GnRH test for the diagnosis of central precocious puberty: is it time to revisit the protocol ?

Early activation of the hypothalamic-pituitarygonadal axis may cause central precocious puberty (CPP), that is, the occurrence of sexual development before 8 yr in girls and 9 yr in boys (1). Idiopathic early maturation of the entire hypothalamic-pituitary-gonadal axis is more frequent in females, whereas organic disorders, such as tumors of the central nervous system, are more frequently involved in CPP in males (2). To date, there is no univocal opinion about the most appropriate diagnostic test to confirm or rule out this condition, although its diagnosis is based on the full spectrum of physical and hormonal changes of puberty, largely suspected on a clinical basis and confirmed by specific blood tests, including basal hormone dosage, radiological assessments, and dynamic tests, such as the GnRH test, which reveals activation of the hypothalamic-pituitary-gonadal axis (1, 2). Such crucial tests are regularly performed by intravenous infusion of up to 100 μg of GnRH, followed by serial doses of LH and FSH at 0, 30, 60, 90, and 120 min (3). Although this test is considered the gold standard for diagnosis, there are important variations in the LH cutoff used: Italian guidelines suggest a cutoff of 3.3 or 5 IU/L (3), while international societies suggest a cutoff of up to 10 IU/L (4). This hormonal variability under stimulation confirms the complexity of this diagnostic procedure, which requires a significant duration (up to 120 min after GnRH administration), peripheral venous access, and serial blood sampling, with a risk of complications, including allergic reactions. This study aimed to evaluate whether a simplified GnRH test could be a valid alternative to the traditional GnRH test for the diagnosis of CPP.