Endocrine Abstracts

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid tumours, and neuroendocrine tumours (NETs) of the pituitary and pancreas. MEN1 is caused by mutations of the tumour suppressor gene MEN1, and MEN1 germline mutations are found in >75% of MEN1 patients. The remaining 25% of patients may have mutations involving as yet unidentified gene...

Idiopathic intracranial hypertension (IIH) is a condition of unknown aetiology characterised by raised intracranial pressure, chronic headaches and blindness. Akin to polycystic ovary syndrome (PCOS), IIH patients are almost exclusively obese females of reproductive age. A distinct androgen excess profile has been noted in PCOS. Here, we aimed to delineate androgen metabolism in IIH compared to PCOS and simple obesity.Women w...

Worldwide, ˜300,000 new cases of differentiated thyroid cancer are reported per annum and thyroid cancer now represents the most rapidly increasing cancer in the US and in the UK. In general terms, outcome is good (10-year survival >90%). However, up to 25% of patients develop local or regional recurrences, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver ...

Thyroid tumor progression is dependent on cell motility, a highly complex process that involves the co-ordination of cell adhesion, actin dynamics and signal transduction. The proto-oncogene pituitary tumor-transforming gene (PTTG)-binding factor (PBF/PTTG1IP) is a transmembrane glycoprotein that is overexpressed in thyroid cancer and associated with a poorer prognosis. PBF significantly promotes thyroid cancer cell migration and invasion through phosphorylation at PBF-Y174 by...

Background: The sodium/iodide symporter (NIS) frequently shows diminished targeting to the plasma membrane (PM) in differentiated thyroid cancer, resulting in suboptimal radioiodine treatment and poor prognosis. However, the mechanisms which govern the endocytosis of NIS away from the PM – its sole site of transport activity – are ill-defined, and may be of direct therapeutic potential. We previously showed that the proto-oncogene PBF binds NIS and enhances its inter...

Introduction: Radioactive iodine (RAI) therapy is a critical component in the post-surgical management of thyroid cancer patients, as well as being a central therapeutic option in the treatment of hyperthyroidism. Previous work suggests that antithyroid drugs hinder the efficacy of RAI therapy in patients. However, the effects of other background medications on RAI treatment efficacy have not been evaluated. Therefore, we performed a systematic review and metanalysis investiga...

Introduction: New drug approaches are urgently required to improve radioiodide (RAI) uptake for efficient ablation of thyroid cancer cells in RAI-refractory disease. Employing high-throughput screening of FDA-approved compounds we recently identified drugs capable of robust induction of sodium iodide symporter (NIS) activity to promote RAI uptake1. In particular, a leading drug candidate – the well-established anti-alcoholism drug disulfiram (DSF) – had no...

New targeted drug strategies are urgently needed to improve radioiodine uptake and efficiently ablate thyroid cancer cells thereby minimising the risk of recurrent disease. High-throughput screening (HTS) offers a promising approach to identify new candidate drugs that will induce sodium iodide symporter (NIS) function to promote iodide uptake. However, significant progress has been limited by a lack of thyroid cell-based assays amenable to HTS. Here, we constructed a thyroid ...

Thyroid cancer is increasing in incidence worldwide. While outcomes are generally good, up to 25% of patients suffer recurrence, and this has a significant impact on their quality of life and life expectancy. We hypothesised that thyroid tumours which recur display a distinct pattern of driver events, present on initial histology. Controlled-access TCGA data on thyroid cancer were downloaded and whole exome sequencing data analysed. An analysis pipeline utilising Platypus, Ann...

Successful responses to radioiodine treatment in differentiated thyroid cancer ultimately depend on uptake via the sodium-iodide symporter (NIS). However, many tumors 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-transforming gene-binding factor (PBF) is partially res...