Endocrine Abstracts

In early 2010, the Addison’s Disease Self-Help Group sent an information pack to 10 500 GP practices across the UK, outlining the GP’s role in diagnosis and care of the Addison’s patient. We asked the practice head to return a reply-paid questionnaire, detailing the number of steroid-dependent patients in the practice, their repeat prescription length, if they had an in-date supply of injectable hydrocortisone, and any comments on the challenges they faced in pr...

Age-related cognitive decline in postmenopausal women is thought to be partially related to the loss of sex steroids. Like women, old female rhesus monkeys (Macaca mulatta) undergo menopause and show an associated decline in circulating estradiol levels. Similarly, they show an age-related decline in the release of dehydroepiandrosterone (DHEA) from their adrenal glands. Because DHEA acts as a substrate for estradiol synthesis in the brain, it is plausible that DHEA sup...

Introduction: We have developed a highly sensitive LC–MS assay in an attempt to improve the measurement of salivary testosterone in female samples.Methods: A 200 μl saliva sample, calibrators or QC were mixed with 10 μl working internal standard (0.1 μg/l) and 1 ml of methyl tert-butyl ether (MTBE). Vortex mixed for 4 min and frozen at −80 °C (1 h). Unfrozen organic layer was transferred to a glass tube and evaporated. The ...

Steroid replacement is life-saving in patients with steroid axis deficiency; education surrounding steroid replacement is vital in their management.We organised ‘Steroid Replacement Education Days’ for patients and their family members/carers to help enhance their knowledge on steroids and intercurrent illness. Lectures detailed manifestations, causes, management of steroid deficiency and the practical issues surrounding steroid replacement. Th...

Introduction: It has been recognised in EQA schemes in Europe and America that the reproducibility between labs using LC–MS for testosterone analysis is not optimal for this technique. We decided to conduct a calibration exercise to investigate the variability seen between labs.Methods: Aqueous and matrix matched serum samples were sent to labs participating in the NEQAS testosterone scheme. The labs were asked to measure these samples blind using t...

Introduction: Prednisolone is well known to interfere in routine immunoassays for cortisol with uncertainty surrounding the degree of this interference. Methods using tandem mass spectrometry technologies offer more specificity, however there have been some reports of prednisolone interference in mass spectrometry assays. We aimed to characterise the extent of prednisolone interference in both an automated immunoassay and a tandem mass spectrometry method (TMS).<p class="a...

Aims/hypothesis: Adrenal incidentaloma (AI) are very common, but optimal management of patients with AI and low-grade excess cortisol secretion is not established. Uncontrolled studies reporting outcomes of adrenalectomy suggest improvements in cardiovascular risk, but all are subject to selection bias, and it is unclear if benefits are due to removal of excess cortisol. We reasoned that short-term use of mifepristone, a rapidly-acting glucocorticoid receptor (GR) antagonist, ...

Aim: In chronic kidney disease (CKD) elevated aldosterone (Aldo) levels are a poor prognostic indicator, particularly in the context of a high dietary sodium intake, through unclear mechanisms. Blockade of the mineralocorticoid receptor (MR) improves surrogate patient outcomes. We hypothesised that regulation of aldosterone biosynthesis is disordered in CKD and aimed to compare this in a cohort of patients with CKD with subjects with essential hypertension (EH).<p class="a...

Aim: Increasing left ventricular mass index (LVMI) is associated with a poor prognosis in patients with chronic kidney disease (CKD). Blockade of the mineralocorticoid receptor (MR) in CKD leads to improvement in proteinuria and LV mass. However, the MR can be activated by aldosterone, cortisol and deoxycorticosterone (DOC) and their relative contribution to adverse events in CKD is unclear. We aimed to assess the correlation between mineralocorticoid excretion and LVMI in pat...

Background and aims: Previously we showed that the bioactive liquorice constituent glycyrrhetinic acid (GA) inhibits not only 11β-hydroxysteroid dehydrogenase enzymes but also the sulphation of corticosteroids by the enzyme sulphotransferase 2A1 (SULT2A1). Since pregnenolone, 17α-hydroxy-pregnenolone, deoxycorticosterone (DOC) and dehydroepiandrosterone (DHEA) are all prime substrates for SULT2A1, GA could have important effects in directing pathways of glucocorticoi...

Introduction: The short synacthen test (SST) is commonly used to assess the hypothalamic pituitary adrenal (HPA) axis in clinical practice. We evaluated the underlying clinical conditions pre-empting the request for a SST in a general medical ward and the adequacy of clinical follow up of patients with suboptimal responses to the test.Methods: All patients with suboptimal SST results (30 min cortisol level 450–540 nmol/l) performed in the Acute Asse...

Glucocorticoid (GC) excess (Cushing’s syndrome) is characterized by central obesity, insulin resistance and in up to 20% of cases, non-alcoholic fatty liver disease (NAFLD). NAFLD is a progressive spectrum of disease ranging from hepatic steatosis to steatohepatitis, fibrosis and cirrhosis. Many processes contribute to lipid accumulation within heaptocytes including de novo lipogenesis which includes the rate-limiting carboxylation of acetyl CoA to malonyl-CoA by a...

Glucocorticoids act through the glucocorticoid receptor (GR) to regulate cell function. GR gamma (GRγ) is a constitutive exon3/4 splice variant, contributing 4–8% of the total GR transcripts and is highly conserved through mammalian evolution, but its biological function remains unknown. Using microarray analysis we identified the transcriptome response for GRγ in stable HEK-Flp cells. This revealed that although GRγ effectively modulated gene expression in...

Background: Human saliva is a valuable and flexible source of endocrine biomarkers, from which several significant steroids representing indices of development, well being, stress and reproduction can be quantified. Although for many disciplines blood represents the ‘gold standard’ for endocrine measurement, it also has its limitations, specifically requiring trained phlebotomists and appropriate facilities. The painful and invasive nature of blood draws can deter re...

Endocrine disruptors are chemicals that can alter functions of the endocrine system by several ways. Their risk assessment with regard to REACH legislation remains a challenge. In the present study, we propose an integrative evaluation for the effects of some endocrine disruptors on hormonal balance in male and female adult rats. We focused our work on the last step of steroidogenesis, where two enzymes are implicated: aromatase, which plays a central role by catalyzing the ir...

Hypercalcaemia is a rare, albeit well-described feature of hypoadrenalism, although the mechanism underlying this is remains controversial. Primary adrenal failure is known to occur secondary to infective agents, and indeed tuberculous infiltration of adrenal tissue represents one of the leading aetiologies worldwide. Primary adrenal failure has also been shown to occur secondary to sepsis with Meningococcus or Pseudomonas species, but classically this presents w...

The short synacthen test (SST) is the first-line test of adrenal insufficiency. Different centres have varying protocols for cortisol response. At Derriford Hospital cortisol is measured at 0, 30 and 60 min post-synacthen 250 μg (i.m./i.v.). A normal response is judged with a measured cortisol >550 nmol/l.A recent national audit questioned the bias created by the discrepancy between true cortisol (measured by mass spectrometry) and many laborato...

Steroids present in human serum can be used to identify a number of conditions such as congenital adrenal hyperplasia, Addison’s disease and Cushing’s disorder. Historically this has been completed using immunoassays; currently there is a move towards mass spectrometry which reduces analysis time, cross reactivity and improves sensitivity. When mass spectrometers are coupled with liquid chromatography systems (LC–MS) it is possible to monitor a number of steroid...

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by unresponsiveness to ACTH and isolated cortisol deficiency. FGD is caused by mutations in genes encoding the ACTH receptor (melanocortin 2 receptor (MC2R)), its accessory protein (MRAP) or the steroidogenic acute regulatory protein (StAR). One significant feature is generalized skin hyperpigmentation which is thought to be due to elevated ACTH acting on the melanocortin 1 receptor (...

A 21-year-old man presented with 2 months history of weight gain, acne, hirsutism, lethargy, and muscle weakness. Examination revealed that he was cushingoid in appearance, had pustular acne and proximal myopathy. Initial 24 h urinary free cortisol was significantly raised at 5320 nmol/day (10–147), with raised ACTH of 120 ng/l (<47). He failed to suppress his cortisol on the low dose dexamethasone suppression test (baseline 708 nmol/l and 48 h 706 nmol/l). Urinary an...

Aim: We present an unusual case of long-term accidental ingestion of androgenic steroid in a young female.Case: A 28-year-old lady presented with male pattern of hair growth, weight gain of three stones, change in voice, and secondary amenorrhea. On direct questioning she admitted she was taking ‘fat bursting pills’ for nearly 6 months, obtained from a gym, to lose weight. Examination revealed a blood pressure of 150/77 mmHg, increased muscle b...

Introduction: Prolonged use of topical corticosteroids causes systemic adverse effects including Cushing’s syndrome and hypothalamic–pituitary–adrenal (HPA) axis suppression, which is less common than that of the oral or parenteral route.History: A 31-year-old female patient was referred from the dermatology clinic with symptoms and signs consistent with Cushing’s syndrome. She has been treated for psoriasis with a prolonged course of...

Introduction: Short synacthen test (SST) is of value in assessing the adequacy of hypothalamic–pituitary–adrenal axis (HPA). Although it is extensively used, it is unclear at what morning cortisol concentration one should consider performing the SST.Methods: Retrospective observational study of consecutively performed SST (250 μg) between January 2009 and March 2010. Plasma cortisol was measured by enzyme immunoassay (Siemens Advia, Siemen...

Background and aims: The melanocortin-2-receptor accessory protein (MRAP) is essential for melanocortin-2-receptor (MC2R) function through receptor trafficking and signalling, enabling adrenal glucocorticoid synthesis in response to ACTH stimulation. Disabling mutations of MRAP result in life-threatening glucocorticoid deficiency, known as familial glucocorticoid deficiency type 2. MRAP has a single paralogue in the human genome, MRAP2. In vitro MRAP2 has a similar acti...

Introduction: Addison’s disease (AD) is a rare condition (reported prevalence of 40–110 per million) that requires prompt recognition and optimal management to prevent the risks associated with cortisol deficiency.Aim: To assess the prevalence, presentation and clinical course of patients diagnosed with AD in the geographical area of Banbury in Oxfordshire.Patients and methods: Notes of subjects with AD currently register...

Circulating estrogens decrease after the menopause from 60–400 to 5–30 pg/ml in postmenopausal women and in men are below 30 pg/ml. These low physiological concentrations present an analytical challenge. Analysis of steroids by tandem mass spectrometry is attractive due to its high specificity compared with immunoassays. However, estrogens do not ionise efficiently and therefore chemical modifications are necessary to achieve the sensitivity required.<p class="ab...

Background: Adrenal incidentalomas (AI) are identified in 4–7% of patients >40 years undergoing abdominal CT/MRI. Evidence of subclinical autonomous glucocorticoid hypersecretion (SAGH) is found in 5–10% of cases depending on the diagnostic criteria/thresholds adopted.Aim: To examine the utility of basal DHEAS measurement in the detection of SAGH in a cohort of patients with AI.Methods: Ninety-six consecutive subjects...

Introduction: Peptide immunotherapy has been shown to be a simple and effective method of restoring tolerance and reversing disease in animal models of type 1 diabetes. It is highly important to administer the peptide interadermally into an environment in which antigen presenting cells such as dendritic cells are maintained in a tolerogenic state.Objective: Our aim was to determine whether topical pre-treatment of the skin has the potential to enhance to...

Nearly all the functions of the liver display zonation in distribution within each the lobule. Hepatic cortisol availability is controlled by enzymes that regenerate cortisol from inactive cortisone (11β-hydroxysteroid dehydrogenase type 1, 11β-HSD1). Dysregulation of hepatic 11β-HSD1 activity has been implicated in insulin resistance. Key processes such as gluconeogenesis are located in the periportal hepatocytes, although current dogma describes hepatic 11&#94...