Searchable abstracts of presentations at key conferences in endocrinology

ea0073aep552 | Pituitary and Neuroendocrinology | ECE2021

A complex case of refractory hypercalcaemia, end-stage diabetic nephropathy with pituitary mass and hypopituitarism– is there a unifying diagnosis?

Fennell David , Holland John A , Corkery Laura , Ludgate Stephen , McQuaid Siobhan

A 54-year-old female presented with one week of weakness, fatigue, headache, worsening constipation, and general malaise. Background history included long-standing type 1 diabetes (glutamic acid decarboxylase positive), on continuous subcutaneous insulin infusion, proliferative diabetic retinopathy, end-stage diabetic nephropathy on haemodialysis and subclinical hypothyroidism. Tertiary hyperparathyroidism was diagnosed (adjusted calcium 2.82 mmol/l, phosphate 1.42 mmol/l, par...

ea0073aep728 | Thyroid | ECE2021

A case of Graves’ disease (GD) associated with HIV disease and late immune reconstitution inflammatory syndrome (IRIS) following initiation of antiretroviral therapy (ART)

Ludgate Stephen , P Connolly Stephen , Fennell David , McQuaid Siobhan

GD following ART occurs rarely, in 3% of HIV-infected women1. It is suggested that CD4 cells increase in a biphasic pattern following ART initiation, with the expansion of naïve CD4 cells following months after the initial redistribution of memory CD4 cells from lymphoid tissue2. A 40-year-old Brazilian lady was diagnosed with HIV in late 2016 following admission with cryptococcal meningitis and salmonellosis, requiring treatment with anti-fungal age...

ea0031p38 | Clinical biochemistry | SFEBES2013

Development of an inductively coupled plasma-mass spectrometry method for measurement of urine iodine and assessment of iodine status in subclinical hypothyroidism

Jones Katie , Rogers Joanne , De Lloyd Anna , Rees Aled , Ludgate Marian , Evans Carol

Iodine deficiency may lead to reduced thyroid hormone production and ultimately hypothyroidism. The UK has previously been considered to be iodine sufficient, however recent evidence suggests the UK may be iodine deficient. Iodine status can be assessed in several ways, including measurement of urinary iodine excretion, for which inductively coupled plasma-mass spectrometry (ICP-MS) is considered the gold standard method.An ICP-MS method for determinatio...

ea0025p334 | Thyroid | SFEBES2011

Depot specific differences in regulation of hyaluronan production of relevance to Graves’ orbitopathy

Zhang Lei , Grennan-Jones Fiona , Lane Carol , Rees D Aled , Dayan Colin , Ludgate Marian

Expansion of the orbital contents, by adipogenesis and hyaluronan (HA) overproduction, causes Graves orbitopathy (GO). Orbital HA is generated predominantly by hyaluronan synthase 2 (HAS2) whose transcription is positively regulated by pAkt in cell lines. GO is most frequently associated with Graves’ disease (GD) in which thyroid stimulating antibodies bind the TSH receptor (TSHR) increasing cAMP. Previous studies highlight a role for TSAB and ‘neutral’ TSHR ant...

ea0021p156 | Diabetes and metabolism | SFEBES2009

Impact of extra cellular matrix changes on adipogenesis

Zhang Lei , Steadman Robert , de Lloyd Anna , Ham Jack , Rees Aled , Ludgate Marian

Obesity (excess adipose tissue generated by hypertrophy and hyperplasia) predisposes to poor health. Adipogenesis (hyperplasia) involves the differentiation of adherent preadipocytes into non-adherent adipocytes and is accompanied by alterations to the extracellular matrix of which hyaluronan (HA) is a component. Used in vitro to promote lineage specific differentiation, little is known of HA’s role in adipogenesis. We hypothesise that HA modifications must occur d...

ea0019oc24 | Cardiovascular metabolism | SFEBES2009

Metformin improves arterial stiffness and endothelial function in young women with PCOS: a randomised, crossover trial

Agarwal N , Rice S , Bolusani H , Newcombe R , Ludgate M , Rees A

Background: PCOS is a metabolic disorder associated with long-term health risks including insulin resistance, type 2 diabetes and dyslipidaemia. Metformin improves insulin sensitivity in PCOS and reduces circulating concentrations of markers of endothelial dysfunction, although it is unclear whether this translates into improvements in vascular function.Objective: To determine whether metformin therapy improves arterial stiffness and endothelial function...

ea0019oc33 | Thyroid, reproduction and endocrine tumours | SFEBES2009

Thyrotropin receptor (TSHR) activation increases hyaluronan (HA) production in preadipocyte-fibroblasts; explanation for HA accumulation in thyroid dysfunction?

Zhang L , Bowen T , Paddon C , Webber J , Giles P , Steadman R , Ludgate M

The thyrotropin receptor (TSHR) is expressed in the thyroid and in precursors undergoing lineage-specific differentiation, e.g adipogenesis. The TSHR is activated by TSH, thyroid stimulating antibodies (TSAB) and gain-of-function mutations (TSHR*). To investigate the role of extra-thyroidal TSHR activation we compared the gene-expression profiles of non-modified human subcutaneous preadipocytes with the parallel TSHR* population. Twenty-seven genes were significantly upregulat...

ea0019p139 | Diabetes, Metabolism and Cardiovascular | SFEBES2009

Effects of DHEA supplementation on vascular function in primary and secondary adrenal insufficiency: a randomised, crossover trial

Rice S , Agarwal N , Bolusani H , Newcombe R , Ludgate M , Rees A

Background: Patients with Addison’s disease (AD) and hypopituitarism have increased mortality, mainly from vascular disease. Both diseases are characterised by DHEA(S) deficiency yet this is not usually corrected. It is unclear whether treatment of these conditions with DHEA improves vascular risk.Objective: To evaluate the effects of DHEA on arterial stiffness and endothelial function in subjects with AD and hypopituitarism.M...

ea0013p303 | Thyroid | SFEBES2007

W546X mutation of the thyrotropin receptor, cause of subclinical hypothyroidism (SH) in various clinical settings

Locantore Pietro , Evans Carol , Zhang Lei , Warner Justin , Gregory John , John Rhys , Lazarus John , Ludgate Marian

Objectives: Pregnancy and early infancy are periods when increased demand for thyroid hormone can result in subclinical hypothyroidism (SH). SH is frequently a prodrome to autoimmunity, but may be a compensation mechanism for an underlying genetic defect. The W546X mutation of the thyrotropin receptor (TSHR) is present at a frequency of 1 in 180 in a Caucasian population. We aimed to investigate whether W546X was the cause of SH presenting in pregnancy and early infancy.<p...

ea0011oc7 | Signal transduction OC1 Novartis Oncology Young Investigator Award | ECE2006

The effect of bone marrow stem cell (BMSC) differentiation on growth hormone receptor (GHR)-associated signalling pathways

Lewis MD , Easter TE , Elford C , Ludgate ME , Evans BAJ , Rees DA , Scanlon MF

GH has diverse direct effects including the induction of lipolysis in adipocytes and mineralisation in bone. Interestingly, pluripotent mesenchymal stem cells can be isolated and cultured from adult bone marrow and induced to differentiate in vitro to both adipocytes and osteoblasts. GHR activation can be coupled to JAK2/STAT5 and the ERK (MAPK) pathway. We have therefore studied the evolution of GHR-associated cell signalling in adult rat BMSC’s during differentia...