Endocrine Abstracts

Background: The adrenal glucocorticoid, cortisol, has a distinct circadian rhythm regulated by the brain’s central pacemaker. This cortisol rhythm acts as a secondary messenger to peripheral tissues and loss of the rhythm is associated with increased morbidity and mortality. This is a specific problem in adrenal insufficiency and congenital adrenal hyperplasia (CAH). Based on pharmacokinetic modelling we have developed a modified-release formulation of hydrocortisone (MR-...

Background: A basic tenet for hormone replacement is to replicate physiology but this is rarely if ever achieved. The adrenal glucocorticoid, cortisol, has a distinct circadian rhythm regulated by the brain’s central pacemaker. Loss of the cortisol circadian rhythm is associated with metabolic abnormalities, depression, fatigue and a poor health-related quality of life. Based on pharmacokinetic modelling we have developed a modified-release hydrocortisone (MR-HC) and test...

AIM: To assess efficacy of GH replacement and safety of stopping treatment in patients aged over 60 years.METHODS: GH-deficient patients were started on GH 0.13 miligram per day and the dose titrated over 4 months to a serum IGF-1 in the upper half of the age-related normal range. After 4 months titration, patients were randomised to either continuing GH or placebo in a double-blind, cross-over study with 2 x 4 month periods of either GH or placebo treatment.RESULTS: 1...

Introduction: LNSC has shown high sensitivity and specificity for the initial diagnosis of CD and detection of disease recurrence; however, the use of LNSC to monitor medical treatment of CD is not well established. The results of an exploratory analysis evaluating changes in LNSC in CD patients receiving long-acting pasireotide during a Phase III study (CSOM230G2304; Lacroix et al. Lancet Diabetes Endocrinol 2018) are reported here.Methods: Pat...

IntroductionOsilodrostat, a potent oral 11β-hydroxylase inhibitor, normalized mean urinary free cortisol (mUFC) in most patients with CD during the 48-week (W) core phase of a Phase III study (LINC3: NCT02180217). We present efficacy and safety results following an extension to LINC3.MethodsCD patients with mUFC > 1.5× upper limit of normal (ULN) received osilodrostat during the core. Patients b...

Background: Central diabetes insipidus (cDI), a rare neuroendocrine condition affecting 1 in 25.000, is characterized by deficiency of arginine vasopressin. Data about treatment-related side effects, psychological co-morbidities, and incidence of wrong management due to confusion with diabetes mellitus are scarce and limited to small studies or case series. Furthermore, increasing interest has arisen on a potential need for re-naming the condition.<p class="abstex...

Introduction: First-line treatment for congenital adrenal hyperplasia (CAH) is hydrocortisone1. When adequate control is not achieved, prednisolone (or its prodrug prednisone) are often used. However, there has been no formal comparison of disease control in CAH comparing prednis(ol)one vs hydrocortisone and patients are often on a glucocorticoid dose that exceeds the guideline recommended dose of hydrocortisone (≤25 mg/day)1,2. We report an interim...

Introduction: Osilodrosat is a potent oral 11β-hydroxylase inhibitor. During the 24-week, single-arm, open-label period of the Phase III LINC 3 study (NCT02180217), osilodrostat treatment demonstrated rapid, sustained reduction in mean urinary free cortisol (mUFC) in most Cushing disease (CD) patients. In the subsequent 8-week, double-blind, randomized-withdrawal phase, a significantly higher proportion of patients receiving osilodrostat maintained normal mUFC at week (W)...

ATL1103 is a second generation antisense 20mer intended to inhibit expression of the GH receptor (GHR) gene. Phosphorothioate and 2′-O-methoxyethyl modifications to nucleotides increase its plasma half-life and affinity for the target RNA to allow post-hybridization RNaseH degradation. We previously reported a phase 2, randomised, open-label, parallel group study of ATL1103 in 26 patients with acromegaly which demonstrated a fall in serum IGF-I of 26% with 200 mg twice w...

ATL1103 is a second generation antisense oligomer directed at the GH receptor. It is a 20mer with a phosphorothioate backbone and 2′-O-methoxyethyl modifications of the five nucleotides at either end intended to increase its plasma half-life and affinity for the target RNA to allow post-hybridization RNaseH degradation. We report a phase 2 randomised, open-label, parallel group study of subcutaneously administered ATL1103 in patients with active acromegaly. Appr...