Endocrine Abstracts

The global epidemic of obesity has heightened the need to understand the mechanisms that underpin its pathogenesis. Clinical observations in patients with Cushing's syndrome have highlighted the link between cortisol and central obesity. However, whilst circulating cortisol levels are normal or reduced in obesity, local regeneration of cortisol, from inactive cortisone, by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) has been postulated as a pathogenic mechanism. W...

Our recent studies have localised 11 beta hydroxysteroid dehydrogenase type 1 (11 beta HSD1), which activates cortisol from cortisone, to the human ocular non-pigmented ciliary epithelium, and in an open blinded study conducted on healthy male volunteers, systemic inhibition of this isozyme with oral carbenoxolone (CBX) resulted in a 17% reduction of intraocular pressure (IOP). The aim of this study was to evaluate whether CBX reduced IOP in patients with ocular hypertension (...

The crucial role of vitamin D in mineral homeostasis is well known. However recent evidence has documented its importance for immunomodulation and inflammation. The kidney is the main source for the endocrine synthesis of the active metabolite 1,25-dihdroxyvitamin D3 (1,25D3), with expression of the key enzyme, 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-OHase). Our aim was to investigate the alteration of the vitamin D hormonal system in renal failure and assess the impact...

A role for local corticosteroid metabolism by 11beta-hydroxysteroid dehydrogenase type 1 (11b-HSD1) has been proposed in bone and adipose tissue physiology. In vivo, 11b-HSD1 predominantly converts inactive cortisone to active cortisol and enzyme activity is critically dependent on substrate concentration. To examine 11b-HSD1 activity in vivo we have analysed the relationship between serum cortisone and markers of bone turnover, BMD and adipose tissue mass in a c...

11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activates cortisol (F) from cortisone (E). Our recent human studies identified 11beta-HSD1 to the non-pigmented layer (NPE) of the ocular ciliary epithelium, confirming that this enzyme is integral to the physiology of aqueous humour (AH) production vital for the maintenance of intraocular pressure (IOP). 11beta-HSD1 has also been implicated in the pathogenesis of obesity, and our previous data have defined this enzyme i...

The epithelial cells of the choroid plexus (CP) are responsible for cerebrospinal fluid (CSF) secretion into the ventricles of the brain, which then drains principally into the dural sinuses. The balance between production and drainage, in part, facilitates a normal intracranial pressure. The secretion of sodium and anions by the CP, creates an osmotic gradient driving the movement of water into the ventricles. This mechanism is analogous to that found in the ocular ciliary ep...

Sodium transport across the human ocular non-pigmented ciliary epithelium (NPE) is fundamental to the production aqueous humour and maintenance of intraocular pressure. In sodium transporting tissues, serum and glucocorticoid regulated kinase isoform 1 (SGK1) has been identified as an early corticosteroid target gene in the activation of pre-existing epithelial sodium channels (ENaC). We previously demonstrated the presence of both the mineralocorticoid (MR) and glucocorticoid...

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...

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 ...

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 ...