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.

Human growth hormone (hGH) replacement therapy has been widely available for clinical purposes for more than fifty years. Starting in 1958, hGH was obtained from cadaveric pituitaries, but in 1985 the association between hGH therapy and Creutzfeldt-Jakob disease was reported. In the same year, the use of recombinant hGH (rhGH) was approved. Side effects of rhGH replacement therapy in children and adolescents include rash and pain at injection site, transient fever, prepubertal gynecomastia, arthralgia, edema, benign intracranial hypertension, insulin resistance, progression of scoliosis, and slipped capital femoral epiphysis. Since GH stimulates cell multiplication, development of neoplasms is a concern. We will review the side effects reported in all rhGH indications.

Context: Recombinant human (rh) IGF-I is now available to treat children with short stature resulting from severe primary IGF-I deficiency. This review from the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society discusses different aspects of rhIGF-I therapy, particularly with regard to potential advantages and disadvantages in comparison with the traditional use of rhGH for treatment of short stature. Evidence Acquisition: We used the Entrez-PubMed search engine to conduct a review of publications addressing IGF-I deficiency, the use of rhIGF-I, and treatment for short stature. Evidence Synthesis: rhIGF-I, as a twice-daily sc injection, is now approved for treatment of short stature in children with severe primary IGF-I deficiency, which may occur as a consequence of mutations in the GH receptor, defects in the post-GH receptor signaling pathway, and IGF-I gene defects. It is also approved for children with GH deficiency who develop neutralizing antibodies to GH. rhIGF-I significantly improves growth in these conditions. However, adult height may still be suboptimal, possibly due to lack of direct GH effects. Dosing regimens for rhIGF-I administration are under investigation, as are other indications for use of rhIGF-I. Conclusion: The use of rhIGF-I is justified in conditions approved by the Food and Drug Administration. Until more substantial data become available, the use of rhIGF-I outside Food and Drug Administration recommendations should only be investigational.

Although recombinant human GH (rhGH) has been available since 1985, there are several questions related to its use that remain unanswered. The Entrez-PubMed search engine was used to conduct a review of publications appearing since 2007 that address growth and GH treatment. Recent publications related to the diagnosis of GH deficiency, genetics of growth, the use of rhGH in different genetic conditions, in idiopathic short stature, and in puberty, and strategies to adjust rhGH dose were reviewed. New studies investigating the genetics of growth and the response to rhGH therapy in different groups are helping in the understanding of the physiology of normal growth. Although in most children treated with rhGH there is a short-term benefit, the clinical relevance of the benefits after long-term treatment in some conditions remains unclear. The challenges are to define milder forms of GH deficiency and to assess the relevance of the benefits, if any, caused by rhGH in different patient populations and the best therapeutic approach for these patients. Well-designed long-term studies using anthropometric, genetic, and laboratory data that will also assess long-term quality of life benefits are needed to help clinicians select patients to initiate treatment with rhGH and to adjust treatment to improve outcome.

The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p<0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p<0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p<0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index.