Evidence for Dissociation between Adrenarche and Gonadarche: Studies in Patients with Idiopathic Precocious Puberty, Gonadal Dysgenesis, Isolated Gonadotropin Deficiency, and Constitutionally Delayed Growth and Adolescence*

Abstract

To test the hypothesis that adrenarche and the activation of the hypothalamic-pituitary-gonadal axis (gonadarche) are independent and dissociated events, controlled by separate mechanisms, we examined the relationship between adrenarche and gonadarche in patients with a variety of clinical disorders of sexual maturation. The concentration of plasma dehydroepiandrosterone sulfate (DHEA-S) was used as a hormonal marker of adrenal androgen secretion. The 26 patients with idiopathic precocious puberty exhibited two distinct patterns. Seventeen patients with onset of puberty before 6 yr of age had a mean plasma concentration of DHEA-S which was not different from that of normal prepubertal, preadrenarchal children of the same sex, chronological age (CA; 1–6 yr), and bone age (BA; 1–10 yr). In contrast, 9 patients with onset of precocious puberty between 6 and 8 yr of age had a mean DHEA-S plasma concentration greater than that of agematched prepubertal children (86.4 ± 13.9 vs. 10.0 ± 2.2 μg/dl; P < 0.004) and age-matched precocious puberty patients with pubertal onset before 6 yr of age (p < 0.03). These 9 patients with onset of puberty between 6 and 8 yr of age had a mean plasma DHEA-S level no different from that of normal children with the same BA. The mean concentrations of plasma estradiol in females and of plasma testosterone in males with precocious puberty were significantly greater than those in normals of the same CA and BA (P < 0.001). Thirty-nine patients with primary hypogonadism due to gonadal dysgenesis had a mean DHEA-S concentration which did not differ from that of normals over the CA and BA range of 1–16 yr. Of 11 patients with isolated gonadotropin deficiency, the 4 patients between 15–16 yr of age had a mean DHEA-S concentration which was not significantly lower than that of agematched normals for either CA or BA. The mean plasma testosterone concentration was significantly lower. However, the 7 patients between 16–20 yr of age had a significantly lower mean DHEA-S concentration for their CA but a mean value appropriate for BA. The plasma concentration of DHEA-S was studied in 32 patients (10 females and 22 males) with constitutionally delayed growth and adolescence. The mean concentration was not significantly different from that of age-matched controls for the 3 females aged 12–14 yr. However, the 7 females and 22 males between 14 and 17 4/12 yr of age had a significantly lower (P < 0.02) mean DHEA-S concentration for CA but a mean DHEAS value appropriate for their delayed BA. The present study documents a discordance between adrenarche and gonadarche in a variety of disorders of sexual maturation. Patients with onset of precocious puberty before 6 yr of age exhibit gonadarche in the absence of adrenarche; patients with both gonadal dysgenesis and isolated gonadotropin deficiency had a normal onset of adrenarche despite the lack of or incomplete gonadarche. In contrast, patients with constitutionally delayed growth and adolescence often exhibit a delay in both adrenarche and gonadarche. These examples of dissociation provide additional evidence for different mechanisms regulating adrenarche and gonadarche and for the existence of a separate and specific adrenal androgen-stimulating hormone.