INSL3 as a Biomarker of Pubertal Activation: Role in Evaluating Precocious and Delayed Puberty (INSL3GNRH)

Pediatric patients of both sexes, aged 0 to 16 years, who are followed for suspected Central Precocious Puberty (CPP) or suspected Delayed Puberty (DP) at the Pediatric Endocrinology Unit of the IRCCS Azienda Ospedaliero-Universitaria of Bologna. These patients must have a clinical indication to undergo a standard GnRH stimulation test as part of their routine diagnostic workup for pubertal evaluation.

Inclusion Criteria:

• Age between 0 and 16 years at the time of enrollment.
• Males with suspected Central Precocious Puberty (CPP), defined by a testicular volume ≥4 mL before 9 years of age.
• Females with suspected CPP, defined by the onset of thelarche before 8 years of age.
• Males with suspected Delayed Puberty (DP), defined by testicular volume <4 mL by 14 years of age.
• Females with suspected DP, defined by the absence of thelarche by 13 years of age.
• Written informed consent for study participation and personal data processing provided by the parents/legal guardians, with the assent of the participating minor.

Exclusion Criteria:

• Presence of congenital or acquired conditions known to primarily alter pubertal development or gonadal function, regardless of HPG axis physiology (e.g., disorders of sex development, anorchia, previous ovariectomy, uncorrected bilateral cryptorchidism, previous iatrogenic gonadotoxicity).
• Primary endocrine diseases interfering with hypothalamic-pituitary-gonadal axis regulation (e.g., congenital hypogonadotropic hypogonadism, panhypopituitarism).
• Use of hormonal therapies or drugs capable of modifying gonadal function or the response to the GnRH test (e.g., exogenous sex steroids, androgens/anabolic steroids).