Plasma Levels Of Deoxycorticosterone Research Articles

Testicular Tumors in Congenital Adrenal Hyperplasia: Steroid Measurements from Adrenal and Spermatic Veins

The present study reports the case of a 25-yr-old man with congenital adrenal hyperplasia due to 21-hydroxylase deficiency in whom bilateral testicular tumors did not regress after suppressive treatment with dexamethasone. Catheterization of left testicular and adrenal veins confirmed the enzyme deficiency in the gonadal lesions. The presence of specific 11 beta-hydroxylated steroids (11 beta-hydroxyandrostenedione, 21-deoxycortisol, and 21-deoxycorticosterone) in the gonadal vein demonstrated the adrenal nature of the testicular tumor. In addition, catheterization allowed further study of the secretion of mineralocorticoids and androgens in the adrenal venous effluent. Plasma levels of deoxycorticosterone were increased in the peripheral vein and decreased in the adrenal vein, confirming the conversion of progesterone by peripheral 21-hydroxylase activity. Plasma levels of delta 5-3 beta-hydroxysteroids, particularly dehydroepiandrosterone and its sulfate, were very low, suggesting a sustained stimulation of 3 beta-hydroxysteroid dehydrogenase activity. This study documents that in patients with congenital adrenal hyperplasia and bilateral testicular tumors, catheterization of a gonadal vein measuring specific 11 beta-hydroxylated steroids confirms the adrenal nature of the gonadal lesions.

Selective Hypoaldosteronism in a Patient with Sjögren’s Syndrome: Insensitivity to Angiotensin II

A 51-year-old Japanese woman with hypokalemia due to distal renal tubular acidosis associated with Sjögren's syndrome exhibited a decreased plasma aldosterone level despite elevated plasma renin activity. Our studies revealed selective hypoaldosteronism with normal adrenoglucocorticoid function. In the presence of a low level of serum potassium (3.6 mEq/l), plasma levels of deoxycorticosterone and corticosterone were normal, while plasma aldosterone was very low. The levels of these three mineralocorticoids showed only minor changes during infusion of angiotensin II. Furosemide administration under almost the same level of serum potassium (3.7 mEq/l) resulted in only a slight increase of plasma aldosterone. Since hypokalemia might possibly suppress the synthesis of aldosterone in the zona glomerulosa, angiotensin II was also infused under a normal level of potassium (4.3 mEq/l). However, angiotensin II also failed to stimulate any secretion of aldosterone, despite a progressive rise in blood pressure and sufficient suppression of plasma renin activity. On the other hand, rapid ACTH administration in the presence of 4.4 mEq/l of serum potassium increased both plasma aldosterone and cortisol. These results suggest that adrenal insensitivity to angiotensin II was the cause of the selective hypoaldosteronism in our patient, possibly due to a dysfunction of adrenal angiotensin II receptors, a disorder of postreceptors or both.

Effects of dibutyryladenosine 3',5'-monophosphate on steroid biosynthesis in humans.

The effects of dibutyryladenosine 3', 5'-monophosphate (DBcAMP), a nucleotide analogue, on blood pressure, serum electrolytes and plasma corticoid concentrations were investigated in 10 normotensive healthy subjects who received a constant diet containing 5-8 g sodium chloride in hospital. The systolic blood pressure did not change after infusion of 0.25 or 0.33 mg/kg/min of DBcAMP for 20 min. On the other hand, the diastolic blood pressure was significantly decreased after the infusion of DBcAMP. The levels of serum sodium and potassium were significantly decreased after the infusion of DBcAMP. After infusion of 0.25 mg/kg/min of DBcAMP for 20 min, the changes in plasma levels of 6 corticoids [progesterone, deoxycorticosterone (DOC), 18-hydroxy-deoxycorticosterone (18-OH-DOC), corticosterone, cortisol and dehydroepiandrosterone sulfate (DHEA-S] revealed no significant changes. After infusion of 0.33 mg/kg/min of DBcAMP for 20 min, the plasma levels of cortisol, corticosterone and 18-OH-DOC were significantly increased and the changes in plasma levels of aldosterone showed a tendency to increase but this was not significant. The plasma levels of DOC and DHEA-S were not appreciably changed, while the plasma levels of progesterone were significantly decreased after the infusion of 0.33 mg/kg/min of DBcAMP. It is speculated therefore that DBcAMP may act to enhance the activity of the sodium-potassium pump and to promote steroid biosynthesis dose-dependently in humans.

Extra-adrenal deoxycorticosterone production in hypoestrogenic pregnancies: Serum concentrations of progesterone and deoxycorticosterone in anencephalic fetuses and in women pregnant with an anencephalic fetus

In a continuing effort to define the origin of and the regulation of the production of deoxycorticosterone, we measured deoxycorticosterone and progesterone in the umbilical cord plasma of 16 anencephalic fetuses and newborn infants (21 to 45 weeks' gestation) and deoxycorticosterone, progesterone, 17 beta-estradiol, and estriol in the plasma of 18 women pregnant (16 to 45 weeks) with an anencephalic fetus. Whereas umbilical cord plasma levels of progesterone in the anencephalic fetuses were similar to those of normal abortuses and newborn infants, those of deoxycorticosterone (1.3 +/- 0.21 ng/ml, mean +/- SE) were significantly lower (P less than 0.001) than those in normal abortuses and newborn infants delivered between 31 and 42 weeks' gestation (3.94 +/- 0.26 ng/ml). We found that plasma levels of deoxycorticosterone were significantly correlated (P less than 0.001) to those of progesterone in women pregnant with an anencephalic fetus, as well as in women pregnant with a normal fetus. Plasma levels of deoxycorticosterone (range = 0.14 to 0.92 ng/ml) in women pregnant with an anencephalic fetus were significantly lower than those in women pregnant with a normal fetus; plasma levels of progesterone were similar in both groups. The plasma levels of 17 beta-estradiol and of estriol were extremely low in women pregnant with an anencephalic fetus compared with those in women with a normal fetus and did not vary as a function of gestational age. In one subject who was pregnant with an anencephalic fetus, we found that estrogen treatment (100 mg of diethylstilbestrol/day) for 6 days caused a progressive increase in the serum levels of deoxycorticosterone and in the ratio of the concentration of concentration of deoxycorticosterone to that of progesterone in serum. Both the serum levels of deoxycorticosterone and the ratio of the concentration of deoxycorticosterone and in the ratio of the concentration of deoxycorticosterone to that of progesterone declined after cessation of estrogen treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

The origin of plasma deoxycorticosterone in the syndrome of congenital adrenal hyperplasia and in acute states of adrenocorticotropin excess.

Studies in men and women indicate that plasma deoxycorticosterone (DOC) is derived both from direct secretion and also peripheral conversion from progesterone (Prog), particularly in the luteal phase of the cycle. The present work explored the role of direct DOC secretion vs. peripheral conversion of Prog to DOC during acute ACTH stimulation and in a chronic state of ACTH excess, congenital adrenal hyperplasia (CAH). Intravenous ACTH (Cortrosyn; 250 μg for 2 h) in four normal men increased plasma Prog 4-fold, while plasma DOC increased from 8 to 39 ng/dl. The MCR and the conversion ratio of Prog to DOC (CRProgD0C) were determined under steady state conditions using the constant infusion technique with [3H]Prog. The calculated MCRProg was 1419 liters/m2·day, compared to 1176 ± 45 previously measured in adults. The calculated morning blood production of Prog after ACTH stimulation was 550 μg/m2·day. We estimated the blood production of DOC by using the plasma levels of DOC and our previously reported MCRDOC...

Regulation of extraadrenal steroid 21-hydroxylase activity. Increased conversion of plasma progesterone to deoxycorticosterone during estrogen treatment of women pregnant with a dead fetus.

We measured deoxycorticosterone (DOC) and progesterone (P) in plasma of 47 women pregnant with a dead fetus and sequentially throughout gestation in 35 women pregnant with a live fetus. When P levels in plasma were low, the plasma levels of DOC in women pregnant with a dead fetus varied but usually were similar to those in women pregnant with a live fetus. However, when P levels were high, the levels of DOC in some women pregnant with a dead fetus were considerably lower than those in women pregnant with a live fetus. To test whether this finding was due to loss of transfer of DOC from fetus to mother or else loss of extraadrenal steroid 21-hydroxylase activity in the mother after death of the fetus, we conducted several studies. The levels of P and DOC in plasma of one woman remained constant from 30 min after fetal death until delivery occurred 13 h later. Estrogen treatment of four women pregnant with a dead fetus brought about an increase in plasma levels of DOC in three of the women. In one woman the ratio of plasma DOC to P was 0.015, a value similar to that found before fetal death, but was 0.003 after fetal death but before estrogen treatment. In two women pregnant with a dead fetus the transfer constants of conversion of plasma P to DOC were 0.011 and 0.005 before, and 0.024 and 0.013, respectively, during estrogen treatment. In one woman pregnant with a deformed fetus with adrenal agenesis, the metabolic clearance rates of DOC before and during estrogen treatment were similar, whereas the plasma production rates of DOC were 2.75 before and 4.31 mg/24 h during estrogen treatment. We suggest that (a) the DOC in plasma of near-term pregnant women arises in part by extraadrenal 21-hydroxylation of plasma P and (b) estrogen stimulates steroid 21-hydroxylase activity in extraadrenal tissues.

Hormone production during pregnancy in the primigravid patient: II. Plasma levels of deoxycorticosterone throughout pregnancy of normal women and women who developed pregnancy-induced hypertension

The plasma concentration of deoxycorticosterone (DOC) was determined serially in a large group of primigravid women from 10 weeks' gestation to term. The plasma level of DOC in women whose pregnancies were uncomplicated (n = 44) was 234 ± 33 pg/ml (mean ± SE), at 10 to 14 weeks' gestation, a level two times that of nonpregnant subjects. The plasma level of DOC in these women rose to 778 ± 65 pg/ml at 23 to 26 weeks' gestation, and at term (39 to 42 weeks) was 1,309 ± 155 pg/ml. The plasma levels of DOC in women (n = 31) who eventually developed pregnancy-induced hypertension (PIH) were similar to those in the women who remained normal at all stages of pregnancy. We also found that, in women with normal pregnancies as well as in women destined to develop PIH, the plasma concentration of DOC fluctuated in a manner parallel to that of progesterone throughout gestation; however, changes in the plasma level of DOC did not mirror those of cortisol. These data suggest that excessive plasma levels of DOC are not necessarily associated with the development of PIH. These data also support the view that, in pregnant women, a fraction of circulating DOC may arise via extra-adrenal 21-hydroxylation of progesterone rather than through adrenal secretion.

The effect of chronic low-dose infusion of ACTH (1-24) on renin, renin-substrate, aldosterone and other corticosteroids in sodium replete and deplete man.

Abstract. Low-dose infusions of ACTH 1-24 (5 U/day) of 4 days duration were performed in 2 healthy young men on a normal sodium diet and in 2 on a low sodium diet, in order to study the mechanism of the transient effect of ACTH on aldosterone secretion described by other authors using larger doses of ACTH. Cortisol secretion was continuously stimulated by ACTH. Plasma aldosterone (P-Al) and its urinary metabolites increased during the first two days of infusion and returned to control or below control levels subsequently. Plasma renin activity (PRA) was also transiently stimulated by ACTH. Changes in PRA were not caused by changes in plasma renin substrate concentration. The correlation between PRA and P-Al (r = + 0.78; n = 52) was highly significant (P < 0.01). Plasma levels of deoxycorticosterone (DOC), 18-OH-DOC and corticosterone were also transiently stimulated in subjects on a normal sodium diet, while the stimulation was better maintained in those on a low sodium diet. The results suggest that the transient effect of low-dose ACTH infusion on aldosterone secretion may in part be mediated by changes in the renin-angiotensin-system. Changes in plasma levels of angiotensin II, which controls early and late steps in the mineralocorticoid biosynthetic pathway, may determine the extent to which chronically elevated ATCH levels stimulate the release of aldosterone and, perhaps, even the release of DOC and corticosterone. On the normal sodium diet, sodium retention and a slight fall in serum potassium levels towards the end of ACTH infusion may have contributed to the depression of aldosterone release.

Response of adrenal steroids to angiotensin II in essential hypertension

The effect of angiotensin II (A II) on the plasma corticosteroid concentration and blood pressure was investigated in five normotensive subjects and 24 patients with essential hypertension (EH). Infusion of A II in normal subjects caused a significant increase in plasma aldosterone and significant decreases in plasma renin activity (PRA), plasma cortisol and dehydroepiandrosterone-sulfate (DHEA-S), while plasma levels of deoxycorticosterone (DOC) and ACTH remained unchanged. In patients with EH, A II infusion caused a significant decrease in PRA and a significant increase in plasma aldosterone. The percent increase in plasma aldosterone was greatest in patients with high PRA when compared to the low and normal PRA groups. The mean plasma levels of cortisol, DOC and DHEA-S after A II infusion were significantly increased in patients with high PRA but no significant changes were observed in patients with low or normal PRA. The mean blood pressure in patients with low PRA was sharply increased during the infusion when compared to the other two groups and did not return to the baseline level after cessation of the infusion. Hepatic blood flow as estimated by the disappearance rate constant of indocyanine green was significantly lower in patients with low PRA than in patients with high PRA. The above results suggest that different responses to A II infusion in steroid biosynthesis may exist between normal subjects and patients with EH. These observed phenomena may be due to biochemical (serum sodium) or functional (plasma A II level) differences in the A II receptor site or to the difference in the metabolic clearance of A II in patients with EH.

Selective Hypoaldosteronism with Hyperreninemia in a Diabetic Patient

A 62-yr-old diabetic woman exhibited low plasma and urinary aldosterone levels in the face of markedly elevated PRA during the course of nonketoacidotic hyperglycemic precoma with dehydration, hyponatremia, and hyperkalemia, for which she was hospitalized. Studies performed after her recovery from precoma revealed hyperreninemic hypoaldosteronism with normal adrenoglucocorticoid function. While the patient was supine, PRA on a 256-meq sodium intake was at or above the upper limit of the normal range for a 200-meq sodium intake; furthermore, after sodium depletion with furosemide and 4 h of ambulation, PRA markedly increased. No increases in plasma inactive renin were found. Plasma renin substrate concentration was normal. Plasma levels and urinary excretion of aldosterone were low and increased slightly during sodium restriction with insulin treatment, accompanied by hyperkalemia and sodium loss, despite markedly elevated PRA. Repository ACTH administration induced sodium retention and potassium loss with a normal increase in urinary 17-hydroxycorticosteroids. Plasma levels of deoxycorticosterone, corticosterone, and 18-hydroxycorticosterone were normal, while plasma aldosterone was low. Levels of these mineralocorticoids remained unchanged during angiotensin II infusion on both 256-meq and 100-meq sodium intakes. Rapid ACTH administration produced normal increases in plasma deoxycorticosterone and corticosterone but caused a subnormal increase in plasma aldosterone. These results suggest adrenal insensitivity to angiotensin II, possibly a defect in adrenal angiotensin II receptors, as the cause of hypoldosteronism with hyperreninemia in this patient.

Assessment of 11β-Hydroxylase Activity with Plasma Corticosterone, Deoxycorticosterone, Cortisol, and Deoxycortisol: Role of ACTH and Angiotensin

In this study we evaluated the role of ACTH and angiotensin on regulation of activities of 11beta-hydroxylases of the adrenal cortex. The ratio of the plasma concentrations of 11 deoxycorticosterone (DOC) to plasma corticosterone (B) reflected the activity of the enzyme of the B and/or aldosterone pathways, and the ratio of plasma 11-deoxycortisol (S) to plasma cortisol (F) as the activity of the enzyme in the F pathway. In normal subjects, both ratios were significantly lower at 0800-0900 h (Doc to B, .01+/-.004, mean+/-SE, n=10; and S to F, .01+/-.003) than at 2000 h (DOC to B, .028+/-.024 and S to F, .015+/-.005). The plasma levels of DOC, B, S and F were all significantly lower at 2000-2100 h than at 0800-0900 h. In contrast 9 patients with Cushing's syndrome exhibited no diurnal change in the ratios. The ratios increased substantially following dexamethasone or metyrapone administration. A high or low salt diet and an angiotensin infusion produced no significant effect on the ratios. The plasma concentration of all four steroids was increased by more than 50% by an infusion of angiotensin. Four hours after administration of 80 mg of Lasix at 0800 h to 10 normal subjects, the ratios of DOC to B and S to F increased significantly (P less than .02), an effect possibly related to a decreased secretion of ACTH. 1) 11beta-hydroxylase activity of the B and/or aldosterone and F pathways appears to change in parallel with ACTH secretion, and 2) although angiotensin stimulates steroidogenesis of the pathways, it has no apparent effect on 11beta-hydroxylase activity.

Secretion rates and plasma levels of deoxycorticosterone and removal rates of deoxycorticosterone and aldosterone in the pregnant dog.

ABSTRACT. Plasma levels and adrenal secretion rates of deoxycorticosterone (DOC) were measured in pregnant and nonpregnant dogs by a double-isotope derivative assay.The removal rates of DOC and aldosterone were also determined following the intravenous injection of these tritiated hormones in pregnant and nonpregnant dogs. Plasma DOC concentrations averaged 2.7 (±1.3 SEM) ng⁄ml for 4 conscious pregnant dogs compared to 4.3 (±0.7) ng⁄ml for 6 nonpregnant dogs. The secretion rate of DOC in 3 anesthetized pregnant dogs averaged 377 (±51) ng⁄min compared to 503 ± 78 ng⁄min for 7 nonpregnant dogs. The differences in plasma DOC concentration and DOC secretion rate in the pregnant and nonpregnant groups were not statistically significant (NS = p > 0.05). In 4 pregnant dogs the plasma half-life ° (t½) for DOC was 24.9 min while the t½ for DOC in 5 nonpregnant dogs averaged 20.7 min (NS); the t½ for aldosterone in 5 pregnant dogs averaged 21.1 min while in 6 nonpregnant dogs the aldosterone t½ averaged 20.3 min (N...

Plasma deoxycorticosterone in man.

ABSTRACT Plasma levels of deoxycorticosterone (DOC) were determined using a newly developed competitive-binding assay employing corticosteroid binding globulin. Normal men, women throughout the menstrual cycle, and women on oral contraceptives had DOC levels ranging from less than 5 to 10 ng/100 ml. Levels rose to over 100 ng/100 ml following an ACTH infusion and to over 1000 ng/100 ml following metyrapone. Neither a 10 mEq sodium diet nor an angiotensin II infusion caused a detectable increase in DOC. Seven patients with Cushing's syndrome due to excess pituitary ACTH had DOC levels ranging from less than 5 to 15 ng/100 ml, whereas 6 patients with Cushing's syndrome caused by ectopic ACTH production had levels in the range of 21 to 390 ng/100 ml. One patient with Cushing's syndrome due to an adrenal adenoma had undetectable DOC, whereas 4 of 6 patients with adrenal carcinoma had elevated DOC levels. Plasma DOC was elevated in patients with hypertension caused by either 11β-hydroxylase or 17-hydroxylase d...