ESPE Abstracts

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....

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/...

Aims: To examine growth, body composition and glucose metabolism during childhood in children born small for gestational age (SGA).Methods: Single centre cohort study of 150 children (63 boys), identified from newborn records as being born SGA (birth weight SDS <−1.5) and assessed between the age of 4 and 7 years. Data collected included: anthropometric parameters (height, weight, BMI: transformed into age- and sex-adjusted SDS), lean and fat m...

Background: Thyroglobulin (Tg) is exclusively synthesised by thyroid tissue and a potentially useful aid to diagnosis in congenital hypothyroidism (CH). However, its role has yet to be fully evaluated.Objective: To examine the sensitivity and specificity of Tg in helping define the etiology of CH.Patients and methods: Tg was measured in a single laboratory by Immulite 2000 chemiluminescent immunometric assay (CVs 9.8, 5.7 and 5.7% ...

Background: The majority of drug developments in type 1 diabetes (T1D) are aimed at preventing decline of beta cell function (BCF), as this has been associated with better glycaemic control and fewer long-term complications. Traditionally, BCF is evaluated by the C-peptide response to the labour-intensive mixed-meal-tolerance-test (MMTT), but there’s a need for a more practical alternative. We developed a new method to measure C-peptide in ‘dried blood spots’ (D...

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...

Background: Insulin treatment in a very low birth weight neonate having persistent hyperglycemia is challenging. The very recently reported novel human genetic cause of neonatal diabetes due to NKX2.2 pancreatic transcription factor mutations is associated with very low birth weight deliveries.Objective and hypotheses: To study the diagnostic process, the molecular genetics, the clinical phenotype, and the significant therapeutic challenges in the manage...

Background: Treatment adherence to daily subcutaneous rhGH is a burden for GHD patients, with noncompliance reported in up to 77% of patients and significantly associated with reduced efficacy (Rosenfeld Endocr Pract 2008; Cutfield PLoS One 2011). Somavaratan, a novel rhGH fusion protein with t1/2 >100 h, demonstrated clinically meaningful improvements in height velocity and IGF-I in prepubertal children with GH deficiency (GHD) in a multicenter, randomized, Pha...

Background: TransCon GH is designed as a once-weekly sustained-release prodrug of recombinant human GH (hGH, somatropin). Based on the inert TransCon prodrug technology unmodified native hGH is released with a Cmax and AUC comparable to daily therapy. TransCon GH leverages the known pharmacology of daily hGH and is being developed for the treatment of GH deficiency (GHD) in children and adults.Objective and hypotheses: Develop a safe and efficacious sust...

Background: The combination of type 1 diabetes mellitus (T1DM) and GH deficiency is uncommon. In a previous study (1) we found that in children with T1DM and GHD with adequate adaptation of insulin dosage, the metabolic control of T1DM did not worsen during GH treatment. However, decreased catch-up growth was observed and no data on GH dose was available.Objective: To analyse first year treatment growth response and GH dosage in prepubertal patients with...