Adrenal Androgens in Children with Short Stature

Abstract

Recent data suggest that adolescent individuals with growth hormone (GH) deficiency have subnormal levels of adrenal androgens (AA). In order to determine the developmental pattern of AA in GH deficiency and to assess whether AA levels can help identify children with GH deficiency, we measured plasma concentrations of dehydroepiandrosterone (DHEA), DHEA sulfate (DHEA-S), Δ⁴-androstenedione (Δ⁴A), and cortisol in the basal state and during prolonged adrenocorticotropin (ACTH) infusion (8 h) in a group of 34 individuals, 26 males and 8 females, with short stature. Their chronological ages (CA) ranged from 1.75 to 17.5 years (median 10.35 years). The subjects were grouped into two categories according to the results of pituitary testing: group 1 = short, non-GH-deficient (n = 16), and group 2 = GH-deficient, ACTH-sufficient (n = 18). Patients in groups 1 and 2 had similar bone ages (BA: 7.2 ± 0.7 vs. 7.5 ± 1.0 years) and Z scores for height ( 3.0 ± 0.2 vs. – 3.2 ± 0.3 units) and height velocity (-2.5 ± 0.4 vs. -2.6 ± 0.2 units). For both groups there were significant increases from basal to peak levels for DHEA, DHEA-S, Δ⁴A and cortisol following prolonged ACTH infusion. Although both basal and peak levels of DHEA-S overlapped in groups 1 and 2 for all CA and BA, levels in group 2 tended to be lower, especially for BA greater than 10 years. Analysis of covariance showed a significant difference in the slopes of the regression lines of DHEA-S between groups 1 and 2 (basal vs. CA: F 4.9, p < 0.05; basal vs. BA: F 9.7, p < 0.005; peak vs. BA; F 8.7, p < 0.01). There were no differences noted between groups 1 and 2 for DHEA and Δ⁴ A, either in the basal state or after ACTH stimulation. Stimulated values of cortisol were similar for groups 1 and 2 (1,180 ± 40 vs. 1,300 ± 70 nmol/l). We conclude that, although differences in the overall pattern of DHEA-S between endocrinologically normal short individuals and those with GH deficiency were significant, measurements of AA in the age group studied are not helpful in the differential diagnosis of children with short stature.

The effect of growth hormone replacement therapy on adrenal androgen secretion in adult onset hypopituitarism

“…Earlier studies have provided information on adrenal androgens in GH‐deficient but ACTH‐sufficient children (Ilondo et al ., 1982b; Sklar and Ulstrom, 1984; Lew et al ., 1988). To our knowledge, this is the first study to demonstrate decreased serum DHEAS levels in GH‐deficient but ACTH‐sufficient adult patients.…”

“…Information regarding serum adrenal androgen levels in GHdeficient individuals has been conflicting and limited to a small number of reports mainly derived from studies performed in children (Cohen et al, 1981;Ilondo et al, 1982b;Lew et al, 1988;Juul et al, 1998). There are few studies available showing decreased adrenal androgen levels in adult panhypopituitary patients (Young et al, 1997;Aimaretti et al, 2000;Miller et al, 2001).…”

“…Previous studies have shown that GH‐deficient patients have significantly lower adrenal androgen levels compared to GH‐sufficient subjects (Cohen et al ., 1981), but there is limited information on the effect of GH replacement therapy on adrenal androgens, particularly in adults (Rudd et al ., 1980; Ilondo et al ., 1982a, 1982b; Sklar and Ulstrom, 1984; Lew et al ., 1988). Furthermore, patients with secondary adrenal insufficiency have disproportionately decreased adrenal androgens compared to cortisol levels, the difference being maintained following stimulation with exogenous ACTH for 48 h, suggesting that a factor additional to ACTH may be necessary to achieve normal adrenal androgen secretion (Cutler et al ., 1979; Albertson et al ., 1984).…”