Endocrine Abstracts

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...

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 ...

Background: Endocrinology is well-established as an outpatient specialty. However, virtually no data exist on the volume, nature, management and disposal of inpatient referrals to inform the design and delivery of a quality-assured service.Methods: We undertook an audit of all activity of the Inpatient Endocrine Service at University Hospitals Birmingham NHSFT (IES@UHB) between January 2010 and December 2015. Referrals received electronically via the Pat...

The most common form of endocrine cancer is differentiated thyroid cancer (DTC). Outcomes of DTC largely depend on radioiodine treatment, which is mediated the sodium-iodide symporter (NIS). However, many tumours exhibit NIS dysregulation, resulting in a poorer prognosis. Since breast cancer can also overexpress NIS, albeit of limited function, radioiodine treatment may be a promising treatment option. Our previous data show that overexpression of the pituitary tumor-transform...

Although the sodium iodide symporter (NIS) is expressed in 70–80% of breast cancers, only 20–30% is located at the plasma membrane (PM) and therefore functional. Previous work in thyroid cells leads demonstrated that PBF redistributes NIS from the PM into intracellular vesicles, potently reducing radioiodide uptake. We therefore examined whether increased membranous NIS could facilitate radioiodide therapy for breast cancer. Immunofluorescent microscopy revealed co-l...

Pituitary tumor-transforming gene binding factor (PBF) is a ubiquitous glycoprotein which is over-expressed in thyroid, breast and other endocrine cancers, and modulates cellular invasion, radioiodine uptake and thyroid hormone efflux. Papillary thyroid cancer patients with high PBF expression show decreased disease-specific survival compared to those with lower expression. PBF expression has recently been correlated with breast cancer metastasis and colon cancer extra-mural v...

Metastasis is a multistep process responsible for the vast majority of endocrine cancer deaths. We have previously identified the proto-oncogene PBF to be upregulated in differentiated thyroid cancer, and recently PBF expression has been correlated with distant thyroid cancer metastasis at diagnosis. Further, PBF potently induces breast cancer cell invasion in vitro, and our recent in vivo data demonstrate that colorectal tumours with higher PBF protein expre...

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...