Endocrine Abstracts

Intrauterine growth restriction (IUGR) is a significant cause of perinatal morbidity, in particular neurodevelopmental delay, and is associated with fetal hypothyroxinemia. Thyroid hormone is essential for the optimal development of the central nervous system (CNS) in the fetus. Transport of the active ligand triiodothyronine (T3) across the cell membrane is required for its biological effects, initiated by binding of T3 to nuclear thyroid receptors (TR). Recently, the membran...

Angiogenesis is the rate-limiting step in tumour progression and metastatic spread. Both promoters and inhibitors of angiogenesis have been implicated in thyroid tumourigenesis. We have reported PTTG overexpression in thyroid and other cancers, and PTTG upregulation of the angiogenic factors FGF-2 and VEGF in vitro. To investigate whether PTTG also transactivates other downstream angiogenic effectors, we employed angiogenesis-specific cDNA arrays. Primary thyroid cells and PTT...

Chromosomal instability (CIN) is a common feature of many malignancies including papillary and follicular thyroid cancer. During mitosis, there are multiple stages which, if dysregulated, may result in CIN. One critical stage is the regulation of sister-chromatid separation at the metaphase-anaphase transition. Three key protein complexes regulate this process: separase, cohesins and securin (also known as pituitary tumor transforming gene). In vivo, most tumours studied demon...

The prognosis of differentiated thyroid cancers is influenced by their ability to accumulate iodine and hence their sensitivity to ablative 131I therapy. Radioiodine concentration is mediated by the sodium-iodide symporter (NIS). We have previously identified PTTG and fibroblast growth factor-2 (FGF-2) as potential prognostic indicators for differentiated thyroid cancers. Furthermore, we demonstrated that FGF-2 reduces iodide uptake in FRTL5 cells and primary human ...

PTTG has been implicated in the pathogenesis of pituitary, thyroid and other tumours. PBF was recently identified as a protein which interacts specifically with PTTG both in vitro and in vivo. PBF facilitates PTTG's nuclear localisation, and mediates its ability to transactivate basic fibroblast growth factor (FGF-2). We investigated PBF expression and function in vitro, and examined its relationship to PTTG action. Transient transfection of wild type PTTG induced a significan...

The critical role of thyroid hormones (TH) in normal human growth and fetal development is well recognised. The availability of tri-iodothyronine (T3) to bind to thyroid hormone receptors is determined by the local concentrations of T3, as well as the local action of deiodinase enzymes that determine conversion of T4.Quantitative real time RT-PCR was used to quantify the expression of mRNAs encoding the specific deiodinase subtypes (D1, D2 & D3) in h...

Differentiated thyroid cancers are the commonest endocrine malignancies, but there are no reliable molecular markers of prognosis. Pituitary tumor transforming gene (PTTG) plays several potential roles in tumour initiation and progression, including regulating mitosis and stimulating expression of fibroblast growth factor-2 (FGF-2). PTTG expression has been identified as a potential prognostic marker in pituitary adenomas and colon carcinomas. We postulated that PTTG and FGF-2...

Objectives: Hyperthyroidism has been linked to long-term cardiovascular and metabolic morbidity and increased mortality. Current evidence indicates differential cardio-metabolic effects from antithyroid drugs (ATD) and definitive treatment options (radioiodine or thyroidectomy). We aimed to assess differences in mortality and cardiometabolic outcomes depending on treatment modality to better inform patient-clinician decision-making.Methods: We identified...

Introduction: New therapeutic strategies are urgently needed to improve radioiodide (RAI) uptake and efficiently ablate thyroid cancer cells, thereby reducing the risk of recurrent disease. We recently utilised high throughput screening and identified FDA-approved compounds capable of inducing sodium iodide symporter (NIS) function to enhance iodide uptake. Categorisation revealed a high proportion of drugs that modulate proteostasis, with 6 of the top 15 targeting activity of...

Hyperthyroidism has been linked to long-term cardiovascular and metabolic morbidity and increased mortality. We aimed to assess differences in mortality and cardiometabolic outcomes depending on treatment modality to better inform patient-clinician decision-making.Methods: We identified 62,474 patients with newly diagnosed hyperthyroidism, treated with antithyroid drugs (ATD), radioiodine or thyroidectomy from a UK population-based GP database (>16M ...