Searchable abstracts of presentations at key conferences in endocrinology

ea0034p398 | Thyroid | SFEBES2014

Neurocognitive and CNS abnormalities in humans with defective thyroid receptor α

Moran Carla , Visser Edward , Schoenmakers Nadia , Muntoni Francesco , Clark Chris , Gadian David , Chong Kling , Kuczynski Adam , Dattani Mehul , Vargha-Khadem Faraneh , Chatterjee Krishna

Background: The severe neurodevelopmental phenotype of untreated congenital hypothyroidism exemplifies the critical role of thyroid hormones (TH) in CNS development, acting via thyroid hormone receptor α1 (TRα1) on cortical neurogenesis, cerebellar development and oligodendrocyte differentiation. We have identified the first humans with defective TRα1 and investigated neurocognitive phenotype and CNS abnormalities in this disorder.Methods:...

ea0092ps2-11-02 | Miscellaneous 2 | ETA2023

Resistance to thyroid hormone alpha: outcomes of twelve years of thyroxine therapy

Moran Carla , Vargha-Khadem Faraneh , Clark Chris , Seunarine Kiran , Muntoni Francesco , Bethlehem Richard , Lindley Keith , Watson Laura , Lyons Greta , Dattani Mehul T. , Chatterjee Krishna

Objectives: In 2011, we described the first case of Resistance to Thyroid Hormone due to a mutation in thyroid hormone receptor a (RTHα) in a six year old child with features of congenital hypothyroidism but near-normal thyroid function tests. Here, we report outcomes following twelve years of thyroxine therapy in this patient.Methods: Colonic contractility, intestinal transit time, growth, resting energy expenditure, heart rate and biochemical para...

ea0028oc1.5 | Young Endocrinologists prize session | SFEBES2012

Growth Retardation and Severe Constipation due to the first human, dominant negative Thyroid Hormone Receptor Alpha mutation

Schoenmakers Nadia , Bochukova Elena , Agostini Maura , Schoenmakers Erik , Rajanayagam Odelia , Keogh Julia , Henning Elana , Reinemund Jana , Gevers Evelien , Sarri Margarita , Downes Kate , Offiah Amaka , Albanese Assunta , Halsall David , Schwabe John , Bain Murray , Lindley Keith , Muntoni Francesco , Vargha-Khadem Faraneh , Dattani Mehul , Farooqi Sadaf , Gurnell Mark , Chatterjee Krishna

Introduction: Thyroid hormones act via receptors encoded by different genes (THRA and THRB) generating receptor subtypes (TRα1, TRβ1, TRβ2) with differing, tissue-specific expression. Resistance to Thyroid Hormone due to THRB defects is well recognised, but no THRA mutations have yet been reported. We describe the first case of human TRα-mediated thyroid hormone resistance due to a dominant negative THRA mutation.Results: A 6-year-old...

ea0027oc1.4 | Oral Communications 1 | BSPED2011

Growth retardation and severe constipation due to the first human, dominant negative thyroid hormone receptor α mutation

Schoenmakers Nadia , Bochukova Elena , Agostini Maura , Schoenmakers Erik , Rajanayagam Odelia , Henning Elana , Gevers Evelien , Sarri Margarita , Offiah Amaka , Albanese Assunta , Halsall David , Schwabe John , Bain Murray , Lindley Keith , Muntoni Francesco , Vargha-Khadem Faraneh , Dattani Mehul , Farooqi Sadaf , Gurnell Mark , Chatterjee Krishna

Introduction: Thyroid hormones act via receptors encoded by different genes (THRA and THRB) generating receptor subtypes (TRα1, TRβ1, TRβ2) with differing, tissue-specific expression. Resistance to thyroid hormone due to THRB defects is well recognised, but no THRA mutations have yet been reported. We describe the first case of human TRα-mediated thyroid hormone resistance due to a dominant negative THRA mutation.<p cl...

ea0021oc3.5 | Young Endocrinologists prize session | SFEBES2009

A multisystem selenoprotein disorder with a thyroid signature

Schoenmakers Nadia , Schoenmakers Erik , Agostini Maura , Mitchell Catherine , Papp Laura , Rajanayagam Odelia , Padidela Raja , Doffinger Rainer , Luan Jian'an , Lu Jun , Campi Irene , Burton Hannah , Muntoni Francesco , O' Donovan Dominic , Dean Andrew , Warren Anne , Guicheney Pascale , Fitzgerald Rebecca , Coles Alasdair , Gaston Hill , Holmgren Arne , Cooke Marcus S , Halsall David , Wareham Nicholas , Beck-Peccoz Paolo , Ogunko Arthur , Dattani Mehul , Gurnell Mark , Chatterjee Krishna

Selenocysteine insertion sequence-binding protein 2 (SECISBP2) mediates translational incorporation of selenocysteine into 25 known human selenoproteins, including iodothyronine deiodinases. Two unrelated male subjects, aged 36 years (P1) and 3.6 years (P2), exhibited markedly elevated free thyroxine (fT4), normal/low free triiodothyronine (fT3), but normal thyrotropin (TSH) levels, indicating reduced T4 to T3 conversion:<table b...