The 24-h profiles of plasma cortisol (F), 11-beta-hydroxyandrostenedione (11OHAD), androstenedione (AD), dehydroisoandrosterone (DHEA) and testosterone (T) were obtained simultaneously in 11 normal males sampled at 15-min intervals. The data were submitted to a detailed quantitative analysis including the estimation of the circadian rhythm and of the episodic variations as well as the evaluation of the concomitance of episodic pulses of different hormones. A bimodal circadian rhythm was detected in the various individual profiles. The major acrophase occurred in the morning earlier for T (around 04:00 h) than for the hormones of totally or partially adrenal origin (around 07:00 h); the secondary acrophase (around 17:00 h) and the main midnight nadir were common to all hormones. The amplitude of the rhythm was highest for purely adrenal hormones (F and 11OHAD), averaging 79 and 75%, respectively, lower for hormones of mixed origin (DHEA and AD), averaging 44 and 42%, respectively, and minimal for T (22%). The possible relationship between the circadian and pulsatile variations of the various steroids was estimated in each individual by calculating Pearson's standard coefficient of variation on all pairs of hormonal profiles. A very tight relationship (r greater than 0.75; p less than 0.001) was found between the 4 adrenal hormones in each individual; a looser but significant correlation (r greater than 0.30; p less than 0.001) was also detected between T and its partial precursors (AD and DHEA) and between T and the purely adrenal hormones: F and 11OHAD (r greater than 0.30; p less than 0.01). The pulsatility of the corticotrophic axis was readily transmitted to the secretory pattern of 11OHAD, DHEA and AD. Ninety-six percent of the F pulses were reflected in at least one other hormonal profile. Finally, we showed that concomitant pulses common to the five adrenal and gonadal patterns were more frequent than would be expected on the basis of chance. These results: demonstrate a total parallelism between the long-lasting secretory events and the episodic bursts of the 4 adrenal hormones showing that the reticular and fascicular zones of the adrenal respond to pituitary control as an homogeneous structure; demonstrate the existence of a partial synchronization of adrenal and testicular pulsatile variations; suggest that, throughout the afternoon, a common mechanism may influence the slow variations of adrenal hormones and of testicular testosterone.

A modified short ACTH test for the detection of heterozygote carriers of 21-hydroxylase deficiency (21-OHD) was applied to twenty-one controls and fourteen parents of children with 21-OHD. The following modifications were introduced: (1) Endogenous ACTH was suppressed by dexamethasone administration prior to the test, (2) Plasma 17-hydroxyprogesterone (17-OHP), cortisol (F), progesterone (P), corticosterone (B) and delta 4- androstenedione (A) were measured, (3) Variables studied were the ratio of plasma increments (delta) between precursors and end products, (4) Data were analysed by a step-wise discriminant analysis. Significant alterations in the metabolic pathway of F, B and A were demonstrated. The discriminant analysis showed that the addition of B pathway data did not improve the discrimination potency of the test performed on F pathway data. The combination of variates which provided the best discrimination was the logarithmic sum of delta 170HP/delta F at 15 and 30 min. It led to a 94% correct classification for normals and carriers.

S U M M A R YA modified short ACTH test for the detection of heterozygote carriers of 2 1-hydroxylase deficiency (2 1 -0HD) was applied to twenty-one controls and fourteen parents of children with 21-OHD. The following modifications were introduced: (1) Endogenous ACTH was suppressed by dexamethasone administration prior to the test, (2) Plasma 17-hydroxyprogesterone (1 7-OHP), cortisol (F), progesterone (P), corticosterone (B) and A4androstenedione (A) were measured, (3) Variables studied were the ratio of plasma increments (A) between precursors and end products, (4) Data were analysed by a step-wise discriminant analysis. Significant alterations in the metabolic pathway of F, B and A were demonstrated. The discriminant analysis showed that the addition of B pathway data did not improve the discrimination potency of the test performed on F pathway data. The combination of variates which provided the best discrimination was the logarithmic sum of A1 70HP/AF at 15 and 30 min. It led to a 94% correct classification for normals and carriers.Deficiency of 2 1-hydroxylase (21-OHD) is the commonest form of congenital adrenal hyperplasia (CAH). This autologous genetic disorder affects one child in about 5 000 (Prader et al., 1962). The frequency ofcarriers of the autologous recessive gene in a whole population has been estimated either at 1 : 125 (Childs et al., 1956) or at 1 : 28 (Prader et al., 1962). The prediction of 21-OHD is important since the disease is often accompanied by severe sodium depletion at birth, and by growth and endocrine disorders later on. In the basal state, it is not possible to distinguish between carriers and non-carriers. Several attempts were made to reveal the eventual latent metabolic block in the biosynthesis of cortisol by adrenal stimulation, which was induced either by exogenous ACTH injection (Childs et al., 1956) or by endogenous ACTH response to metyrapone administration

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The aim of the study was to determine the main metabolic parameters of 11-beta-hydroxy-androstenedione (11 OHAD) in man. Seven normal subjects were investigated at 1-3 months interval by 2 types of isotope dilution techniques using a tritiated tracer: constant infusion and bolus iv injection. 3H-11 OHAD and 3H-11-beta-hydroxy-androsterone (3H-11 OA) were isolated by gel column chromatography, unlabeled 11 OHAD was determined by RIA, unlabelled 11 OA by GLC. The results included computation of free and conjugated catabolite fractions. 3H-11 OHAD MCR determined from the infusion or the injection data averaged ca 1250 ml/min or 1800 L/d (CV: +/- 10%) providing a mean estimation of unlabelled 11 OHAD BPR of 1.5 +/- 0.15 mg/d. UPR estimations gave similar values. 3H-11 OHAD fractional catabolic rate drawn from the postinfusion or the injection curve averaged ca 1.4% per min (CV: +/- 7%). Mean total distribution volume ranged between 90 and 120 L according to the type of experiment. Extrapolation to time zero of the injection curve (2 exponentials) provided an estimation of 32 +/- 5 L for rapid exchange compartment. Urinary recovery of labelled compounds was complete within 24 h whereas the excretion of undegraded 3H-11 OHAD was undetectable; urinary clearance rate of 3H-conjugates approached that of creatinine. The present data show that: the secretion rate of 11 OHAD is equivalent to that of its direct precursor, adrenal androstenedione; its large MCR value results from the size of its exchange volume-equivalents.(ABSTRACT TRUNCATED AT 250 WORDS)