Diurnal Variation of Plasma Renin Activity, Aldosterone and Cortisol in Idiopathic Edema FRED H. KATZ Division of Endocrinology, Department of Medicine, University of Colorado Medical Center, and Veterans Administration Hospital, Denver, Colorado Comparison of the circadian hormone levels in the patients with those previously found in normals revealed only one subject who had significantly lower PRA than normals, and one patient with a higher PA during the midnight to 0800 h period than controls. The other levels were not significantly different from the controls. Furthermore, baseline levels of PA and PRA, supine and upright, on normal and low sodium diets, were usually within normal limits and two patients lacked the posture-induced rise in PRA. It is therefore concluded that excessive renin and aldosterone are not usually found in recumbent patients with idiopathic edema. (J Clin Endocrinol Metab 45: 419, 1977)

ABSTRACT. The plasma levels of aldosterone (PA), renin activity (PRA) and cortisol were measured every 30 min in the supine position in 4 women with idiopathic edema. The circadian rhythm of PA was similar to that previously reported in normal subjects: peak secretory episodes occurred during the latter part of sleep and shortly after awakening. Moreover the levels of PA were statistically significantly correlated with PRA and cortisol in 3 of the 4 patients (P < .005). Secretory spikes followed meals by 30 min and furosemide administration by 4 h. It is concluded that, 1) as in normals, a central nervous system rhythm may be important in control of PA, and 2) potassium is suggested as the secretagogue of aldosterone after meals.

P

ATIENTS with idiopathic edema have been reported to have excessive responses of plasma renin activity (PRA)1 as well as aldosterone excretion to upright posture by Kuchel et al. (1) as a cause for their abnormal sodium and water retention. Oelkers et al. (2), however, could not document excessive renin and aldosterone in careful metabolic ward studies on 5 patients, although 4 of these patients retained sodium in the upright position. Streeten et al. (3), on the other hand, were able to demonstrate excessive aldosterone in 9 idiopathic edema patients who demonstrated orthostatic sodium retention (as differentiated from water retention only). They had elevation of aldosterone excretion or secretion in 20 of 50 determinations while receiving a 200

meq sodium diet (3). Renin was however normal in that study. We have shown that, even in the supine position, aldosterone is secreted in normals in spurts which are most frequent and maximal during the latter part of sleep and upon arising (4,5). Furthermore, secretory spurts of aldosterone coincide with those of cortisol. Other reports have confirmed this circadian episodic secretory rhythm and the correlation with cortisol (6-8). The purpose of the present study was to determine whether the circadian rhythm of aldosterone is altered in supine patients with idiopathic edema and to investigate the relationship between secretory spurts of aldosterone and concurrent levels of cortisol and plasma renin activity in such patients.

Received November 3, 1976. Supported by Grant RR-51 from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health, Veterans Administration Project 4844-01, and a grant from The Population Council. Reprint requests to: Fred H. Katz, M.D., 4545 East Ninth Avenue, Denver, Colorado 80220. 1 Abbreviations used in this paper: PRA, plasma renin activity; PA, plasma aldosterone.

Materials and Methods Four women with idiopathic edema of 3 to 20 years duration were hospitalized on the metabolic ward. The diagnosis was made on the basis of recurrent edema, despite lack of evidence for renal, hepatic, gastro-intestinal, venous and nutritional disorders. Baseline fasting supine levels of PRA and plasma aldosterone were obtained at 0800 h on normal (113 meq/day) and

419

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 08:09 For personal use only. No other uses without permission. . All rights reserved.

JCE & M • 1977 Vol 45 • No 3

KATZ

420

low (10 meq) sodium diets given for 5 days as previously described (10,11). Following breakfast the patients were restudied after 2 h in the upright position. Three patients were given constant normal sodium diets containing 95 to 120 meq sodium and 54 to 78 meq potassium prior to the circadian study. In order to observe the effects of an often-used therapeutic regimen, the fourth patient was receiving a constant very low sodium and potassium diet, (rice diet), less than 1 meq sodium daily, and 10 meq potassium during the circadian study, with 50 meq potassium supplements. She was also given her previous maintenance dose of furosemide, 40 mg twice daily, during the day of her diurnal study. All 4 patients had received no diuretics for at least 7 days before the circadian sampling. All patients demonstrated mild to moderate generalized edema at the time of the study. The two menstruating women, patients A and B, were studied during the two weeks post catamenia, in order to avoid the post-ovulatory increase in supine aldosterone and PRA levels (9). Patients C and D had evidence of post-menopausal cessation of ovulation, in that patient C had stopped menstruating and patient D now had hot flashes 15 years post-hysterectomy. All the patients except A were unable to excrete more than 50% of a water load of 20 ml/kg in 4 h in the upright position. Patient A had normal water excretion. Of the other 3 patients, B and C were able to excrete the load in the supine position, but D could not excrete the load in the supine position either. Patients B, C and D were unable to excrete 100 meq daily sodium ioads until they had retained several hundred meq but patient A did not demonstrate this abnormality at the time of study. The 30-min sampling for plasma levels of

aldosterone (PA), PRA and cortisol was performed when the patients had come into balance on their diets. They were kept supine in bed during the entire 24 h except for brief periods up to the bathroom immediately after a sample was obtained. Our previous studies in normals (5) showed that this brief period up did not stimulate renin or aldosterone reaction. The measurement of the 3 hormones and the computations of the correlation coefficients between the hormones were performed by the same methods as in the previous study (5). Informed consent was obtained and the protocol was approved by the University Medical Center's Human Subject Committee.

Results

The baseline levels of PRA and PA, supine and upright, on normal and low sodium diets, are shown in Table 1. Excessive levels of either hormone were not the pattern. Only one of the two upright normal sodium PA values in C and the low sodium PRA in D were elevated. To the contrary, several patients, as shown in Table 1, had levels below the normal range. Moreover two patients showed failure to increase their PRA with upright posture, A on low sodium and B on normal sodium. The circadian rhythms in the 4 patients are depicted in Figs. 1-4 and the data are summarized in Table 2. It can be seen that, just as was true for normals, peak PA values occurred during the latter part of sleep and after awakening. Furthermore PA as well as PRA were highly correlated with plasma

TABLE 1. Baseline PRA (ng/ml/h) and PA (pg/ml) in patients with idiopathic edema Low Sodium

Normal Sodium 2 h up

Supine PRA

PA

PRA

PA

PRA

PA

PRA

PA

0.02* 1.91,1.69 0.35,0.27 0.42

57 26,*31* 74,82 149

0.12* 1.59,1.68 1.3,2.05 4.69

216 220,132* 328,5931 423

2.78

288

2.40

782

1.08* 28.9f

92* 490

6.9*

1,005

0.2-3.6

32-200

0.6-11.7

150-480

2.1-13.8

134-580

9.2-24.5

416-1700

Patient, Age (years) A B C D

49 21 60 51

Controls (ref. 10,11)

2 h up

Supine

* Below normal range, t Above normal range.

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 08:09 For personal use only. No other uses without permission. . All rights reserved.

421

ALDOSTERONE RHYTHM IN IDIOPATHIC EDEMA

500 400 g UJ

300 g

s

200 2 < 100 •

0800

1100

1400

1700

2000 TIME

2300

0200

2800

0800

FlG. 1. Supine circadian rhythm of PA, PRA and cortisol in patient A with idiopathic edema. Thick downward arrows are meals and inverted triangles brief periods up to the bathroom right after sampling. The shaded bar indicates sleep.

cortisol (P < .005, Table 2) in 3 of the 4 patients. In patient B, in whom this correlation was not significant, regression of PA on both PRA and cortisol gave an R value of 0.32 but P was 0.0803. Patient B (Fig. 2) demonstrated a mean PRA level significantly (P < .05) below the mean of the normal subjects previously

studied (Table 2). Patient A (Fig. 1) had a significantly higher mean PA level during the period from 2400 to 0800 h than the mean of the normals previously studied (268 ± 124 vs. 108 ± 54 pg/ml, P < .05). These two were the only statistically significant differences in PA or PRA between the patients with idiopathic edema and the con-

mm

I 300 0 g

2 0 0900

1200

1500

1800

2100 TIME

2400

0300

0600

0900

0 •

FIG. 3. Supine hormone levels in patient C. Symbols as in Fig. 1.

trols in the previous study, although the statistically significantly greater than the entire 24 h and each of the 3 periods of the normals (P > .10). day were analyzed, as in the previous study In all 4 patients (Figs. 1-4) spikes of PA (5). Although patient C (Fig. 3) had several and cortisol sometimes occurred shortly high spikes of PA during sleep and after after meals and in patient D these followed awaking, her mean value (215 ± 63), even each of the 4 oral doses of supplementary during the 8 h period of sleep, was not potassium by about 30 min. Statistical 36 G.D. 30 24 28 16 24



1200

2O.c •

16 9

.

12

800 5

s

at a.

IU



600g -a

8

FIG. 4. Supine hormone levels in patient D who was on a low sodium, low potassium diet and received furosemide 40 mg BID. Dotted arrows indicates furosemide dose and thin solid arrows indicate potassium supplement (12.5 meq each dose). Rest of symbols as in Fig. 1.

400 • 200

0800

1100

1400

1700 2000 TIME

2300

0200

0500

The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 18 November 2015. at 08:09 For personal use only. No other uses without permission. . All rights reserved.

423

A L D O S T E R O N E RHYTHM IN I D I O P A T H I C E D E M A TABLE 2. PRA, PA and cortisol levels (mean ± SD) obtained every 30 min for 24 h in 3 patients with idiopathic edema and correlation between hormones Regression PA on PRA Patient

PRA (ng/ml/h)

Normal sodium diet A 0.98 B 0.28 C 0.58 Controls 1.43 (Ref. 5)

PA on Cortisol

PA (pg/ml)

(A^g/dl)

R

P

R

P

± 0.36 ± 0.27 ± 0.55

136 ± 123 76 ± 27 150 ± 75

5.9 ± 3.6 7.6 ± 4.6 10.9 ± 4.4

0.75 0.23 0.75

0.0001 0.1065 0.0001

0.48 0.20 0.72

0.0008 0.16891 0.0001

± 0.33

88 ± 30 9.8 ± 8.6

0.50

0.0011

0.63

0.0001

Low sodium

Diurnal variation of plasma renin activity, aldosterone and cortisol in idiopathic edema.

Diurnal Variation of Plasma Renin Activity, Aldosterone and Cortisol in Idiopathic Edema FRED H. KATZ Division of Endocrinology, Department of Medicin...
450KB Sizes 0 Downloads 0 Views