Endocrine Abstracts

Radioiodine is a central treatment modality for differentiated thyroid cancer. Whilst its utility for post-surgery ablation in some patients remains controversial, the importance of radioiodine in the treatment of recurrent and metastatic disease is clear. Advanced disease which no longer takes up radioiodine (radioiodine-refractory DTC (RR-DTC)) is commonly associated with a poor prognosis, with 10-year survival rates for metastatic RR-DTC <10%. Although new systemic ther...

Radioiodine is a central treatment modality for differentiated thyroid cancer. Whilst its utility for post-surgery ablation in some patients remains controversial, the importance of radioiodine in the treatment of recurrent and metastatic disease is clear. Advanced disease which no longer takes up radioiodine (radioiodine-refractory DTC (RR-DTC)) is commonly associated with a poor prognosis, with 10-year survival rates for metastatic RR-DTC <10%. Although new systemic ther...

Effective treatment of differentiated thyroid cancer relies on a multifaceted approach often including administration of 131I to ablate residual cancer cells post-surgery. The success of this treatment hinges upon adequate uptake of iodide by malignant thyroid follicular cells. In a subset of patients, dedifferentiation of the carcinoma can result in aberrant expression and trafficking of the iodide transport protein, the sodium iodide symporter (NIS), resulting in ...

Introduction: Generously supported by IPSEN)-->Pituitary infarction is rare in the paediatric age. In adolescents and adults it is often secondary to haemorrhage into an underlying lesion such as pituitary adenoma or cyst. Lymphocytic hypophysitis is rare in children and usually peri-tumoral due to germinoma, craniopharyngioma or Rathke’s cyst and often associated with hypopituitarism and diabetes insipidus.<p class="abstext...

Whilst the majority of differentiated thyroid cancers (DTC) have oncogenic mutations, a significant minority may be driven by the overexpression of proto-oncogenes. PTTG and PBF are proto-oncogenes which are induced in DTC, elicit tumours in xenograft models and interact in vitro, where PBF shuttles PTTG into the nucleus. However, the relative contributions of each gene to DTC has not been delineated. Here, we constructed a bi-transgenic murine model over-expressing b...

Pituitary tumor transforming gene (PTTG) is a multifunctional oncogene implicated in the pathogenesis of pituitary and thyroid tumours. In breast cancer, PTTG expression is a prognostic marker for lymph node invasion and tumour recurrence. PTTG expression is regulated in vitro and in vivo by oestrogen treatment. PTTG binding factor (PBF) is also a transforming gene, and was isolated due to its functional interaction with PTTG. In the current study, we examined PB...

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most differentiated thyroid tumours exhibit reduced iodide uptake, however, and the mechanisms accounting for this remain poorly understood. Pituitary tumor transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We recently reported that PTTG and its binding factor PBF, also a potent transfo...

Thyroid hormones play vital roles in fetal brain development. Mutations in MCT8, recently recognised as a specific thyroid hormone transporter, define a novel syndrome of severe X-linked psychomotor retardation and thyroid hormone resistance.N-TERA-2 (NT2) cells (human embryonal cells with characteristics of CNS precursors) were transiently transfected with either WT MCT8 or its L471P, R271H or S448X mutations, described in males affected by severe psych...

The sodium iodide symporter (NIS) mediates the uptake of iodide into thyroid follicular cells. The pituitary tumor transforming gene (PTTG) is a multifunctional oncogene which stimulates expression of fibroblast growth factor-2 (FGF-2) via PTTG binding factor (PBF). PTTG and FGF-2 inhibit iodide uptake in rat thyroid FRTL5 cells and PTTG and PBF repress NIS mRNA expression and iodide uptake in primary human thyroid cultures. To determine whether this regulation is a direct tra...

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...