Searchable abstracts of presentations at key conferences in endocrinology

ea0065op3.4 | Metabolism and Obesity | SFEBES2019

Mice with a gain-of function Gα11 mutation have autosomal dominant hypocalcaemia, but not impaired glucose metabolism

Gluck Anna , Lines Kate , Gorvin Caroline , Babinsky Valerie , Piret Sian , Sarbu Stefan , Stewart Michelle , Bentley Liz , Wells Sara , Cox Roger , Ecker Rupert , Ellinger Isabella , Hannan Fadil , Thakker Rajesh

The calcium-sensing-receptor (CaSR) is a G-protein-coupled receptor that plays a fundamental role in extracellular calcium homeostasis, but is also implicated in non-calcitropic disorders including colon cancer and asthma. In addition, CaSR is highly expressed in pancreatic islets where it has a role in insulin secretion. Patients with gain-of-function CaSR mutations, and mice (referred to as Nuf) with a gain-of-function CaSR mutation (Leu723Gln), develop autosomal dominant hy...

ea0065p137 | Endocrine Neoplasia and Endocrine Consequences of Living with and Beyond Cancer | SFEBES2019

Long term outcomes following parathyroidectomy in patients with multiple endocrine neoplasia type 1: A retrospective cohort study

Healy Ultan , English Katie , Bacon Hannah Elizabeth , Grossman Ashley B , Shine Brian , Thakker Rajesh V , May Christine JH , Pal Aparna , Mihai Radu , Jafar-Mohammadi Bahram

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 ...

ea0044p78 | Clinical biochemistry | SFEBES2016

Management of multiple endocrine neoplasia type 1 (MEN1) and sporadic pancreatic neuroendocrine tumours (PNETS) in relation to the clinical guidelines: a single centre audit

Ntali Georgia , Newey Paul J , Stokes Victoria , Talbot Denis , Soonawalla Zahir , Sadler Greg , Karavitaki Niki , Grossman Ashley B , Thakker Rajesh V

Introduction and aim: Pancreatic neuroendocrine tumours (PNETs) may occur sporadically (sPNETs) or as part of the multiple endocrine neoplasia type 1(MEN1) syndrome, which is characterised by occurrence of PNETs, parathyroid and anterior pituitary tumours. Our aim was to review the management of these patients in relation to the clinical practice MEN1 guidelines, and the ENETS and UKINETS guidelines for PNETs.Patients and methods: Patients attending with...

ea0059oc1.4 | Translational highlights | SFEBES2018

Whole genome sequence analysis establishes correct diagnosis for a syndromic form of hyperuricaemia

Stevenson Mark , Pagnamenta Alistair T , Reichart Silvia , Mennel Stefan , Philpott Charlotte , Lines Kate E , Gorvin Caroline M , Lhotta Karl , Taylor Jenny C , Thakker Rajesh V

Whole genome sequencing (WGS) has the potential to identify nearly all forms of genetic variation. In complex disorders with multiple manifestations WGS can establish a definitive diagnosis that may change clinical management (Stavropoulos et al. 2016 Genomic Med). Here, we report on the utility of WGS in establishing the correct diagnosis in a family with hyperuricaemia. Hyperuricaemia may occur as: part of a syndromic disorder (e.g. Lowe syndrome, renal col...

ea0059p052 | Bone and calcium | SFEBES2018

Utility of Whole Genome Sequencing in diagnosing complex disorders: lesson from renal tubular disorders

Stevenson Mark , Pagnamenta Alistair T , Mack Heather G , Savige Judith A , Lines Kate E , Taylor Jenny C , McCredie David A , Thakker Rajesh V

Bartter’s syndrome (BS) and Gitelman’s syndrome (GS) are renal tubular disorders affecting reabsorption of sodium, potassium and chloride. Common clinical features include muscle cramps and weakness, hypokalaemia, hypochloraemic metabolic alkalosis and elevated plasma aldosterone concentrations. Urinary calcium excretion and plasma magnesium concentrations may be differentiating features, such that hypomagnesaemia and hypocalciuria are typical of GS, and hypercalciur...

ea0034oc1.6 | Young Endocrinologists prize session | SFEBES2014

A loss-of-function mutation in the prolactin receptor causes familial hyperprolactinaemia

Gorvin Caroline , Newey Paul , Cleland Stephen , Willberg Christian , Bridge Marcus , Azharuddin Mohammed , Drummond Russell , van der Merwe Anton , Klenerman Paul , Bountra Chas , Thakker Rajesh

The prolactin receptor (PRLR) is a member of the class I cytokine receptor family that signals predominantly through the JAK2–STAT5 pathway. To date, PRLR mutations have not been established to be associated with any disorders. Here, we report a PRLR mutation (His188Arg) that caused familial hyperprolactinaemia in three sisters, two of whom presented with oligomenorrhea and one with infertility. The hyperprolactinaemia was not associated with pituitary tumours, which were...

ea0034oc5.1 | Pituitary | SFEBES2014

Increased frequency and earlier onset of pituitary tumours in mice deleted for a multiple endocrine neoplasia type 1 allele and null for prolyl hydroxylase domain protein 1 (Men1+/−/Phd1−/−)

Stevenson Mark , Piret Sian , Javid Mahsa , Bishop Tammie , Reed Anita , Walls Gerard , Gaynor Katie , Newey Paul , Christie Paul , Nicholls Lynn , Ratcliffe Peter , Thakker Rajesh

Cumulative genetic abnormalities within an oncogenic pathway may contribute to earlier onset or increased aggressiveness of cancers. An example in human and murine cancer is the dysregulation of Wnt signalling by inactivation of the adenomatous polyposis coli (APC) gene that results in accumulation of nuclear β-catenin and earlier onset of renal cell carcinoma, which can be accelerated by p53-deficiency. We therefore investigated the effects of such cumulative genetic abn...

ea0034p406 | Thyroid | SFEBES2014

Hypoxic incubation favours the development and growth of primary human parathyroid adenoma cells

Lines Kate E , Stevenson Mark , Mihai Radu , Grigorieva Irina V , Baban Dilair , Gaynor Katherine U , Jeyabalan Jeshmi , Javid Mahsa , Thakker Rajesh V

Hypoxia is a primary stimulus for angiogenesis, which is important for tumour proliferation and survival. The effects of hypoxia on parathyroid tumour cells, which may be important for parathyroid autotransplantation in patients, are however, not known. We therefore assessed the effects of hypoxia on gene expression in parathyroid adenoma cells from patients with primary hyperparathyoridism. Cell suspensions from human parathyroid adenomas (n=5) were cultured and afte...

ea0031oc5.1 | Pituitary and neoplasia | SFEBES2013

Genetic background influences tumour phenotype in heterozygous Men1 knockout mice

Lines Kate E , Javid Mahsa , Reed Anita A C , Piret Sian E , Walls Gerard V , Stevenson Mark , Christie Paul T , Thakker Rajesh V

Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterised by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumours, is due to mutations of a tumour suppressor gene, MEN1. MEN1 mutations have also been reported to cause familial isolated primary hyperparathyroidism (FIHP). Moreover, 15 identical MEN1 mutations have been reported to cause MEN1 or FIHP in unrelated families; thereby implicating a r...

ea0028p186 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

Mutations of the Chloride/Proton Antiporter, CLC-5, lead to Impaired Endosomal Acidification in Human Proximal Tubule Epithelial Cell-lines

Gorvin Caroline , Wilmer Martijn , Piret Sian , Harding Brian , Lippiat Jonathan , O'Hare Michael , Jat Parmjit , Wrong Oliver , van den Heuvel Lambertus , Levtchenko Elena , Thakker Rajesh

Dent’s disease is a renal proximal tubular disorder characterised by low-molecular-weight proteinuria, glycosuria, hypercalciuria, phosphaturia, nephrolithiasis and abnormal urinary loss of other proteins which include insulin, parathyroid hormone (PTH) and vitamin D-binding protein, due to defective receptor-mediated endocytosis (RME). Mutations in CLC-5 cause Dent’s disease-1 whilst mutations in OCRL1 cause Dent’s disease-2 and the oculocerebrorenal syndrome o...