Background: Complete androgen insensitivity syndrome (CAIS) is a rare disorder of sex development characterized by 46,XY karyotype and testes, yet presenting with a complete female phenotype, which is related to mutations in the androgen receptor (AR) gene. Case presentation: We herein present the case of a 14-year-old adolescent with primary amenorrhea and suspected delayed puberty whose diagnostic journey led to the identification of CAIS through the demonstration of a novel AR variant (c.159_207del). Case-based review: Our report encompasses the complexity of CAIS management, focusing on the risk of malignancy, surveillance options, hormone replacement therapy, timing of an eventual gonadectomy, and the psychosocial impact of such a diagnosis. An algorithm has been formulated for the management of CAIS starting in adolescence, highlighting the conservative approach for those patients unwilling to undergo gonadectomy. Conclusions: Primary amenorrhea and delay in puberty development may provide clues, ultimately leading to a diagnosis of CAIS. This review emphasizes the cruciality of a multidisciplinary approach in managing patients with CAIS, needing for an individualized care to optimize the overall outcome.

Background: Among the potential indications for growth hormone (GH) therapy is the presence of mutations in the SHOX (short stature homeobox-containing) gene, located in the telomeric pseudotautosomal region (PAR1) on the short arm of both sex chromosomes. Despite general recommendations supporting GH therapy in these cases, there is a lack of comprehensive evidence specifically evaluating its efficacy and safety in this subgroup of pediatric patients. Aim: The objective of this scoping review was to evaluate the efficacy and safety of growth hormone therapy in patients with SHOX gene variants, providing a narrative synthesis of the included studies. Materials and Methods: This scoping review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews. We summarized information extracted from 22 articles identified by our search strategy. Currently, only one randomized clinical trial has analyzed the efficacy profile of GH in patients with SHOX mutations. Results: Growth hormone is a valuable therapeutic aid for these patients. However, its prescription in children with SHOX gene mutations should consider the specific characteristics of each patient, similar to the approach taken for patients with idiopathic growth hormone deficiency (GHD). Conclusion: Growth hormone therapy in patients with SHOX gene alterations appears to be both safe and effective. However, longitudinal prospective studies and targeted clinical trials are necessary to confirm these findings. Despite this, GH remains one of the preferred hormonal therapies for patients with short stature and confirmed SHOX gene mutations.

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.

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: A correlation between plasma lipids and timing of pubertal development has been hypothesized, though lipid influence remains unclear in central precocious puberty (CPP). Aim: To assess any possible alterations in the lipid profile and triglyceride glucose index (TyG) in children diagnosed with CPP. Patients and Methods: Retrospective single-center study conducted on children (aged 6.3 ± 2.1 years) evaluated for the suspicion of CPP. Results: Based on the results of the gonadotropin releasing hormone (GnRH) test, considering 5 IU/L as cut-off of the luteinizing hormone peak, CPP was confirmed in 43 patients (57.3%). Sixteen (37.2%) had a pathologic body mass index (BMI), with 9 (20.9%) being overweight and 7 (16.27%) obese. High total cholesterol was found in 3 patients with CPP (6.97%), high triglycerides were found in 11 patients with CPP (25.58%), high LDL cholesterol was found in 5 patients with CPP (11.62%), low HDL cholesterol was found in 12/43 patients with CPP (27.9%), a pathologic TyG was found in 13/43 patients with CPP (30.23%). No significant association was observed in the lipid profile for patients with or without CPP, except for HDL cholesterol, which was lower in the CPP group (47.1 ± 10.9; p = 0.033). However, the association between serum HDL cholesterol and CPP was not confirmed at the multivariate logistic regression analysis adjusted for patients’ sex and age (p = 0.1; OR: 1.035; 95% CI: 0.993–1.078). Conclusion: The overall lipid profile of our pediatric patients diagnosed with CPP did not differ from patients having idiopathic precocious thelarche or normal variants of puberty development.

Traumatic brain injury (TBI) in childhood is a major global health concern and a leading cause of morbidity and mortality in the pediatric population. Its incidence is rising worldwide, with early childhood and adolescence representing the most vulnerable age groups. Beyond acute neurological injury, post-traumatic endocrine dysfunction has emerged as an underrecognized but clinically significant sequela, with potential long-term consequences for growth, puberty, metabolism, and overall quality of life. The hypothalamic–pituitary axis (HPA) is uniquely vulnerable due to its anatomical and vascular characteristics, making pituitary cells—particularly somatotrophs and gonadotrophs—susceptible to ischemic, traumatic, and inflammatory damage. Reported prevalence of post-TBI pituitary dysfunction in children ranges from 5 to 57%, reflecting a deep heterogeneity in injury severity, diagnostic methods, and timing of evaluations. Growth hormone deficiency (GHD) is the most frequently reported abnormality, with presentations varying from transient to persistent forms. Gonadal axis disturbances, including hypogonadotropic hypogonadism and, less commonly, central precocious puberty, highlight the impact of TBI on pubertal development. Adrenal dysfunctions, though less frequent, may be life-threatening if unrecognized, while posterior pituitary disorders, such as diabetes insipidus, usually revealed acutely, are often transient. Importantly, many endocrine sequelae manifest months to years after the initial trauma, complicating a timely diagnosis. Current evidence underscores the need for structured, longitudinal endocrine surveillance after pediatric TBI, with baseline and follow-up assessments at defined intervals. Early recognition and intervention, including hormone replacement when appropriate, may improve neurocognitive recovery and overall rehabilitation outcomes. Future multicenter studies and standardized screening protocols should be considered essential to clarify incidence, natural history, and optimal management strategies for post-traumatic endocrine dysfunction in children.