Endocrine Abstracts

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 individuals. Rapid detection and treatment by neonatal screening and administration of T4, is essential to prevent severe mental retardation and impaired growth.We report on two Welsh siblings, detected by neonatal screening, which had normal sized and placed glands but negative isotope uptake. Mutations resulting in CH are known to occur in 11 known genes, given the clinical presentation, we investigated the...

Congenital hypothyroidism (CH) occurs in approximately 1 in 3000 individuals. Rapid detection by neonatal screening and T4 administration is essential to prevent severe mental retardation and impaired growth. About one third of CH is due to mutations in known genes including the thyrotropin receptor (TSHR).Two Welsh male siblings with CH were detected, both had normally sized and located thyroid glands, no iodide uptake and were negative for thyroid bloc...

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...

Does Iodide Modulate The Biological Outcome of Activating Thyrotropin Receptor Mutations?Dr. F. Al-Khafaji and Dr. M. LudgateHyperthyroidism is caused by pathogenic activation of the thyrotropin receptor (TSHR) either by the thyroid stimulating antibodies of Graves' disease (GD) or activating TSHR mutations. These produce nodular goitre or familial hyperthyroidism. The pathogenic mechanism predominating varies according to the iodide intake, with nodular goitre account...

The rising prevalence of type 2 diabetes can be directly related to increasing levels of population obesity and associated insulin resistance. Adipose tissue has neuroanatomically well characterized sympathetic innervation (with activation initiating lipid mobilization), but little evidence to support the presence of a (putatively counter-regulatory) parasympathetic input (Bartness & Song 2007). Parasympathetic actions are mediated through muscarinic acetylcholine receptor...

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 ...

Dehydroepiandrosterone (DHEA) is an adrenal sex steroid whose levels decline during normal aging. Epidemiological studies demonstrate inverse correlation between circulating DHEA-sulphate and body fat mass while DHEA administration in elderly subjects reduces visceral and subcutaneous fat accumulation. Although previous studies have shown that some effects may be mediated via DHEA-induced inhibition of white pre-adipocyte proliferation, mechanisms remain unknown. Furthermore, ...

Patients with non-functional FOXE1 (forkhead transcription factor) display congenital hypothyroidism, ‘spikey’ hair and other abnormalities. In the thyroid, FoxE1 controls migration of the developing gland and adult expression of thyroid specific genes. Our earlier studies demonstrated FOXE1 protein expression in keratinocytes of the epidermis and hair-follicle outer root sheath.We aimed to characterise the expression and functional activity of...

In addition to its central role in the control of thyrocyte growth and function, the TSHR is expressed during the differentiation of mesenchymal precursors. To explore further, we have developed an in vitro model in which TSHR activation is achieved by introducing constitutively active (M453T, L629F) TSHR, using retroviral vectors.We aimed to investigate the effect of TSHR activation on body composition, via the production of TNFα and express...

Adipogenesis is induced when intracellular cAMP increases and follows cell cycle arrest. During preadipocyte differentiation expression of the TSHR, which signals via cAMP and the inositol phosphate cascade, is upregulated. To investigate the role of TSHR activation in adipogenesis, we have developed an in vitro model in which constitutively active TSHR mutants (L629F, M453T) are introduced by retroviral vectors (RV).We aimed to compare the effect...