Radiological, biochemical, and endocrine abnormalities in children and adolescents with empty sella: A 25-year mini-review

Background: Empty sella syndrome (ESS) is an increasingly recognized radiological entity in children and adolescents, often detected incidentally during neuroimaging. Unlike adults, pediatric ESS has distinct clinical implications, particularly regarding growth, pubertal development, and pituitary hormone function. However, available evidence remains fragmented, largely derived from small cohorts and case series. Objective: To systematically review radiological characteristics and associated biochemical and endocrine abnormalities in children and adolescents with empty sella (ES), and to clarify their clinical significance over the past 25 years. Methods: A mini-review was conducted following PRISMA 2020 principles. PubMed, Scopus, Web of Science, and supplementary sources were searched for studies published between 2000 and 2025. Inclusion criteria focused on pediatric populations (≤18 years) with radiologically confirmed empty sella and reported endocrine or biochemical outcomes. Adult-only studies, isolated case reports, and studies lacking endocrine data were excluded. Data were synthesized narratively due to heterogeneity. Results: Twelve moderate-quality studies were included. Radiologically, partial ES was more frequent than complete ES and was commonly associated with pituitary flattening and cerebrospinal fluid herniation. Endocrine abnormalities were reported in 30–70% of affected children, with growth hormone deficiency (GHD) being the most prevalent, followed by hypogonadotropic hypogonadism, central hypothyroidism, and, less commonly, ACTH deficiency. Multiple pituitary hormone deficiencies were observed particularly in symptomatic or secondary ESS. Biochemical abnormalities often correlated with impaired growth velocity and delayed puberty, while incidental ESS cases frequently showed preserved pituitary function. Conclusions: Empty sella in children and adolescents is frequently associated with clinically relevant endocrine abnormalities, particularly involving the GH–IGF-1 axis. Careful hormonal evaluation and longitudinal follow-up are essential, even in asymptomatic cases. The paucity of large, prospective pediatric studies in children and adolescents highlights the need for standardized diagnostic and follow-up protocols.