Vol. 46, No. 4
Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Printed in U.SA.
Plasma Aldosterone Response to ACTH in Primary Aldosteronism and in Patients with Low Renin Hypertension* DAVID C. KEM.t MYRON H. WEINBERGER, JOHN R. HIGGINS, NORMAN J. KRAMER, CELSO GOMEZ-SANCHEZ, AND 0. BRYAN HOLLAND Departments of Medicine, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, Oklahoma 73190; and University of Texas Health Sciences Center, Dallas, Texas; and Indiana University School of Medicine, Indianapolis, Indiana ABSTRACT. ACTHa1'24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal adenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P < 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median
aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing. {J Clin Endocrinol Metab 46: 552, 1978)
T
HE ROLE OF aldosterone seems to be of primary importance in the genesis of hypertension in patients with hyperaldosteronism from adrenal adenomas or hyperplasia, but its importance in patients with essential hypertension is still unclear. Several investigators have reported that 20-40% of patients with essential hypertension have suppressed plasma renin activity and normal or subnormal levels of mineralocorticoids (1). Others (2, 3) have pointed out that although aldosterone production continues at normal or only slightly decreased levels in some low renin hypertensive patients, these levels should be considered inappropriately elevated in the
face of the subnormal plasma renin activity. These observations of "normal" aldosterone production in patients with low renin essential hypertension have suggested an abnormality in the traditionally accepted control of aldosterone production in such patients. Collins et al. (4), moreover, have reported that some patients with essential hypertension have an abnormal elevation of plasma aldosterone after upright posture and a diminished suppression of aldosterone secretion after oral salt loading. Grim (5) has therefore suggested that these patients may have a forme fruste, or intermediate form of primary (1°) aldosteronism. Since isolated measurements of aldosterone Received April 28, 1977. production have generally been normal in low * These studies were supported in part by grant-in-aids from the Oklahoma, Texas, and Indiana Heart Associa- renin hypertensive patients, measures must be tions, the H.E. and Carolyn Bailey Endocrine Research used which stimulate or suppress aldosterone Fund, and NIH Grants HL-10279, HL-14159, GCRC RR62, RR-00633, and RR-00750. Part of this work was ac- to determine if there is an inherent defect in complished while Dr. Kem was a recipient of the Ameri- its control. This has generally been performed can Heart Association John L. Dickson Memorial Award. through maneuvers to suppress the renin-anf Address reprints to: David C. Kem, M.D., University of Oklahoma Health Sciences Center, P.O. Box 26901, giotensin system and thereby decrease endogenous aldosterone production after intraveOklahoma City, Oklahoma 73190. 552
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 04:03 For personal use only. No other uses without permission. . All rights reserved.
553
ALDOSTERONE RESPONSE TO ACTH nous or oral salt loads (2, 6) or after administration of other salt retaining steroids (7, 8). In general, these studies have shown some differences in suppression of aldosterone production but to a degree that remains unconvincing to many investigators in the field. We have reported preliminary data suggesting that patients with primary aldosteronism are hyperresponsive to ACTH compared with normal subjects on a regular salt intake (9, 10). This suggested an alternative to the traditional method of identifying patients with 1° aldosteronism by suppression of the renin angiotensin system after volume overload. Such an approach also might permit detection of abnormalities of aldosterone production in patients with low renin essential hypertension similar to that in patients with primary aldosteronism. We have, therefore, examined additional patients with hyperaldosteronism from an adrenal adenoma or hyperplasia for comparison with patients with normal and low renin essential hypertension.
Materials and Methods A total of 37 patients with hypertension were studied. Nineteen patients had primary aldosteronism characterized by the presence of hypertension, hypokalemia, elevated plasma concentrations of aldosterone which failed to suppress after recumbency and infusion of 2 liters of isotonic saline, and low plasma renin activity unresponsive to stimulation by upright posture, low sodium diet, or after acute diuretic depletion. This group was subsequently divided into those with diffusely hyperplastic adrenal glands (n = 11) and those with a unilateral adrenocortical adenoma or adenomas (n = 8) on the basis of pathological examination after resection of the gland or from information gained by adrenal venography and measurement of adrenal effluent for aldosterone and cortisol. Twelve patients with normal plasma aldosterone concentrations and suppressed plasma renin activity after furosemide stimulation and upright posture (11) were classified as low renin hypertensives. Six other patients with normal renin responsiveness comprised a control for the low renin hypertensives. Normotensive control data have previously been published (12). The patients with primary aldosteronism were eating a regular hospital diet containing approximately 130 mEq sodium and 60-80 mEq potassium. When potassium supplements had been
taken before testing, they were discontinued 1 week before study except in 2 patients with serum values
CO
t> CO
r-> ©
t> CD OS CM 00 © CM
CM CM
CO
o CD
cd m
oo
O
co
14-20
S
|
o o m
6.7
m
4-23
8
CO
^-i
co co
© CM CM !"H CM •—1 ©
I ©
co
00
S
CM CM
J>
Oi i-H rH
6.8
CO
in
t> CM
5.8-50
g/dl)
8
t> CO
m
CM CO
s
CD
I-H
(N CD CO i-H
•*"
CM
8-54
co
CM
oo
4.1-50
200 •«fr
CD CO O CD 00 CD CM
6-4
00
in
CM CM
o
Journal of Clinical Endocrinology and Metabolism Copyright © 1978 by The Endocrine Society
Printed in U.SA.
Plasma Aldosterone Response to ACTH in Primary Aldosteronism and in Patients with Low Renin Hypertension* DAVID C. KEM.t MYRON H. WEINBERGER, JOHN R. HIGGINS, NORMAN J. KRAMER, CELSO GOMEZ-SANCHEZ, AND 0. BRYAN HOLLAND Departments of Medicine, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, Oklahoma 73190; and University of Texas Health Sciences Center, Dallas, Texas; and Indiana University School of Medicine, Indianapolis, Indiana ABSTRACT. ACTHa1'24 was infused at incremental rates of 12.5-200 mIU/30 min in dexamethasone-suppressed hypertensive patients on a regular sodium diet. The plasma aldosterone response to this stimulus in 8 patients with hyperaldosteronism due to an adrenal adenoma and 11 with adrenal hyperplasia was significantly greater at all infusion rates (P < 0.05) when compared with the response in 6 normal subjects on a similar diet. This responsiveness to ACTH in the patients with primary hyperaldosteronism was similar to that of the normal subjects on a low sodium diet. Twelve patients with low renin and 6 patients with normal renin essential hypertension were similarly studied. There was no significant difference in the median
aldosterone response between these 2 groups and the normal subjects on a normal diet, but the response was significantly lower compared with that in patients with primary hyperaldosteronism. These data show that patients with hyperaldosteronism from an adrenal adenoma or hyperplasia have a consistent and exaggerated response to ACTH. The hyper-responsiveness is not apparently shared by the majority of patients with low renin essential hypertension and does not support the concept that this group is an intermediate form of primary aldosteronism. Individual patients within this group, however, may have such a response and might be identified by this type of testing. {J Clin Endocrinol Metab 46: 552, 1978)
T
HE ROLE OF aldosterone seems to be of primary importance in the genesis of hypertension in patients with hyperaldosteronism from adrenal adenomas or hyperplasia, but its importance in patients with essential hypertension is still unclear. Several investigators have reported that 20-40% of patients with essential hypertension have suppressed plasma renin activity and normal or subnormal levels of mineralocorticoids (1). Others (2, 3) have pointed out that although aldosterone production continues at normal or only slightly decreased levels in some low renin hypertensive patients, these levels should be considered inappropriately elevated in the
face of the subnormal plasma renin activity. These observations of "normal" aldosterone production in patients with low renin essential hypertension have suggested an abnormality in the traditionally accepted control of aldosterone production in such patients. Collins et al. (4), moreover, have reported that some patients with essential hypertension have an abnormal elevation of plasma aldosterone after upright posture and a diminished suppression of aldosterone secretion after oral salt loading. Grim (5) has therefore suggested that these patients may have a forme fruste, or intermediate form of primary (1°) aldosteronism. Since isolated measurements of aldosterone Received April 28, 1977. production have generally been normal in low * These studies were supported in part by grant-in-aids from the Oklahoma, Texas, and Indiana Heart Associa- renin hypertensive patients, measures must be tions, the H.E. and Carolyn Bailey Endocrine Research used which stimulate or suppress aldosterone Fund, and NIH Grants HL-10279, HL-14159, GCRC RR62, RR-00633, and RR-00750. Part of this work was ac- to determine if there is an inherent defect in complished while Dr. Kem was a recipient of the Ameri- its control. This has generally been performed can Heart Association John L. Dickson Memorial Award. through maneuvers to suppress the renin-anf Address reprints to: David C. Kem, M.D., University of Oklahoma Health Sciences Center, P.O. Box 26901, giotensin system and thereby decrease endogenous aldosterone production after intraveOklahoma City, Oklahoma 73190. 552
The Endocrine Society. Downloaded from press.endocrine.org by [${individualUser.displayName}] on 19 November 2015. at 04:03 For personal use only. No other uses without permission. . All rights reserved.
553
ALDOSTERONE RESPONSE TO ACTH nous or oral salt loads (2, 6) or after administration of other salt retaining steroids (7, 8). In general, these studies have shown some differences in suppression of aldosterone production but to a degree that remains unconvincing to many investigators in the field. We have reported preliminary data suggesting that patients with primary aldosteronism are hyperresponsive to ACTH compared with normal subjects on a regular salt intake (9, 10). This suggested an alternative to the traditional method of identifying patients with 1° aldosteronism by suppression of the renin angiotensin system after volume overload. Such an approach also might permit detection of abnormalities of aldosterone production in patients with low renin essential hypertension similar to that in patients with primary aldosteronism. We have, therefore, examined additional patients with hyperaldosteronism from an adrenal adenoma or hyperplasia for comparison with patients with normal and low renin essential hypertension.
Materials and Methods A total of 37 patients with hypertension were studied. Nineteen patients had primary aldosteronism characterized by the presence of hypertension, hypokalemia, elevated plasma concentrations of aldosterone which failed to suppress after recumbency and infusion of 2 liters of isotonic saline, and low plasma renin activity unresponsive to stimulation by upright posture, low sodium diet, or after acute diuretic depletion. This group was subsequently divided into those with diffusely hyperplastic adrenal glands (n = 11) and those with a unilateral adrenocortical adenoma or adenomas (n = 8) on the basis of pathological examination after resection of the gland or from information gained by adrenal venography and measurement of adrenal effluent for aldosterone and cortisol. Twelve patients with normal plasma aldosterone concentrations and suppressed plasma renin activity after furosemide stimulation and upright posture (11) were classified as low renin hypertensives. Six other patients with normal renin responsiveness comprised a control for the low renin hypertensives. Normotensive control data have previously been published (12). The patients with primary aldosteronism were eating a regular hospital diet containing approximately 130 mEq sodium and 60-80 mEq potassium. When potassium supplements had been
taken before testing, they were discontinued 1 week before study except in 2 patients with serum values
CO
t> CO
r-> ©
t> CD OS CM 00 © CM
CM CM
CO
o CD
cd m
oo
O
co
14-20
S
|
o o m
6.7
m
4-23
8
CO
^-i
co co
© CM CM !"H CM •—1 ©
I ©
co
00
S
CM CM
J>
Oi i-H rH
6.8
CO
in
t> CM
5.8-50
g/dl)
8
t> CO
m
CM CO
s
CD
I-H
(N CD CO i-H
•*"
CM
8-54
co
CM
oo
4.1-50
200 •«fr
CD CO O CD 00 CD CM
6-4
00
in
CM CM
o
