Abstract
The determinants of an increased risk of an organic pathology underlying central precocious puberty (CPP) in girls remain contentious. The present study aimed to determine the clinical and hormonal findings that can be used to differentiate organic and idiopathic CPP in girls as a screening method so that only those considered likely to have organic CPP undergo cranial magnetic resonance imaging (MRI). The medical records of 286 girls that received GnRH agonist (GnRHa) therapy for CPP were retrospectively evaluated. Chronological and bone age, height, pubertal stage, and basal/stimulated gonadotropin and estradiol (E2) levels, as well as cranial MRI findings at the time CPP was diagnosed were recorded. Clinical and hormonal parameters that can be used to differentiate between girls with organic and idiopathic CPP were identified using ROC curves. Organic CPP was noted in 6.3% of the participants. Puberty started before age 6 years in 88.9% of the girls with organic CPP. Mean E2 and peak luteinizing hormone (LH) levels were higher in the girls with organic CPP than in those with idiopathic CPP that were matched for pubertal stage, as follows: early stage puberty (Tanner 2 and 3): E2: 62.4 ± 19.8 pg/mL vs. 29.1 ± 9.5 pg/mL; peak LH: 16.8 ± 3.2 IU/L vs. 12.2 ± 3.7 IU/L; advanced stage puberty (Tanner 4): mean E2: 87.6 ± 3.4 pg/mL vs. 64.6 ± 21.2 pg/mL; peak LH: 20.8 ± 0.4 IU/L vs. 16.6 ± 5.8 IU/L (P < 0.001 for all). Thresholds for differentiating organic and idiopathic CPP in girls with early-stage puberty were 38.1 pg/mL for E2 (100% sensitivity and 80.4% specificity) and 13.6 IU/L for peak LH (100% sensitivity and 66.4% specificity). Pubertal symptoms and signs generally begin before age 6 years and hormone levels are much higher than expected for pubertal stage in girls with organic CPP. Based on the present findings, cranial MRI is recommended for girls aged < 6 years, as the risk of diagnosing an organic pathology is highest in this age group. Hormone levels higher than expected for pubertal stage might be another indication for cranial MRI, regardless of patient age. Cranial MRI should be performed in girls with early-stage puberty, and an E2 level > 38 pg/mL and/or a peak LH level > 13.6 IU/L.
Highlights
Organic lesions are present in 5%-10% of girls with central precocious puberty (CPP) [1,2,3]
Among the 11 girls that were neurologically symptomatic at the time CPP was diagnosed, 9 were previously followedup for mental motor retardation and epilepsy, of which 3 had a developmental anomaly of the CNS, 3 had a parenchymal injury based on cranial magnetic resonance imaging (MRI), and 3 had hydrocephalus
Among the other 2 girls with organic CPP that were neurologically symptomatic, 1 had neurofibromatosis type 1, with characteristic cafe-au-lait spots and axillary freckles that were noted during physical examination, as well as an optic pathway glioma based on cranial MRI
Summary
Organic lesions are present in 5%-10% of girls with central precocious puberty (CPP) [1,2,3]. Cranial MRI is recommended in girls with pubertal onset before age 6 years. Neurological findings can suggest an organic cause of CPP, but cranial MRI in girls with pubertal onset after age 6 years is controversial [2,3,4,5,6]. A few studies on the clinical and hormonal factors that might be predictive of an organic pathology in girls with CPP have been published [1,7,8]. The present study aimed to determine the clinical and hormonal findings that can be used to differentiate organic and idiopathic CPP in girls as a screening method so that
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