Sex differences in the clinical presentation, management and long-term outcomes of pituitary tumors in children and adolescents.

Pituitary adenomas (PAs) are rare in children and adolescents. Despite their typically benign histology, these tumors raise significant clinical challenges because they occur during critical developmental windows, impacting growth, puberty, and long-term quality of life. This review aims to focus on the sex-specific patterns in the epidemiology, clinical presentation, and outcomes of pediatric PAs. Prolactinomas are the most frequent subtype, showing a marked post-pubertal female predominance. Adolescent girls typically present early with endocrine symptoms like amenorrhea, whereas boys are often diagnosed after a longer delay, bearing larger, more aggressive macroadenomas and presenting mass-effect symptoms such as headaches and visual disturbance. In Cushing disease (CD), a striking sex reversal occurs in epidemiology. A male predominance is observed in pre-pubertal children, which progressively shifts toward a female predominance during late adolescence. Furthermore, CD seems to affect boys more severely than girls. Pediatric growth hormone excess also displays distinct genetic sex-specificities, with X-linked acrogigantism (X-LAG) predominantly affecting infant girls and somatotroph macroadenomas related to AIP mutations appearing more frequently in adolescent boys. While management strategies are often extrapolated from adult data, the pediatric population exhibits higher rates of treatment resistance and a greater risk of long-term hypopituitarism. Recognizing these sex-related biological and clinical differences is essential for early diagnosis and the implementation of personalized therapeutic approaches to preserve future general health, fertility and quality of life.