Pituitary-Adrenal Axis Activity in Treated Congenital Adrenal Hyperplasia: Static and Dynamic Studies*

Abstract

The pituitary-adrenal axis activity was evaluated in 43 patients, treated for congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, by measuring plasma ACTH, 17-hydroxyprogesterone (17-OHP), testosterone, and aldosterone. Dynamic studies were performed by injecting 250 micrograms synthetic ACTH im and collecting blood samples 1 h later for steroid analysis. Twelve to fourteen hours after the last hydrocortisone dose given the evening before, plasma ACTH fluctuated widely from less than 10-475 pg/ml, 17-OHP exceeded normal values and varied from 1-275 ng/ml, while testosterone ranged from 3-151 ng/100 ml. The correlations between ACTH and 17-OHP (n equal 61, r equal 0.665, P less than 0.001) and between 17-OHP and testosterone (n = 43, r = 0.761, P less than 0.001) were good, while that between 17-OHP and aldosterone (n = 64, r = 0.512, P less than 0.001) was rather poor. One hour after ACTH injection, the mean level of 17-OHP was significantly increased as compared to the mean basal level [96.8 ng/ml +/- 10.6 (SE) as compared to 67.0 ng/ml +/- 8.1 (SE)]. However, only 12 out of the 48 tests showed a positive response equal to or greater than 100%, and the majority of these responses (10 out of 12) occurred when basal levels of 17-OHP were between 10-70 ng/ml. This suggests that when basal levels fall outside these values, the pituitary-adrenal axis is either too inhibited or too stimulated to react to exogenous ACTH. Of the 48 tests where 17-OHP was measured, 23 had basal level values within these limits, the mean being 40.3 ng/ml. The corresponding mean ACTH level was 99 pg/ml with a wide range (1-230 pg/ml). On the other hand, in prepubertal children who exhibited 17-OHP concentrations between 10-70 ng/ml, testosterone varied from 3-30 ng/100 ml, with a mean of 16.0 ng/100 ml +/- 1.9 (SE) which is not different from the mean level found in normal children [14.0 ng/100 ml +/- 1.3 (SE)]. Thus, under the influence of endogenous ACTH which is moderately increased, 17-OHP concentrations far exceed normal values, whereas plasma testosterone seems to be unaffected.

Adrenal Nodules in Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency: Regression after Adequate Hormonal Control

“…It is known, however, that even patients with good hormonal control have ACTH levels above the normal range, and therefore we cannot rule out the possibility of finding nodules in this group of patients 17 . All of these patients showed considerable nodule size reduction or even disappearance after one-year follow up with good hormonal control.…”

Transient hyper-17-hydroxyprogesteronemia: a clinical subgroup of patients diagnosed at neonatal screening for congenital adrenal hyperplasia

“…The majority (93.3%) presented abnormal 17-OHP values in relation to the normal reference values in the literature (40,43,44); moreover, if we plot these results on New's nomogram (45) 13 infants (86.7%) were in the range of heterozygotes, 1 in the range of patients with a non-classic form of CAH, and 1 in the range of unaffected infants. This normal result was found for a girl who was submitted to the Figure 1 Blood spot 17-OHP levels in the screening of three groups of newborns in relation to gestational age.…”

Phenotype-Genotype Correlation in 56 Women with Nonclassical Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency

“…Patients were diagnosed as having NC-CAH on the basis of late-onset symptoms and a short-term ACTH-stimulated (0.25 mg, im) 17hydroxyprogesterone (17OH-P) plasma level higher than 10 ng/mL (30.25 nmol/L) (16). Basal plasma levels of androgens, testosterone, and ⌬ 4 -androstenedione, were radioimmunoassayed (17).…”