Department of Endocrinology Faculty of Medicine Pontificia Universidad Católica de Chile Santiago, Chile
Address correspondence to: Carlos E. Fardella, M.D., Department Endocrinology, Faculty of Medicine, P. Universidad Católica de Chile, Marcoleta 391, Santiago, Chile. E-mail: cfardella{at}med.puc.cl
To the editor:
The prevalence of primary aldosteronism (PA) has been estimated in unselected patients with hypertension in less than 1% when the hypokalemia is used as screening. However, recent studies have demonstrated that PA may not be uncommon when determinations of serum aldosterone (SA), PRA, and the SA/PRA ratio are used in the screening and the fludrocortisone, saline infusion, or the captopril tests are used to confirm the diagnosis.
In our work, we studied 305 unselected "essential" hypertensive
subjects using the screening procedure previously mentioned and the
fludrocortisone test to confirm the diagnosis (1). We
found 29 patients with PA and a prevalence of 9.5%, which is very
similar to those reported by Lim et al. (9.2%) and Gordon
et al. (8.5%) in different populations (2, 3).
In the present millennium, other works have been published; three of
them were performed with a similar diagnostic approach as the one used
in our study (3, 4, 5). These studies (including our work)
grouped 2140 unselected hypertensive subjects giving a total prevalence
of PA close to 7% (range, 4.69.5). However, because not all subjects
who screened positive underwent confirmatory studies, the prevalence of
PA could be higher, probably close to 8% of all cases. These studies
also found a higher frequency of idiopathic hyperaldosteronism (IHA)
than the one traditionally described, being even higher or at least
equal than those communicated for aldosteronoma. The hypokalemia was
uncommon (16%) and probably reflects the most severe form of the
disease (Table 1). In our study, we did
not find patients with hypokalemia, probably because we only included
unselected "essential" hypertensive subjects, in which a normal
potassium level is currently required before to be named essential.
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In the present, the molecular elucidation of the genetic bases of PA should be one of the most important contributions for the diagnosis of this disease. In this sense, the identification of the genetic form of glucocorticoid-remediable aldosteronism (GRA), also called familial hyperaldosteronism type I, had provided useful information for the diagnosis and treatment of affected patients. Moreover, a novel genetic locus has been recently described for a familial form of hyperaldosteronism that is not glucocorticoid-remediable, named familial hyperaldosteronism type II. This disease is currently presented as an adrenocortical hyperplasia or aldosteronoma or both and is frequently transmitted as an autosomal dominant disorder (7). Thus, it is highly probable that in the near future, the genetic test may be the gold standard tool for the correct diagnosis of some forms of PA.
In relation to the positive dexamethasone suppression test (DST) seen in some of our patients without the classical genetic for GRA, we speculate several explanations. First, we attributed it to mishandling when carrying out the test. However, Mulatero et al. (8) found a similar high frequency of false positives, even using a lower cut-off (2 ng/dl) for the aldosterone levels. We also studied whether a more prolonged DST could affect the aldosterone response performing a 5-day test that did not show differences with the shorter 2-day suppression test previously communicated (1). Moreover, we evaluated the commercial kit from Diagnostic Products Corp. (DPC; Los Angeles, CA) to measure SA concentration with an "in house" method previously described in our laboratory, and we did not find differences between both methods. The in house method is a traditional RIA, where the samples are extracted with dichloromethane and use aldosterone labeled with tritium as a tracer. This RIA was also validated for serum and urine samples with commercial controls from DPC and from the College of American Pathology, respectively. Finally, we evaluated whether other genetic alterations could exist in CYP11B genes to explain a positive DST and determine another genetic cause of GRA; the results of this work were recently submitted for publication.
We agree with Dr. Ganguly that a "gray zone" exists between patients with low renin essential hypertension and mild forms of PA. Probably, separating both entities will be easier in the future with the development of more sophisticated molecular genetic studies and more reliable and specific biochemical determinations (i.e. 18-hydroxicortisol). However, today the key issue should be the response to treatment with a specific aldosterone antagonist (i.e. spironolactone). It is our experience and the others that the treatment with a low dose of spironolactone monotherapy is enough to normalize the blood pressure or significantly to reduce the use of other antihypertensives agents in these patients (3).
Received May 15, 2001.
References