Edward N. Ehrlich

Desoxycorticosterone in normal pregnancy:I. Sequential studies of the secretory patterns of desoxycorticosterone, aldosterone, and cortisol

Plasma concentrations of desoxycorticosterone (DOC) and aldosterone are markedly elevated in pregnancy. Although DOC secretion in nongravid women has been assumed to be dependent mainly on adrenocorticotropic hormone (ACTH), in a previous study of women in the third trimester of pregnancy it was found to be unresponsive to ACTH, dexamethasone, and variations in salt intake. In this study plasma DOC, aldosterone, and cortisol levels, as well as their responses to ACTH stimulation and overnight dexamethasone suppression, were observed sequentially in seven normal women during the course of pregnancy and at three months post partum. Plasma DOC, aldosterone, and cortisol levels rose substantially during gestation, but increments in DOC did not necessarily coincide with those of the other two. Responses of all three corticosteroids to ACTH were enhanced during the first two trimesters compared to the nongravid state; DOC became unresponsive in the third trimester, while aldosterone and cortisol rose to an even greater extent. Elevated maternal DOC was not decreased significantly by dexamethasone at any stage of pregnancy, while plasma cortisol was suppressed. Nonsuppressibility of DOC with dexamethasone and also the lack of correlation of the rise in DOC with the increase in cortisol during the course of pregnancy suggest that increased DOC secretion in pregnancy does not arise from ACTH-dependent pathways of the maternal adrenal. The loss of responsiveness of DOC to ACTH in the third trimester suggests that the maternal adrenals have undergone an alteration in their steroidogenic response to ACTH, but also may indicate that their output of DOC has reached a maximal rate.

Desoxycorticosterone in normal pregnancy

Desoxycorticosterone (DOC) secretion increases during pregnancy. Administration of adrenocorticotropic hormone (ACTH) to women during the third trimester of pregnancy was noted previously to result in marked sodium retention, while aldosterone excretion declined. Since urinary tetrahydrodesoxycorticosterone increased substantially, sodium retention resulting from ACTH was ascribed to enhanced DOC secretion. Surprisingly, the elevated plasma DOC in late pregnancy failed to respond consistently to ACTH. Effects of ACTH upon total plasma concentrations and free indexes of DOC and cortisol were studied in pregnant women in the third trimester. As a result of ACTH, plasma cortisol and the free cortisol index increased strikingly; the plasma free DOC index rose markedly in those subjects in whom the total plasma DOC level was not altered appreciably and was unchanged or even increased slightly in the few subjects in whom the total DOC level decreased. The results support the proposition that the plasma free DOC fraction is increased because of displacement from corticosteroid-binding globulin by the ACTH-induced increment in cortisol. Resultant elevations of free DOC would not be evident from customary measurements of the total DOC concentration but, nonetheless, could contribute to sodium retention and also would be available for hepatic metabolism.

Heparinoid-induced inhibition of aldosterone secretion in pregnant women: The role of augmented aldosterone secretion in sodium conservation during normal pregnancy☆

Abstract Aldosterone secretion is strikingly elevate during normal pregnancy. In order to study the role of the increased aldosterone in sodium conservation, aldosterone secretion was inhibited by administering the heparinoid RO1-8307 for 12 to 18 days to 3 normal pregnant subjects. The lowering of aldosterone was accompanied by the occurrence of natriuresis in all subjects; one subject developed severe sodium depletion. It is noteworthy that natriureses occurred even though aldosterone was not reduced below normal nongravid levels and the reversal of natriureses after heparinoid treatment was stopped did not occur until aldosterone excretion had risen to much higher than normal levels. These results indicate that sodium conservation during pregnancy is dependent upon the augmented secretion of aldosterone and support the proposition that there are potent sodium-losing factors in pregnancy, which result in a compensatory increase in aldosterone secretion.

Care of patients.

Excerpt To the editor: The American medical profession is being criticized more vigorously than at any time in the past. Some of us have wondered why. Certainly the widespread attitude of disaffect...

Cortisol responses to diazoxide in man and their possible relationship to effective blood volume

Abstract In previously reported studies, oral salt loading resulted in increases in urinary cortisol and the cortisol secretion rate, and, conversely, the potent diuretics, hydrochlorothiazide or ethacrynic acid, resulted in decreased cortisol excretion. Because of its structural similarity to hydrochlorothiazide and also because it reduces the effective blood volume without inducing sodium depletion it seemed that diazoxide would be useful in further studies of the cortisol responses noted above. The administration of oral diazoxide, 200–400 mg./day, to five normal subjects resulted in evidences of diminished cortisol secretion in every instance; mild sodium retention was noted, although aldosterone excretion did not increase significantly except in one subject. The results of all these studies are consistent with the proposition that cortisol production increases with factors tending toward volume hyperexpansion and decreases with those tending to reduce the effective blood volume. It is tempting to speculate that these cortisol responses reflect another mechanism involved in the maintenance of volume homeostasis.

The anabolic influence of aminopyrine

Abstract Aminopyrine was anabolic when administered to 5 normal, young male subjects in usual therapeutic dosages, as indicated by diminished urinary nitrogen, creatine and inorganic phosphorus. The anabolic effect with the dosages of aminopyrine employed in this study was slightly less than but comparable in magnitude to that resulting from the intramuscular administration of 25 mg. daily of testosterone propionate. In 1 study the anticipated catabolic influence of intramuscular progesterone was partially offset by the simultaneous oral administration of aminopyrine. Although the effect of aminopyrine upon electrolyte metabolism was variable, a weak sodium retaining influence was suggested by the occurrence of sodium retention during treatment in 1 study and of moderate natriuresis in every instance after treatment was discontinued. Aminopyrine is a highly effective analgesic, antipyretic agent which has virtually been discarded from the therapeutic armamentarium because of the frequency of agranulocytosis associated with its administration. Renewed interest in aminopyrine or its congeners by clinical pharmacologists might be warranted on the basis of the anabolic property noted in this study.

Sodium Metabolism in Normal Pregnancy and in Preeclampsia

During the course of normal gestation, major changes in volume, distribution, and concentration of body fluids occur in the maternal organism, in order to meet the requirements of the developing conceptus. In pregnant as in nonpregnant subjects, sodium and water balance are governed by hypothalamic centers that control the release of antidiuretic hormone and influence thirst sensation, by renal adjustments of sodium and fluid excretion, and by secretion of gluco- and mineralocorticoids by the adrenal cortex. These homeostatic mechanisms in pregnant women must accommodate increasing levels of salt-retaining, natriuretic, and vasodepressor factors associated with advancing pregnancy if sodium and water balance are to be maintained.