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Review Pediatric Endocrinology Key Developments in Pediatric Endocrinology in 2015 Nazaneen Eshragh and Stephen H LaFranchi Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, US T he year 2015 brought many exciting discoveries and key developments in the field of pediatric endocrinology. Examples range from reports of a family with the first discovered insulin-like growth factor-2 gene mutation to a description of the first clinical trials of an ‘artificial pancreas’ in children with diabetes mellitus, along with publication of important society guidelines, such as those for management of thyroid nodules and cancer in children, the diagnosis of polycystic ovary syndrome in adolescents, and for neonatal hypoglycemia. This short review will describe some of these key developments over the past year that we believe to be of interest to pediatric endocrinologists, organized by endocrine categories. Keywords Growth/growth hormone/insulin-like growth factors Aggrecan, artificial pancreas, diabetes insipidus, differentiated thyroid cancer, human growth hormone, hypoglycemia, hypogonadism, insulin- like growth factor-1 (IGF-1), insulin-like growth factor-2 (IGF-2), polycystic ovary syndrome Evidence has long supported insulin-like growth factor-2 (IGF-2) as an important fetal growth factor. Begemann and co-workers from Germany and the Netherlands report four patients from a multigenerational family with the combination of severe intrauterine and postnatal growth retardation, relative macrocephaly, and Russell–Silver syndrome-like features, found to be caused by a paternally inherited IGF2 nonsense mutation. 1 Neurodevelopment ranged from normal to modest impairment. Skeletal maturation typically was delayed by a few years compared to chronological age. Endocrine evaluation showed normal to elevated serum growth hormone (GH) and IGF-1 levels, while serum IGF-2 levels were low for age (246–380 ng/mL). Adult height in three patients ranged from 148.0 to 170.0 cm (-4.0 to -1.6 standard deviation [SD]). GH treatment resulted in modest improvement in height standard deviation score (SDS), with one patient reaching 170 cm. Disclosure: Nazaneen Eshragh and Stephen H LaFranchi have nothing to disclose in relation to this article. No funding was received for the publication of this article. Compliance with Ethics: This article involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: March 11, 2016 Accepted: April 21, 2016 Citation: US Endocrinology, 2016;12(2):87–9 Corresponding Author: Stephen H LaFranchi, Department of Pediatrics, Oregon Health and Science University, Portland, Oregon, 97239-3098, US. E: lafrancs@ohsu.edu Adding another piece to the ‘idiopathic’ short stature puzzle, Nilsson et al. describe 11 patients from three families with autosomal dominant short stature. 2 Endocrine evaluation, including GH–IGF axis function, was normal. They had features of a skeletal dysplasia, including brachydactyly, short thumbs, and mid-face hypoplasia. Using whole exome sequencing, these patients were discovered to have a heterozygous mutation in ACAN, a gene which codes for aggrecan, a proteoglycan in the extracelluar matrix of the growth plate and other cartilaginous tissues. While most children with short stature have delayed bone age, the unique feature in patients with aggrecan mutation is advanced bone age and premature growth cessation. Moving from new etiologies to unique treatment paradigms, Backeljauw et al. reported results from the first study of combination GH/IGF-1 therapy in children with short stature. 3 In this randomized, multicenter trial, enrolled children were below -2 SD in height, were GH sufficient, but had a serum IGF-1 below -1 SD for age and gender. The rationale for combination therapy was that such children might need an increase in both locally generated IGF-1 (from GH) and systemic IGF-1. In the first year, children treated with GH/IGF-1 grew 9.7–11.2 cm/year (three groups, all receiving the same dose of GH and incremental doses of IGF-1), compared to 9.3 cm/year in the GH alone group (highest IGF-1 dose significantly greater growth velocity vs. GH alone). Improved growth rate was sustained over three years; the GH/IGF-1 group receiving the highest dose gained 1.9 SD in height, compared to 1.3 SD in the GH-alone subjects. Adverse effects were similar in the GH/IGF-1 vs. GH alone, with the exception of a higher frequency of lipohypertrophy and hypoglycemia in patients receiving the combination therapy, perhaps because a significant proportion of these subjects had serum IGF-1 levels >+2 SD. A potential adverse effect of GH treatment is the risk of neoplasia, either primary or secondary malignancies in children with a history of prior cancer. This issue was explored in a PubMed search carried out by the Pediatric Endocrine Society Drug and Therapeutics Committee. 4 In children without TOU CH MED ICA L MEDIA 87