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Reduced urinary aldosterone excretion rates with normal plasma concentrations of aldosterone in the very elderly
REDUCED URXNARY ALDOSTERONE EXCRETIONRATES WITH NORMAL OF ALDOSTERONE IN THE VERY ELDERLY
CON~~~~T~ONS
J.
Howard Pratt,
James J.
The Department of Wicine,
Hawthorne,
and David J.
IndianaUniversity School of
Medicine, Indianapolis,IN 46223; and the V.A. Helical Center, Indianapolis,IN 46202, USA Received February27,
1987
Revised September 12, 1987
ABSTRACT Although aldosterone production declines with age, so does the aldosterone metabolic clearance rate (MCR), and the net effect of age on the circulating level of aldosterone may be less than can be predicted from production rates slone. The effect of age on aldosterone production and plasma levels was studied in a group of elderly individuals at a very advanced age when susceptibility to the impacts of age might be particularly pronounced. Seventeen nursing home patients, ages 35-99 (mean age 86 years), had aldosterone production assessed from the urinary excretion rate of the acid hydrolyzahle lf+glucuronide conjugate of aldosterone. Aldosterone excretion was low in the elderly when compared to a group of healthy, young to middle-aged subjects: 123219 (SW) vs. 234+18 rig/h (P( 0.001). However. plasma aldosterone concentrati&s in the elderly were well within a range observed in much younger and fully ambulatory subjects: 14,X+1.3 in the elderly vs. 15.921.8 np/dL in the young. The plasma aldoeterone concentration was apparently maintained at a normal level, by a coincident decrease in both the metabolic clearance rate and the aldosterone production rate. In conclusion, an aldosterone deficiency state resulting from an age-correlated reduction in aldosterone production is probably uncommonin the elderly.
INTRODUCTION Aldosterone
production
decreases
as people get older
This is thought to be secondary to an age-related plasma renin activity of aldosterone
(2-7).
The metabolic
decline
clearance
also decreases with advancing age (l),
of age on aldosterone
rate
(I-7). in (MCR)
an effect
dynamics which could cause plasma aldo-
STEROIDS 51 / 1-2
January - February 1988
Debono
PIJUNA
164
Prattet al
sterone levels to be more nearly normal, despite lower production rates.
What effect. if any, these changes in the rates
of production and clearance of aldosterone have on the physiologic well being of the elderly individual is not known.
In
the present study we examined a group of individuals at a very advanced age for evidence of aldosterone deficiency.
As is
typical for such a population, subjects had age-related physical disabilities. and almost all required medical therapy of one kind or another.
Because of their age and physical impairments. this
group of subjects in particular might demonstrate abnormalities related to altered aldosterone dynamics.
MATERIALS AND METHODS Seventeen bedridden subjects from the Masonic Home in Franklin. IN, ages 75-99 years, were studied (14 women and 3 men). They had no clinical or biochemical evidence of significant cardiac or hepatic dysfunction, and none had diabetes mellitus. Most were receiving medical treatment. including medication known to affect renin and aldosterone secretion (diuretics and betaadrenergic antagonists). All patients had chronic indwelling catheters (for management of severe chronic urinary incontinence) and urine was collected for 10 hr (1000 PM to 800 AM) for measurement of aldosterone excretion. Plasma samples were obtained while subjects were still recumbent (in a few instances subjects had been sitting up in bed or sitting in a wheel chair for several minutes before blood samples were drawn). A control group consisted of 34 healthy individuals. ages 22-42 (mean age 35) consuming an -ad libitum intake of sodium. They had urines collected for 24 hr for measurement of urinary excretion of aldosterone. Plasma samples were also obtained from 13 normal subjects (many of the same individuals as provided urine samples) ages 25-46 (mean age 34) in the morning after subjects had been upright for 3-5 hours. Aldosterone was measured in urine after acid hydrolysis of the aldosterone l&glucuronide and also in plasma utilizing a radioimmunoassay with antisera to aldosterone lactone (8). Plasma renin activity (PRA) was measured by determining the -in
STEROIDS
51 / l-2
January - February 1988
ALDOSTERONE
MEASUREMENTS
IN THE ELDERLY
vitro generation of angiotensin I (9). Electrolytes and creatinines were measured on a Beckman Astra (Beckman Instruments, Inc.. Fullerton, CA). Data were examined by the non-paired t-test and are expressed as the mean+SEM. RESULTS Table 1. shows individual data for all 17 subjects. Six elderly subjects were treated with a diuretic, a drug which typically increases secretion of renin and aldosterone; 3 subjects received beta-adrenergicantagonists (metoprololor methyl-dopa). drugs which have the potential to lower renin and
TABLE 1. Clinical data, plasma renin activity. aldosterone excretion rates and plasma concentrationsin the elderly
No. & 1. 2.
99 99
3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.
96 9.5 89 88 87 87 86 85 83 82 81 81 79 75 75
Serum Creatinine PEAa Treatment Lrg+ clearance 'YFF (niib /L) '-GlzizJ 1 142 3.9 42 4.0 metoprolol 130 3.5 16 81 + z&x01yn 142 4.1 37 3.0 8 16 141 5.3 134 4.3 53 8.4 Dyaxided 138 2.8 64 21 122 3.9 28 Dyazide 4.0 134 4.3 -6.2 Dyazide 141 4.3 29 13 140 4.0 56 4.0 137 3.2 28 0.5 22 139 4.8 17 72 134 4.3 3.0 furosemide 131 4.3 100 1.0 62 metoprolol 138 5.0 2.0 141 3.6 33 6.0 Dyazide 135 3.0 32 7.3 + methyl-dopa
u/h (nab) 150 100
PAC (nzdL) 22 18
180 70 60 170 70 --170 30 60 80 70 350 120 170 120
16 15 12 16 16 18 16 4 12 15 1.4 21 12 16 10
a. PEA = plasma renin activity. b. UA = urinary aldosterone. c. PA= plasma aldosterone. d. Dyazide = triamterene 50 mg and hydrochlorothiazide25 mg.
STEROIDS
51 / 1-2
January - February 1988
165
166
Pratt et al
aldosterone levels.
Six subjects had low serum sodium levels
(122-134 nnr/L,. Three had low potassium levels (<3.5rr4/L). whereas none had clearly elevated potassium levels (4.8 and 5.0 nEtq/Lwere the highest values observed).
Creatinine clearance
rates were in a range consistent with the advanced age of the subjects, with the exceptions that in one subject the creatinine clearance was only 8 mL/min. another had a value of 16 mL/min and there were several with creatinine clearances in the 20's. There was a wide range of PRA values, from 0.5 to 81 ng/mL/3 h. The highest PRA was in a 99 year old patient (C2) receiving the diuretic Zaroxolyn, Aldosterone excretion rates ranged from 30 to 350 rig/h.. whereas plasma aldosterone concentrations were relatively constant from one subject to another with only 2 subjects showing low values (1.4 and 4.0 ng/dL). In Figure 1. aldosterone excretion rates and plasma aldosterone concentrations in the elderly are compared with values obtained in younger subjects.
The mean aldosterone
excretion rate in the elderly was 12.3+19, whereas the mean value for excretion of aldosterone in the younger group was nearly twice this value at 234218 rig/h.. On the other hand, mean values for plasma aldosterone in the 2 groups were nearly identical: 14.1~1.3 in the elderly and 15.921.8 ng/dL in the young.
STEROIDS
51 / l-2
January - February
1988
ALDOSTERONE
1
MEASUREMENTS
IN THE ELDERLY
p
I
N.S.
YOUNG
(n=34)
ELDERLY (n=16)
YOUNG
ELDERLY
(n=13)
(nc17)
Figure 1. The mean urinary excretion rate of aldosterone and the mean plasma aldosterone concentration in young persons and in the elderly. Aldosterone excretion in the elderly was only half the rate observed in the young. Plasma aldosterone concentrations in the two groups were the same. DISCUSSION This study differs from previous studies of the effect of age on aldosterone production in that our subjects were significantly older (l-7).
All were confined to a nursing home.
and. for the most part, were under treatment with one or more medications.
Although a heterogenous group, they were considered
an important population to study because their age and degree of physical disability would make them particularly susceptible to the effect of age on aldosterone production and metabolic clearance.
STEROIDS
Futhermore. they would be vulnerable to and apt to
51 / l-2
January - February 1988
167
168
Prattet al
manifest any metabolic consequences of aldosterone deficiency. We found that aldosterone production was reduced to about half what was observed in a much younger group of controls.
These
findings are consistent with previous observations by others (l-7).
Despite a lower rate of aldosterone production, plasma
aldosterone levels were similar to values observed in a much younger. healthy and fully ambulatory group of subjects.
Based
on plasma levels of aldosterone. and the lack of an elevation in plasma potassium concentration
(a sensitive clinical sign of
aldosterone deficiency), the elderly population under study was not deficient in aldosterone. Although aldosterone measurements in nighttime urine collections were
compared to measurements in 24 h collections. we
feel such comparisons were valid.
The previously described
diurnal variation in aldosterone production
(lo-111 results from
the effect of the daytime ambulatory activity to raise production rates and the nighttime recumbency and relative inactivity to lower it.
Individuals who are continuously recmbent show no
diurnal variation in aldosterone production
(10-11). Samples
collected during the night were representative of 24 h excretory patterns in the elderly since the elderly were essentially recumbent all day as well as at night.
In part the lower
aldosterone excretory rate in elderly subjects of the present study was due to their continuous recumbency, which contrasted with the inclusion of daytime ambulatory activity in controls.
STEROIDS
51 /’ l-2
January - February
1988
ALDOSTERONE
MEASUREMENTS
IN THE ELDERLY
To account for the normal plasma aldosterone concentrations in the elderly in the face of reduced aldosterone excretion, there must have been a corresponding decrease in the aldosterone NCR. Flood -et al. (1) found that the aldosterone MCR was reduced by 20% in a group of healthy men of average age 75 yr when compared to their control group. Our subjects were older (mean age 86) and in overall poorer health. Quite conceivably, the aldosterone clearance rate was even lower in our elderly group of subjects. This could explain why we did not find reduced plasma aldosterone concentrationsas others have in previous studies of elderly populations (2.4-7). It should be noted that if there were higher plasma aldosterone concentrationssecondary to the reduced MCR. then there would be inhibition of the renin-angiotensinsystem and this in turn would serve to lower the aldosterone production rate. Thus, the reduced MCR would tend to further lower the aldosterone production rata in elderly individuals. The aldosterone UGR is determined to a major extent by the rate of hepatic perfusion. A reduction in cardiac output as a result of the aging process itself (12). or from mild heart failure in some, could have lowered hepatic perfusion and decreased the
aldO6terOne
MCR in our study population. In
addition. beta-adrenetgicantagonists, used by several subjects, are known to lower hepatic perfusion and to reduce aldosterone clearance through either a direct effect on hepatic vasculature
STEROIDS 51 / 1-2
January - February 1988
169
170
Prattet al
or secondarily by lowering cardiac output (13).
However.
specific measurements of the aldosterone MCR were not possible because of the overall frail physical condition of our subjects, and, in many instances, subjects were unable to give informed consent. In summary, individuals at a very advanced age did not show evidence of aldosterone deficiency despite a decrease in aldosterone production.
A significant reduction in the
aldosterone MCR appears to offset a decrease in aldosterone production.
NOTES AND REFERENCES This work was supported by the grant AGO5042-01 and by the Veterans Administration. Requests for reprints should be addressed to: J. Howard Pratt. M.D.. V.A. Medical Center. 1481 West 10th Street, Indianapolis, IN 46202. 1. 2. 3. 4. 5. 6. 7.
F1ood.C.. Gherondache. C., Pincus. G.. Tait. J-F.. Tait. (1960). S.A.S.. Willoughby. S.A., J. CLIN. INVEST. 2. Weidmann. P.. De Myttenaere-Bursztein. S.. Maxwell. M-H.. De Lima, J.. KIDNEY INT. 2. 329 (1975). Crane. M.G.. Harris, J.J.. J. LAB. CLIN. MED. 87. 947 (1976). Noth, R.H.. Lassman, M.N.. Tan. S.Y.. Frenandes-Cruz. Jr.. A-. Mulrow. P.J.. ARCH. INTERN. MED. 137. 1414 (1977). Tan, S.Y., Noth, R., Mulrow. P.J.. CLIN. CHEM. 2. 1531 (1978). Hegstad, R., Brown, R.D.. Jiang. N-S., Kao. P.. Weinshilboum, R.M., Strong. C.. Wisgerhof. J. AM. J. MED. 2, 442 (1983). Tsunoda. K., Abe, K.. Goto. T.. Yesujima. M.. Sata. Ma. Omata, K., Seino. M.. Yoshinaga. K.. J. CLIN. ENDOCRINOL. METAB.. 62. 384 (1986).
STEROIDS
51 / 1-2
January - February
1988
ALDOSTERONE
MEASUREMENTSIN
THE ELDERLY
Antunes, J.R.. Dale. S.L.. Malby. J.C.. STEROIDS 28. 621 (1976). 9. Wainberger, M.H., Ramsdell. Y.W., Rosner. D.R., Geddes. Y.Y.L.. AM. J. PHYSIOL. 223. 1049 (1972). 10. Wolfe, L.K., Gordon, R.D., Island, D.P.. Liddle, G.W., J. CLIN. ENDOCRINOL.2. 1261 (1966). 11. Wainberger. M.H.. Kexn. D.C., Gomez-Sanchez,C., Kramer. N.J., Martin, B.T.. Nugent. C.A., 3. LAB. CLIN. P%D. 85* 957 (1972). 12. Ladatta, E.G.. FED. PROC. 38, 163 (1979). 13. Pratt, J.H., Grim. C.E.. Parkinson, C.A.. J. LAB. CLIN. MED. 95, 693 (1980). 8.
STEROIDS
51 / l-2
January - February 1988
171
CON~~~~T~ONS
J.
Howard Pratt,
James J.
The Department of Wicine,
Hawthorne,
and David J.
IndianaUniversity School of
Medicine, Indianapolis,IN 46223; and the V.A. Helical Center, Indianapolis,IN 46202, USA Received February27,
1987
Revised September 12, 1987
ABSTRACT Although aldosterone production declines with age, so does the aldosterone metabolic clearance rate (MCR), and the net effect of age on the circulating level of aldosterone may be less than can be predicted from production rates slone. The effect of age on aldosterone production and plasma levels was studied in a group of elderly individuals at a very advanced age when susceptibility to the impacts of age might be particularly pronounced. Seventeen nursing home patients, ages 35-99 (mean age 86 years), had aldosterone production assessed from the urinary excretion rate of the acid hydrolyzahle lf+glucuronide conjugate of aldosterone. Aldosterone excretion was low in the elderly when compared to a group of healthy, young to middle-aged subjects: 123219 (SW) vs. 234+18 rig/h (P( 0.001). However. plasma aldosterone concentrati&s in the elderly were well within a range observed in much younger and fully ambulatory subjects: 14,X+1.3 in the elderly vs. 15.921.8 np/dL in the young. The plasma aldoeterone concentration was apparently maintained at a normal level, by a coincident decrease in both the metabolic clearance rate and the aldosterone production rate. In conclusion, an aldosterone deficiency state resulting from an age-correlated reduction in aldosterone production is probably uncommonin the elderly.
INTRODUCTION Aldosterone
production
decreases
as people get older
This is thought to be secondary to an age-related plasma renin activity of aldosterone
(2-7).
The metabolic
decline
clearance
also decreases with advancing age (l),
of age on aldosterone
rate
(I-7). in (MCR)
an effect
dynamics which could cause plasma aldo-
STEROIDS 51 / 1-2
January - February 1988
Debono
PIJUNA
164
Prattet al
sterone levels to be more nearly normal, despite lower production rates.
What effect. if any, these changes in the rates
of production and clearance of aldosterone have on the physiologic well being of the elderly individual is not known.
In
the present study we examined a group of individuals at a very advanced age for evidence of aldosterone deficiency.
As is
typical for such a population, subjects had age-related physical disabilities. and almost all required medical therapy of one kind or another.
Because of their age and physical impairments. this
group of subjects in particular might demonstrate abnormalities related to altered aldosterone dynamics.
MATERIALS AND METHODS Seventeen bedridden subjects from the Masonic Home in Franklin. IN, ages 75-99 years, were studied (14 women and 3 men). They had no clinical or biochemical evidence of significant cardiac or hepatic dysfunction, and none had diabetes mellitus. Most were receiving medical treatment. including medication known to affect renin and aldosterone secretion (diuretics and betaadrenergic antagonists). All patients had chronic indwelling catheters (for management of severe chronic urinary incontinence) and urine was collected for 10 hr (1000 PM to 800 AM) for measurement of aldosterone excretion. Plasma samples were obtained while subjects were still recumbent (in a few instances subjects had been sitting up in bed or sitting in a wheel chair for several minutes before blood samples were drawn). A control group consisted of 34 healthy individuals. ages 22-42 (mean age 35) consuming an -ad libitum intake of sodium. They had urines collected for 24 hr for measurement of urinary excretion of aldosterone. Plasma samples were also obtained from 13 normal subjects (many of the same individuals as provided urine samples) ages 25-46 (mean age 34) in the morning after subjects had been upright for 3-5 hours. Aldosterone was measured in urine after acid hydrolysis of the aldosterone l&glucuronide and also in plasma utilizing a radioimmunoassay with antisera to aldosterone lactone (8). Plasma renin activity (PRA) was measured by determining the -in
STEROIDS
51 / l-2
January - February 1988
ALDOSTERONE
MEASUREMENTS
IN THE ELDERLY
vitro generation of angiotensin I (9). Electrolytes and creatinines were measured on a Beckman Astra (Beckman Instruments, Inc.. Fullerton, CA). Data were examined by the non-paired t-test and are expressed as the mean+SEM. RESULTS Table 1. shows individual data for all 17 subjects. Six elderly subjects were treated with a diuretic, a drug which typically increases secretion of renin and aldosterone; 3 subjects received beta-adrenergicantagonists (metoprololor methyl-dopa). drugs which have the potential to lower renin and
TABLE 1. Clinical data, plasma renin activity. aldosterone excretion rates and plasma concentrationsin the elderly
No. & 1. 2.
99 99
3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17.
96 9.5 89 88 87 87 86 85 83 82 81 81 79 75 75
Serum Creatinine PEAa Treatment Lrg+ clearance 'YFF (niib /L) '-GlzizJ 1 142 3.9 42 4.0 metoprolol 130 3.5 16 81 + z&x01yn 142 4.1 37 3.0 8 16 141 5.3 134 4.3 53 8.4 Dyaxided 138 2.8 64 21 122 3.9 28 Dyazide 4.0 134 4.3 -6.2 Dyazide 141 4.3 29 13 140 4.0 56 4.0 137 3.2 28 0.5 22 139 4.8 17 72 134 4.3 3.0 furosemide 131 4.3 100 1.0 62 metoprolol 138 5.0 2.0 141 3.6 33 6.0 Dyazide 135 3.0 32 7.3 + methyl-dopa
u/h (nab) 150 100
PAC (nzdL) 22 18
180 70 60 170 70 --170 30 60 80 70 350 120 170 120
16 15 12 16 16 18 16 4 12 15 1.4 21 12 16 10
a. PEA = plasma renin activity. b. UA = urinary aldosterone. c. PA= plasma aldosterone. d. Dyazide = triamterene 50 mg and hydrochlorothiazide25 mg.
STEROIDS
51 / 1-2
January - February 1988
165
166
Pratt et al
aldosterone levels.
Six subjects had low serum sodium levels
(122-134 nnr/L,. Three had low potassium levels (<3.5rr4/L). whereas none had clearly elevated potassium levels (4.8 and 5.0 nEtq/Lwere the highest values observed).
Creatinine clearance
rates were in a range consistent with the advanced age of the subjects, with the exceptions that in one subject the creatinine clearance was only 8 mL/min. another had a value of 16 mL/min and there were several with creatinine clearances in the 20's. There was a wide range of PRA values, from 0.5 to 81 ng/mL/3 h. The highest PRA was in a 99 year old patient (C2) receiving the diuretic Zaroxolyn, Aldosterone excretion rates ranged from 30 to 350 rig/h.. whereas plasma aldosterone concentrations were relatively constant from one subject to another with only 2 subjects showing low values (1.4 and 4.0 ng/dL). In Figure 1. aldosterone excretion rates and plasma aldosterone concentrations in the elderly are compared with values obtained in younger subjects.
The mean aldosterone
excretion rate in the elderly was 12.3+19, whereas the mean value for excretion of aldosterone in the younger group was nearly twice this value at 234218 rig/h.. On the other hand, mean values for plasma aldosterone in the 2 groups were nearly identical: 14.1~1.3 in the elderly and 15.921.8 ng/dL in the young.
STEROIDS
51 / l-2
January - February
1988
ALDOSTERONE
1
MEASUREMENTS
IN THE ELDERLY
p
I
N.S.
YOUNG
(n=34)
ELDERLY (n=16)
YOUNG
ELDERLY
(n=13)
(nc17)
Figure 1. The mean urinary excretion rate of aldosterone and the mean plasma aldosterone concentration in young persons and in the elderly. Aldosterone excretion in the elderly was only half the rate observed in the young. Plasma aldosterone concentrations in the two groups were the same. DISCUSSION This study differs from previous studies of the effect of age on aldosterone production in that our subjects were significantly older (l-7).
All were confined to a nursing home.
and. for the most part, were under treatment with one or more medications.
Although a heterogenous group, they were considered
an important population to study because their age and degree of physical disability would make them particularly susceptible to the effect of age on aldosterone production and metabolic clearance.
STEROIDS
Futhermore. they would be vulnerable to and apt to
51 / l-2
January - February 1988
167
168
Prattet al
manifest any metabolic consequences of aldosterone deficiency. We found that aldosterone production was reduced to about half what was observed in a much younger group of controls.
These
findings are consistent with previous observations by others (l-7).
Despite a lower rate of aldosterone production, plasma
aldosterone levels were similar to values observed in a much younger. healthy and fully ambulatory group of subjects.
Based
on plasma levels of aldosterone. and the lack of an elevation in plasma potassium concentration
(a sensitive clinical sign of
aldosterone deficiency), the elderly population under study was not deficient in aldosterone. Although aldosterone measurements in nighttime urine collections were
compared to measurements in 24 h collections. we
feel such comparisons were valid.
The previously described
diurnal variation in aldosterone production
(lo-111 results from
the effect of the daytime ambulatory activity to raise production rates and the nighttime recumbency and relative inactivity to lower it.
Individuals who are continuously recmbent show no
diurnal variation in aldosterone production
(10-11). Samples
collected during the night were representative of 24 h excretory patterns in the elderly since the elderly were essentially recumbent all day as well as at night.
In part the lower
aldosterone excretory rate in elderly subjects of the present study was due to their continuous recumbency, which contrasted with the inclusion of daytime ambulatory activity in controls.
STEROIDS
51 /’ l-2
January - February
1988
ALDOSTERONE
MEASUREMENTS
IN THE ELDERLY
To account for the normal plasma aldosterone concentrations in the elderly in the face of reduced aldosterone excretion, there must have been a corresponding decrease in the aldosterone NCR. Flood -et al. (1) found that the aldosterone MCR was reduced by 20% in a group of healthy men of average age 75 yr when compared to their control group. Our subjects were older (mean age 86) and in overall poorer health. Quite conceivably, the aldosterone clearance rate was even lower in our elderly group of subjects. This could explain why we did not find reduced plasma aldosterone concentrationsas others have in previous studies of elderly populations (2.4-7). It should be noted that if there were higher plasma aldosterone concentrationssecondary to the reduced MCR. then there would be inhibition of the renin-angiotensinsystem and this in turn would serve to lower the aldosterone production rate. Thus, the reduced MCR would tend to further lower the aldosterone production rata in elderly individuals. The aldosterone UGR is determined to a major extent by the rate of hepatic perfusion. A reduction in cardiac output as a result of the aging process itself (12). or from mild heart failure in some, could have lowered hepatic perfusion and decreased the
aldO6terOne
MCR in our study population. In
addition. beta-adrenetgicantagonists, used by several subjects, are known to lower hepatic perfusion and to reduce aldosterone clearance through either a direct effect on hepatic vasculature
STEROIDS 51 / 1-2
January - February 1988
169
170
Prattet al
or secondarily by lowering cardiac output (13).
However.
specific measurements of the aldosterone MCR were not possible because of the overall frail physical condition of our subjects, and, in many instances, subjects were unable to give informed consent. In summary, individuals at a very advanced age did not show evidence of aldosterone deficiency despite a decrease in aldosterone production.
A significant reduction in the
aldosterone MCR appears to offset a decrease in aldosterone production.
NOTES AND REFERENCES This work was supported by the grant AGO5042-01 and by the Veterans Administration. Requests for reprints should be addressed to: J. Howard Pratt. M.D.. V.A. Medical Center. 1481 West 10th Street, Indianapolis, IN 46202. 1. 2. 3. 4. 5. 6. 7.
F1ood.C.. Gherondache. C., Pincus. G.. Tait. J-F.. Tait. (1960). S.A.S.. Willoughby. S.A., J. CLIN. INVEST. 2. Weidmann. P.. De Myttenaere-Bursztein. S.. Maxwell. M-H.. De Lima, J.. KIDNEY INT. 2. 329 (1975). Crane. M.G.. Harris, J.J.. J. LAB. CLIN. MED. 87. 947 (1976). Noth, R.H.. Lassman, M.N.. Tan. S.Y.. Frenandes-Cruz. Jr.. A-. Mulrow. P.J.. ARCH. INTERN. MED. 137. 1414 (1977). Tan, S.Y., Noth, R., Mulrow. P.J.. CLIN. CHEM. 2. 1531 (1978). Hegstad, R., Brown, R.D.. Jiang. N-S., Kao. P.. Weinshilboum, R.M., Strong. C.. Wisgerhof. J. AM. J. MED. 2, 442 (1983). Tsunoda. K., Abe, K.. Goto. T.. Yesujima. M.. Sata. Ma. Omata, K., Seino. M.. Yoshinaga. K.. J. CLIN. ENDOCRINOL. METAB.. 62. 384 (1986).
STEROIDS
51 / 1-2
January - February
1988
ALDOSTERONE
MEASUREMENTSIN
THE ELDERLY
Antunes, J.R.. Dale. S.L.. Malby. J.C.. STEROIDS 28. 621 (1976). 9. Wainberger, M.H., Ramsdell. Y.W., Rosner. D.R., Geddes. Y.Y.L.. AM. J. PHYSIOL. 223. 1049 (1972). 10. Wolfe, L.K., Gordon, R.D., Island, D.P.. Liddle, G.W., J. CLIN. ENDOCRINOL.2. 1261 (1966). 11. Wainberger. M.H.. Kexn. D.C., Gomez-Sanchez,C., Kramer. N.J., Martin, B.T.. Nugent. C.A., 3. LAB. CLIN. P%D. 85* 957 (1972). 12. Ladatta, E.G.. FED. PROC. 38, 163 (1979). 13. Pratt, J.H., Grim. C.E.. Parkinson, C.A.. J. LAB. CLIN. MED. 95, 693 (1980). 8.
STEROIDS
51 / l-2
January - February 1988
171