The natural history of premature adrenarche

The growth and pubertal development of patients with premature adrenarche are reported to be normal, but the effects of this condition on pubertal growth are not well documented. In the present study the growth kinetics of a group of 38 female patients with isolated premature adrenarche followed in our institution for a period of 5.77 (SD=1.7) yr were evaluated to assess whether and how premature adrenarche affects pubertal growth and final height. Birth weight and length, height, skeletal maturation, onset of puberty, age at menarche, height prognosis and final height were documented. To examine the shape of growth kinetics, growth profiles of each girl were fitted with Preece-Baines nonlinear function (PB1) and mean constant curves were obtained by a 2-stage linear model. The biokinetic constants of the patients were compared both with those obtained by Preece and Baines in normal British girls participating in the Harpenden study and by Milani et al. in normal Italian girls. Birth weight and length of premature adrenarche patients were within the normal range for a northern Italian population [+0.29 (1.57) and -0.40 (1.49) SDS, respectively]. Analysis of the biokinetic constants showed that in PA girls the prepubertal component of height velocity, ie. the one preceding the diagnosis of PA, was consistently higher than that of both normal Italian and Harpenden girls, accounting for the increased height of the patients at the beginning of puberty. In contrast, the pubertal component of height velocity was reduced with respect to control groups, leading to a final height similar to the one estimated by the PB1 model and to the target height. In conclusion, the transient acceleration of growth and bone maturation observed in girls with premature adrenarche did not negatively influence the onset and progression of puberty but modified the growth pattern of these patients. Prepubertal growth was enhanced with respect to normal controls, and this enhancement was compensated for by a reduction of the pubertal growth component leading to a final height in accordance with the target height. This abnormal growth shape is not due to an altered tempo of growth but it is rather a consequence of premature adrenarche.