Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES

ea0013p266 | Steroids | SFEBES2007

A case of Addison’s disease associated with hypogonadotrophic hypogonadism

Zachariah Sunil , Hyer Steve

A 30 year old gentleman was admitted to our department with symptoms of tiredness and weight loss over the past 3 weeks. He also gave a history of erectile dysfunction for several years. His only significant past history was asthma well controlled on inhalers. On examination he appeared tanned. There was no buccal or skin crease pigmentation. Smell sensation was normal and he had normal external genitalia and secondary sexual characteristics.Initial inve...

ea0013p267 | Steroids | SFEBES2007

Identification of a novel, point mutation in helix 11 of the ligand-binding domain of the human glucocorticoid receptor-α (hGRα) gene and molecular characterization of the mutant receptor hGRαF737L

Charmandari Evangelia , Kino Tomoshige , Ichijo Takamasa , Zachman Keith , Chrousos George

Background: Generalized glucocorticoid resistance is a rare condition characterized by partial, end-organ insensitivity to glucocorticoids, compensatory elevations in ACTH and cortisol secretion, and increased production of adrenal steroids with androgenic and/or mineralocorticoid activity. We identified a new case of glucocorticoid resistance caused by a novel, heterozygous point mutation at nucleotide position 2209 (T → C) of the hGRα gene, resulting in phenylalan...

ea0013p268 | Steroids | SFEBES2007

A case of “cured” late-onset congenital adrenal hyperplasia

Fountain Annabel , Johnston Colin

We present a 46 year old female referred in 1990 with hirsutism, hypertension and irregular menses. She was not overweight at 50.3 kg. The facial hair was controlled with electrolysis; blood pressure controlled with Enalapril and Bendrofluazide.Initial biochemistry showed an elevated LH/FSH ratio (19.6:4.2 U/L), raised testosterone (3.9 nmol/L), high DHEA (14.7 umol/L) SynACTHen test revealed a significant increase in 17-hydroxyprogesterone basal 3.9 nmo...

ea0013p269 | Steroids | SFEBES2007

What factors influence serum testosterone levels when initiating Nebido®?

Moisey Robert , Swinburne Julie , Orme Steve

It is important when initiating intramuscular Nebido (testosterone undecanoate) to monitor the serum testosterone level to ensure physiological replacement is achieved. Following a loading regimen of Nebido the manufacturer recommends measuring testosterone levels to determine the frequency of subsequent injections.We conducted a retrospective study of 36 hypogonadal men [12 (33%) primary hypogonadism, 24 (67%) secondary hypogonadism] to establish what f...

ea0013p270 | Steroids | SFEBES2007

Establishing a reference range for urine cortisol:creatinine ratio

Reynolds Rebecca , Ho Clement , Sawyers Louise , Gough Kathleen , Shearing Catherine

Background: Measurement of urinary cortisol is commonly used in the investigation of suspected Cushing’s Syndrome and is most often performed using immunoassay. This approach exhibits significant assay variability necessitating the use of method specific reference ranges. A reference range for cortisol nmol/L: creatinine mmol/L ratio is reported based on the results from 104 early morning urine samples collected from healthy individuals and analysed using the AutoDelfia A...

ea0013p271 | Steroids | SFEBES2007

A new source of ectopic ACTH

Butt Muhammad , Robinson Anthony

A 60 years old man was referred to the ENT department with a three week history of swelling in the left parotid gland region. Examination revealed a firm mass involving the left parotid gland. Fine needle aspiration cytology of the mass raised the suspicion of a malignancy. MRI scan of head and neck was consistent with metastatic involvement of the ipsilateral lymph glands. He underwent left radical neck dissection and left parotidectomy. Histology confirmed adenocarcinoma of ...

ea0013p272 | Steroids | SFEBES2007

A central physiological role for attenuated circulating DHEAS levels in aged female Rhesus Macaques?

Urbanski Henryk , Lemos Dario , Sitzmann Brandon , Garyfallou Vasilios , Kohama Steven

In humans and rhesus monkeys (Macaca mulatta) the zona reticularis of the adrenal gland produces large amounts of dehydoepiandrosterone (DHEA) and its sulfated form, DHEAS. The circulating levels of these steroids are particularly high during early adulthood, and they then decline gradually during aging, especially in females. To help elucidate the physiological function of this steroidal loss we examined the 24-hour plasma profiles of DHEAS in female rhesus monkeys, us...

ea0013p273 | Steroids | SFEBES2007

Aldosterone induces collagen synthesis via activation of ER1/2 in renal proximal tubular epithelial cells

Xu Guoshuang , Chen Wei , Liu Xiaowei , Wang Hanmin , Liu Hongbao , Bai Shurong

Aldosterone play pivotal roles on renal fibrosis by inducing mesangial cells proliferation and stimulating collagen synthesis in renal fibroblasts. However, whether renal proximal tubules are involved in aldosterone-induced renal fibrosis is not yet identified. The aim of this study was to examine the potential role of aldosterone in collagen expression via activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) in cultured human renal proximal tubular epit...

ea0013p274 | Steroids | SFEBES2007

A life threatening presentation of addisons disease

Watchorn James , Sikri Shankar , Barrington-Ward Elaine , Hatfield Emma

A 25 year old man, with no significant past medical history and on no medication, presented to Accident and Emergency with collapse. He was anuric, hypotensive, with a sodium of 107 and a potassium of 8.8. Electrocardiographic changes showed widening of the QRS complex and tall tented T waves. He was in prerenal renal failure with a creatinine of 377 and urea of 36.9.This presentation came after a week of feeling non-specifically unwell, progressive fati...

ea0013p275 | Steroids | SFEBES2007

Genetic variation at the CYP11B locus accounts for heritabilities of aldosterone excretion and 11-beta hydroxylase activity

Freel E Marie , Imrie Helen , Avery Peter , Ingram Mary , Mayosi Bongani , Farrall Martin , Watkins Hugh , Fraser Robert , Davies Eleanor , Connell John , Keavney Bernard

Aldosterone is a key cardiovascular hormone: 15% of hypertensives have altered aldosterone regulation, defined by a raised ratio of aldosterone to renin. However, the causes of aldosterone excess are not understood. Polymorphic variation in the gene encoding aldosterone synthase (CYP11B2) is associated with hypertension, but the most robust phenotype is a relative reduction in efficiency of 11ß-hydroxylation (conversion of deoxycortisol to cortisol), which reflects functi...

ea0013p276 | Steroids | SFEBES2007

ACTH insensitivity syndromes; rare causes of glucocorticoid deficiency we should not forget

Kumar Rajeev , Banerjee Ritwik

ACTH insensitivity syndromes comprise a rare, and underrecognised, group of disorders, which include familial glucocorticoid deficiency (FGD) and triple A or Allgrove syndrome (ACTH insensitivity, alacrima, achalasia and neurological involvement). They are characterised by undetectable cortisol and very high circulating ACTH with resultant hyperpigmentation and are inherited in an autosomal recessive manner. Distinction between FGD and triple A syndrome may be difficult and is...

ea0013p277 | Steroids | SFEBES2007

The effect of septic serum on adenylyl cyclase and adrenocortical responsiveness in vitro and in vivo

Chung Teng-Teng , King Peter J , Hinds Charles , Clark Adrian J

Attenuation of the adrenocortical response to ACTH in septic shock is a well recognised phenomenon, although the underlying mechanisms remain poorly understood. The evidence points towards factors in septic serum that dampen the adrenocortical responsiveness. The aim of this work is to investigate the cellular function of adrenocortical cells in septic shock and to determine the components within serum that could influence their function. Septic rat serum was collected from ma...

ea0013p278 | Steroids | SFEBES2007

Testosterone and frailty in ageing men

Srinivas-Shankar Upendram , Oldham Jackie A , Connolly Martin J , Wu Frederick CW

Introduction: Frailty, a common cause of disability and dependency in the elderly is a multifactorial condition; ageing-associated endocrine dyregulations may play an important role. It is not known if testosterone (T) deficiency contributes to frailty, through its effects on muscle (sarcopenia) and physical function.Objective: To investigate the relationship between T and frailty in elderly men in a cross-sectional observational study in community-dwell...

ea0013p279 | Steroids | SFEBES2007

Comparison of 24 hour urine free cortisol measurement and hydrocortisone day curve in the assessment of hydrocortisone replacement in hypoadrenal patients

George Ajith , Twine Gina , Flanagan Daniel

Hydrocortisone day curves, Salivary cortisols, timed urinary free cortisols and 24 hour urine cortisols have been used to estimate hydrocortisone replacement in hypoadrenal patients.We looked at 39 patients who had hydrocortisone day curve estimations in our hospital. 35 of those patients had simultaneous 24 hour urine free cortisol estimation. All hypothyroid patients were on adequate replacement dose of thyroxine.The commonest cl...

ea0013p280 | Steroids | SFEBES2007

Subclinical Addison’s disease

Hughes Katherine , Sandeep Thekkepat , Adamson Karen

A young female presented concerned that she may have Addison’s disease. She had noted increasing pigmentation and reported her sister had died from undiagnosed Addison’s disease. She was hypotensive, with no postural drop in her blood pressure. She was hyponatraemic and hyperkalaemic. An initial 250 μg Synacthen test performed in the afternoon gave a baseline cortisol of 258 nmol/L and a 30 minute cortisol of 291 nmol/L. In view of this, the Synacthen test was r...

ea0013p281 | Steroids | SFEBES2007

An adrenal ‘coming full circle’

Zachariah Sunil , Nussey Steve , Bano G

37 year old gentleman presented with Cushing’s disease at the age of 15 with obesity, growth retardation, and vertebral fracture. After bilateral adrenalectomy and pituitary irradiation he was treated with hydrocortisone and fludrocortisone. After being lost to follow up for a number of years he was referred to our endocrine clinic in 1999. Clinical examination revealed that he was obese (BMI 39.2), hypertensive and had marked abdominal striae. Investigations revealed an ...

ea0013p282 | Steroids | SFEBES2007

Acute improvement in insulin sensitivity by PPARgamma-agonists is not mediated by inhibition of glucocorticoid action in humans

Stimson Roland , Wake Deborah , Andrew Ruth , Walker Brian

PPARgamma-agonists improve insulin sensitivity and discourage visceral fat accumulation but mechanisms remain uncertain. In rodents, PPARgamma-agonists downregulate 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) in adipose tissue (AT), thereby potentially decreasing intra-adipose glucocorticoid (GC) concentrations. We tested whether PPARgamma-agonists regulate 11b-HSD1 in humans, and if their insulin-sensitising effect is GC-dependent.12 healthy m...

ea0013p283 | Steroids | SFEBES2007

Regulation of insulin signalling across differentiation and following glucocorticoid treatment in human skeletal myocytes

Morgan Stuart , Gathercole Laura , Bujalska Iwona , Stewart Paul , Smith David , Tomlinson Jeremy

Glucocorticoid (GC) excess is characterized by increased adiposity, skeletal myopathy and insulin resistance. Despite the increasing use of GCs as therapeutic agents, the molecular mechanisms that underpin the GC mediated changes in insulin signalling are not clear. The majority of previous studies have used rodent models and have shown regulation at the level of the insulin receptor (IR), IRS-1 and PI3 kinase.Primary cultures of human skeletal myocytes ...

ea0013p284 | Steroids | SFEBES2007

Identification of novel modulators of glucocorticoid sensitivity

Berry Andrew , Ray David , Donn Rachelle

Glucocorticoids (GCs) are potent anti-inflammatory agents, but a variable therapeutic response occurs. We have used microarray analysis to explore the basis for inter-individual differences in the GC sensitivity of a healthy volunteer population, and identified genes predictive of response to GCs. Three such discriminating genes were then selected to be investigated for their potential to interact with the Glucocorticoid Receptor (GR). These are the Bone Morphogenetic Protein ...

ea0013p285 | Steroids | SFEBES2007

Does ginseng ingestion influence salivary testosterone and DHEA levels in females

Al-Dujaili Emad , Chalmers Ruth , Sharp Martin

Ginseng, a traditional herbal adaptogen, historically used in the Far East, has gained popularity in the West for its restorative properties.Ginsenosides, the active component of ginseng are known to exert a variety of actions by targeting ‘multireceptor systems’ both extracellular and intracellular. As a result many of its physiological effects remain unclear, particularly in humans. This study aims to investigate whether ginseng can influence...

ea0013p286 | Steroids | SFEBES2007

Effect of Glycaemic index of the diet on salivary cortisol and testosterone levels in females

Al-Dujaili Emad , Ashmore Sophie

There has been great interest in the effect of Glycaemic index (GI) of food on weight reduction, obesity, metabolic syndrome and general well being in women. The majority of research into GI was focussed towards improving blood glucose control in diabetes. Also, favourable changes in blood lipids and some beneficial effect in cancers have been reported. The aim of this pilot study is to investigate the impact of ingesting food with varying GI on salivary cortisol and testoster...

ea0013p287 | Steroids | SFEBES2007

Unusually mild phenotypic presentation in a family with CYP17A1 deficiency detected by urinary steroid profiling

Arun CS , Ivison HE , Taylor Norman , Arlt Wiebke , Cheetham Tim

The human CYP17A1 enzyme exerts two activities, 17a-hydroxylase and 17,20 lyase, catalysing key steps in human adrenal steroid biosynthesis. An in frame deletion of 3 bp in exon 1 of the CYP17A1 gene, resulting in the loss of phenylalanine in position 53 (F53del), is one of the first CYP17A1 mutations described (JBC 1989, 264:18076). Reported patients have invariably presented with severe hypokalaemic hypertension, reflecting 17α-hydoxylase deficiency, and s...

ea0013p288 | Steroids | SFEBES2007

Glucose-6-phosphate disposal and regulation of 11β-hydroxysteroid Dehydrogenase type 1: A new link between cellular glucose metabolism and the HPA axis

Ahmed Adeeba , Lavery Gareth , Tomlinson Jeremy , Cooper Mark , Chou Janice , McKiernan Patrick , Elias Elwyn , Walker Elizabeth , Stewart Paul

Microsomal glucose-6-phosphatase (G6Pase) and glucose-6-phosphate transporter (G6PT) are key enzymes in regulation of blood glucose concentration. Deficiency of G6Pase gives rise to glycogen storage disease type Ia (GSDIa) whilst mutations in G6PT cause GSDIb. Both are characterized by growth retardation, hypoglycemia, hepatomegaly, nephromegaly. G6Pase shares its substrate (G6P) with hexose-6-phosphate-dehydrogenase (H6PDH), an ER enzyme functionally coupled with, and which c...

ea0013p289 | Steroids | SFEBES2007

Is the rate of fall in total testosterone steeper among men in the eighth decade of life?

Srinivas-Shankar Upendram , Oldham Jackie A , Connolly Martin J , Wu Frederick CW

Background: Testosterone (T) levels decline gradually with increasing age in men. However, age-related decline in several functional domains (e.g. frailty, cognitive deficits, osteoporosis) accelerates in the eighth decade. It is not known if the loss of function in the oldest old is related to a more precipitous fall in T.Objective: To determine if total testosterone (TT) declines more rapidly in men in the eighth compared to those in the sixth and seve...

ea0013p290 | Steroids | SFEBES2007

Glucocorticoid treatment and the consequences in adults with congenital adrenal hyperplasia

Doherty Emma , Powrie Jake , Breen Louise , Thomas Stephen , Brackenridge Anna , Carroll Paul

No guidelines exist for the management of Congenital Adrenal Hyperplasia (CAH) in adults. With no ideal glucocorticoid regimen to replicate normal physiology, best practice remains unclear. Concerns have been raised regarding overtreatment, particularly with longer acting steroids, and potential adverse effects on body composition and bone mineral density (BMD).We examined the case records of all 35 patients currently under review in our unit. Mean±...

ea0013p291 | Steroids | SFEBES2007

The effects of glucocorticoids on the expression of gluconeogenic and lipogenic enzymes in a rodent model of Cushing’s Syndrome

Lolli Francesca , Christ-Crain Mirjam , Kola Blerina , Fekete Csaba , Wittman Gabor , Grossman Ashley B. , Korbonits Marta

Background: Cushing’s syndrome results from chronic exposure to excessive levels of glucocorticoids (GC). The clinical manifestations associated with hypercortisolaemia are variable and differ widely in severity, including hypertension, apparent obesity and metabolic aberrations such as diabetes, dyslipidaemia, ultimately leading to changes similar to the metabolic syndrome. We hypothesised that GC might influence the expression of the genes involved in lipogenesis and gl...