Background/Objectives: Growth in childhood and adolescence is influenced by a complex interaction of genetic, environmental, and hormonal factors, with growth hormone (GH) and insulin-like growth factor 1 (IGF-1) playing crucial roles in linear growth and development. However, chronic inflammation, often detected in situations like inflammatory bowel disease and juvenile idiopathic arthritis, can significantly disrupt the GH/IGF-1 axis, causing a relevant growth impairment. Methods: We conducted a retrospective review focusing on the role of cytokines in the GH-IGF-1 axis and growth. Results: Inflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 have been shown to contribute to GH resistance through an array of mechanisms that involve the downregulation of GH receptors and alterations in IGF-1 metabolism. This disruption negatively impacts the growth plate, particularly by impairing chondrocyte proliferation and differentiation, which are essential for proper bone elongation. This review delves into the intricate relationship among growth, chronic inflammation, and GH-IGF-1 axis, emphasizing the contribution of inflammatory cytokines in modulating GH signaling. It also highlights how cytokines can interfere with the molecular pathways that regulate skeletal growth, ultimately leading to growth disturbances in children suffering from chronic inflammatory diseases. Conclusions: The findings underscore the importance of controlling inflammation in affected individuals to mitigate its detrimental effects on growth and ensure that children may reach their growth full potential.

Background/Objectives: Hypothyroidism can profoundly affect growth, particularly if it insidiously arises during early childhood. Congenital hypothyroidism is now detected through newborn screening, significantly improving the overall growth outcomes of these children. Conversely, acquired hypothyroidism often results in delayed somatic growth and shorter stature, with many affected children initially remaining non-symptomatic. The main objective of this review is to summarize the current knowledge about the impacts of acquired hypothyroidism on children’s growth outcomes. Methods: We performed a literature review to analyze growth and final height in children with acquired hypothyroidism, matching the following keywords: “hypothyroidism & growth”, “hypothyroidism & height”, “hypothyroidism & stature”, “hypothyroidism & development”, “hypothyroidism & auxological parameters”. We reviewed each article that met the eligibility criteria, and after a thorough selection, we included 16 studies. Results: Growth arrest is frequently noted as a symptom in hypothyroidic children, with substantial portions of affected children presenting below the third percentile for height. The timing of diagnosis significantly influences growth outcomes: those diagnosed during puberty tend to experience less catch-up growth due to accelerated skeletal maturation. Even if thyroxine replacement can induce rapid catch-up growth, it may be incomplete if treatment begins during puberty or if there is a markedly prolonged deficiency of thyroid hormones. While levothyroxine therapy typically results in some degree of catch-up growth, many children do not reach their expected genetic height. Conclusions: This review highlights the necessity of both early diagnosis and treatment of acquired hypothyroidism. Even if many children show improvements in height velocity post-treatment, the complete normalization of growth may remain elusive.

Background: Recent advances in genetic research have significantly expanded our understanding of the molecular bases of growth hormone deficiency (GHD), and numerous genes have been identified as impacting final stature through isolated or combined abnormalities of growth hormone (GH), GH insensitivity, and insulin growth factor-1 (IGF-I) resistance. Objective: This review summarizes the current knowledge on the genetic causes of GHD in the context of pediatric short stature, emphasizing the role of next-generation sequencing technologies in real-life clinical practice and the potential impact of genetic diagnosis over therapeutic decisions regarding GH replacement therapy. Materials and methods: Articles from PubMed up to April 2025 dealing with GHD were retrieved and analyzed, focusing on genes influencing the GH pathway and stunted growth, with focused attention on relevant molecular and clinical studies. Results: Our analysis, besides cataloguing well-established and novel contributors to growth failure among genes associated with the GH–IGF1 axis, also emphasizes the crucial role of genetic testing and strategies that should be used to maximize the likelihood of identifying a specific genetic etiology, such as prioritizing genetic tests when a monogenic cause is strongly suspected or when there are peculiar clinical features that could be linked to specific genetic conditions. Conclusions: We have highlighted the most recent genetic etiologies of short stature related to GHD, providing an updated framework that is expected to be helpful in the diagnostic and therapeutic management of individuals with mutations related to the GH-IGF1 axis.

Sleep is a cardinal biological process that backstops central nervous system function, which also plays a crucial role in regulating systemic homeostasis, including immune activities. Cytokines, particularly interleukin-1β and tumor necrosis factor-α, act as mediators bridging sleep and inflammation, also influencing both sleep architecture and sleep–wake cycle. Sleep deprivation and sleep disorders such as insomnia, narcolepsy, hypersomnia, or obstructive sleep apnoea may disrupt cytokine production, alter their circadian rhythm of release, and shift secretion peaks from night to day. These changes contribute to daytime fatigue, impaired cognitive and physical performance, increased susceptibility to infections and/or systemic inflammation. Molecular studies indicate that insufficient sleep primes immune cells to enhance pro-inflammatory responses, creating a feedback loop with neuroendocrine pathways that further exacerbates sleep patterns and inflammatory dysregulation. Understanding the bidirectional relationship between sleep and cytokines may highlight the role of sleep as an active component of immunity regulation and underscore the potential usefulness of multilevel interventions that include complementary and integrative health approaches restoring sleep, normalizing cytokine rhythms and mitigating inflammation.

Background/Objectives: Central precocious puberty (CPP) is defined by the premature onset of secondary sexual characteristics prior to the age of 8 and 9 years in girls and boys, respectively. The administration of GnRH analogs (GnRH-a) has become a cornerstone in the management of CPP, but effects on metabolic processes, particularly body mass index (BMI), remain a subject of ongoing investigation. This study aimed to investigate the relationship between GnRH-a treatment and BMI changes in a cohort of Italian children with CPP. Methods: We conducted a retrospective cohort study of 34 girls with idiopathic CPP, all treated with GnRH-a. Anthropometric parameters including BMI were collected at three time points: baseline, one year after treatment, and one year after treatment cessation. A comprehensive review of the medical literature concerning GnRH-a and BMI was performed. Results: Statistical analysis using the Wilcoxon and McNemar tests revealed a significant increase in BMI-for-age z-scores after one year of GnRH-a, with a slight increase also observed one year post-treatment of CPP. These findings suggest that GnRH-a treatment contributes to an increase in BMI, particularly in CPP children with a normal weight at baseline, although the overall impact on the progression of obesity remains minimal. A review of the existing literature supports the notion that changes in BMI during GnRH-a treatment are influenced by various factors, including baseline BMI, gender, and metabolic processes. Conclusions: Despite our findings suggesting the potential impact of GnRH-a on BMI, further longitudinal studies are necessary to fully understand the long-term metabolic consequences of GnRH-a therapy in children with CPP.

Background: Hypothyroidism is the most common thyroid dysfunction in childhood, resulting from the decreased biological activity of thyroid hormones in tissues. Pediatric patients with hypothyroidism, when left untreated or when thyroid hormone levels fail to normalize despite treatment, may exhibit various complications such as growth retardation, obesity, and hypercholesterolemia. Aim: We conducted a monocentric retrospective study to evaluate potential differences in obesity rates and auxological parameters between healthy patients and children with hypothyroidism undergoing levothyroxine replacement therapy. Additionally, we examined possible differences in lipid and glucose metabolism between the two groups. Materials and Methods: We collected and analyzed data from the electronic medical records of 108 patients who were regularly followed up for thyroid dysfunction at the Pediatric Endocrinology Unit of the Fondazione Policlinico Universitario A. Gemelli IRCCS from January 2016 to June 2024. We also included 104 healthy controls who underwent thyroid function testing during the same period, followed up in the same department for regular auxological check-ups. Results: Our findings revealed that patients with acquired hypothyroidism had a lower height z-score compared to healthy controls (t(210) = −2.6; p = 0.01). Additionally, they exhibited higher blood glucose and triglyceride levels, although these values remained within the normal range. Conclusions: We highlight the critical importance of the early diagnosis of hypothyroidism to initiate levothyroxine replacement therapy promptly and mitigate the long-term effects of hypothyroidism on children’s growth.