Endocrine Abstracts

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 ...

Background: Data on the relationship between the hormonal response to somatostatin analogues and morphological subtype of somatotroph adenomas are sparse. We have previously shown that nadir GH <1.75 μg/l on the octreotide suppression test (OST) has positive and negative predictive value 94 and 100%, respectively in predicting achievement of ‘safe’ GH levels following treatment with octreotide LAR (Karavitaki et al. 2005).Aim: T...

The insulin tolerance test (ITT) is the gold standard for assessing growth hormone (GH) and cortisol production in pituitary disease, However it is potentially hazardous, requires medical supervision and adequate hypoglycemia may not be achieved. We retrospectively examined the records of 185 consecutive patients aged 14-76 years with pituitary disease who underwent the ITT over 18 months. Testing was performed in the endocrine day ward by an experienced endocrine nurse. Absol...

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...

Dysregulation of sodium-iodide symporter (NIS) function is common in differentiated thyroid cancer, resulting in sub-optimal radioiodide therapy and poorer clinical outcome. Recent developments in identifying proteins that regulate the function of the sodium iodide symporter have highlighted two proteins involved in internalisation of NIS from the plasma membrane: AP-2 and moesin. Clathrin-mediated endocytosis (CME) of NIS is facilitated through the adaptor protein 2 (AP2) com...

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...

Prader-Willi syndrome (PWS) is a rare genetic condition characterised by hypotonia, early feeding difficulties, hyperphagic obesity, hypogonadism and short stature; with an incidence between 1/15 000 and 1/25 000 live births in the UK. It is caused by failed expression of paternally inherited genes in the imprinting region of chromosome 15q11.2–q13. Recombinant human GH (rhGH) is the main pharmacological treatment used in PWS.Aims: We aimed to revie...

The proto-oncogene pituitary tumor transforming gene binding factor (PTTG1IP/PBF) is overexpressed in multiple tumours and associated with tumour progression. One of the tumourigenic processes that PBF can mediate is cell motility. PBF can induce cell invasion in both thyroid and breast cancer cell lines. However, in contrast to wild-type (WT) PBF, the Y174A PBF mutant was not able to induce the invasiveness of thyroid or breast cancer cells. The Y174 residue is highly phospho...

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...