Endocrine Abstracts

Intracellular nicotinamide phosphoribosyltransferase (NAMPT) is the rate-limiting enzyme in the NAD salvage pathway. Abnormally elevated NAMPT can promote autoimmune and inflammatory processes. Many of these processes are key to type 1 diabetes (T1D) pathogenesis. Whilst NAMPT has been examined in other inflammatory diseases, the role of NAMPT in T1D remains unclear. To investigate the role of NAMPT in T1D, we used small molecule NAMPT modulators to determine the role of abnor...

Background: NEQAS data demonstrate a divergence in bias of cortisol immunoassays over the last 10 years. Despite this, a serum cortisol of 50 nmol/l has been universally applied as the cut-off for the overnight dexamethasone suppression test (ONDST), the commonest screening test for Cushing’s syndrome.Aims: To assess the effect of assay bias on interpretation of the ONDST and determine the necessity for a method-specific cut-off.<p class="abstex...

Introduction: The effects of mild subclinical hypothyroidism (SH; TSH <10 mU/l) on metabolic outcomes are unclear. This may relate to differences in aetiology, including thyroid autoimmunity or genetic factors such as TSH-receptor mutations (TSHR-M) and FOXE1 polyalanine tract length (FOXE1–PTL) polymorphisms, which are associated with altered thyroid function. We hypothesised that the metabolic manifestations of SH may depend upon its aetiology.<p class="abstext"...

The pattern of food consumption has a profound influence on metabolic hormone secretion, but until recently only crude manipulations of feeding events have been possible in rodents. Using a CLAMS-based system to overcome this problem, we have investigated the effect of 3 weeks of grazing (consumption of 1/24th of the total daily food intake of ad libitum-fed controls every 30 min during the dark phase (18.00–06.00 h)) and meal feeding (three 1-h periods of ad...

Introduction and aims: The short Synacthen test (SST) is used to diagnose underactivity of the HPA axis, with a cortisol response <550 nmol/l at 30 min widely accepted as diagnostic of adrenal insufficiency. Earlier studies of the SST have shown variation in cortisol concentrations measured by different immunoassays, suggesting the need for method-specific cut-offs. We sought to define the cortisol response to Synacthen in healthy volunteers (HV) and establish method-speci...

Kyphosis and scoliosis are common spinal disorders that lead to significant morbidity in childhood, adolescence and adulthood. Familial and twin studies have implicated a genetic involvement, although the causative genes remain to be identified. To facilitate these studies, we investigated 12-week-old progeny of mice treated with the chemical mutagen N-ethyl-N-nitrosourea (ENU) using phenotypic assessments that included dysmorphology, radiography and dual-energy ...

Bone marrow stem cells (BMSCs) are able to differentiate along multiple lineages including adipogenic and osteogenic lineages. The adenosine A1 receptor (A1R) modulates adipose tissue function causing an inhibition of lipolysis. We therefore studied A1R expression in BMSCs induced to differentiate along the adipogenic lineage.BMSCs were isolated from rat femur (10 wk male Wistar), cultured in control medium (alphaMEM 10% FCS) and then plated into adipocy...

Background: Serum thyroglobulin (Tg) is a useful marker of recurrent or persistent disease in the follow-up of patients with differentiated thyroid carcinoma (DTC); the presence of interfering Tg antibodies (TgAb), even in low concentrations, can lead to a distorted evaluation of this marker. However, TgAb by itself has been shown to be a marker of disease following surgery. TgAb recognition of Tg epitopes differs in pathological and non-pathological states and may thus have p...

Introduction: Adrenal lymphoma and its association with intravascular lymphoma is rare but needs consideration in cases presenting with bilateral adrenal masses and unexplained neurological symptoms. We present two recent cases presenting with multiple cerebral infarcts associated with primary adrenal lymphoma.Case 1: A 67-year-old male was admitted to the stroke unit with symptoms of middle cerebral artery (MCA) stroke. MRI demonstrated multiple infarct...

Objectives: The crystal structures of the TSH receptor (TSHR) leucine rich repeat domain (LRD) bound to TSHR stimulating monoclonal autoantibody M22TM or to TSHR blocking monoclonal autoantibody K1-70TM and antibody free have been solved previously. Cryo-electron microscopy (cryo-EM) was now used to solve the structure of full length TSHR in complex with K1-70TM.Methods: Recombinant human TSHR expressed in CHO cells was i...