Searchable abstracts of presentations at key conferences in endocrinology

ea0044pl4 | Society for Endocrinology Dale Medal Lecture | SFEBES2016

The ever changing facets of Cushing’s syndrome

Stewart Paul

100 years have passed since Harvey Cushing linked a basophilic pituitary adenoma to bilateral adrenal hyperplasia, and in doing so elegantly depicted the clinical phenotype of “Cushing’s syndrome. Today we are uncovering the molecular basis for these tumours and pioneering novel surgical and medical therapies to improve clinical outcome, but fortunately they remain rare. Conversely iatrogenic Cushing’s with concomitant adrenal suppression is seen in the 1% of th...

ea0028d1 | (1) | SFEBES2012

Debate: This house believes that all adrenal patients with incidentalomas who fail to suppress after dexamethasone should have an adrenalectomy

Stewart Paul

Incidentalomas are common affecting 1% and 7% of 40 and 70 year olds respectively. By contrast endogenous Cushing’s syndrome is excessively rare. 10% of cases of Cushing’s syndrome are caused by an autonomous adrenal tumour where, having confirmed the diagnosis (symptoms and signs, cortisol excess, suppressed ACTH, suppressed contralateral adrenal) the treatment of choice is indeed adrenalectomy. Complexities arise around the suggestion that 10–15% of all incide...

ea0021cm2.3 | Endocrine incidentalomas: what to do with lumps and bumps | SFEBES2009

Adrenal lumps & bumps

Stewart Paul

The widespread use of abdominal CT/MRI has resulted in a new and common diagnosis for the clinical endocrinologist – the management of patients with adrenal incidentalomas. Defined as an adrenal mass discovered incidentally in the work-up or treatment of clinical conditions not related to suspicion of adrenal disease, incidentalomas cover a spectrum of underlying adrenal pathologies with a common pathway of discovery. Because of the risk of malignancy, they raise uncertai...

ea0020pl8 | 11β HSDs-common lessons from rare mutations | ECE2009

11β-hydroxysteroid dehydrogenases: common lessons from rare mutations

Stewart Paul

In mammalian tissues, two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) catalyze the interconversion of hormonally active cortisol (F) and inactive cortisone (E). 11β-HSD2 is a high affinity dehydrogenase expressed in adult kidney that inactivates F to E protecting the mineralocorticoid receptor (MR) (which has equal affinity for F and aldosterone in vitro) from cortisol excess. ‘Cushing’s disease of the kidney’ occurs in the hyper...

ea0015s15 | System-specific effect steroids | SFEBES2008

Glucocorticoids, liver, fat and metabolic syndrome

Stewart Paul

The seminal studies of Harvey Cushing informed us of the deleterious consequences of circulating cortisol excess – hypertension, osteoporosis and obesity that contributes to diabetes and premature mortality. As such Cushing’s syndrome offers an excellent paradigm for the metabolic syndrome. However circulating cortisol concentrations are invariably normal in patients with metabolic syndrome. The tissue-specific generation of cortisol, independent of circulating level...

ea0090s20.1 | Update on consequences of long-term exposure/treatment with glucocorticoids | ECE2023

Impairment of the HPA axis after treatment with glucocorticoids

Stewart Paul M

1% of western populations take chronic oral corticosteroids and this rises to 3% in subjects aged over 70 years old. When inhaled, topical and parenteral steroids are added to this burden, iatrogenic Cushing’s becomes a major health issue. High doses of medroxyprogesterone acetate can cause glucocorticoid effects and drug interactions may impair the metabolism of some glucocorticoids (eg fluticasone), thereby increasing their potency. Patients may develop the classical fe...

ea0041d4.2 | Are we ready for pharmacological therapy of obesity? | ECE2016

Should we treat subclinical Cushing’s syndrome?

Stewart Paul M

The term subclinical Cushing syndrome arose at the turn of the millennium with the description of large Italian study of adrenal incidentalomas. Of 1096 patients from 26 centres, 9.2% had ‘subclinical Cushing’s’ (JCEM, 2000; 85:637-644). Since then over 300 publications have detailed this newly discovered endocrine diagnosis, and herein lies the main issue. The definition of Cushing’s syndrome is not in doubt – a ‘constellation of symptoms and sig...

ea0090ep857 | Pituitary and Neuroendocrinology | ECE2023

Controlling intracellular cortisol: Can HSD-1 inhibition reduce Cushing’s syndrome morbidity and minimize adrenal insufficiency risk?

Czerwiec Frank , Katz David A. , M Stewart Paul

Endocrinologists focus on circulating and excreted cortisol for diagnosis of, and to assess severity and treatment response in, Cushing’s syndrome (Cs). However, in Cs, morbidity is mediated by excess cortisol binding to intracellular glucocorticoid (GC), mineralocorticoid (MC), and non-genomic receptors. We and others have demonstrated that 11b-hydroxysteroid dehydrogenase type 1 (HSD-1) is the source of about half of intrahepatocellular cortisol in healthy adults, patie...

ea0028p172 | Obesity, diabetes, metabolism and cardiovascular | SFEBES2012

Effect of secreted frizzled-related protein 2 (sFRP2) from adipose tissue on pancreatic cell function.

Bujalska Iwona , Rabbitt Elizabeth , Stewart Paul

Background: The detrimental effect of excessive obesity on insulin resistance has been well established. The expansion of adipose tissue is closely dependent on two processes: adipogenesis and angiogenesis and the Wnt signalling pathway has been reported to affect both. In adipose tissue the Wnt signalling pathway functions in a converse manner: increasing commitment of mesenchymal stem cells to preadipocytes and inhibiting differentiation of preadipocytes to mature adipocytes...

ea0044p30 | Adrenal and Steroids | SFEBES2016

Suppression of 11β-hydroxysteroid dehydrogenase type 1 target gene regulation by hypoxia

Shammout Bushra , Alase Adewonuola , Wittmann Miriam , Stewart Paul , Tiganescu Ana

Delayed wound healing (WH), characterized by ischemia, is exacerbated by glucocorticoid (GC) excess. Local GC availability is regulated by the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) which generates the GC cortisol from inactive cortisone. We previously reported improved WH in 11β-HSD1-null mice but regulation of 11β-HSD1 by hypoxia in human skin remains unknown. Primary human dermal fibroblasts (HDF, biological n=3), were treated...