Comparison of Two Tests for Heterozygosity in Congenital Adrenal Hyperplasia (Cah)

Abstract

The increase of plasma cortisol (F), androstenedione (A), 17\g=a\-hydroxyprogesterone (17-OH-P) and testosterone (T) was measured after iv administration of ACTH in heterozygotes for CAH and in controls under two different conditions:Test 1: ACTH stimulation was performed without any particular preparation.Test 2: 1.5 mg of dexamethasone (dex.) was given the evening before the ACTH stimulation. Plasma F, A, 17-OH-P and T were measured by specific radioimmunoassays (RIA). Following ACTH stimulation, the increase of 17-OH-P was significantly higher in CAH-heterozygotes than in controls in both tests (P < 0.0005). Heterozygotes were characterized by a 17-OH-P increase after ACTH stimulation exceeding the +2 sd limit of the 17-OH-P increase found in controls. The detection of female heterozygotes was considerably improved by the administration of dex. before testing (test 2). In males, however, a better identification of heterozygotes was obtained without previous administration of dex. (test 1). By these tests, 100% of female (test 2) and 79% of male (test 1) CAH heterozygotes could be correctly identified. There were no significant differences in the levels of F, A and T between heterozygotes and controls except for decreased T levels in test 1 (2P < 0.01) in most male heterozygotes after ACTH stimulation.

Augmented 17α‐hydroxyprogesterone response to ACTH stimulation as evidence of decreased 21‐hydroxylase activity in patients with incidentally discovered adrenal tumours ('incidentalomas')

“…Decreased 21-hydroxylase activity was assumed when the 17-OHP increment exceeded 7.9 nmol/l, irrespective of the basal or the stimulated 17-OHP concentrations. Differentiation was in accord with previous studies giving recommendations for the identification of CAH heterozygotes by biochemical screening (Child et al, 1979;New et al, 1979;Weil et al, 1979;Knorr et al, 1983). Adequate adrenal glucocorticoid release was defined as a peak cortisol concentration > 550 nmol/l.…”

“…The 17-OHP response to exogenous ACTH stimulation was measured to evaluate 2 1 -hydroxylase reserve (Weil et al, 1979). 17-OHP was determined before and 60minutes after an i.v.-bolus injection of 0.25mg 1-24 ACTH (tetracosactrin, Synacthen, Ciba Geigy).…”

Heterozygotes and Cryptic Patients in Families of Patients with Congenital Adrenal Hyperplasia (21-Hydroxylase Deficiency)

“…has been demonstrated. Urinary excretion of metabolites and later 17-OHP determination have been used, especially during ACTH stimulation or in combination with dexamethasone suppression [1,[21][22][23]. However, there has been a considerable overlap be tween the heterozygotes and the control pop ulation, making it difficult to predict which siblings are carriers.…”

Detection of heterozygous carriers for 21-hydroxylase deficiency by plasma 21-deoxycortisol measurement

“…However, measurements of the plasma levels of the various precursors (like 17-OHP, progesterone) or of the urinary metabolites (like pregnanetriol, pregnandiol) have not been found to permit reliable detection of heterozygosity within the general population because of the significant overlap with control values (Childs et al 1956;Lee & Gareis 1975;Weil et al 1979;Mauseth et al 1980). Our results for 17-OHP levels confirm these findings: after ACTH stimu¬ lation the levels of 71% of the heterozygous sub¬ jects fell within the normal range.…”

“…Plasma radioimmunoassays have been used to detect increased levels of 17-hydroxyproge¬ sterone (17-OHP) after ACTH administration (Lee & Gareis 1975;Krensky et al 1977). Some authors have attempted to sensitize this test by expressing the results in terms of either the ratio of cortisol to 17-OHP (Bercovici et al 1981) or the rates of increase of both 17-OHP and progester¬ one (Gutai et al 1977;Rosenwaks et al 1979), or by performing the ACTH test on dexamethasonetreated subjects (Child et al 1979) or during the follicular phase in women (Weil et al 1979). The mean level of 17-OHP has regularly been found to be higher in heterozygous carriers than in con¬ trols, but whatever the procedure used, there were always overlaps between the two groups.…”