Searchable abstracts of presentations at key conferences in endocrinology
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Society for Endocrinology BES 2010

ea0021p329 | Steroids | SFEBES2009

Metyrapone interference in serum cortisol immunoassay

Halsall David , Owen Laura , Viljoen Adam , Taylor Kevin , Simpson Helen , Chatterjee Krishna , Gurnell Mark

Metyrapone (MT) is used in the medical management of Cushing’s syndrome as it decreases serum cortisol (CT) levels by inhibiting adrenal β-hydroxylation of 11-deoxycortisol, the final step in CT synthesis. CT precursors, in particular 11-deoxycortisol (DOC), increase following MT therapy. Monitoring glucocorticoid replacement in patients taking MT could therefore be confounded as DOC cross-reacts in commonly used immunoassays (IA) for serum CT. Serum CT results from ...

ea0021p330 | Steroids | SFEBES2009

Cyclical epilepsy associated with testosterone replacement

Jayashekara Acharya , Flanagan Daniel

Introduction: High testosterone level lowers the seizure threshold in patients previously well controlled on medication.Clinical scenario: A 59-year-old male, with a history of complex partial seizure, having 12 years of seizure free period on phenytoin and lamotrigine, presented with short history of vomiting, positional headache, and visual impairment. A diagnosis of pitutary macro adenoma was made following a MRI scan of his head. He underwent a trans...

ea0021p331 | Steroids | SFEBES2009

Group education improves patient confidence in managing steroid sick day rules

Munday Linda Jean , Chong Lina , Kar Partha

Background: Group education for patients with diabetes is a well validated method of enhancing self-management skills. More recently some departments have used group education to teach endocrine patients how to administer IM hydrocortisone.Innovation: Patients on steroid replacement, identified by the endocrine nurse and GPs, were invited to attend a group session. The aim was to ensure every relevant patient in the locality had the opportunity to be edu...

ea0021p332 | Steroids | SFEBES2009

Steroid analysis in patients receiving metyrapone therapy

Owen Laura , Halsall David , Yates Alexandra , Keevil Brian

Clinical guidance recommends titrating the dose of metyrapone against serum cortisol concentrations. These serum samples are usually measured by immunoassays; however it has been well documented that there are interferences in these assays in patients with altered steroid metabolism due to a pathological process or drug treatment. The increasing availability of mass spectrometry (MS) assays for steroid hormones may circumvent this issue and assays that measure multiple steroid...

ea0021p333 | Steroids | SFEBES2009

Reference range data on androsterone glucuronide in healthy male and female volunteers and clinical uses of the assay

Adaway Joanne , Miller Adrian , Wu F C W , Keevil Brian

Androsterone glucuronide (ADG) is a major metabolite of the androgen dihydrotestosterone and has also been shown to arise from the intracrine conversion of other adrenal androgens such as androstenedione and androsterone. ADG has been shown to be raised in some women with clinical signs of hyperandrogenism such as acne and hirsutism, even when levels of androgens, e.g. testosterone or DHEA-S are normal. This indicates that raised ADG levels may be an early indication of hypera...

ea0021p334 | Steroids | SFEBES2009

A rare cause of massive bilateral adrenal enlargement complicating management of congenital adrenal hyperplasia

Nag Sath , Munir Atif , Ullah Arif , Santhakumar Anjali

A 33-year-old lady presented to the surgeons with history of abdominal pain. CT scan abdomen done revealed massive adrenal enlargements reported as adrenal myelolipomas (left gland measuring 8.0×10.9×11.8 cm and multifocal lesions on the right with the larger one measuring 5.2×4.3×3.6 cm). She was referred to the endocrinology team where further history was elicited. She had been diagnosed as a child to have congenital adrenal hyperplasia (CAH) but was lost...

ea0021p335 | Steroids | SFEBES2009

Diagnostically difficult Cushing’s syndrome in a pharmacy student

Marath Haris , Dhatariya Ketan

Twenty-two years old pharmacy student was urgently referred from primary care with a history of recent weight gain of 15 kg and an elevated 24 h urinary free cortisol (UFC) of 4517 nmol/l (<330). Clinically she described increasing hirsutism, low mood, loss of libido and symptoms suggestive of proximal myopathy.Her past medical history included recurrent low impact wrist fractures, asthma, PCOS, depression and epilepsy.On exami...

ea0021p336 | Steroids | SFEBES2009

Post-traumatic hypoadrenalism case report

Deshpande Sarika , Wijenaike Nishan , Clark John

Direct trauma to the adrenal glands resulting in adrenal gland failure is relatively rare. We present two cases of post-traumatic hypoadrenalism.Case 1: A 53-year-old male who was trapped under a lorry trailer. He was found to have fractures of T6 (unstable), T12, rib and sternal fractures. He was transferred to the orthopaedic ward and required a spinal splint. He was slowly recovering until day 20 of his admission when he became hypotensive and tachyca...

ea0021p337 | Steroids | SFEBES2009

Determination of tandem mass spectrometry specific reference ranges for testosterone, androstenedione and DHEAS

Macdonald Philip , Wu Frederick , Owen Laura , Keevil Brian

Testosterone, androstenedione and DHEAS are commonly measured by immunoassays. Variations in antibody specificity and calibration of assays results in non-commutability of measurements. Even more specific mass spectrometry (LC–MS/MS) assays still exhibit differences in calibration. As the use of mass spectrometry for measuring steroids is becoming more common in the clinical laboratory, the development of LC–MS/MS reference ranges for these analytes is essential to h...

ea0021p338 | Steroids | SFEBES2009

A sensitive and specific tandem mass spectrometry assay for the measurement of salivary testosterone

Macdonald Philip , Owen Laura , Keevil Brian

Saliva contains the free unbound fraction of testosterone, which has been shown to correlate with the free circulating serum testosterone, and may better reflect the physiologically active form. Recently, measurement of free testosterone has gained international recommendations for the diagnosis of hypogonadism in the ageing male. Saliva collection is a non-invasive technique, offering more flexibility to the patient, e.g. the collection of samples at home. Liquid chromatograp...

ea0021p339 | Steroids | SFEBES2009

Analysis of cortisol by stable isotope dilution liquid chromatography–tandem mass spectrometry (LC–MS/MS): pitfalls of rapid LC–MS/MS analysis of clinical samples

Homer Natalie , Denham Scott , Stimson Roland , Watson David , Walker Brian , Andrew Ruth

The glucocorticoid hormone, cortisol, regulates fuel metabolism, inflammation and stress–responses. Its circulating concentrations are tightly controlled by the hypothalamic–pituitary–adrenal axis. However, 11β-hydroxysteroid dehydrogenase 1 (11βHSD1) generates additional cortisol in tissues, by reduction of inert cortisone. Using a tracer (9,11,12,12[2H]4-cortisol; d4-cortisol), the velocity of 11βHSD1 can be determined as t...

ea0021p340 | Steroids | SFEBES2009

Steroid replacement: an unusual alternative to oral therapy via 24-h s.c. infusion device

Stewart Sue , Narendon Parth , Hudson Barbara , Hindmarsh Peter , Krone Nils , Arlt Wiebke

Background: Adrenal insufficiency is a well-recognised feature of congenital adrenal hyperplasia (CAH).CAH is commonly treated with oral steroid replacement, taken 2–3 times a day, at doses that aim to reproduce normal diurnal variation. Though acceptable for most patients, this does not control others, resulting in high levels of 17-hydroxyprogesterone-acetate (17OHP), ACTH, and the need for increased doses of steroid replacement, with associated c...

ea0021p341 | Steroids | SFEBES2009

Moderate liquorice consumption enhances salivary DHEA and testosterone levels in healthy volunteers

Al-Dujaili Emad A S , Macdonald Claire , Kenyon Chris

Liquorice root has been used medicinally for many years to treat dry cough, asthma, hunger, thirst, sterility of women, fever, digestive problems and pathologies of organs such as lungs, stomach, intestines and kidney. Glycyrrhetinic acid (one of the active constituents in liquorice) has diverse in vitro effects as an inhibitor of 11β hydroxysteroid dehydrogenase (11HSD), 5α reductase and hormone receptor binding. The aim of this study is to investigate the ef...

ea0021p342 | Steroids | SFEBES2009

Is a raised DHEAS significant when analysed as part of an androgen profile

Chadwick Carrie , Keevil Brian

Aim: The investigation of female androgen status in our laboratory is measured as a profile. Androstenedione, testosterone and DHEAS are analysed by liquid chromatography–tandem mass spectrometry. SHBG is analysed by immunoassay, and all results are reported simultaneously. The main aim was to investigate the management of patients who have a raised DHEAS level.Method: Ethical approval was granted for this study. Females with DHEAS levels >6.9 n...

ea0021p343 | Steroids | SFEBES2009

Application of a highly specific and sensitive ELISA for the estimation of cortisone in biological fluids

Baghdadi Hussam , Al-Dujaili Emad , Almoosawi Suzana , Howie Forbes , Mason Ian

It is now generally acknowledged that local tissue concentrations of cortisol and cortisone are modulated by site-specific actions of 11β-hydroxysteroid dehydrogenase (11β-HSD) isoenzymes 1 and 2. Cortisone, the inactive metabolite of cortisol is produced by type 2 11β-HSD. To assess 11β-HSD type 1 and 2 activity, the cortisone/cortisol ratio has to be accurately determined. Immunoassays to measure cortisone levels are not widely available and tend to lack ...

ea0021p344 | Steroids | SFEBES2009

Successful fecundity with addition of night-time dexamethasone to hydrocortisone in a patient with congenital adrenal hyperplasia (CAH) and testicular adrenal rest tumours (TART)

Haniff Haliza , Gilbey Stephen

A 26-year-old man with known CAH (21-hydroxylase deficiency) presented with infertility. Investigations revealed azoospermia and USS showed bilateral grossly abnormal testes replaced to a large extent by multiple mixed echogenic, ill defined nodules with flecks of calcification. Clinically, given the bilateral lesions and his poorly controlled CAH, the testicular lesions were felt to be ACTH-dependent testicular adrenal rest tumours (TART). Owing to overproduction of adrenal a...

ea0021p345 | Steroids | SFEBES2009

Dexamethasone testing and visceral:subcutaneous fat ratios in patients with adrenal incidentalomas

Debono Miguel , Hughes Tim , Durrington Charlotte , Williams Scott , Newell-Price John

Background: The Endocrine Society clinical practice guidelines suggest use of the 1 mg overnight dexamethasone suppression test (ONDST) to screen for cortisol excess in patients with adrenal incidentalomas, followed by the 48-h, 2 mg/day, low-dose dexamethasone-suppression test (LDDST), to confirm a positive result. Visceral fat accumulates in cortisol-excess and accounts for increased cardiovascular risk. In this study, we investigate whether the LDDST offers additional infor...

ea0021p346 | Steroids | SFEBES2009

Salivary aldosterone is a useful marker of serum aldosterone in normotensive individuals

McMurray Emily , Atkinson Brew , Mullan Karen , Cundick Jennifer , Sheridan Brian , Bell Patrick

Primary aldosteronism is an important cause of secondary hypertension though its diagnosis can prove challenging. In normal individuals aldosterone release follows a diurnal pattern, with a morning peak and low levels in the evening. Aldosterone is present in saliva and due to its lipophilic nature it passes into saliva along a concentration gradient. Salivary steroid testing is well established for cortisol and testosterone, but not yet for aldosterone....

ea0021p347 | Steroids | SFEBES2009

Regulation of glucocorticoid receptor activity by cellular stress

Davies Laura , Sadeq Malihah , Demonacos Constantinos , Krstic-Demonacos Marija

Cofactors of the nuclear hormone receptors are crucial in regulating their transcriptional activity. The glucocorticoid receptor (GR) is a member of the nuclear hormone receptor superfamily, involved in the regulation of metabolism, inflammation and stress–responses and many GR cofactors are known, including p300. Here, we identify a new cofactor for GR: TTC5/Strap, tetratricopeptide repeat domain 5/ stress–responsive activator of p300. Strap is a TPR motif containin...

ea0021p348 | Steroids | SFEBES2009

−344 C/T polymorphism of aldosterone synthase gene (CYP11B2) and cortisol synthesis in heart failure patients

Tsorlalis Ioannis , Fraser Robert , Jackson Colette , Ingram Mary , Holloway Christine , McMurray John , Connell John

Background: Increased levels of cortisol are associated with worse prognosis in heart failure (HF). The final step in cortisol production is catalysed by 11β-hydroxylase encoded by CYP11B1, which is highly homologous with CYP11B2. A common polymorphism in the aldosterone synthase gene (CYP11B2 −344T) is associated with a raised ratio of 11-deoxycortisol/ cortisol (S/F). We examined the relationship between −344C/T polymorphism and corticos...

ea0021p349 | Steroids | SFEBES2009

Urinary steroid metabolite profiling in 11β-HSD1 and H6PDH transgenic mice

Semjonous Nina , Hughes Beverly , Walker Elizabeth , Lavery Gareth , Stewart Paul

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts inactive glucocorticoid to their active form (cortisone to cortisol in humans, 11-dehydrocorticosterone (11-DHC) to corticosterone in mice), and is dependent upon the presence of cofactor NADPH generated by the enzyme hexose-6-phosphate (H6PDH) for its activity. The 11β-HSD1/H6PDH system is implicated in the pathogenesis of the metabolic syndrome by generating tissue specific glucocorticoid excess. The ...

ea0021p350 | Steroids | SFEBES2009

Epitopes of pterin-dependent hydroxylases in autoimmune polyendocrine syndrome type 1

Magitta Ng'weina Francis , Bratland Eirik , Wolff Anette S B , Haavik Jan , Knappskog Per Motern , Husebye Eystein Sverre

Background: Autoimmune polyendocrine syndrome type 1 (APS1) is a disorder caused by mutations of the autoimmune regulator (AIRE) gene, that controls central tolerance. Tetrahydrobiopterin (BH4)-dependent hydroxylases, consisting of tryptophan hydroxylase (TPH1 and TPH2), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH) are commonly targeted autoantigens. Nevertheless, detailed characterization of their epitopes and independent roles of TPH isoforms has ...

ea0021p351 | Steroids | SFEBES2009

Responses of putative adrenocortical stem/progenitor cells and transiently amplifying cells to ACTH

Morrison Hamish , Nilsson Frida , Chang Su-Ping , West John , Kenyon Christopher , Morley Steven

Steroidogenic cells of the adrenal cortex are thought to originate from a peripherally-located self-renewing population of undifferentiated stem or progenitor cells. These cells divide infrequently to give daughters, which proliferate transiently (termed transiently amplifying (TA) cells), migrate and differentiate to replenish the functionally-differentiated zones of the adrenal cortex, or remain in situ as undifferentiated stem cells. Theoretically such stem cells can...

ea0021p352 | Steroids | SFEBES2009

Assessing adrenal status in patients before and after coronary artery bypass graft surgery

Debono Miguel , Sheppard Lorcan , Irving Sarah , Brookes Zoe , Newell-Price John , Ross John , Ross Richard

Background: Cortisol is an essential stress hormone and deficient patients suffering a systemic inflammatory response (SIR) will rapidly die if not replaced. However, controversy remains on the definition for a normal adrenal response in critically ill patients. We investigated cortisol status in patients undergoing coronary artery bypass surgery (CABG), surgery frequently associated with a SIR, varying in severity from sub-clinical, to life-threatening....

ea0021p353 | Steroids | SFEBES2009

Ongoing symptoms in treated Addison’s disease significantly impair health-related quality of life

White Katherine , Mackay Alick

Impaired quality of life in patients with treated Addison’s (primary adrenal insufficiency) has been identified in several recent studies, which have also identified high rates of working-age disability. However, causation in patients whose replacement endocrine medications appear adequate remains unclear.To try and identify factors influencing this reduced quality of life, we analysed demographic information reported by a UK patient sample (n</i...

ea0021p354 | Steroids | SFEBES2009

Low testosterone and androgen receptor insensitivity results in decreased AMP-activated protein kinase activity (AMPK) in the liver in the testicular feminised (Tfm) mouse

Igreja Susana , Nettleship Joanne E , Jones Richard D , Channer Kevin S , Jones T Hugh , Korbonits Marta

There are controversial data on the beneficial/detrimental effects on the cardiovascular as well as on the metabolic system by the sex hormone testosterone. Recent data support the hypothesis that low levels of androgens are associated with adverse cardiovascular risk factors including an atherogenic lipid profile, obesity, insulin resistance and hypertension. AMPK is a sensor of energy balance at both the cellular and whole-body level. Once activated by low energy status, it ...

ea0021p355 | Steroids | SFEBES2009

Salivary annexin 1 has a diurnal rhythm but does not share an awakening response with cortisol at 30 min

Renshaw Derek , Korbonits Marta , Flower Rod , Perretti Mauro , Fowkes Robert

Several hormones, including cortisol, have a circadian rhythm in plasma and saliva. Salivary cortisol is now extensively used for screening and following patients with various conditions where the regulation of hypothalamo-pituitary–adrenal axis is abnormal, for example in major depression where salivary cortisol levels show a disruption or loss of the circadian rhythm.Annexin 1 is a glucocorticoid-induced protein, which is responsible for mediating...

ea0021p356 | Steroids | SFEBES2009

Use of bioluminescence resonance energy transfer to reveal the structural dynamics of the ACTH receptor complex

Cooray Sadani , Clark Adrian

The melanocortin 2 receptor accessory protein (MRAP) is essential for the functional expression of the ACTH receptor/melanocortin 2 receptor (MC2R). The pituitary hormone ACTH acts via this complex to stimulate glucocorticoid production in the adrenal cortex. Using the bioluminescence resonance energy transfer (BRET) system we investigated the formation of MC2R–MRAP homo/heterodimers in living cells and the influence of ACTH on these interactions. ACTH was found to have a...

ea0021p357 | Steroids | SFEBES2009

6-Phosphogluconate dehydrogenase: an NADPH-generating enzyme in the lumen of the endoplasmic reticulum

Bujalska Iwona , Ride Jonathan , Stewart Paul , Walker Elizabeth

6-Phosphogluconate dehydrogenase (6PGDH) is the third enzyme of the oxidative phase of the pentose phosphate pathway. The cytosolic form of this pathway is well characterised, but the details and significance of the endoplasmic reticulum (ER) version are only beginning to be understood. We have previously identified hexose-6-phosphate dehydrogenase (H6PDH), which catalyses the first two steps of this pathway within the lumen of the ER, as a pivotal regulator of ER reductases s...

ea0021p358 | Steroids | SFEBES2009

Hepatic vein cannulation and stable isotope tracer infusion reveals that liver cortisol regeneration by 11β-HSD1 is sustained in obese men with type 2 diabetes mellitus, providing a target for enzyme inhibition

Stimson Roland , Andrew Ruth , McAvoy Norma , Tripathi Dhiraj , Hayes Peter , Walker Brian

Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) are being developed to prevent cortisol regeneration from cortisone in liver and adipose tissue in type 2 diabetes (T2DM). However, the target patient group is uncertain. In obesity 11β-HSD1 activity is increased in adipose tissue but decreased in liver, as judged indirectly by plasma cortisol levels after oral cortisone administration. However, in T2DM, urinary steroid ratios suggest liver 11&#946...

ea0021p359 | Steroids | SFEBES2009

Variation in the aldosterone synthase gene may alter gene transcription via altered transcription factor binding

McManus Frances , Sands William , Davies Eleanor , Connell John

The aldosterone synthase gene encodes the final step in the production of aldosterone. The aldoststerone synthase gene is polymorphic and variants within the gene and the regulatory region have been associated with hypertension and a phenotype of relatively higher level of aldosterone and its metabolites. However to date; none of the polymorphisms in the regulatory region of CYP11B2 have been shown to alter transcription. Seven novel polymorphisms in the promoter region of CYP...

ea0021p360 | Steroids | SFEBES2009

Replicated association of regions at CYP11B1/B2 locus with hypertension in Caucasians

Alvarez-Madrazo Samantha , Padmanabhan Sandosh , Friel Elaine , MacKenzie Scott , Brown Morris , Caulfield Mark , Munroe Patricia , Farrall Martin , Webster John , Samani Nilesh , Dominiczak Anna , Melander Olle , Davies Eleanor , Connell John

The locus comprising the genes that catalyse the final steps of cortisol and aldosterone synthesis (CYP11B1 and CYP11B2 respectively) is a plausible candidate risk region for hypertension and other cardiovascular diseases. Nevertheless, there remains uncertainty as to the strength of the relationship between polymorphisms at this locus and increased blood pressure. In this study, association with hypertension at the CYP11B1/CYP11B2 locus in a Caucasian cas...

ea0021p361 | Steroids | SFEBES2009

Anti-inflammatory effects of SGRMs: are they dependent on DUSP1?

Joanny Eugenie , Martins Joana , Clark Andrew

Glucocorticoids (GCs) are steroid hormones, products of the hypothalamic–pituitary–adrenal axis. Synthetic GCs, such as dexamethasone, have been widely used in the treatment of inflammatory diseases like rheumatoid arthritis or asthma, but their long-term use causes severe side effects (osteoporosis, diabetes, hypertension, etc). The ligand-bound GC receptor (GR) can activate gene expression via binding to GC response elements (GREs), a mechanism known as transactiva...

ea0021p362 | Steroids | SFEBES2009

MicroRNA expression profiling of non-tumorous adrenal tissue and modulation of 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes by miR-24

Wood Stacy , MacKenzie Scott , Stewart Paul , Fraser Robert , Connell John , Davies Eleanor

The CYP11B1 and CYP11B2 genes encode 11β-hydroxylase and aldosterone synthase, which catalyse the production of cortisol and aldosterone, respectively, and have been implicated in the development of hypertension. For this study, we wished to investigate the role of microRNAs (miRNAs), a novel class of post-transcriptional gene regulators. To that end, we generated a profile of human adrenal miRNAs to study, and then investigated the action of one adrenal miR...

ea0021p363 | Steroids | SFEBES2009

Is increased 11β-HSD1 expression a key factor underpinning intrinsic and extrinsic skin aging?

Tiganescu Ana , Mayes Andrew , Hardy Rowan , Stewart Paul , Walker Elizabeth

Glucocorticoids are highly detrimental to skin integrity and function both when used locally for anti-inflammatory treatments and during conditions of raised systemic concentrations such as Cushing’s syndrome. Many of the adverse effects of glucocorticoids on skin are also symptoms associated with natural intrinsic aging and extrinsic photoaging.Locally, glucocorticoid availability is regulated independently of circulating levels by 11β-hydroxy...

ea0021p364 | Steroids | SFEBES2009

Functional characterisation of 21-hydroxylase gene mutations is a valuable tool for genetic counselling: in vitro and in silico analysis of six novel CYP21A2 sequence variants

Parajes Silvia , Loidi Lourdes , Dhir Vivek , Morey Marcos , Dominguez Fernando , Arlt Wiebke , Krone Nils

Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency (21OHD) is the commonest inborn error in steroid biosynthesis. It is caused by mutations in the 21-hydroxylase gene (CYP21A2). A good genotype–phenotype correlation exists allowing for prediction of the expressed adrenal phenotype. We performed functional and structural analysis of six novel CYP21A2 variants (p.Trp22Cys; p.Asp184Asn; p.Leu198Phe; p.Val305Gly; p.His310Asn; p.Thr443Asn), i...

ea0021p365 | Steroids | SFEBES2009

Chronic glucocorticoid treatment causes de novo methylation of Tpit and causes continued reduction in POMC expression after glucocorticoid withdrawal

Munir Alia , Powell Rachel , Eltobgi Adim , Newell-Price John

Introduction: Long-term repression of the HPA axis is a major side effect of chronic glucocorticoid administration, even after attempted withdrawal of therapy, and complicates management in patients. We have previously shown that the effect of chronic glucocorticoid treatment in vitro is in part mediated by inhibition of expression the POMC transcription factors Neuro D1 and Tpit, and that this is sustained on treatment withdrawal. We have now furth...