Endocrine Abstracts

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...

Introduction: Hypophosphatasia is a very rare inherited condition due to ALPL variants and is associated with a variable presentation.Case description: The index case initially presented at 7 months with bulging anterior fontanelle, failure to thrive and mild developmental delay. She was born at 34 weeks gestation and had amniotic bands causing digital anomalies. She was sitting at 8 months, crawling by 15 months and a hearing test was normal. A...

Primary hyperparathyroidism (PHP), usually due to multigland hyperplasia, occurs in >90% of patients with multiple endocrine neoplasia type 1 (MEN1). The literature is divided on the optimal surgical management for such patients. We report a retrospective cohort study on the long-term outcomes associated with limited, subtotal, or total parathyroidectomy as initial surgery for PHP in MEN1. The primary endpoint was recurrent PHP defined as an adjusted serum calcium >2.6 mmol/l ...