Distinguishing organic from idiopathic central precocious puberty: clinical characteristics and predictive factors for organic etiology in a multicenter Italian cohort study

Objectives: Central precocious puberty (CPP) is characterized by the early onset of secondary sexual characteristics before the age of 8 in girls and 9 in boys. While rapid progression of sexual development may indicate an underlying organic cause, such as the presence of anatomical abnormalities of the hypothalamic-pituitary axis, no definitive diagnostic standard exists. Therefore, diagnosis requires a comprehensive assessment incorporating clinical, biochemical, and radiological evaluations. The aim of this study is to identify clinical, hormonal, and radiological factors that differentiate idiopathic from organic CPP, in order to establish predictive criteria for the identification of organic etiology. Methods: A multicenter retrospective study was conducted on female patients diagnosed with CPP at two major Italian hospitals between January 2015 and February 2025. Clinical, hormonal, and radiological data were analyzed to differentiate between idiopathic and organic CPP. A total of 134 patients were included, all of whom underwent a GnRH stimulation test for diagnosis. Results: Among the 134 patients, 12 (9 %) were diagnosed with organic CPP. Patients with organic CPP were diagnosed at a younger age, exhibited higher growth velocity, and showed elevated basal and stimulated gonadotropin levels. Multivariate analysis identified several significant predictors of organic CPP, including age at diagnosis, LH peak, LH/FSH ratio, height SD, and growth velocity. ROC curve analysis demonstrated that an LH peak >9.1 mIU/mL and growth velocity >1.75 standard deviations (SD) were highly sensitive (80 %) and specific (85 %) indicators of organic CPP. Conclusions: Organic CPP is characterized by a younger age at diagnosis, faster progression of puberty, and higher gonadotropin levels compared to idiopathic CPP. An LH peak >9.1 mIU/mL and a growth velocity >1.75 SD should be considered key diagnostic markers for identifying organic causes of CPP and guiding further investigation and treatment.