On the Rate of Hydrocortisone Clearance From Plasma in Pregnant Women and in Patients With Laennec's Cirrhosis*

Abstract

The question of whether or not there is an increase in adrenal cortical secretion during pregnancy remains unsettled. Morphologic studies of the adrenal during gestation have revealed enlargement of the gland in some species (1) and no enlargement in others (2). In the human female, several groups of investigators have observed a progressive rise in the plasma 17-hydroxycorticosteroid (17-OH-corticosteroid) level during pregnancy (3-8). Paper chromatographic studies (9), confirmed in this laboratory (10), have indicated that the elevated plasma 17-OH-corticosteroid level is due to an increase in circulating hydrocortisone, and not to a nonspecific chromogen. Measurement of urinary 17-OH-corticosteroids has given equivocal results. Jayle, Desgrez, Serpicelli and Rozeg (11), Devis (12), Mills (13), and Appleby and Norymberski (14) found that the rise in urinary 17-OH-corticosteroids and 17-ketogenic steroids during pregnancy was of only moderate degree. Contradictory results have been obtained from studies of urinary 11-oxygenated 17-ketosteroids, the principal C19 metabolites of hydrocortisone (15). Dobriner, Lieberman, Rhoads and Taylor (16) crepancy between the finding of elevated plasma and of relatively normal urinary 17-OH-corticosteroid levels in pregnancy, Migeon, Bertrand and Wall investigated the rate of disappearance of injected 4-C14-hydrocortisone from plasma of pregnant women near term and found it to be delayed (20). These workers also observed a reduced rate of appearance of plasma and urine 17-OHcorticosteroid conjugates (glucuronides) after the administration of labeled hydrocortisone. These data suggested that the co-existence of high plasma (unconjugated) 17-OH-corticosteroid values and normal urine (unconjugated plus conjugated) 17-OH-corticosteroid values might be partly explained by the presence in both plasma and urine of a greater proportion of free hydrocortisone and a smaller proportion of conjugated hydrocortisone metabolites than normal (20). Devis (12) and Gray (21) have reported increased amounts of free 17-OH-corticosteroid in the urine of pregnant women. The present report describes studies upon the rate of hydrocortisone clearance from plasma in late pregnancy and in Laennec's cirrhosis, a condition in which hydrocortisone disposal rate is reportedly delayed (22)(23)(24). The data suggest that a delay in hydrocortisone clearance may not completely account for the elevated plasma 17-OHcorticosteroid levels observed in the pregnant state. MATERIALS AND METHODSPatients. Subjects were pregnant women in the third trimester of pregnancy who were not acutely ill and who showed no evidence of rheumatic heart disease, diabetes mellitus or pre-eclampsia. The women were hospitalized for premature rupture of the membranes or in anticipation of elective Caesarian section. Patients with Laennec's cirrhosis were six men and one woman with the typical clinical and laboratory features of parenchy-299

Studies of the Blood-Cerebrospinal Fluid Barrier to Cortisol in the Dog*

“…These high values constitute (18). As will be seen (Section 3 below), the same distribution between plasma and CSF is found with cortisol-21-hemisuccinate as with free cortisol.…”

“…As will be seen (Section 3 below), the same distribution between plasma and CSF is found with cortisol-21-hemisuccinate as with free cortisol. is considerably more rapid than that found in normal human subjects (27 per cent per hour) (18) or "half-time" of 138 minutes (19).…”

Changes in the Diurnal Rhythms of Plasma Cortisol in Women during the Third Trimester of Pregnancy

“…The rise in CBG concentration is thought to lead to a decrease in the met abolic clearance rate of cortisol in pregnancy [13]. It is interesting that Cohen et al [2] found a half-life for exogenously administered cortisol of 204 min in pregnant women.…”

Studies on the Mechanism of the Plasma 17-Hydroxycorticosteroid Elevation Induced in Man by Estrogens*

“…The last trimester of pregnancy is associated with similar changes in levels of plasma 17-OHCS and in their response to exogenous ACTH (3)(4)(5)(6)(7)(8)(9). In the last trimester of pregnancy there is a variable increase in urinary 17-OHCS excretion, a decrease in the rate of clearance of exogenous cortisol from plasma (9)(10)(11), a decrease in the rate of clearance of exogenous tetrahydrocortisone from plasma (11) and an increase in corticosteroid-binding protein (12). The apparently normal adrenal status of pregnant women and of patients treated with estrogens for long periods of time suggests that the administration of estrogens to man elevates plasma 17-OHCS levels by altering the normal metabolism of endogenous cortisol by a mechanism similar to that seen in pregnancy.…”