THE SECRETION AND DISPOSITION OF CORTISOL DURING PREGNANCY*

The following findings were obtained which bear on the mechanisms concerned in the rise of plasma free 17-hydroxycorticoid (17-OHCS) levels during pregnancy: 1) Cortisol accounted for approximately 90 per cent of the plasma free 17-OHCS in pregnant women during the third trimester. 2) No cortisol (F), cortisone (E), tetrahydrocortisol (THF) or tetrahydrocortisone (THE) were detected in the urine of 2 adrenalectomized pregnant patients maintained on 1 mg. of 9-alpha-fluorohydrocortisone daily during the third trimester. 3) When ACTH was administered intravenously to a woman with intact adrenals during pregnancy and the postpartum period, there was a greater response during pregnancy as determined by the excretion of F+E and the rise in the level of plasma free 17-OHCS, but no greater response as determined by the excretion of F+E+THF+THE. 4) In a normal woman followed throughout pregnancy there was a marked rise in plasma free 17-OHCS levels but little change in urinary total 17-OHCS excretion. 5) When cortisol was administered intravenously to an adrenalectomized woman, there was a diminished rate of removal of free 17-OHCS from the plasma and a smaller apparent distribution volume of the injected F during the third trimester as compared to the postpartum period. The first of these findings was reproduced by one week’s administration of estrogen to a woman who was receiving prednisone therapy. It is concluded that the rise in the level of plasma cortisol during pregnancy is due mainly to a diminished rate of transformation of F to certain of its metabolites and to a greater retention of the hormone within the intravascular compartment. Two factors are described which may prevent the development of more marked signs of Cushing’s syndrome during pregnancy: first, a diurnal variation in plasma free 17-OHCS levels such that for part of the day the levels are within the normal range; and second, a greater retention of cortisol within the intravascular compartment.