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...

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 uncerta...

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...

One percent of the UK population takes 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 (e.g. fluticasone), thereby increasing their potency. In each case, patients may ...

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...

Nuclear pore complexes (NPCs) facilitate the transport of macromolecular cargoes across the nuclear envelope by carrier molecules. The energy for this active transport mechanism is provided by the Ras-family GTPase, Ran, that orchestrates most nuclear trafficking cycles. The RanGEF (RCC1) is located in the nucleus while its GAP is located in the cytoplasm. The nuclear import of steroids, bound to their receptor, is mediated by importins alpha and beta. In the cytoplasm, import...

Adrenal insufficiency may occur because of primary failure of the adrenal cortex but can also arise through a secondary failure of ACTH drive to the adrenal. 'Endogenous' suppression of the adrenal cortex may occur in patients with structural abnormalities affecting the hypothalamus/pituitary and in other patients with deficiency of pituitary ACTH secretion and action including those recovering from successful treatment of Cushing's syndromes. 'Exogenous' suppression is found ...

A series of reports have highlighted the lack of career structure and incentive for both clinical and non-clinical scientists wishing to pursue an academic career. For non-clinical personnel this is particularly critical as Endocrinology risks losing some of its identity to newer disciplines such as cell biology and signalling. The current inability to train clinical academics and basic scientists in Endocrinology represents a major threat to the discipline as a whole and must...