18-Hydroxy-11-Deoxycorticosterone (18-OH-DOC) Secretion in Experimental and Human Hypertension

Jc, Melby; Sl, Dale; Rj, Grekin; Gaunt, Richard A.; Wilson, TE

doi:10.1007/978-3-642-65343-8_45

Cited by 75 publications

(38 citation statements)

References 3 publications

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“…The data in human hypertension are controversial. Melby et al (9,10) 17-ketosteroid excretory rates. If the upright renin activity in the sodium-depleted state was subnormal, a saline load was given to show that the aldosterone secretory rate was suppressible.…”

Section: Introductionmentioning

confidence: 46%

The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man.

Williams¹,

Braley²,

Underwood³

1976

J. Clin. Invest.

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A B S T R A C T 18-hydroxy 11-deoxycorticosterone (18-OH DOC), a weak mineralocorticoid, was estimated by a radioimmunoassay procedure after purification in 49 patients with hyper,tension and 38 normal control subjects. The sensitivity of the method was 2-4 pg; there was no detectable blank, and the precision was 9-10%. In normal subjects the absolute plasma levels were similar to those of aldosterone. ACTH administration produced a 23-fold increase, and sodium restriction resulted in a 4-fold increase (5.4+-0.7-20.5±3.0 ng/dl). On the other hand, the plasma levels of 18-OH DOC declined by nearly 50% with upright posture or angiotensin II infusion. During both of these procedures, plasma aldosterone levels significantly increased. Patients with normal and low renin hypertension had similar changes in plasma 18-OH DOC levels with sodium restriction. However, the mean high sodium level in the normal renin essential hypertension group (11.6±-1.6 ng/dl) was significantly greater (P < 0.001) than in the control group (5.4±0.7 ng/dl). In addition, at least 22% and perhaps as high as 37% of the hypertensive subjects had levels greater than the upper limits of normal on a high sodium intake. Differences between the groups were less impressive in the sodiumrestricted studies. There were no significant differences in age, duration of hypertension, sodium balance, serum sodium, potassium, or blood urea nitrogen in those patients who had elevated levels of plasma 18-OH DOC. Patients with primary aldosteronism had levels within -the normal range on both dietary intake. However, in contrast to the other groups there were no significant changes in the plasma levels with sodium restriction. Thus, a significant number of patients with essential hypertension presumably have an alteration in 18-OH DOC secretion.

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Section: Introductionmentioning

confidence: 46%

The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man.

Williams¹,

Braley²,

Underwood³

1976

J. Clin. Invest.

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“…Japon. June 1976 There have been numerons reports on various abnormalities in steroid metabolism in essential hypertension (EH) (Cooper et al, 1958;Genest et al, 1960;Vermeulen and Van der Straeten, 1963;Shao et al, 1970;Melby et al,1971;Brown et al, 1972;Melby et al, 1972;Mendelsohn et al, 1972;Nowaczynski et al, 1972 a and b;Sasaki et al, 1972;Sekihara et al, 1973;Grim et al, 1974;Nowaczynski et al, 1975). However, in many of these studies, steroids have not been investigated systematically and also, steroids other than aldosterone have not commanded much attention.…”

Section: Synopsissupporting

confidence: 44%

“…Furthermore, several reports from other laboratories (Melby et al, 1971;Melby et al, 1972;Nowaczynski et al, 1972 a) have shown that the secretion rates of 18-hydroxy-11-deoxycorticosterone (18 -OH DOC) and the urinary excretion of 18-hydroxy-tetrahydro-deoxycorticosterone were significantly higher in patients with EH and suppressed PRA. On the other hand, previous studies have indicated that many of these patients, especially those with low PRA, have signiwhile cortisol and corticosterone concentrations were below the normal mean (Mendelsohn et al, 1972;Nowaczynski et al, 1972b ;Sasaki et al, 1972 was found that the increased responses of plasma aldosterone to ACTH infusion were found in EH with normal PRA as well as low PRA, while the patients with low PRA showed, moreover, significantly higher responses of plasma DOC to ACTH infusion (Honda et al, in press).…”

Section: Synopsismentioning

confidence: 44%

Effects of ACTH on Plasma Levels of Adrenal Steroids in Essential Hypertension

Honda

1976

Endocrinol Japon

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SynopsisPlasma concentrations of progesterone (P), deoxycorticosterone (DOC), 17-hydroxyprogesterone (17-OH P), corticosterone (B), deoxycortisol (S), cortisol (F) and aldosterone (A) in 8 control subjects (mean age: 40.5 years) and 10 patients with essential hypertension (EH) (mean age: 48.5 years) were determined before, 4 and 8 hours after an infusion of ACTH at a rate of 25 units per 8 hours.Secretion rates (SR) of 18-hydroxy-11-deoxycorticosterone (18-OH DOC) were measured 24 hours before and again on the day of ACTH infusion.All subjects were studied on the fourth day of a diet containing 135 mEq of sodium and 90 mEq of potassium.There was no statistically significant difference between 8 control subjects and 10 patients with FH in the 7 plasma steroid levels and the SR of 18-OH DOC before ACTH infusion.The mean plasma presponse to ACTH was slightly lower in controls than in patients with EH, while that of 17-OH p(in male subjects) was slightly higher. The mean plasma B response was significantly lower atter 4 nours or At., in infusion (p<0.01), while that of DOC was significantly higher after 8 hours of ACTH infusion (p<0.05) in patients with EH. The mean plasma S rose significantly more in patients with EH (p<0.025) at 4 and 8 hours after ACTH infusion.The mean plasma F response to ACTH infusion was slightly lower in patients with EH than in controls.The mean response of 18-OH DOC SR to ACTH infusion was slightly higher in patients with EH than in controls.The mean plasma A response was significantly higher in patients with EH than in controls 4 (p<0.05) and 8 hours (p<0.001) after an ACTH infusion.These results could be explained in part by abnormalities in the 17-and 11-hydroxylase systems, and that the abnormality in 11-hydroxylation was more pronounced than that in the 17-position.Furthermore, we suspect that the sensitivity of adrenal aldosterone to ACTH might be increased or another accelerated pathway to aldosterone biosynthesis might exist in patients with EH.

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“…These clincal findings suggest that the correct diagnosis in this case is bilateral 1 8-OH-DOC-producing adrenal hyperplasia and a non-functional mass in the right adrenal gland. is largely derived from the zona fasciculata in the rat adrenal cortex (12), this evidence also supports hyper production of 18-0H-D0Cin the zona fasciculata in this case. The standing and dexamethasone tests suggested that the serum concentration of 18-0H-D0Cwas mainly regulated by that of ACTHand was little affected by that of ANGII.…”

Section: Discussionmentioning

confidence: 44%

“…In addition, hypertension and hypokalemia were ameliorated as the serum 18-OH-DOCconcentration decreased following right adrenalectomy. These findings suggest that the high concentration of 18-OH-DOCwas at least partially responsible for the hypertension and hypokalemia, although the mineralocorticoid activity of 18-OH-DOCwas 3% as effective as that of aldosterone on transepithelial sodium transport in the toad urinary bladder (12).…”

Section: Discussionmentioning

confidence: 46%

Effect of Uni-adrenalectomy on Blood Pressure in a Patient with Excessive Adrenal 18-hydroxy-11-deoxycorticosterone Production Bilaterally

et al. 2003

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A 46-year-old womanwas presented with mineralocorticoid excess syndromeand a large massoriginating from the right adrenal gland. Clinical examination before right adrenalectomy revealed elevated serum concentrations of 18-hydroxy-ll-deoxycorticosterone (18-OH-DOC) both systemically and in the adrenal veins bilaterally. Histopathological and immunohistochemical analyses of the surgical specimen demonstrated adrenal hyperplasia of outer fasciculata cells, and the presence of cystic mass. The adrenalectomy ameliorated her blood pressure (BP) from 156/96 mmHgto 148/87 mmHg with a concomitant increase of serum potassium concentration from 3.1 mEq/l to 3.5 mEq//. These results suggest that uni-adrenalectomy is, at least in part, effective in ameliorating not only BP but also potassium concentration in a patient of adrenal hyperplasia with excessive bilateral 18-OH-DOCproduction. (Internal Medicine 42: 507-512, 2003)

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18-Hydroxy-11-Deoxycorticosterone (18-OH-DOC) Secretion in Experimental and Human Hypertension

Cited by 75 publications

References 3 publications

The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man.

The regulation of plasma 18-hydroxy 11-deoxycorticosterone in man.

Effects of ACTH on Plasma Levels of Adrenal Steroids in Essential Hypertension

Effect of Uni-adrenalectomy on Blood Pressure in a Patient with Excessive Adrenal 18-hydroxy-11-deoxycorticosterone Production Bilaterally

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