Endocrine Abstracts

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:...

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...

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...

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...

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...