ESPE Abstracts

Background: Hereditary vitamin D resistant rickets (HVDRR) or vitamin-D dependent rickets type II is an autosomal recessive disorder caused by mutations in the vitamin D receptor (VDR) gene, causing end-organ resistance to the action of 1,25-dihydroxyvitamin D (calcitriol), thus resulting in the distinct characteristics of early-onset rickets, hypocalcemia, and secondary hyperparathyroidism. The currently accepted treatment modality is bypassing the affected r...

Patients with discordant thyroid function tests (TFTs) are common clinical conundrums for the practising paediatric and adult endocrinologist. In order to avoid unnecessary investigation and treatment, a structured approach to the work up is required. During this session I will use a case based approach to review common causes of discordant TFTs, such as confounding physiological and pathophysiological factors, analytical errors, binding protein abnormalities and genetic cause...

Background: CTP-modified hGH (MOD-4023) has been developed for once weekly administration in GH deficient (GHD) adults and children. Immunogenicity samples of once-weekly s.c. administration of MOD-4023 were detected for the presence of binding and neutralizing anti-MOD-4023 Ab’s in pediatric Phase 2 study.Objective and hypotheses: During the first year of the study, 53 pre-pubertal GHD children were treated with once-weekly s.c. injections of one o...

Background: Isolated persistence of Müllerian ducts in an otherwise normally virilised 46,XY newborn, a condition known as PMDS, is a disorder of sex development (DSD) due to a defect limited to AMH-dependent Müllerian duct regression.Objective and hypothesis: We report the case of a patient with PMDS and extremely low serum AMH in whom no mutations were detected in the AMH gene coding sequences. A single base deletion identified in th...

Background: Congenital adrenal hyperplasia (CAH) patients are clinically often less severely affected by cortisol deficiency than anticipated from their enzymatic defect.Objective and hypotheses: We hypothesize that adrenal steroid hormone precursors that accumulate in untreated or poorly controlled CAH have glucocorticoid activity and partially compensate for cortisol deficiency. We aimed to determine the in vitro binding, translocation and tra...

Background: DICER1, a ribonuclease, cleaves non-coding small RNA precursors to generate mature microRNAs (miRNAs), of ~21 nucleotides in length. MiRNAs alter gene expression post-transcriptionally by directly binding to mRNA transcripts and subsequently down-regulating gene expression. It is estimated that expression of ~30–70% of all mammalian protein-coding genes are regulated in this manner.Method: Sequencing of DICER1 in various tumors, accompan...

Background: Silver Russell syndrome (SRS) is genetically heterogenous and around 30% of patients with clinical SRS have no genetic diagnosis. Mutations in HMGA2 have recently been identified causing growth failure and an SRS-like phenotype. Despite strong evidence of the crucial role of HMGA2 in growth across species, the mechanism of action of HMGA2 in human linear growth is unclear.Objective:...

Background: For many patients with high-risk cancers, allogeneic stem cell transplant (SCT) is the only curative option. A major risk of SCT is acute graft versus host disease (aGVHD). About 50% of SCT patients develop aGVHD as a part of their course. Glucocorticoids are the mainstay of therapy in aGVHD patients. Of the patients that develop aGVHD, about 50% develop a steroid refractory/resistant form. These patients tend to require higher doses of steroids and many will requi...

Although Endocrinologists have focused for decades on circulating concentrations of cortisol, arguably the important concentrations are those within tissues which are available at corticosteroid receptors. Tissue concentrations are influenced by plasma proteins binding cortisol, by physicochemical characteristics of the steroid, by active transport across cell membranes, and by steroid metabolism within target tissues. Many of these factors vary between individuals, and within...

Background: TransCon hGH, is a once-weekly prodrug releasing unmodified hGH, for the treatment of Growth Hormone Deficiency (GHD) in children and adults. To date, TransCon hGH has demonstrated comparable efficacy, safety and anti-hGH immunogenic profile to daily hGH, with no occurrence of neutralizing antibodies.Objective and hypotheses: Protein-based therapies may be associated with generation of drug-specific antibodies, which may impact efficacy, part...