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Endocrine Abstracts (2016) 44 PL4 | DOI: 10.1530/endoabs.44.PL4

SFEBES2016 Plenary Lectures Society for Endocrinology Dale Medal Lecture (1 abstracts)

The ever changing facets of Cushing’s syndrome

Paul Stewart


University of Leeds, Leeds, UK.

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 the population (3% over 70 years) treated with corticosteroids and represents a major management dilemma. More subtle abnormalities may occur in patients on glucocorticoid replacement therapy and those with adrenal incidentalomas.

Our expertise has focussed on aberrant cortisol metabolism causing “tissue-specific” cushings in the face of normal circulating cortisol concentrations. 11b-hydroxysteroid dehydrogenases type 1 and 2 (11b-HSD1,2) interconvert active cortisol to inactive cortisone (and prednisolone to prednisone). Apparent mineralocorticoid excess (caused by mutations in the gene encoding 11b-HSD2) result in Cushings disease of the kidney and florid cortisol-induced hypertension. 11b-HSD1 is expressed in liver and fat, muscle and skin where it augments cortisol induced hepatic glucose output, central adiposity, sarcopenia and dermal atrophy. Mice lacking 11b-HSD1 have favourable metabolic traits and are protected from the phenotype of exogenous Cushing’s syndrome. In collaboration with major Pharma, selective 11b-HSD1 inhibitors have shown therapeutic benefit in patients with Metabolic syndrome and hepatic steatosis but probably not of a magnitude that will see further clinical development. Reversal of poor wound healing and skin thinning and their use as steroid sparing agents preventing the side effects of therapeutic prednisolone are likely to be more fruitful translational outcomes.

Volume 44

Society for Endocrinology BES 2016

Brighton, UK
07 Nov 2016 - 09 Nov 2016

Society for Endocrinology 

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