Research report: Editorial: Growth and pubertal development in paediatric endocrinology: from physiological pathways to clinical challenges

A research collection on growth and pubertal development finds that early puberty may be associated with inherited variants, circulating microRNAs and environmental exposures, while studies of adolescence and short stature show why diagnosis and follow-up benefit from more than a single laboratory measurement. Published as an editorial in Frontiers in Pediatrics, the collection brings together genetic, metabolic, developmental and safety research in paediatric endocrinology. Its central message is that growth and puberty remain biologically complex, and that further investigation and larger validation samples are needed before many of the reported associations can be regarded as firmly established.

Central precocious puberty, which results from early activation of the hypothalamic-pituitary-gonadal axis, provides the largest focus of the collection. In one study, Liu and colleagues analysed polymorphisms in the estrogen receptor beta, or ERβ, gene in girls with idiopathic central precocious puberty. Certain polymorphisms, described primarily as the ERβ RsaI and Rraa haplotypes, appeared to be associated with an increased risk of the disorder.

The authors suggested that these variants may serve as prognostic or risk factors, but the editorial presents them as associations requiring further investigation rather than as established clinical tests. Research on circulating microRNAs offered another possible route into the biology of early puberty. Morrou and colleagues compared girls with central precocious puberty and healthy controls and reported differential expression of microRNA pathways.

In particular, miR-148a-3p was markedly increased in extracellular vesicles in the affected group. Because the increase concerned pathways associated with a neurological condition, the result supported a hypothesis that post-transcriptional regulation may help explain the early activation of the hypothalamic-pituitary-gonadal axis. The investigators also described the work as groundwork for identifying minimally invasive biomarkers, a step that does not amount to clinical validation.

Environmental factors form another strand of the collection. Nie and colleagues used computational analyses to examine bisphenol A, a substance widely used in plastic manufacturing, and identify potential molecular targets associated with precocious puberty. This was a computational study and did not demonstrate that bisphenol A exposure causes precocious puberty in children.

A mini-review by Amodeo and colleagues separately brought together the genetic and environmental causes of peripheral precocious puberty in males. The editorial also notes that many centres, including the editors’ own, reported a significant increase in central precocious puberty cases during the COVID-19 pandemic, when environmental pressure was greatest. That observation provides clinical context but does not identify why the increase occurred.

The relationship between metabolism and diagnosis was examined in a study of 1,077 premenarcheal girls with idiopathic central precocious puberty. Yuan and colleagues found that body mass index correlated with basal luteinising hormone, or LH, and with other markers of pubertal development. These findings align with the editorial’s emphasis on assessing patients beyond isolated biochemical values and considering a broader range of factors.

The research is especially relevant to the use of basal LH as a marker of hypothalamic-pituitary-gonadal-axis activation. The editors also connect this approach with the Endocrine Society’s 2026 guidelines, which they describe as favouring an integrated assessment rather than one limited to biochemistry. Puberty also creates an opportunity to evaluate adrenal function.

Zhang and colleagues studied adolescent girls with polycystic ovary syndrome using liquid chromatography coupled with tandem mass spectrometry. The researchers documented multiple alterations in androgen metabolic pathways in this population and reported that the free androgen index was particularly effective for diagnosis, in line with other studies. The work provides information about metabolic profiling and diagnostic performance in a defined group of adolescent girls.

It does not report a treatment, nor does it establish that any of the observed pathway changes causes polycystic ovary syndrome. Longitudinal development became the focus in a retrospective cohort of 171 children examined by Gürlek and colleagues. The study considered familial, constitutional and combined forms of idiopathic short stature and found that children with these diagnoses did not necessarily follow the same developmental course.

Pubertal timing was important when interpreting growth over time, and some children experienced spontaneous improvement, particularly after puberty. The authors therefore advocated a longitudinal growth assessment before starting recombinant growth hormone therapy, using a broad range of parameters rather than a single initial measurement. Recombinant GH has a favourable overall safety profile, but its systemic growth-promoting effects require appropriate clinical surveillance.

Two contributions addressed the heart during childhood endocrine treatment. Ruiz del Olmo-Izuzquiza and colleagues prospectively assessed cardiac morphology, function and aerobic performance. Although an increase in left ventricular mass was expected, the researchers observed physiological cardiac remodeling rather than pathological hypertrophy.

Systolic function remained preserved, and the study also recorded early subclinical improvements in cardiac contractility. A separate review by Li and Wang examined systemic glucocorticoid exposure during childhood and its effects on myocardial structure and function. Evidence broken down by age group remains limited.

Available findings suggest that structural changes most often manifest as treatment-reversible myocardial hypertrophy, while evidence for permanent structural damage remains insufficient. The collection also includes an effort to make follow-up more individualized. Ly and colleagues applied interpretable predictive models to boys receiving growth hormone therapy.

Current IGF-1 SDS was the strongest predictor of subsequent IGF-1 levels, while treatment-related and puberty-related variables provided additional predictive information. The model identifies statistical relationships within the studied group rather than guaranteeing an individual response or replacing clinical assessment. In a separate contribution, Zhang and colleagues described a patient with P450 oxidoreductase deficiency carrying a previously unreported POR variant.

By combining the case with a systematic review of 167 reported patients, the study illustrated the diagnostic value of integrating endocrine phenotyping with molecular genetics. Taken together, the studies portray growth and pubertal development as processes that cannot be captured adequately through a single hormone value, genetic marker or physical measurement. The reported findings cover central precocious puberty, peripheral precocious puberty, adolescent adrenal metabolism, idiopathic short stature, growth-hormone treatment, steroid exposure, cardiac safety, predictive modelling and a rare disorder of steroidogenesis.

Their scope varies from individual case reports and computational work to retrospective and prospective cohorts, each with its own population and limitations. The editors conclude that the issue provides new evidence and useful questions for paediatric endocrinologists, while explicitly calling for further investigation and larger validation samples as the field works through the clinical challenges surrounding growth and puberty.

Subject of Research: Research on genetic, environmental, metabolic and clinical influences on paediatric growth and pubertal development.

Article Title: Editorial: Growth and pubertal development in paediatric endocrinology: from physiological pathways to clinical challenges

Article References: Candela, E., Zucchini, S., & Baronio, F. (2026). Editorial: Growth and pubertal development in paediatric endocrinology: from physiological pathways to clinical challenges. Frontiers in Pediatrics, 14, Article 2020433. https://doi.org/10.3389/fped.2026.2020433

Image Credits: AI Generated

DOI: 10.3389/fped.2026.2020433

Keywords: paediatric endocrinology, puberty timing, central precocious puberty, growth hormone therapy, IGF-1, bisphenol A, polycystic ovary syndrome, idiopathic short stature, microRNAs, P450 oxidoreductase deficiency, Editorial, Growth