Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2012

ea0028p302 | Steroids | SFEBES2012

Reversal of age-induced dermal atrophy in 11β-hydroxysteroid dehydrogenase type 1-null mice

Tiganescu Ana , Parish W , Walker Elizabeth , Cooper Mark , Lavery Gareth , Stewart Paul

Glucocorticoid (GC) excess, whether exogenously- or endogenously-derived, induces many adverse effects in skin including thinning, decreased cellularity and reduced collagen synthesis. Consequently, skin exhibits reduced dermal structural integrity, increased atrophy/fragility/bruising and impaired wound healing, effects that perfectly mimic skin ageing. Local GC levels are regulated in a tissue-specific manner by 11β-hydroxysteroid dehydrogenase (11β-HSD) isozymes i...

ea0028p303 | Steroids | SFEBES2012

Demonstration of blood pressure-independent diffuse cardiac fibrosis in Primary Aldosteronism- a cardiac MRI study

Freel Ellen , Mark Patrick , Weir Robin , McQuarrie Emily , Allan Karen , Dargie Henry , Jardine Alan , Davies Eleanor , Connell John

Background: Primary Aldosteronism (PA) is common and associates with excess cardiovascular morbidity independent of blood pressure. Animal and in vitro studies have demonstrated that exposure to aldosterone and sodium leads to cardiac fibrosis and hypertrophy and this may, partly, be mediated by inflammation and oxidative stress. We aimed to clarify the effects of aldosterone excess on myocardial structure and composition in humans using contrast-enhanced cardiac MRI as well a...

ea0028p304 | Steroids | SFEBES2012

HSD11B1 promoter binding of the NF-κB p65 subunit in response to TNF-α suppresses 11β-HSD1 expression and activity in C2C12 muscle cells

Doig Craig , Bashir Jamila , Zielinska Agnieszka , Cooper Mark , Stewart Paul , Lavery Gareth

A counter-regulatory rise in GC levels is important to the inflammatory response, that when impaired is associated with high mortality in inflammatory states. 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) regenerate’s intracellular glucocorticoids (GC), amplifying their actions, and has been postulated to play a role in the development of inflammation-associated arthritis, obesity and myopathy. Pro-inflammatory cytokines (e.g. TNF-α) increase expressio...

ea0028p305 | Steroids | SFEBES2012

Ageing and social isolation increase susceptibility to anxiety in mice lacking 5α-reductase type 1

Di Rollo Emma , Livingstone Dawn , Walker Brian , Andrew Ruth

Glucocorticoid excess is associated with increased anxiety and accelerated cognitive decline. Concentrations of glucocorticoids within tissues, including the brain, are influenced by local metabolism. 5α-Reductase 1 (5αR1), expressed in brain, converts corticosterone to its A-ring reduced metabolites, which have a different spectrum of activities. Here, we investigated if mice homozygous for disrupted 5αR1 alleles (5αR1-KO) experience heightened anxiety and...

ea0028p306 | Steroids | SFEBES2012

Genotype-phenotype correlation in 153 adult patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency - analysis of the United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE) cohort

Krone Nils , Rose Ian , Willis Debbie , Wild Sarah , Hodson James , Doherty Emma , Hahner Stefanie , Parajes Silvia , Stimson Roland , Han Thang , Carroll Paul , Conway Gerard , Walker Brian , Macdonald Fiona , Ross Richard , Arlt Wiebke , CaHASE The UK CAH Adult Study Executive

In congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency a genotype-phenotype correlation exists for paediatric cohorts, helping to predict the severity of disease expression. Data on the correlation in adults is lacking. Here we report the genetic analysis of the UK CaHASE cohort, comprising CAH adults seen at 17 endocrine tertiary care centres. CYP21A2 mutation analysis was performed in 153 patients (median age 35 (range 18–69) yrs; 103 f, 50 m) by multi...

ea0028p307 | Steroids | SFEBES2012

Adipose depot specific regulation of insulin signalling by glucocorticoids

Gathercole Laura , Morgan Stuart , Bujalska Iwona , Nasiri Maryam , Stewart Paul , Tomlinson Jeremy

Intra-abdominal adiposity is associated with insulin resistance and increased cardiovascular morbidity and mortality. Consequently, there is a need to identify factors involved in adipose tissue distribution. Patients with glucocorticoid (GC) excess develop a classic phenotype characterized by central, but not peripheral, obesity. Differences in gene expression between omental (om) and subcutaneous (sc) adipose tissue have been described, however, the molecular mechanisms unde...

ea0028p308 | Steroids | SFEBES2012

Negative regulation of 11β-HSD1 by GH in key metabolic tissues may contribute to metabolic disease in GH deficient patients

Morgan Stuart , Berryman Darlene , List Edward , Lavery Gareth , Kopchick John , Stewart Paul

Patients with growth hormone deficiency (GHD) have many clinical features in common with Cushing’s syndrome (glucocorticoid excess) - notably visceral obesity, insulin resistance, osteoporosis and increased vascular mortality. Within key metabolic tissues, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to the active glucocorticoid, cortisol, and thus amplifies local glucocorticoid action. We hypothesise that 11β-HSD1 expression is neg...

ea0028p309 | Steroids | SFEBES2012

Modifying impact of 17-hydroxyprogesterone and sex steroids on mineralocorticoid receptor transactivation by aldosterone

Mooij Christiaan , Parajes Silvia , Arlt Wiebke , Claahsen-van der Grinten Hedi , Krone Nils

Context: Congenital adrenal hyperplasia (CAH) is caused by 21-hydroxylase deficiency in 95% of the cases. This leads to accumulation of steroid precursors prior to the enzymatic block and increased adrenal androgen production; accordingly serum concentrations of 17-hydroxyprogesterone (17OHP), androstenedione and testosterone are elevated in affected patients.Objective: To analyse the effect of 17OHP, androstenedione and testosterone on aldosterone-media...

ea0028p310 | Steroids | SFEBES2012

Oxidative stress in the pathogenesis of triple a syndrome

Prasad Rathi , Clark Adrian , Storr Helen

Background: Triple A Syndrome is a rare, autosomal recessive cause of adrenal failure that usually manifests in the first decade. Most cases have isolated glucocorticoid deficiency, but this is accompanied by mineralocorticoid deficiency in approximately 10% of cases. Additional features include alacrima (~90%), achalasia of the oesophageal cardia (~75%), and a progressive neurodegenerative process (~60%). The AAAS gene product is the nuclear pore complex protein ALADIN...

ea0028p311 | Steroids | SFEBES2012

Adrenal expression of the melanocortin-2-receptor and its accessory proteins during sepsis.

Gorrigan Rebecca , Elias Lucila , Clark Adrian , Chan Li

Background: The melanocortin 2 receptor (MC2R)/melanocortin 2 receptor accessory protein (MRAP) are critical components of the hypothalamo-pituitary-adrenal axis (HPA). MRAP2, homologue of MRAP, can also regulate the MC2R in vitro, however, the physiological significance of this is unclear. We studied the expression of the MRAPs and MC2R in a well-defined rat model of endotoxin induced septic shock. These animals have been shown to have higher ACTH and corticosterone le...

ea0028p312 | Steroids | SFEBES2012

Effects of In-Utero Exposure to Endocrine Disruptors on the Ovine Fetal Adrenal Gland

Buckley Charlotte , Danga Mercy , Hogg Kirsten , Amezaga Maria , Rhind Stewart , Fowler Paul , Rae Michael , Morley Steven

Introduction: The repercussions of long-term exposure to low level mixtures of endocrine disrupting compounds (EDCs) which are present, ubiquitously, in the environment are not well understood. Heat-treated sewage sludge, an EDC-rich product used as fertiliser, has been shown to compromise testicular and ovarian development. However, to date, there has been limited investigation in exposed animals of the adrenal glands, the steroid hormone products of which play key roles in f...

ea0028p313 | Steroids | SFEBES2012

Pomegranate juice intake enhances salivary testosterone levels and improves mood and well being in healthy men and women

Al-Dujaili Emad , Smail Nacer

Background: Through out history, pomegranate symbolizes fertility and has been postulated to enhance sexual function and drive. Recently, we have shown that pomegranate juice rich in polyphenolic antioxidants can alleviate stress and cardiovascular risk factors by reducing systolic and diastolic blood pressure and inhibiting 11βHSD1 activity. The aim of this study was to investigate whether pomegranate juice intake influences mood and salivary testosterone levels in healt...

ea0028p314 | Steroids | SFEBES2012

Development of a highly sensitive and specific ultra high performance liquid chromatography tandem mass spectrometry method for the quantitation of aldosterone in human plasma

Hinchliffe Edward , Carter Stephanie , Owen Laura , Adaway Joanne , Keevil Brian

Introduction: Aldosterone is a potent adrenal steroid hormone which regulates renal sodium reabsorption and potassium secretion. Clinically, measurement of aldosterone is important to identify patients with primary hyperaldosteronism, and has traditionally been performed by immunoassay. The specificity of immunoassays is often poor due to antibody cross reactivity to other structurally related steroid hormones, resulting in falsely elevated concentrations. To overcome these li...

ea0028p315 | Steroids | SFEBES2012

Suppression of adrenal cortisol metabolism by type 2 11β-hydroxysteroid dehydrogenase enzyme (11βHSD2) in the luteal phase of the ovine oestrous cycle

Tennant Laura , McIlvride Saraid , Abayasekara Dilkush , Michael Anthony

We have previously investigated the ability of glucocorticoids secreted by the adrenal cortex to directly influence gonadal function. In contrast, the primary aim of the present study was to assess whether increased progesterone output from the corpus luteum on day 14 of the ovine oestrous cycle can alter adrenal metabolism (and hence output) of cortisol relative to oestrous cycle day 5. Since cortisol-cortisone inter-conversion by the cloned 11β-hydroxysteroid dehydrogen...

ea0028p316 | Steroids | SFEBES2012

Impact of prenatal androgens on glucocorticoid metabolism in an ovine model of PCOS.

McIlvride Saraid , Ellison Alicia , Hogg Kirsten , McNeilly Alan , Duncan Colin , Michael Anthony

Within target cells, cortisol-cortisone inter-conversion is catalysed by both a NADP(H)-dependent, bidirectional type 1 11β-hydroxysteroid dehydrogenase (11βHSD1) enzyme and by a NAD+-dependent, unidirectional type 2 11βHSD (11βHSD2) isoenzyme. Since several published studies have reported altered glucocorticoid metabolism in polycystic ovary syndrome (PCOS), the current study assessed whether prenatal exposure of lambs to testosterone propionate...

ea0028p317 | Steroids | SFEBES2012

Effects of mitotane on exogenous and endogenous steroid metabolism

Ghataore Lea , Chakraborti Indira , Aylwin Simon , Schulte Klaus-Martin , Taylor Norman

Objective: Mitotane (o,p’DDD) is an effective adrenolytic agent for treatment of advanced adrenocortical carcinoma (ACC). Suppression of cortisol biosynthesis, including inhibition of 11β-hydroxylation, has been described. Decreased cortisol bioavailability is indicated by increased dose requirement for hydrocortisone replacement during mitotane treatment. Urinary excretion of common cortisol metabolites (CM) has been reported to be normal but with increase of 6&#946...

ea0028p318 | Steroids | SFEBES2012

The cortisol response to hypobaric hypoxia at rest and post-exercise

Stacey Mike , Davison Andrew , Mellor Adrian , Smith Chris , Hooper Tim , Neely Dermot , Peaston Bob , Turner Steve , Woods David

High altitude exposure leads to a marked natriuresis and diuresis facilitated by a reduced resting and subdued post-exercise aldosterone. There is a strong correlation between aldosterone and cortisol at high altitude and although most, but not all, investigators report a rise in cortisol with ascent very little data exist regarding the post-exercise response in cortisol. We therefore measured salivary cortisol in a cohort of 45 subjects post-exercise and 20 subjects at rest w...

ea0028p319 | Steroids | SFEBES2012

The use of nocturnal salivary cortisol and urinary cortisol to creatinine ratio in the evaluation of cycling in patients with Cushing’s syndrome

Graham Una , Hunter Stephen , McDonnell Margaret , Mullan Karen , Atkinson Brew

Cyclical Cushing’s syndrome is typically detected by collecting sequential daily early morning urine (EMU) samples for cortisol to creatinine ratio over a 28 day period. More recently nocturnal salivary cortisol (NSC) measurement has been shown to be a sensitive means of screening for Cushing’s syndrome. The Endocrine Society have suggested that NSC may be used to assess patients for cyclical Cushing’s however there is limited evidence that it correlates with th...

ea0028p320 | Steroids | SFEBES2012

Use of the 250mcg short synacthen test to differentiate between patients with primary aldosteronism and essential hypertension

Graham Una , Hunter Stephen , McCance David , Atkinson Brew , Mullan Karen

Aberrant and upregulated eutopic receptors have been identified in vitro in patients with primary aldosteronism (PA). We previously identified an exaggerated aldosterone response to synacthen in patients with PA versus healthy controls. In this study we aimed to evaluate whether the synacthen test differentiates between patients with PA and essential hypertension (EH). The 250 mcg intramuscular synacthen test was performed after 30 minutes recumbency in the morning and off int...

ea0028p321 | Steroids | SFEBES2012

Rare variants of sialic acid acetylesterase in autoimmune Addison’s disease

Gan Earn , Mitchell Anna , MacArthur Katie , Pearce Simon

Sialic acid acetylesterase (SIAE) has been found to be essential for the maintenance of immune tolerance in mice by negatively regulating B lymphocyte antigen receptor signalling. Recently, numerous rare heterozygous loss-of-function germline variants and a homozygous functionally defective variant of the SIAE gene (M89V) have been identified as conferring a strong genetic susceptibility to several autoimmune disorders, including T1DM and rheumatoid arthritis. We performed a c...

ea0028p322 | Steroids | SFEBES2012

Modified-release prednisolone increases quality of life compared to standard prednisolone in patients with adrenal insufficiency

Quinkler Marcus , Ventz Manfred , Hinz Andreas , Langenheim Jorinde

Context: Patients with adrenal insufficiency (AI) receive glucocorticoid replacement therapy, which tries to imitate physiological adrenal secretion. However, the first glucocorticoid dose is usually given after waking in the morning resulting in a 3–5 h delay compared to physiological secretion. Impaired quality of life (QoL) might be, in part, due to this delayed dose scheme. Therefore, modified-release glucocorticoid preparations might have therapeutical advantages.</p...

ea0028p323 | Steroids | SFEBES2012

Mitogen mediated Gc resistance, development of model using serum shock

Yang Nan , Trebble Peter , Matthews Laura , Ray David

Glucocorticoids (Gc) are the most potent anti-inflammatory agents known. A major factor limiting their clinical use is the wide variation in responsiveness to treatment between individuals and over time. Generating a reversible model of Gc resistance in vitro that will mimic the cellular microenvironment in vivo is critical in (i) defining biomarkers that predict patient steroid responsiveness; (ii) provide a model to screen new GR modulators capable of potentiating GR ...

ea0028p324 | Steroids | SFEBES2012

Ethanolic extract of Medicago sativa exhibits estrogen-like activity, increases serum total proteins and decreases serum total cholesterol contents in immature female rats

Ahmad Nazir , Akhtar Nafees , Rahman Zia , Ali Shujait

Medicago sativa plants are commonly used as green fodder. In this study, estrogen-like activity of ethanolic extract of Medicago sativa plants and its possible effects on serum biochemical metabolites in immature female rats were investigated. Crude extract of dried Medicago sativa plants was prepared in 90% ethanol using Soxhlet’s apparatus. Fifteen immature female rats were divided into 3 equal groups. Rats of groups A and B were given the extract at the dose of 250 (lo...

ea0028p325 | Steroids | SFEBES2012

Emergency hospital admission rates in patients with adrenal insufficiency

Iliopoulou Amalia , Peacey Steven

There are limited morbidity data regarding patients with adrenal insufficiency. We undertook a retrospective study to examine the aetiology and frequency of emergency hospital admissions. We identified 69 patients receiving hydrocortisone replacement for adrenal insufficiency. 50 medical records were obtained; 20 patients had primary adrenal failure (including CAH) and 30 patients had ACTH deficiency. All emergency admissions that occurred within the last 10 years were reviewe...

ea0028p326 | Steroids | SFEBES2012

Beware the mean: Addison’s diagnoses may present from ages 3–85

White Katherine , Willson Nicholas , Mackay Alick

Recent epidemiological studies of primary adrenal insufficiency (Addison's disease) in Scandinavia have identified an average age at diagnosis of less than 40 (Bergthorsdottir 2006 n=1675, Erichsen 2009 n=426). They also found a broader range of ages than earlier UK studies, which had suggested that the majority of diagnoses occur in the third to fifth decades of life (Kong 1994, n=86). We analysed all membership records for the UK Addison’s Disease S...

ea0028p327 | Steroids | SFEBES2012

Medroxyprogesterone acetate-induced Adrenal Insufficiency

Overend Louise , McLorinan Joanna , Mason Ryan , Yunus Ajmal , Srinivas-Shankar Upendram

Case History: We report the case history of a 64-year-old woman who was admitted to hospital for evaluation of unsteadiness associated with postural hypotension. There was no history of headache, visual blurring, weight loss, diarrhoea or steroid treatment. She was taking high dose medroxyprogesterone acetate (MPA) 100 mg three times per day for 5 years following diagnosis of complex hyperplasia on endometrial biopsy for postmenopausal bleeding. Her past history included ischa...

ea0028p328 | Steroids | SFEBES2012

Hypercalcaemia - A diagnostic dilemma

Manjunatha Rashmi , Pearson Dominique , Warner Darren

Case Report: A lady of 43 presented with an insidious onset of weight loss, lethargy, muscle pains, and more recently; polydipsia, nausea and vomiting. She had been recently started on levothyroxine for primary hypothyroidism. She was hypotensive and tachycardic. Investigations revealed Sodium 123 mmol/L (133–146), Potassium 5.0 mmol/L (3.5–5.3), Urea 16.2 mmol/L (2.5–7.8), Creatinine 153 umol/L (45–90) and calcium 3.4 mmol/L (2.1–2.6). PTH was <0....

ea0028p329 | Steroids | SFEBES2012

Risk of iatrogenic Cushings syndrome and adrenal suppression in antiretroviral regimes including CYP450 3A4 inhibitors

McManus Frances , White Bethanna , MacConnachie Alisdair , Perry Colin

A 60 year old female from Zimbabwe with an eight year history of HIV infection presented with malaise and facial swelling. She had been established on antiretroviral treatment (Kivexa (lamivudine / abacavir) and Kaletra (lopinivir / ritonavir)) since shortly after her initial diagnosis. One month earlier she had received an injection of intramuscular triamcinolone acetate to treat an inflammatory polyarthropathy. She was also prescribed inhaled salmeterol xinafoate 50 mcg/flut...

ea0028p330 | Steroids | SFEBES2012

Isolated Hypoaldosteronism - management challenge during pregnancy: a case report

Rathi Manjusha

Isolated hypoaldosteronism is a rare condition. It can present with postural hypotension with or without significant hyponatraemia, hyperkalemia or heart block. For patients with Hypoaldosteronism, pregnancy raises issues regarding management of hyperkalemia and adequate blood pressure maintenance. A 17 yr girl presented with symptoms of tiredness, dizziness and routine blood test revealed marked isolated hyperkalemia (Serum potassium 7.1 mmol/L) with normal renal function. Sh...

ea0028p331 | Steroids | SFEBES2012

Life, Death and Modern technology

Anthonypillai Fiona , Espina Maricel

Rapid and appropriate response to an Adrenal crisis is a matter of life and death. Could greater patient and professional awareness together with modern technology assist in preventing mortality? Patients often first present with adrenal crisis in A&E departments. Whether the cause is primary or secondary adrenal failure, the initial treatment remains the same. Our objective was threefold: Educate and give greater awareness of steroid therapy to hospital staff, educate and...

ea0028p332 | Steroids | SFEBES2012

Bilateral adrenal enlargement with Hypoadrenalism

Krishnasamy Senthilkumar , Moulik Probal , Macleod Andrew

Background: Primary hypoadrenalism with bilateral adrenal enlargement is a relatively rare condition. We present four such patients. Case 1: 60 year old male presented with malaise, weight loss and hyponatremia. Short synacthen test was abnormal and ACTH was raised (309 ng/L). CT adrenals showed bilateral adrenal enlargement with uniform texture and low attenuation with no change in repeat CT. FNAC of adrenal gland showed infarcts. Further tests confirmed antiphospholipid anti...

ea0028p333 | Steroids | SFEBES2012

Recovery of the HPA axis after Prolonged Exogenous Steroids - Experience with Three Cases

Neary Nicola , Collins Michael , Abraham Smita , Nieman Lynnette

Exogenous glucocorticoids lead to suppression of the HPA axis via negative feedback on the hypothalamus and pituitary and may be associated with increased morbidity and mortality (Wei L. Ann Intern Med. 2004). Many patients whose steroids are no longer required for their underlying disease find withdrawal challenging. Presentations: Case 1: 68-year old male treated with steroids for hepatic graft versus host disease following a stem cell transplant for EBV-lymphoproliferative ...

ea0028p333A | Steroids | SFEBES2012

Regulation of de novo lipogenesis in human liver by 5α-reductase

Nasiri Maryam , Gathercole Laura , Stewart Paul , Tomlinson Jeremy

The potent effects of glucocorticoids (GCs) upon carbohydrate metabolism are well described. However, their actions upon lipid metabolism are poorly characterized. Patients with GC excess (Cushing’s syndrome) develop central obesity, insulin resistance and hepatic steatosis in up to 20% of cases. The A-ring reductases (5α-reductase type 1 [5αR1] and type 2 [5αR2]), inactivate cortisol as well as generate dihydrotestosterone (DHT) from testosterone (T) and a...