The records of 109 patients with premature pubarche, evaluated in the Pediatric Endocrinology Unit during January 1990-2000, were reviewed, aiming to study the etiology and outcome of this condition. They were divided in 4 groups: group 1, G1, n: 41, 6 boys, 35 girls, at ages ranging from 11 months to 7.11 years (median: 7.1ys). In this group, basal steroid levels (17-OH-progesterone, DHEA, DHEA-S, delta4- androstenedione, total and free testosterone), LH and FSH stimulated by acute GnRH test (100mug iv, Relisorm®) were determined. In a second group, G2, n: 28, 8 boys and 20 girls, at ages between 9 months and 8.11 ys (median: 7ys), besides G1 tests, 21-hydroxylase deficiency (CYP21A2) was investigated by the 17-OH-progesterone response to acute ACTH test (250mug iv, Cortrosyn®, basal and 60min.), A third group, G3, n: 23, 4 boys, 19 girls at ages between 1.2ys and 8.10ys (median: 7.6ys) underwent the same tests as formers groups, but in addition, the 11 beta-hydroxylase (CYP11B1) and 3beta-hydroxysteroid dehydrogenase (3betaHSD) deficiencies were ruled out according to 11-deoxycortisol level and the DHEA/delta4-androstenedione ratio respectively, during acute ACTH test. Plasma concentrations of total and free testosterone, DHEA-S and estradiol (in girls) were determined in the 3 groups. A fourth group, n: 14, 12 girls and 2 boys, at ages between 1.1y and 8.9ys (median: 6.5ys) had the diagnosis on a clinical basis only. Three girls aged 6 months, 2.1 years and 2.7 years were considered apart, they had premature pubarche and hyperandrogenic signs heralding an adrenal adenocarcinoma. Investigation showed increased DHEA-S level due to adrenal tumor. A control group of 18 pre-pubertal normal children (8 girls and 10 boys) underwent an acute ACTH test. During stimulation with GnRH an increment of 7mUI/ml (delta-LH) was considered suggestive of pubertal response. Androgens and estradiol levels were measured by RIA (kits from DPC; Los Angeles, California); LH and FSH were measured by immunometric methods. Statistical analysis used Mann-Whitney test. In groups 1, 2 and 3 only 4 patients responded to GnRH acute test with deltaLH > or = 7UI/ml and 2 of them developed true precocious puberty. The 17-OH-progesterone response to acute ACTH (G2 and G3, n: 51) underscored 2 cases of 21-hydroxylase deficiency. In group 3 there wasn't accumulation of other precursors after the acute ACTH stimulation. We observed that very few children with premature adrenarche developed precocious puberty or had congenital adrenal hyperplasia, suggesting that after ruling out adrenal tumors, clinical follow-up would be more practical, less expensive and that the tests would be performed when some evolutive clinical finding indicates.
Precocious pubarche; Precocious adrenarche; Adrenal hyperplasia; Adreno adenocarcinoma
