Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective

The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.info:eu-repo/semantics/publishedVersio

Insulin production and resistance in cystic fibrosis: Effect of age, disease activity, and genotype

Aim: To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD). Subjects and methods: One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic beta-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR). Results: The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMA-IR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the age-group, and to the HOMA-IR and insulinogenic indexes. Conclusions: IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, beta-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect. (J. Endocrinol. Invest. 35: 246-253, 2012) (C) 2012, Editrice Kurtis353246253Italian Cystic Fibrosis Research Foundation [18/2006]University HospitalDepartment of Paediatrics in Parma, ItalyItalian Cystic Fibrosis Research Foundation [18/2006