Endocrine Abstracts

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...

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...

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...

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...

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...

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...

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...

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...

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...

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...