Searchable abstracts of presentations at key conferences in endocrinology

ea0084ps1-04-34 | Thyroid Hormone Transporters and Development | ETA2022

The dawning of deiodinases: an outer ring deiodinase activity in the social amoeba dictyostelium discoideum with high affinity for reverse t3

Meima Marcel , Schaap Pauline , Edward Visser W.

Background: Conservation of genes involved in TH transport, metabolism and action can reveal clues about the origins of TH signaling. A deiodinase homologue (DdDio) was previously identified in the social amoeba Dictyostelium discoideum (Singh, 2014). Dictyostelium cells live as single cell amoebae in soil where they feed on bacteria. However, upon starvation a developmental program is initiated that results in the formation of a multicellular fruiti...

ea0084ps1-04-31 | Thyroid Hormone Transporters and Development | ETA2022

The role of type 3 deiodinase in a human model for early brain development

Lopez Marti Anna , Gunhanlar Nilhan , Meima Marcel , Edward Visser W.

Background: Disrupted thyroid hormone (TH) homeostasis has devastating effects on human neurodevelopment. THs are critical signaling molecules in neurodevelopment, acting on differentiation of neural cells, migration, synaptogenesis and myelination, with deiodinases governing intracellular TH concentrations in a spatiotemporal manner. It is remarkable that fetal neural cells, while being key target cells of TH, exhibit strong activity of the TH inactivating enzyme DIO3. Curren...

ea0084op-02-11 | Oral Session 2: Pregnancy | ETA2022

Association of thyroid function and tpoab positivity with the risk of postpartum depression: A population-based cohort study, systematic review, and meta-analysis

Sileo Federica , Osinga Joris , Edward Visser W. , Derakhshan Arash , Citterio Valeria , Persani Luca , Korevaar Tim

Background: Postpartum depression (PPD) is a common mental health disorder with a major impact on maternal health and wellbeing and offspring development. Thyroperoxidase antibody (TPOAb) positivity is a major risk factor for postpartum thyroiditis and via this link, it is hypothesized that TPOAb positivity is a risk factor for PPD. However, the results of currently available single center studies are heterogeneous and affected by major study limitations.<p class="abstext"...

ea0084ps1-04-36 | Thyroid Hormone Transporters and Development | ETA2022

Thyroid hormone signaling in a human cellular model for early brain development

Gunhanlar Nilhan , Tellez Garcia Juan , Lopez Marti Anna , Shokrollahi Faezeh , Meima Marcel , Edward Visser W.

Background and Objective: Disrupted thyroid hormone (TH) signaling has devastating effects on human neurodevelopment. The molecular mechanisms underlying TH regulation and action are largely based on animal models. However, animal models are limited in revealing some of the most fundamental aspects of neurodevelopment that are unique to humans. We employed human induced pluripotent stem cell (iPSC) technology to study the effects of T3 on neurodevelopmental processes in a huma...

ea0084ps2-09-84 | Thyroid Hormone ACTION | ETA2022

Molecular mechanisms underlying action of triac in resistance to thyroid hormone BETA (RTHβ)

Liao Wenjun , van Geest Ferdy , Marelli Federica , Campi Irene , Moran Carla , Lyons Greta , Agostini Maura , Peeters Robin , Chatterjee Krishna , Persani Luca , Meima Marcel , Edward Visser W.

Background: Resistance to thyroid hormone (TH) beta (RTHβ), caused by mutations in THRB, is characterized by elevated serum (F)T4 accompanied by non-suppressed TSH concentrations. Disease features arise from variable resistance to TH action in tissues expressing Thyroid Hormone Receptor (TR) β (hypothalamus, pituitary, liver) and from thyrotoxic effects in tissues expressing TRα (heart, bone, brain). In symptomatic patients, treatment mainly involves be...

ea0084op-08-40 | Oral Session 8: Basic 2 | ETA2022

Disrupted trans-placental thyroid hormone transport in a human model for MCT8 deficiency

Chen Zhongli , Leeuwenburgh Selmar , Zijderveld Wouter , Broekhuizen Broekhuizen M. , Tan Lunbo , Neuman Neuman R.I. , Jongejan Rutchanna , de Rijke Yolanda , K. Reiss Irwin , H. J. Danser Danser A. , Peeters Robin , Meima Marcel , Edward Visser W.

Objectives: During prenatal neurodevelopment, maternal-to-fetal thyroxine (T4) transfer is critical, particularly during the first half of pregnancy when the fetal thyroid gland is immature. Transcellular transport of thyroid hormones (TH) is facilitated by TH transporters. Monocarboxylate transporter 8 (MCT8) is a specific TH transporter that is crucial for transport of TH with a prominent expression at the blood-brain barrier. MCT8 deficiency is a rare disorder consisting of...

ea0084op-11-58 | Oral Session 11: Young Investigators / Basic | ETA2022

Integrated genomic, phenomic, functional and structural mapping of variants in thyroid hormone transporter MCT8

Groeneweg Stefan , Van Geest Ferdy , martin mariano , Dias Mafalda , Frazer Jonathan , Sterenborg Rosalie , de rooij linda , dolcetta-capuzzo anna , teumer alexander , Meima Marcel , Medici Marco , pablo nicola juan , marks debora , Edward Visser W.

Background: MCT8 deficiency is caused by loss-of-function (LoF) mutations in thyroid hormone (TH) transporter MCT8. Patients have developmental delay and abnormal thyroid function tests (TFTs). The large phenotypic variability is not understood. Moreover, phenotypes arising from LoF mutations could be employed to enhance understanding of physiology in the general population. Also, computational disease variant classifiers have poor predictive power to ascertain impact of MCT8 ...

ea0084op-01-04 | Oral Session 1: Topic Highlights | ETA2022

Selenoprotein deficiency disorder predisposes to aortic aneurysm formation

Schoenmakers Erik , Marelli Federica , Jorgensen Helle , Edward Visser W. , Moran Carla , Groeneweg Stefan , Avalos Carolina , Figg Nichola , Finigan Alison , Wali Neha , Agostini Maura , Wardle-Jones Hannah , Lyons Greta , Rusk Rosemary , Gopalan Deepa , Johannes Visser Jacob , Goddard Martin , Nashef Samer , Heijmen Robin , Clift Paul , Sinha Sanjay , Busch-Nentwich Elisabeth , Ramirez-Solis Ramiro , Persani Luca , Bennett Martin , Chatterjee Krishna

Objectives: Mutations in SECISBP2 cause deficiency of selenoproteins, resulting in a multisystem disorder with abnormal circulating thyroid hormone and selenium levels and features due to lack of specific selenoproteins or loss of antioxidant selenoenzymes. Having observed early-onset, aneurysmal thoracic aortic dilatation in four patients with this disorder, we studied zebrafish and murine Secisbp2 mutant models to determine whether the aortic phenotype and selenopro...

ea0056p677 | Paediatric endocrinology | ECE2018

Awareness & participation in rare disease registries within the European reference network on rare endocrine conditions (Endo-ERN)

Ali Salma R , Bryce Jillian , Cools Martine , Korbonits Marta , Beun Johan G , Taruscio Domenica , Beuschlein Felix , Danne Thomas , Dattani Mehul , Dekkers Olaf , Linglart Agnes , Netchine Irene , Nordenstrom Anna , Patocs Attila , Persani Luca , Smyth Arlene , Sumnik Zdenek , Edward Visser W , Hiort Olaf , Pereira Alberto M , Faisal Ahmed S

Background: Registries are of key importance for a centre of expertise. Endo-ERN consists of 71 reference centres (RCs) that cover several groups of rare endocrine conditions within 8 themes ( It is unclear if awareness, participation and availability of registries is uniform for all conditions within Endo-ERN.Objective: To determine the extent of engagement in registries of Endo-ERN members.Methods: Endo-ERN RC le...

ea0084op-08-37 | Oral Session 8: Basic 2 | ETA2022

Resistance to thyroid hormone alpha: molecular, biochemical and physiological approach to diagnosis and therapy

Agostini Maura , Pietzner Maik , Marelli Federica , Prapa Matina , Moran Carla , Edward Visser W. , Brown Dave , Thomas Ellen , Schoenmakers Erik , Romartinez-Alonso Beatriz , Scheuplein Rabea , Tylki-Szymanska Anna , Lyons Greta , Watson Laura , Rajanayagam Odelia , Schwedhelm Edzard , F. Hartmann Michaela , Wudy Stefan , Probst Maiken , MacDonald Stephen , Thomas William , Arlt Wiebke , Volker Uwe , M. Main Katharina , Feldt-Rasmussen Ulla , T. Dattani Mehul , Koren Dahll Louise , Demir Korcan , Kara Cengiz , Kirbiyik Ozgur , Mammadova Jamala , Cayır Atilla , Yarali Oguzhan , Phan-Hug Franziska , Sakremath Rajesh , Mohamed Zainaba , Shinawi Marwan , Gill Harpreet , pacaud Daniele , Perrier Renee , Poke Gemma , Hunter Wendy , Douzgou Sofia , Wakeling Emma , Gardham Alice , Lim Derek , Shears Deborah , Freel Marie , Omladic Jasna , Tansek Mojca , Writzl Karin , Farooqi Sadaf , Kopp Peter , Schwabe John , Persani Luca , Chatterjee Krishna

Objectives: THRA mutations cause Resistance to Thyroid Hormone α (RTHα), an underdiagnosed disorder with hypothyroid features but near-normal thyroid function tests (TFTs). We developed a pathway, combining molecular analyses, new biomarkers and physiological measurements, to better diagnose and treat this disorder.Methods: Structural and functional analyses of THRA variants, discovered by next generation sequencing in specifi...