The influence of adrenarche on bone age and final height prediction of patients with central precocious puberty before and during GnRH analog therapy

The aim of this study was to evaluate the onset or adrenarche in patients with central precocious puberty (CPP) and to determine whether adrenarche may counteract the effect on growth and skeletal maturation of GnRH analog (GnRHa) therapy in patients with CPP. Forty patients (39 F, 1 M) with CPP were studied before and during GnRHa therapy. Mean age at the initial evaluation and at the start of GnRHa therapy were 7.57 +/- 1.58 and 7.73 +/- 1.60 years, respectively. DHEA-S serum levels >0.60 mu g/ml were used as a hormonal marker of adrenarche. Before GnRHa therapy, 30 out of 40 patients had pre-adrenarcheal DHEA-S levels that were similar to those of prepubertal age-matched controls; the other 10 patients older than 7 years (8.27 +/- 0.84 years) showed adrenarcheal DHEA-S levels that were similar to those of normal pubertal children. Before GnRHa therapy, the children with adrenarche did not show significant differences in height SDS, bone age (BA) advance and predicted adult height compared with pre-adrenarcheal patients; in the former BMI SDS tended to be higher than in the latter, but not significantly. During GnRHa therapy, the improvement in predicted adult height and in CA/BA ratio was not significantly different in drenarcheal and pre-adrenarcheal patients. However, in two girls who manifested exaggerated adrenarche (DHEA-S values >1.2 mu g/ml) during GnRHa therapy, the BA progressed more rapidly the year after the elevation of DHEA-S, and the predicted adult height was reduced in both patients, by 4 cm and 6 cm, respectively. In conclusion, this study shows that young patients with CPP do not exhibit adrenarche; DHEA-S elevation was found only in patients with onset of CPP after 7 years of age. Patients with CPP and adrenarche did not show any difference in clinical characteristics and BA advance from the pre-adrenarcheal patients before and during GnRHa therapy. On the contrary, exaggerated adrenarche, with DHEA-S values higher than is typical, may reduce the efficacy of GnRHa therapy on growth and skeletal maturation.