hrp0092lb-3 | Late Breaking Posters | ESPE2019

Insights into the Regulation of Androgen Biosynthesis from Males with Congenital Hypogonadotropic Hypogonadism: Quantification of Bioactive Steroid Hormones Reveals Differences Between Gonadotropin Replacement and Testosterone Replacement

Rohayem Julia , Holterhus Paul-Martin , Kliesch Sabine , Nieschlag Eberhard , Zitzmann Michael , Kulle Alexandra

Background: In males with congenital hypogonadotropic hypogonadism (CHH), LH/FSH stimulation of gonads is deficient. In clinical practice, two hormone replacement strategies are employed to induce and maintain virilisation: Treatment with testosterone and gonadotropin replacement with hCG/rFSH.Objective: To delineate the role of gonadotropins in pathways of male androgen biosynthesis and to thereby better define the gona...

hrp0089fc10.2 | Late Breaking | ESPE2018

Efficacy and Safety of Once-Weekly Somapacitan in Childhood Growth Hormone Deficiency: Results of a Randomised Open-Label, Controlled Phase 2 Trial

Savendal Lars , Rasmussen Michael , Horikawa Reiko , Khadilkar Vaman , Battelino Tadej , Saenger Paul

Background: Growth hormone deficiency (GHD) requires long-term daily injections with GH replacement therapy and is associated with considerable treatment burden by patients and caregivers. Somapacitan is a long-acting GH derivative that is being developed for once-weekly dosing in adults and children with GHD. A well-established protraction method, which is successfully in use to extend the half-life of insulin and glucagon-like peptide (GLP)-1, has been applied in developing ...

hrp0089fc10.5 | Late Breaking | ESPE2018

A 5-Year Single-Centre Experience on the Safety and Efficacy of Sirolimus Therapy used for the Treatment of Congenital Hyperinsulinaemic Hypoglycaemia

Guemes Maria , Dastamani Antonia , Ashworth Michael , Morgan Kate , Ellard Sian , Flanagan Sarah , Dattani Mehul , Shah Pratik

Background: Case reports have documented variable glycaemic response to the mTOR inhibitor Sirolimus in severe diazoxide+/−octreotide unresponsive forms of congenital hyperinsulinaemic hypoglycaemia (CHI). A high incidence of adverse effects has been reported in patients receiving this medication.Objective(s): To describe the efficacy and safety of Sirolimus use over a 5-year period in the largest cohort of CHI patients treated to date.<p class...

hrp0089p1-p013 | Adrenals and HPA Axis P1 | ESPE2018

Role of Mast Cells in the Establishment of the Mineralocorticoid Pathway in the Developing Mouse

Naccache Alexandre , Louiset Estelle , Lamaziere Antonin , Thomas Michael , Arabo Arnaud , Lefebvre Herve , Castanet Mireille

Mast cells are known to control mineralocorticoid synthesis and secretion in human normal adrenal gland and aldosterone-producing adenomas through release of serotonin. We recently detected these immune cells in human fetal adrenal from 18 weeks of gestation in the subcapsular layer, in correlation with the expression of steroidogenic enzymes required for aldosterone biosynthesis. This observation suggests the implication of mast cells in the mineralocorticoid synthesizing pat...

hrp0089p2-p035 | Adrenals and HPA Axis P2 | ESPE2018

Pseudopubertas Praecox in a 4 Year Old Boy with Bilateral Atypical Adrenocortical Adenomas

Brichta Corinna , Wurm Michael , Hodde Franka , van der Werf-Grohmann Natascha , Schwab Karl Otfried

Introduction: Adrenocortical tumors are very rare in children, with a prevalence of just 0.3 cases/million/year. Autonomic hormone production by adrenal cortical tumors may cause peripheral precocious puberty.Case report: A 4-year-old boy was presented by his parents because of pubertal behavior with aggressive features and a significant increase in the size of the penis. The parents also noticed a strong growth spurt and sweat odor. The boy had a good g...

hrp0089p2-p146 | Fat, Metabolism and Obesity P2 | ESPE2018

Body Composition and Cardiovascular Function in Pre-adolescent Children of South Asian and White European Origin: Relationship to Maternal Status in Pregnancy

Whatmore Andrew , Khan Sophia , Vyas Avni , Maresh Michael , Cruickshank Kennedy , Clayton Peter

South Asian (SA), British-born adults have increased cardiovascular (CV) risk factors compared to White Europeans (WE). Early detection of CV risk may allow intervention. The Manchester HAPO (Hyperglycaemia and Adverse Pregnancy Outcomes) cohort showed babies of SA origin were born significantly shorter, lighter and had a lower mean BMI SDS than those of WE origin. We now report ethnic differences in body composition and CV markers in childhood. Measurements on 102 children (5...

hrp0089p2-p218 | GH &amp; IGFs P2 | ESPE2018

The Rationale and Design of TransCon GH

Sprogoe Kennett , Beckert Michael , Mortensen Eva , Karpf David B , Leff Jonathan A

Background: The fundamental challenge of developing a long-acting growth hormone (LAGH) is to create a more convenient growth hormone (GH) dosing profile while retaining the excellent safety, efficacy, and tolerability of daily GH. With GH receptors on virtually all cells, replacement therapy should achieve the same tissue distribution and effects of daily (and endogenous) GH while maintaining levels of GH and resulting IGF1 within the physiologic range....

hrp0089p2-p219 | GH &amp; IGFs P2 | ESPE2018

Baseline Demographics of the TransCon GH Phase 3 heiGHt Trial

Beckert Michael , Karpf David B , Shu Aimee , Lin Zhengning , Leff Jonathan A

Background: TransCon GH is a novel sustained-release recombinant human GH (somatropin) prodrug in development for children with GH deficiency (GHD). It is designed to release unmodified GH and intended to provide comparable efficacy, safety, tolerability, and immunogenicity to daily GH with once-weekly dosing. Based on results from a phase 2 trial, which demonstrated comparable efficacy (annualized height velocity for TransCon 0.21 mg GH/kg per week of 12.9 cm/year vs 11.6 cm/...

hrp0086rfc4.5 | Pathophysiology of Obesity | ESPE2016

Steroid Metabolomic Signature of Liver Disease in Childhood Obesity

Gawlik Aneta , Shmoish Michael , Hartmann Michaela F. , Malecka-Tendera Ewa , Wudy Stefan A. , Hochberg Ze'ev

Background: Analysis of steroids by gas chromatography-mass spectrometry (GC-MS) defines a subject’s steroidal fingerprint. Here, we compare the steroidal fingerprints of obese children with or without liver disease to identify the ‘steroid metabolomic signature’ of childhood non-alcoholic fatty liver disease.Methods: Urinary samples of 85 children (43 girls) age 8.5–18.0 with obesity (BMI >97%) were quantified for 31 steroid meta...

hrp0086rfc8.2 | Growth: Clinical | ESPE2016

Pharmacokinetic Modelling Predicts Native hGH Levels Following Administration of a Sustained-Release Prodrug, TransCon hGH, to Children with GHD

Sprogoe Kennett , Beckert Michael , Christoffersen Eva Dam , Gilfoyle David , Wegge Thomas

Background: TransCon Growth Hormone is a once-weekly sustained-release prodrug of recombinant human growth hormone (hGH, somatropin). Based on the inert TransCon prodrug technology unmodified hGH is released with a Cmax and AUC comparable to daily therapy. TransCon hGH leverages the known pharmacology of daily hGH and is being developed for the treatment of growth hormone deficiency (GHD).Objective and hypotheses: Both hGH levels and resulting IGF-I leve...