Endocrine Abstracts

An established murine model of thyroid eye disease is induced by transfer of thyrotropin receptor (TSHR) primed T-cells to syngeneic recipients. Our aim was to extend the model to determine if: there are gender differences, Rundle's curve occurs and magnetic resonance imaging (MRI) could be applied as an in vivo marker. Orbital MRI on non-living mice used a surface coil and 1.5T MRI. 0.75mm slices have resolution sufficient to image ocular muscles. TSHR primed T-cells were gen...

Hyperthyroidism is a common disorder, most usually caused by Graves' Disease (GD), in which thyroid-stimulating antibodies (TSAB) mimic thyrotropin. Since the diagnosis of GD is made clinically and its signs and symptoms are indistinguishable from those of patients harboring an activating germline thyrotropin receptor (TSHR) mutation, incorrect diagnoses have been made. Point mutations in more than 30 residues, predominantly in exon 10, of the TSHR cause constitutivity making ...

The TSHR is expressed during adipogenesis. We have employed in vitro models to investigate how TSHR activation affects this process. Gain-of-function TSHR mutants were introduced into preadipocytes using retroviral vectors. We have demonstrated that TSHR activation inhibits their proliferation and PPAR-gamma agonist (pioglitazone) induced adipogenesis. The aim of this study was to investigate the mechanisms operating.Non-modified primary human preadipocy...

Neonates harbouring germline gain-of-function TSHR mutations (M453T, L629F) have been reported with transient proptosis. This resolves once euthyroidism is achieved. In contrast children expressing TSHR mutations (V597L, I486T) fail to thrive, with weight gain and height between the 0.4th and 2nd centiles. We have previously demonstrated TSHR expression in preadipocytes undergoing adipogenesis. We now investigate the consequences of constitutively active TSHR mutation expressi...

A male patient treated with a thiazolidenedione (TZD) PPAR gamma agonist for Type 2 diabetes had a dramatic worsening of his thyroid eye disease (TED), which had been stable and inactive for more then two years. Expansion of the orbital fat seemed to be the underlying cause and we have investigated the effects of a PPAR gamma agonist (and subsequently an antagonist) on the adipogenesis of preadipocytes from 10 different patients, representing several fat depots, including TED ...