High prevalence of abnormal adrenal response in girls with central precocious puberty at early pubertal stages

Abnormal adrenal response is often observed in girls with precocious adrenarche (1). We studied the adrenal response in 112 girls with idiopathic true central precocious puberty (CPP) at early stages of puberty compared to that in 21 girls with normal puberty (controls). The aims of this study were to determine the prevalence of abnormal adrenal response at early stages of puberty, the possible correlation of abnormal adrenal response with pubertal signs at onset of puberty and with plasma androgen levels, and a possible association with the activity of the hypothalamic-pituitary-gonadal (HPG) axis. All participants underwent a combined iv adrenocorticotropic hormone (ACTH)-gonadrotropin-releasing hormone (GnRH) test at Tanner stage 2-3: 62 of the CPP girls before and 50 during treatment with GnRH analog. The stimulated levels of 17-hydroxypregnenolone (170HPreg) and the stimulated 170HPreg/17-hydroxyprogesterone ratio were analyzed and compared to previously reported norms. The result revealed three patterns of adrenal response: normal (170HPreg ≤ 24 nmol/l and 170HPreg/170HP ratio ≤ 7) in 50/112 (44.6%) CPP patients and 17/ 21 (80.9%) controls: exaggerated (170HPreg > 24 nmol/l, 170HPreg/170HP ratio ≤ 7) in 50/112 (44.6%) CPP patients and 3/21 (14.3%) controls; and non-classical 3β-hydroxysteroid dehydrogenase deficiency (170HPreg > 24 nmol/l and 170HPreg/170HP ratio > 7) in 12/112 (10.8%) CPP patients and 1/21 (4.8%) controls. The clinical features at onset of puberty were comparable in all girls with the CPP in spite of the different adrenal response patterns. The levels of androstenedione and testosterone were within normal range in all cases. Dehydroepiandrosterone sulfate was significantly elevated only in 3β-hydroxysteroid dehydrogenase deficiency, 4.8 ± 2.7 (p < 0.03) as expected. The adrenal response was not affected by GnRH analog therapy. In conclusion, an abnormal adrenal response was found in 55.4% of girls with CPP in early puberty. This response did not cause clinical signs and laboratory findings of a hyperandrogenic state at early stages of puberty and was not affected by the activity of the HPG axis. Its role in evoking precocious puberty remains to be explored further.