Editor’s page

We welcome you all to an exciting issue of the Journal of Pediatric Endocrinology and Diabetes, covering a selection of original articles, case reports, images, reviews, and journal updates. We hope that these articles intellectually stimulate the readers, especially the postgraduate students and fellows in training.

In our regular series titled “Genetics for the Pediatric Endocrinologist,” Parminder Kaul et al., Chandigarh, India, discuss the genetics of idiopathic short stature (ISS) and provide new perspectives on growth regulation and the importance of genetic studies.^[1] ISS is characterized by a height that falls more than 2 standard deviation scores (SDSs) below the mean for a child’s age, gender, and population, without any underlying systemic, endocrine, nutritional, or chromosomal abnormalities. The growth hormone insulin-like growth factor (GH-IGF) axis has a significant role in the regulation of growth and development. The use of advanced molecular genetic approaches such as copy number variation analysis, whole-exome sequencing (WES), and single-gene testing helps to identify genetic causes in approximately 25–40% of cases of ISS. A good discernment of the genetic basis of ISS will improve diagnostic accuracy and detection of comorbidities, provide appropriate genetic counseling, and help in the identification of those who may benefit from targeted therapies with GH, IGF-1, and newer agents. There is a felt need for further research to unravel the complex etiology of ISS and improve management strategies for affected individuals.

Anjana Hulse and Sushma Rai, from Bengaluru, India, in an original article,^[2] address the concern of decreasing height velocity and a possible increase in body mass index (BMI) during gonadotropin-releasing hormone (GnRH) analog therapy for central precocious puberty (CPP) in girls. In a retrospective study of 80 girls with CPP from an urban area before the age of 8 years and discontinuation of treatment at 10.5–11.5 years with a bone age of 12 years, there was a decline in height velocity during treatment, but it did not seem to affect the final height. BMI SDS increased during treatment with 49/80 girls either becoming obese or overweight. This increase was present throughout the 1^st year of the treatment period, stabilizing in the subsequent 2 years of observation.

In an accompanying editorial commentary, Lokesh Sharma and Preeti Dabadghao, Lucknow, India,^[3] investigate whether GnRH analog therapy for CPP in girls affects BMI. GnRH analogs are generally safe, but there are conflicting reports on the increase in BMI. The observed increase in obesity/overweight is usually during the treatment period, stabilizing later. It could be a reflection of the current population trends in urban areas, or girls with excess adiposity are more prone to developing early or precocious puberty. The authors suggest that patients and their parents should receive anticipatory counseling on the importance of a healthy diet and physical activity with BMI monitoring during GnRH analog therapy for CPP.

Dubois and Carel JC, Paris, France,^[4] while commenting on this study, note that this Indian cohort appears older and more advanced in puberty, with 20% having experienced menarche than those typically seen in European or American series. Several studies have commented on the conflicting results on adiposity, and the increase in BMI following GnRHa therapy was observed. Increasing adiposity is a major risk factor for precocious puberty, while suppression of the hypothalamic-pituitary-gonadal (HPG) axis tends to promote fat mass accumulation. Further long-term studies are necessary to evaluate the impact of treatment on growth trajectories and the HPG axis.

Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis, steatohepatitis, fibrosis, and cirrhosis and is a common comorbidity associated with obesity in children and adolescents. Early detection of NAFLD may help to implement appropriate early lifestyle interventions, as it is currently non-reversible. Liver biopsy, the gold standard for the diagnosis of hepatic fibrosis and cirrhosis, is invasive and is not a preferred modality for screening NAFLD. Transient elastography, a relatively recent non-invasive technique used for assessing hepatic steatosis and stiffness, is being increasingly tried for early diagnosis of hepatic fibrosis. Risha Saxena et al., from Kanpur, India,^[5] evaluated serum alanine transaminase (ALT) levels and transient elastography in 62 obese children and compared them with 61 age-matched controls. They observed a high prevalence of steatosis and fibrosis in obese children by transient elastography. Serum ALT levels above 69 IU/L were associated with an increased risk for hepatic fibrosis identified by transient elastography. The authors have recommended multicenter studies for early screening for NAFLD using alkaline phosphatase levels and transient elastography as markers and assessing the impact of lifestyle interventions in children and adolescents.

Raquel Suay Romero et al., from Valencia, Spain,^[6] describe an unusual presentation of two siblings with Wolfram syndrome type 1 in a family. The elder girl manifested optic atrophy, followed by insulin-dependent diabetes mellitus and diabetes insipidus. The diagnosis was confirmed by WES. A targeted Sanger sequencing analysis revealed that both parents were heterozygous carriers of the mutation. The youngest brother, at 8 years of age, was homozygous for the mutation and had features of optic atrophy without other features of WS type 1.

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in the neonatal period. CHI, due to mutations in ABCC8 or KCNJ11 and those with diffuse involvement of the pancreas, is generally unresponsive to conventional diazoxide and octreotide therapy. Cristina Pellicer Viudes et al., Valencia, Spain,^[7] describe two infants with diffuse pancreatic involvement due to compound heterozygous mutations in ABCC8 and KCNJ11, each of who were refractory to standard medical treatment, who received long-term therapy with sirolimus, a mammalian target of rapamycin inhibitor, with good response during follow-up.

Osteogenesis imperfecta (OI) and Ehlers–Danlos syndrome (EDS) are two inherited connective tissue disorders with overlapping phenotypic features. Mutations in COL1A1 or COL1A2 may lead to a phenotype combining phenotypes of OI and EDS, referred to as COL1-related overlap disorder (C1ROD). Dhanya Soodhana et al., Kozhikode, India,^[8] report a 3.5-year-old boy who had short stature, developmental delay, recurrent fractures following trivial trauma, and osteopenia on dual-energy X-ray absorptiometry (DXA) scan with a heterozygous splice-site mutation in COL1A2 (c.432 + 1G>A), confirming the diagnosis of C1ROD. The child received an intravenous zoledronic acid biannually, along with calcium and vitamin D supplementation.

In the “Fellow’s Corner” section, Sukanya Priyadarshini, New Delhi, India, details her reflections on her journey through postgraduate training in pediatric endocrinology.^[9] Opportunities for admission to a formal training program in pediatric endocrinology in India are limited to a few institutions. We hope that her experience and advice will be useful to those seeking a pediatric endocrinology career.

In our regular feature on “Ped Endo Journal Scan,” Kriti Joshi, Brisbane, Australia, discusses five recent fascinating publications.^[10] The first is a study on the safety and efficacy of stem cell-derived fully differentiated islets for type 1 diabetes – a new oral therapeutic option. The second review highlights phenotypic variations and pubertal outcomes in males and females with 46, XY partial gonadal dysgenesis. The third study details the GH excess seen in children with neurofibromatosis and optic pathway glioma and summarizes the treatment results with long-acting somatostatin analogs. The fourth commentary describes the efficacy and safety of automated insulin delivery in children aged 2–6 years in an open-label, multicenter, randomized, crossover trial. The fifth report describes maturity-onset diabetes of the young in a racially/ethnically diverse population. The editors hope that these new research publications will add insights into better and optimal management of children with chronic endocrine disorders.

We have endeavored our best to present to you a variety of interesting clinical situations requiring astute observations, clinical acumen, and supportive laboratory in the diagnosis and management of common and not-so-common endocrine situations. We look forward to your comments and suggestions and welcome contributions to the forthcoming issues of our journal.

Happy reading!