Pediatric acute-onset neuropsychiatric syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), represent an overlapping group of disorders which is characterized by acute-onset obsessive compulsive disorders, eating restriction, tics, cognitive and behavioral deterioration which typically follows a relapsing-remitting course but some patients have a primary or secondary persistent progress. This condition is likely caused by heterogeneous inflammatory mechanisms (autoantibodies, complement activation, pro-inflammatory cytokine production) involving the basal ganglia as evidenced by imaging studies (patients vs. controls), sleep studies that found movements and/or atonia during REM sleep, and neurological soft signs that go along with basal ganglia dysfunction. The condition causes significant psychiatric and behavioral symptoms, caregiver burden and sleep abnormalities. Autoantibodies resulting from molecular mimicry of infectious agents (namely group A Streptococcus) and neuronal autoantigens that map to the basal ganglia play also a subtle role. This narrative review aims to describe the key immunological features documented thus far and that likely play a role in the pathogenesis and clinical manifestations of this disorder.

Idiopathic short stature (ISS) represents one of the most frequent yet enigmatic conditions in pediatric endocrinology. Traditionally defined by auxological parameters in the absence of identifiable causes, ISS has long served as a diagnosis of exclusion. However, with the advent of next-generation sequencing, our understanding of the etiological landscape has significantly evolved. Recent studies have revealed that many children previously labeled as idiopathic actually harbor monogenic variants in genes related to the growth hormone–insulin-like growth factor axis, extracellular matrix components, or growth plate signaling pathways. This review integrates auxological assessment with current knowledge on molecular diagnostics to propose a more accurate and individualized approach to short stature. We examine emerging genotype–phenotype correlations, criteria for selecting candidates for genetic testing, and implications for recombinant human growth hormone therapy. Additionally, we advocate for a shift in clinical mindset: from a descriptive to a biologically grounded framework. ISS should be regarded as a transitional label pending further endocrine and genetic clarification. Recognizing this paradigm shift will improve diagnostic accuracy, personalize treatment strategies, and ultimately enhance care for children with growth failure in the genomic era.

The onset of puberty is a critical developmental milestone regulated by complex neuroendocrine networks that integrate genetic, metabolic, and environmental cues. Among the molecular systems coordinating this transition, neurotrophins—including brain-derived neurotrophic factor (BDNF), nerve growth factor, neurotrophin-3, and neurotrophin-4/5—have emerged as important modulators of hypothalamic maturation and the activation of gonadotropin-releasing hormone (GnRH) neurons. Beyond their established roles in neuronal survival and differentiation, neurotrophins contribute to hypothalamic circuit plasticity, influence GnRH neuronal activity, and participate in the integration of metabolic and environmental signals relevant to reproductive maturation. Experimental studies, primarily based on animal and cellular models, demonstrate that BDNF and its receptor play a role in normal pubertal onset, whereas disruptions in neurotrophin signaling have been implicated in central precocious puberty, delayed puberty, and hypogonadotropic hypogonadism. In humans, available evidence is more limited and derives mainly from genetic studies, circulating neurotrophin measurements, and clinical observations. This review provides an integrative synthesis of current experimental and clinical data on neurotrophin-mediated regulation of pubertal timing, highlighting both physiological mechanisms and pathological conditions. While neurotrophins represent promising modulators at the intersection of neurodevelopment, metabolism, and reproduction, further longitudinal and translational human studies are required to define their diagnostic and therapeutic potential in pediatric endocrinology.

Calcium ions (Ca²⁺) serve as universal second messengers regulating endocrine, neuronal, and metabolic processes. In children and adolescents, tight calcium signaling control is crucial for growth, hormone homeostasis, neuromuscular function, and neurodevelopment. Disruptions in Ca²⁺-dependent pathways—whether genetic, metabolic, or acquired—underlie a spectrum of pediatric endocrine diseases often presenting with neurological manifestations This review summarizes calcium’s roles in hormone secretion, parathyroid and vitamin D metabolism, and neuronal excitability, and discusses monogenic and metabolic disorders affecting calcium sensing and signaling, including CASR, GNA11, AP2S1, STIM1, and ORAI1 mutations. Diagnostic challenges, therapeutic strategies, and future directions for precision medicine in pediatric neuroendocrinology are highlighted, emphasizing early recognition and improved clinical outcomes.

Oxytocin (OXT), traditionally linked to reproductive physiology, is now recognized as an important regulator of metabolic, skeletal, and socio-emotional processes. In children and adolescents, oxytocin deficiency (OXT-D) represents a significant but frequently underdiagnosed neuroendocrine disturbance, particularly in hypothalamic–pituitary disorders and syndromic conditions such as Prader–Willi and Schaaf–Yang. Experimental and clinical evidence suggests that OXT-D may contribute to altered appetite regulation, reduced energy expenditure, impaired bone health, and socio-emotional vulnerability, even when other pituitary axes are adequately replaced. Diagnostic evaluation remains challenging due to OXT’s short half-life, pulsatile secretion, and the limited reliability of current assay platforms, which restrict the clinical utility of peripheral measurements or dynamic testing in pediatric practice. Intranasal OXT—the most extensively studied therapeutic approach—shows good short-term tolerability and context-dependent behavioral benefits, though long-term efficacy and safety remain insufficiently defined. Advancing the field will require standardized diagnostic criteria, more reliable biomarkers, and precision-medicine strategies accounting for developmental stage and genetic background. This review summarizes current knowledge on pediatric OXT-D and highlights priorities for future translational and clinical research.