Endocrine Abstracts

Background: Pathogenic IGFI gene mutations causing childhood growth failure are extremely rare. Only five autosomal recessive mutations, one IGFI copy number variant and two heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations haven’t previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnatal growth failu...

We have shown that Type I IFN paradoxically inhibits autoimmune diabetes in the NOD mouse and BB rat. We assessed the structure function relationship and potential mechanism of this interferon action by determining: (1) the diabetes sparing effect of several type 1 IFNs: recombinant human IFN-A/D bgl 11 (rIFN-alpha), rIFN-alphaB/D, rIFN-alpha-consensus (CIFN), IFN-taumod1 in NOD mice (2) the effect of IFN-tau administration in IL-4 KO and IFN-gamma KO NOD mice (3) the effect o...

Introduction: Ageing is associated with a decrease in activity of the growth hormone / IGF-1 axis. However, there is little normative data for serum IGF-I levels in the very elderly and the relationship of IGF-1 levels to muscle function and physical performance in geriatric inpatients has not been fully explored. We studied elderly patients rehabilitating after proximal femoral fracture (PFF), hypothesising that patients with lower circulating IGF-1 levels would have poorer p...

Background:The growth hormone/insulin-like growth factor-I (GH/IGF-I) axis has been increasingly implicated in the development of breast cancer. Previously we have demonstrated the local expression of IGF-I in normal and malignant breast tissue. However the correlation of this local expression with clinical factors has not fully been investigated.Aims: (i) To quantify the mRNA levels of IGF-I in normal and malignant breast tissue and (ii) to identify any correlation betwee...

Section 1: Case history: A 10-year-old girl presented with significant postnatal growth failure. Her birth weight was normal (–0.15SDS) but poor growth was observed from a few months of age. She had no other symptoms. On examination, height was –3.4SDS and head circumference –1.6SDS. She had no dysmorphic features and normal development. Section 2: Investigations: Baseline serum analyses were unremarkable. Karyotype was normal (46XX). Bone age was delayed by 2.5...

Somapacitan is a long-acting growth hormone (GH) intended for once-weekly subcutaneous administration. As for GH, the mechanism of action of somapacitan is either directly or indirectly via insulin-like growth factor I (IGF-I). A PK/PD model of somapacitan was developed from the pharmacokinetics (PK) and IGF-I levels from three phase 1 trials data: a single dose/multiple dose trial (0.02–0.24 mg/kg per week) in healthy adults, a multiple dose trial in adults with growth h...

Introduction: IGF-I and its binding proteins may modulate cardiovascular risk. As part of our Manchester Mothers’ Cardiovascular study, we tested in pre-menopausal women the hypothesis that higher circulating IGF-I concentrations would be associated with lesser arterial stiffness and lower cardiac (LV) mass, while higher IGFBP1, reflecting less pre-hepatic insulin, would be positively related to small vessel function.Methods: About 193 women aged 32...

Background: Previous studies have implicated the GH/IGF-I axis in the pathogenesis of breast cancer and the development of tamoxifen resistance. IGF-I is a known proliferative and anti-apoptotic agent. In order to characterize the growth changes that occur when elements of the GH/IGF-I axis are disrupted we have used siRNA to transcriptionally silence the IGF-IR in the MCF-7 human breast cancer cell line.Methods: MCF-7 cells were cultured in phenol red-f...

Background: Growth hormone deficiency (GHD) is the most frequent endocrinological disorder inchildren with short stature, but there are significant controversies in the diagnosis due to lack of reliablediagnostic criteria. Moreover, at final height (FH) attainment, many subjects diagnosed withisolated GHD re-test normal. It is not clear whether this represents a form of transient GHD or a false positive diagnosis during childhood.Aim: To evaluate differe...

The sodium/iodide transporter (NIS) mediates active I− uptake in thyroid, lactating breast, salivary gland, and stomach epithelial cells. NIS-mediated I− transport is electrogenic with a 2:1 Na+:I− stoichiometry, i.e. when NIS activity is measured electrophysiologically in NIS-expressing oocytes, inward positive currents are recorded upon addition of I− or other anions that are NIS substrates. Howev...