Endocrine Abstracts

Pituitary and adrenal gland assessment, is one of the most important aspects of the management of a pituitary and adrenal adenoma.Clinical practice varies widely with regard to assessment of pituitary and adrenal status pre- and post-operative. Pre-operative testing includes dynamic testing to assess function which is not practical in the immediate post-operative period. Instead a single morning serum total hormones are measured while a more definitive a...

Background: 1-mg overnight dexamethasone-suppression test (DST) is commonly used to screen for hypercortisolism. Sensitivity is high (95%), but specificity is low (80%), leading to false positive results. Identifying individuals with abnormal dexamethasone absorption or metabolism could enhance diagnostic accuracy.Aim: Use serum dexamethasone (s-DXT) to increase diagnostic accuracy of DST.Methods: Prospective study of DST for clini...

Background: Hormones oscillate in circadian and ultradian rhythms. Single time point samples are difficult to interpret and high frequency measurements are time consuming, expensive and invasive. We developed a minimally invasive technique of ambulatory, automated microdialysis. This allows frequent 24-hour sampling of interstitial fluid while participants continue normal daily activities.Methods: Healthy volunteers (age 18–68, no regular medication...

The current conventional glucocorticoid (GC) replacement therapy in primary adrenal insufficiency (Addison’s disease) and congenital adrenal hyperplasia (CAH) renders the cortisol levels unphysiological, resulting in very high levels alternating with almost undetectable levels of cortisol over the day. This reduces not merely the patient’s quality of life but increases the patient’s morbidity and mortality. The HPA axis is characterised by a dynamic circadian va...

Introduction: An increased frequency of autoimmune diseases and an elevated incidence of autoantibodies have been observed in Turner syndrome (TS), but indirect immunofluorescence (IIF) has not been able to demonstrate autoantibodies against the adrenal cortex. We asked if the more sensitive radioimmunosorbant assay employing recombinant human 21-hydroxylase was able to identify autoantibodies against 21-hydroxylase, (21OH-Ab) in TS patients; 21-hydroxylase is the major adrena...

BackgroundNon-classical congenial adrenal hyperplasia (NCCAH) is an important differential diagnosis in women with acne, hirsutism, menstrual abnormalities and infertility. To diagnose NCCAH can be challenging, and currently used cutoff levels are based on unstandardized immunological assays, no longer in use.ObjectiveDefine LC-MS/MS based cut-off levels for steroid hormones, to improve diagnosis of NCCAH and...

Autoimmune Polyendocrine Syndrome type-1 (APS-1) is a rare monogenic disease (1:100 000 frequency), caused by mutations in the autoimmune regulator (AIRE) gene, which plays a crucial role in the thymus for negative selection of self-reacting T cells. With tissue damage caused by self-reactive immune cells from early stages of life and gradually presenting with symptoms in following years, APS-1 is clinically diagnosed by presence of minimum two components of the classical tria...

Background: Establishing endocrine diagnoses including pituitary Cushing’s remains challenging with delayed or misdiagnosis being very costly for both patient and the health care system. A key issue is that standard diagnostic tests are typically single time point, single analyte samples, which do not consider dynamic variation intrinsic to endocrine systems. Having previously demonstrated that free tissue hormones correlate strongly with plasma concentrations, we present...

The 21-hydroxylase (21OH) gene, CYP21A2, encodes the 21OH steroidogenic enzyme which is the primary autoantigen in autoimmune Addison’s disease (AAD). It is located on chromosome 6p21, in a copy number repeat termed RCCX, adjacent to the 21OH pseudogene (CYP21A1P). CYP21A1P is highly homologous to CYP21A2 but contains an 8 bp deletion in exon 3 (707-714delGAGACTAC) which results in a frameshift. The predicted protein product is...

Background: Conventional glucocorticoid replacement therapies result in unphysiological variation in plasma cortisol levels; concern has been raised regarding long-term metabolic consequences. Glucocorticoid replacement is technically feasible by continuous subcutaneous hydrocortisone infusion (CSHI), which can mimic the normal diurnal cortisol rhythm. The aim of this study was to compare insulin sensitivity in patients with Addison’s disease (AD) on CSHI vs three daily d...