The maternal adrenal cortex seems to be involved in the adaptation to pregnancy. To study in detail adrenocortical secretion during pregnancy, we measured plasma aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, and cortisone simultaneously by RIA after extraction and automated Sephadex LH-20 chromatography of 10 normal pregnant women longitudinally throughout pregnancy at weeks 8-10, 14-17, 21-24, 28-32, and 38 as well as at the time of admission to the delivery room. The mean plasma progesterone and 17-hydroxy-progesterone concentrations increased from 37.2 +/- 6.5 (+/- SE) and 8.2 +/- 1.0 nmol/L, respectively, in early gestation to maximum levels of 138.0 +/- 25.7 and 22.8 +/- 2.2 nmol/L at week 38 (P less than 0.01). Plasma glucocorticoid levels rose 2- to 3-fold (P less than 0.01) from weeks 8-10 (corticosterone, 18.5 +/- 5.4; 11-deoxycortisol, 1.9 +/- 0.2; cortisone, 24.2 +/- 4.2; cortisol, 195.5 +/- 37.6 nmol/L) to week 38 (corticosterone, 42.9 +/- 11.2; 11-deoxycortisol, 4.6 +/- 0.5; cortisone, 71.5 +/- 13.6; cortisol, 420 +/- 63 nmol/L). Similarly, plasma mineralocorticoid levels increased 5- to 7-fold (P less than 0.01) from weeks 8-10 (11-deoxycorticosterone, 0.69 +/- 0.12; aldosterone, 0.41 +/- 0.08 nmol/L) to maximum levels at week 38 (5.3 +/- 0.9 and 2.1 +/- 0.3 nmol/L, respectively). At the time of admission to the delivery room, plasma 11-deoxycortisol, corticosterone, and cortisol concentrations were higher (P less than 0.02) than at 38 weeks, but plasma progestin and mineralocorticoid concentrations were not. We conclude that the source of the elevated maternal corticosteroid levels in pregnancy in addition to the estrogen-mediated rise in corticosteroid-binding globulin is the maternal adrenal cortex itself. The peak glucocorticoid levels at admission to the delivery room reflect increased maternal and fetal stress with the onset of labor.

In a prospective controlled trial we investigated the effect of an induction dose of etomidate (0.26 mg/kg i.v.) on plasma ACTH, progesterone, 17 alpha OH-progesterone, 11-deoxycortisol, cortisol, cortisone, corticosterone, 11-deoxycorticosterone, and aldosterone in seven males undergoing general anaesthesia. Seven other male patients receiving thiopentone at induction (5.0 mg/kg i.v.) served as controls. Plasma ACTH concentrations rose higher in the etomidate group (346 +/- 124 vs. 117 +/- 74 pg/ml, mean +/- SEM), but the difference was not significant. After etomidate we found a clear suppression of plasma cortisol (P less than 0.01), cortisone (P less than 0.01), corticosterone (P less than 0.01), and aldosterone (P less than 0.05) compared to corticosteroid levels after induction with thiopentone. Plasma 11-deoxycortisol and 11-deoxycorticosterone concentrations were grossly elevated 210 min after etomidate (91 +/- 28 nmol/l and 7.04 +/- 0.47 nmol/l, respectively, P less than 0.01) demonstrating inhibition of 11 beta-hydroxylation of both glucocorticoid and mineralocorticoid intermediates. In contrast, no significant difference in plasma progesterone and 17 alpha-OH-progesterone levels was found between the two groups indicating that the cholesterol-side-chain cleavage enzyme is less sensitive to etomidate than 11 beta-hydroxylase. Our results suggest that after induction of anaesthesia with a single bolus of etomidate, inhibition of other enzymes in the corticosteroid-synthetic pathway (e.g. cholesterol-side-chain cleavage enzyme) is of little clinical relevance.

We investigated basal and ACTH stimulated levels of cortisol, corticosterone, 17 alpha-hydroxyprogesterone, 11-deoxycortisol and 11-deoxycorticosterone as well as plasma levels of ACTH before and during the oral administration of ketoconazole in five patients with Cushing's syndrome (3 with bilateral adrenal hyperplasia, 1 with adrenal adenoma and 1 with adrenal carcinoma) and in three controls. The influence of ketoconazole on the transformation of 3H-17 alpha-hydroxyprogesterone to 3H-11-deoxycortisol and 3H-cortisol and of 3H-11-deoxycortisol to 3H-cortisol as well as of 3H-11-deoxycorticosterone to 3H-corticosterone was also examined in slices or homogenates of normal and hyperplastic adrenal tissue from four patients. Ketoconazole induced a rise of 11-deoxycortisol and 11-deoxycorticosterone, but not of cortisol and inconsistently of corticosterone which were increased by ACTH. Thus the ratio 11-deoxycortisol/cortisol rose more after ketoconazole than after ACTH and the ratio 11-deoxycorticosterone/corticosterone rose after ketoconazole but fell after ACTH. Plasma ACTH levels were stimulated 2-50 fold by ketoconazole. Incubation studies of adrenal tissue slices with 3H-17 alpha-hydroxyprogesterone showed that ketoconazole inhibited the transformation of 3H-17 alpha-hydroxyprogesterone to 3H-cortisol but not to 3H-11-deoxycortisol so that the ratio 3H-11-deoxycortisol/3H-cortisol increased 15-80 fold. After incubation of adrenal slices with 3H-11-deoxycortisol or 3H-11-deoxycorticosterone and ketoconazole, a 2-260 fold increase of the ratios 3H-11-deoxycortisol/3H-cortisol and 3H-11-deoxycorticosterone/3H-corticosterone were also found.

ABSTRACT. Plasma levels of aldosterone, corticosterone, 11-deoxycorticosterone, progesterone, 17-hydroxyproge.sterone, 11-deoxycortisol, cortisol, and cortisone were measured simultaneously by a micromethod of multisteroid analysis in eight vaginally delivered premature infants (PI) of 33-36 wk gestation with uneventful peri-and postnatal course. Mean concentrations (nglml) in umbilical arterial and in peripheral venous or capillary plasma sampled longitudinally at age 2 h to 7 days were compared with the same kind of data obtained from a group of 12 term infants (TI) who served as controls. Mean aldosterone was two to five times higher in PI than in TI (umbilical artery, 2 h to 7 days; p < 0.05), whereas 11-deoxycorticosterone was lower in PI from 2 h ( p < 0.01) until 7 days (NS).Corticosterone was significantly higher in PI than TI at 6 and 24 h after birth, whereas cortisol was slightly lower (NS) in PI in umbilical artery and 2 h after birth, but higher (p c 0.02) at 6 h, showing less variation in PI than in TI. 17-Hydroxyprogesterone levels in PI were two to three times higher ( p c 0.02) during 6 h until 7 days after birth. The data suggest that PI are able to maintain high aldosterone levels in the early neonatal period. Higher levels of the active glucocorticoids (cortisol and corticosterone) seen after delivery point to a more stressful extrauterine adaptation of PI. Furthermore, the data demonstrate that the adrenal cortex is fully functioning in premature infants (33-36 wk gestation) as well as in term infants. (Pediatr Res 23: 525-529,1988) Abbreviations RDS, respiratory distress syndrome UA, umbilical artery Aldo, aldosterone DOC, 11-deoxycorticosterone E, cortisone S, 11-deoxycortisol B, corticosterone F, cortisol P. progesterone 170HP, 17-hydroxyprogesterone Abrupt cessation of steroid supply from the placenta after severing the umbilical cord, and rapid postnatal involution of the fetal zone of the adrenal cortex dramatically changes the hormonal milieu of the fetus after birth. There is increasing evidence that the adrenal cortex plays an important role in the postnatal adaptation of newborns (1). For full-term healthy infants, data on plasma steroid levels in the neonatal period are available (2, 3), but studies on adrenal steroids in healthy premature infants are still lacking. Our micromethod of multisteroid analysis (4, 5) enabled us to measure simultaneously in a single small plasma sample individual mineralocorticoids, glucocorticoids, and progestins in premature infants at birth and longitudinally during the first hours and days of life.Herein we assess in detail the adrenocortical function of healthy moderately premature infants after birth and provide reference data for the physiologically most important corticosteroids. MATERIALS AND METHODSEight premature appropriate for gestational age infants (33-36 wk gestation) of both sexes (three males, five females) with uneventful peri-and postnatal courses were studied longitudinally from birth to day 7. Their mothers (20-36 yr) were heal...