regulation. Nat Commun. 2018 Oct 26;9(1):4455.
• Medici M, Visser WE, Visser TJ, Peeters RP. Genetic determination of the hypothalamic-pituitary-thyroid axis: where do we stand? Endocr Rev. 2015 Apr;36(2):214-44.

Collaboration within Erasmus MC

• Department of Clinical Chemistry
• Department of Molecular Psychiatry
• Dept of Epidemiology
• Dept of Child Psychiatry
• Dept of Pharmacology
• Dept Of Obstertics and Gynecology
• Dept of Neurology

Collaboration outside of Erasmus MC

• The Thyroidomics Consortium
• The consortium on Thyroid and Pregnancy
• The Thyroid Studies Collaboration

• Eurostars (Horizon2020)
• Sherman Foundation
• Erasmus MC fellowship
• NWO Replicatie Grant
• Erasmus MC MRACE PhD Grant 2016
• Horizon 2020-SC1-BHC-2018-2020
• ZonMW VIDI subsidie

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  R.P. (Robin) Peeters, MD

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  W.E. (Edward) Visser, MD