Endocrine Abstracts

Dysfunctional regulation of sodium-iodide symporter (NIS) trafficking can result in ineffective radioiodide uptake in patients with differentiated thyroid cancer. Understanding the trafficking pathways of this key protein can be used to optimise radioiodide therapy. Recently, we identified via HiLo microscopy that the protein ADP-ribosylation Factor 4 (ARF4) helps shuttle NIS to the plasma membrane. To understand how ARF4 interacts with NIS mechanistically, we utilised advance...

Background: Early glycaemic control improves long-term outcomes in children with Type I diabetes. The NICE target for children with T1DM is HbA1c ≤ 48 mmol/mol. 2018 data from our newly diagnosed patients (pre-QI) demonstrated mean HbA1c 50 mmol/mol at 3 months and 62 mmol/mol at 12 months.Aims and methods: Our aim is to improve average blood glucose levels at day 28 post diagnosis and achieve a median HbA1c of <48 mmol/mol at 3 and 12 months p...

The incidence of thyroid cancer is rapidly increasing worldwide. Whilst outcome in thyroid cancer is generally good, up to 25% of patients develop recurrence, and have a significantly reduced life expectancy. We hypothesise those thyroid tumours which subsequently recur display a distinct pattern of driver events. Whole exome sequencing data were downloaded from The Cancer Genome Atlas (TCGA). Bioinformatic analysis of data on N=43 patients whose tumours recurred was ...

Abstract: Idiopathic intracranial hypertension (IIH) is a devastating neurological condition, with elevated intracranial pressure of unknown aetiology. IIH is largely a disease of obese females of reproductive age. The clinical phenotype of IIH overlaps with polycystic ovary syndrome (PCOS), with prevalent obesity, hyperandrogenism and anovulation. In this study, we aimed to delineate the androgen excess phenotype of IIH women compared to those with PCOS and simple obesity. Wo...

In thyroid cancer, a reduction in sodium iodide symporter (NIS) expression at the basolateral plasma membrane (PM) of thyrocytes decreases the efficacy of radioiodine imaging, ablative therapy and treatment of metastases. NIS overexpression in breast cancer has resulted in radioiodine being widely proposed as a novel therapeutic strategy. However, uptake is insufficient for tumour destruction. Augmenting NIS PM localisation represents an important therapeutic strategy for incr...

By exploiting the canonical function of the sodium iodide symporter (NIS) ablative radioiodine therapy is an effective treatment for thyroid cancer. However, a subset of patients are unable to accumulate sufficient radioiodine for effective treatment due to the dysregulation of NIS, which can occur through decreased expression and/or reduced plasma membrane localisation. Although NIS localisation at the plasma membrane is critical for radioiodine uptake the mechanism of NIS tr...

Despite extensive genomic profiling a better understanding of the contributory factors that promote aggressive thyroid cancer is urgently needed. The proto-oncogenes PBF and PTTG have been implicated in thyroid cancer but there is a lack of information regarding their co-expression and specific roles in tumour progression. Separate studies have previously indicated that PBF and PTTG may disrupt pathways associated with the tumour suppressor p53 that are central to DNA-damage r...

PBF is a multifunctional proto-oncogene overexpressed in thyroid and other endocrine cancers. Previously we identified a functional interaction between PBF and the tumour suppressor p53 in well-differentiated thyroid cancer (WDTC). Here, we delineate the oncogenic mechanisms of PBF, along with its binding partner PTTG, in head and neck cancer (HNSCC), in which TP53 mutations (mutTP53) are common (>50%). HNSCC tissue revealed significant upregulation of PBF and PTTG mRNA (&...

Patients termed to have radioiodine-refractory differentiated thyroid cancer (RR-DTC) cannot accumulate sufficient radioiodine for a therapeutic response due to sodium iodide symporter (NIS) dysregulation via diminished expression and/or altered plasma membrane (PM) localisation. Currently, the regulation of NIS localisation remains poorly defined and despite protein-protein interactions being well-described to modulate trafficking events, the NIS interactome is limited. Previ...

Introduction: Despite adequate treatment with LT4 monotherapy, many patients with primary hypothyroidism still report complaints, as this treatment can not exactly imitate the endogenous homeostasis. We examined whether the different domains of HR-QOL were affected by the existence of a thyroid disorder and use of LT4 substitution, and whether a lower ratio of free triiodothyronine (fT3)–free thyroxine (fT4)</sup...