Searchable abstracts of presentations at key conferences in endocrinology

ea0025pl7 | The British Thyroid Association Pitt-Rivers Lecture | SFEBES2011

An expanded view on resistance to thyroid hormone

Refetoff Samuel

At least six major steps are required for secreted thyroid hormone to exert its action on target tissues: thyroid hormone transport into cells, intracellular activation of the prohormone thyroxine, transfer of the hormone from the cytoplasm to the nucleus, intact thyroid hormone receptors and intact nuclear and cytosolic machinery required for the mediation of thyroid hormone action. Mutations interfering with three of these steps have been so far identified and are the subjec...

ea0025pl7biog | The British Thyroid Association Pitt-Rivers Lecture | SFEBES2011

British Thyroid Association Pitt-Rivers Lecture

Refetoff Samuel

Samuel Refetoff, University of Chicago, IL, USA. AbstractSamuel Refetoff is known for his discovery (1967) of resistance to thyroid hormone (Refetoff Syndrome) and elucidation of its genetic and molecular basis (1989/92).Devoted to the study of inherited thyroid disorders, his laboratory was first to identify mutations in: serum TH transport proteins [TBG (1989) and albumin (1994)]; the TSH rece...

ea0069p28 | Poster Presentations | SFENCC2020

A case of macroTSH masquerading as subclinical hypothyroidism

D'Arcy Robert , McDonnell Margaret , Spence Kirsty , Refetoff Samuel , Hunter Steven

Case history: A 47 year old male presented to his GP with non-specific symptoms of fatigue and weight gain. Thyroid function tests revealed elevated TSH (28.4 mU/l) with normal Free T4 (14.3 pmol/l). Anti-TPO antibodies were undetectable. A presumptive diagnosis of subclinical hypothyroidism was made and he was commenced on Levothyroxine which was titrated over 9 months to 150 mcg/d given a persistently elevated TSH. The patient was unable to tolerate this dose due to the deve...

ea0084op-13-66 | Oral Session 13: Basic 3 | ETA2022

Generation of human thyroid organoids from embryonic stem cells to rescue hypothyroidism

Romitti Mirian , Tourneur Adrien , Lasolle Helene , Detours Vincent , Singh Sumeet , Refetoff Samuel , Costagliola Sabine

Organoids are tiny, self-organized three-dimensional versions of an organ that are produced in vitro. Human organoids offer unique opportunities to model the development, physiology, and diseases of human tissues while complementing animal models and reducing the need for animal testing. In the thyroid field, there is a lack of a functional human in vitro thyroid model which allows to further explore various aspects related to thyroid development and disease....

ea0016p722 | Thyroid | ECE2008

Thyroid hormone receptor beta gene mutation (P453A) in a family producing resistance to thyroid hormone

Bayraktaroglu Taner , Noel Janet , Alagol Faruk , Colak Nese , Mukaddes Nahhit Motavalli , Refetoff Samuel

Background: Resistance to thyroid hormone (RTH) is a dominantly inherited syndrome characterized by decreased responsiveness of target tissues to thyroid hormone. Two members of a Turkish family, a mother and son, had thyroid function tests suggestive of resistance to thyroid hormone (RTH).Methods: The clinical presentation was, however, different. The mother (proposita) had palpitation, weakness, tiredness, nervousness, dry mouth and was misdiagnosed as...

ea0070oc5.1 | Thyroid | ECE2020

TSH-Independent upregulation of thyroid-specific gene expression in dehal1 knockout mice

Alikhani Pouya , Gonzalez-Guerrero Cristian , Liao Xiao-Hui , Borsò Marco , Peluso Teresa , Zucchi Riccardo , Refetoff Samuel , Moreno Jose Carlos

Background: Most thyroid specific genes are transcriptionally regulated by TSH-TSHR signalling and T4-driven negative feedback of TSH secretion at the pituitary. However, local autoregulation of transcription has been described from IGF-IGFR, follicular thyroglobulin, or iodine. We aimed to investigate the TSH dependency of thyroid transcriptional regulation in the Dehal1 knockout, devoid of iodide-recycling capacity from iodotyrosines.Methods: ...

ea0020oc5.4 | Thyroid: Basic and Clinical | ECE2009

Selenium supplementation fails to improve thyroid hormone metabolism in subjects with SBP2 gene mutations

Schomburg Lutz , Dumitrescu Alexandra M , Liao Xiao-Hui , Bin-Abbas Bassam , Hoeflich Johanna , Kohrle Josef , Refetoff Samuel

Selenium (Se) is an essential trace element needed for the biosynthesis of selenoproteins. Biosynthesis of such proteins depends on the selenocysteine incorporation sequence binding protein 2 (SBP2), which represents a key trans-acting factor during the translation process. We recently described children with mutations in SBP2 gene who displayed an abnormal thyroid function test(s) and reduced selenoprotein concentrations. Now we aimed to improve selenoprotein biosynthesis and...

ea0070aep965 | Thyroid | ECE2020

Constitutive activation of Nrf2 antioxidant pathway leads to age-dependent goiter and compensated hypothyroidism in mice

Chartoumpekis Dionysios , Ziros Panos , Renaud Cédric , Bongiovanni Massimo , Habeos Ioannis , Liao Xiao-Hui , Refetoff Samuel , Kopp Peter , Brix Klaudia , Sykiotis Gerasimos

Background: KEAP1 gene (Kelch-like ECH-associated protein 1) that encodes the main inhibitor of nuclear factor erythroid 2-related transcription factor 2 (Nrf2), a central mediator of antioxidant responses, has been found to be one of the mutated genes that lead to familial multinodular goiter (MNG). The proposed association of KEAP1 with familial MNG is based on only two loss-of-function mutations in respective Japanese families. To date, there is no experim...

ea0032s26.1 | Novel technologies and inspiring ideas: From basic endocrine research to clinical practice (European Young Endocrine Scientists (EYES) Symposium) | ECE2013

Making a functional thyroid in a dish

Antonica Francesco , Kasprzyk Dominika Figini , Opitz Robert , Iacovino Michelina , Liao Xiao-Hui , Dumitrescu Alexandra Mihaela , Refetoff Samuel , Peremans Kathelijne , Manto Mario , Kyba Michael , Costagliola Sabine

During the last decade induced overexpression of defined transcription factors has been shown to have a driving effect on the differentiation of embryonic stem cells (ESCs) into many specific cell types. Nevertheless, the generation of protocols promoting a coordinate self-assembly of differentiated cells into distinct morphological units with also functional properties reminiscent of organs and tissues in vivo are still very sparse. Recently, we have reported the gen...

ea0050oc1.5 | Early Career Oral Communications | SFEBES2017

An essential physiological role for MCT8 in bone

Leitch Victoria D. , Di Cosmo Caterina , Liao Xiao-Hui , O'Boy Sam , Galliford Thomas M. , Evans Holly , Croucher Peter I. , Boyde Alan , Dumitrescu Alexandra , Weiss Roy E. , Refetoff Samuel , Williams Graham R. , Duncan Bassett J.H.

T3 is an important regulator of skeletal development and adult bone maintenance. Thyroid hormone action requires efficient transport of T4 and T3 into target cells. We hypothesized that monocarboxylate transporter-8, encoded by Mct8 on the X-chromosome, is an essential thyroid hormone transporter in bone. To test this hypothesis, we determined the juvenile and adult skeletal phenotypes of male Mct8 knockout mice (Mct8KO) and Mct8D1D2KO compo...