Searchable abstracts of presentations at key conferences in endocrinology

ea0059oc5.2 | Adrenal | SFEBES2018

Residual adrenal function in autoimmune addison s disease effect of dual therapy with rituximab and depot tetracosactide

Napier Catherine , Gan Earn H , Mitchell Anna L , Gilligan Lorna C , Rees Aled , Moran Carla , Chatterjee Krishna , Vaidya Bijay , Arlt Wiebke , Pearce Simon HS

In patients with autoimmune Addison’s disease (AAD), exogenous glucocorticoid (GC) therapy is an imperfect substitute for physiological GC secretion; patients on long-term steroid replacement have increased morbidity, reduced life expectancy and poorer quality of life. Recent early-phase studieshave demonstrated that some endogenous steroidogenic function – Residual Adrenal Function (RAF) - is maintained at the point of diagnosis in a proportion of AAD patients; this...

ea0059cc6 | Featured Clinical Cases | SFEBES2018

What lies beneath: cutaneous Kaposi’s sarcoma as a first manifestation of ectopic ACTH-dependent Cushing’s syndrome

Tresoldi Alberto S , Elhassan Yasir S , Asia Miriam , Elshafie Mona , Lane Peter , Manolopoulos Konstantinos N , Velangi Shireen S , Watkins Steven , Arlt Wiebke , O'Reilly Michael W

Introduction: Immune dysregulation is a feature of Cushing’s syndrome (CS). We report a case of CS that presented with rapidly developing cutaneous Kaposi’s sarcoma (KS).Case description: A previously well 59-year-old heterosexual man presented with a two-month history of proximal muscle weakness, recurrent mouth ulcers, and purplish skin lesions. He had a background history of hypertension. Skin biopsies were compatible with KS. History of pas...

ea0038oc2.3 | Translational pathophysiology and therapeutics | SFEBES2015

Further advances in diagnosis of adrenal cancer: a high-throughput urinary steroid profiling method using liquid chromatography tandem mass spectrometry (LC-MS/MS)

Taylor Angela , Bancos Irina , Chortis Vasileios , Lang Katharina , O'Neil Donna , Hughes Beverly , Jenkinson Carl , Deeks Jon , Shackleton Cedric , Biehl Michael , Arlt Wiebke

Context: Differentiating adrenocortical adenoma (ACA) from adrenocortical carcinoma (ACC) represents a continuous challenge in patients with (often incidentally discovered) adrenal masses, with unfavorable sensitivities and specificities provided by tumor size, imaging and even histology. We have previously developed urine steroid metabolomics as a tool for the detection of adrenal malignancy employing gas chromatography mass spectrometry (GC-MS) for the detection of 32 distin...

ea0037oc9.2 | Adrenal 2 | ECE2015

Alternative pathway synthesis dominates androgen production in patients with congenital adrenal hyperplasia and is decreased by Chronocort® more than by conventional glucocorticoid therapy

Jones Christopher , Mallappa Ashwini , Reisch Nicole , Hughes Beverley , O'Neil Donna , Krone Nils , Whitaker Martin , Eckland David , Merke Deborah , Ross Richard , Arlt Wiebke

Suppression of excess androgen production poses a considerable clinical challenge in the management of patients with congenital adrenal hyperplasia (CAH). Whilst the major route of androgen synthesis in humans is the classic pathway via androstenedione and testosterone, the relative contribution of the alternative pathway originating from 17-hydroxyprogesterone to androgen excess in CAH has not been defined. Androgen effects of both pathways are elicited in androgen target tis...

ea0037gp.01.05 | Adrenal | ECE2015

Prevention of adrenal crisis in stress (The PACS Study): serum cortisol during elective surgery, acute trauma and sepsis in comparison to ‘stress dose' hydrocortisone administration in adrenal insufficiency

Taylor Angela , Karavitaki Niki , Smith David , Bancos Irina , Foster Mark , Meier Sibylle , O'Neil Donna , Komninos John , Vassiliadi Dimitra , Mowatt Christopher , Lord Janet , Wass John , Arlt Wiebke

Patients with adrenal insufficiency require increased hydrocortisone (HC) replacement doses during surgery, trauma and infection to avoid life-threatening adrenal crisis. However, currently administered HC doses are chosen empirically rather than on rational grounds, with huge variability in administration modes, total dose and dosing intervals. To conclusively determine serum cortisol levels observed under stress conditions, we firstly collected blood samples from healthy con...

ea0037gp.04.02 | Steroids | ECE2015

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

Sherlock Mark , Behan Lucy Ann , Hannon Mark , Alonso Aurora Aragon , Thompson Christopher , Murray Robert , Crabtree Nicola , Hughes Beverly , Arlt Wiebke , Agha Amar , Toogood Andrew , Stewart Paul M

Context: Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate around the optimum glucocorticoid replacement therapy.Objective: To assess the effect of glucocorticoid replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.Design and patients: We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body ...

ea0037gp.05.02 | Developmental and paediatric endocrinology | ECE2015

The differential impact of PAPS synthase isoforms on DHEAS may be explained by an isoform-specific interaction of SULT2A1 with PAPSS2, but not PAPSS1

Mueller Jon W , Idkowiak Jan , Hardman Rebecca E , House Philip J , McNelis Joanne C , Rose Ian T , Dhir Vivek , Rosta Edina , Arlt Wiebke

Human sulfation depends on provision of the universal sulfate donor PAPS by the two PAPS synthase isoforms PAPSS1 and PAPSS2. Mutations in PAPSS2 have been identified as a monogenic cause of androgen excess presenting with premature adrenarche and polycystic ovary syndrome, due to decreased sulfation of the androgen precursor DHEA by DHEA sulfotransferase (SULT2A1) and hence increased conversion of DHEA to active androgens (New Eng J Med 2009 360 (22)...

ea0035oc5.2 | Adrenal & Thyroid | ECE2014

Relationship between final height and cardiometabolic risk and quality of life in adults with congenital adrenal hyperplasia: United Kingdom Congenital adrenal Hyperplasia Adult Study Executive (CaHASE)

Han Thang S , Conway Gerard S , Krone Nils , Aled Rees D , Stimson Roland H , Arlt Wiebke , Walker Brian R , Ross Richard J

Background: Treatment of CAH in childhood focuses on growth and development; however the impact of final height (FH) on adult health is not known. We examined the relationship between FH, adiposity, cardiometabolic risk and quality of life (QoL) in a cohort of adult patients.Methods: Cross-sectional analysis of 199 adults with CAH. FH, waist circumference (WC) and QoL were expressed as z-scores adjusted for mid-parental target height (FHTH<...

ea0034p374 | Steroids | SFEBES2014

Differential impact of PAPS synthases on human sulfation pathways

Mueller Jonathan W , Idkowiak Jan , House Philip J , McNelis Joane , Rose Ian I , van den Boom Johannes , Schlereth Florian , Dhir Vivek , Arlt Wiebke

Mutations in the gene for 3′-phospho-adenosine-5′-phosphosulfate synthase 2 (PAPSS2) are linked to bone and cartilage mal-formation. More recently, we could identify PAPSS2-mutations as mono-genetic cause for androgen excess in women due to apparent SULT2A1 deficiency, the enzyme responsible for sulfation of the testosterone precursor DHEA that relies on PAPS provision by PAPS synthases. The only human orthologue, PAPSS1, is expressed in the affected tissu...

ea0034p378 | Steroids | SFEBES2014

The Prevention of Adrenal Crisis in Stress (PACS) study: serum cortisol during elective surgery and acute trauma in comparison to stress dose hydrocortisone in adrenal insufficiency

Taylor Angela , Karavitaki Niki , Foster Mark , Meier Sibylle , O'Neil Donna , Komninos John , Vassiliadi Dimitra , Mowatt Christopher , Lord Janet , Wass John , Arlt Wiebke

Patients with adrenal insufficiency (AI) require adjustment of hydrocortisone (HC) dose to avoid life-threatening adrenal crisis during illness, surgery and trauma. However, current dose recommendations are based on empirical grounds only and choice of dose and administration modes vary considerably. We designed the PACS study to compare cortisol levels achieved by currently recommended HC stress doses to those in i) healthy controls (n=85, 21–70 years), ii) mili...