J. A. Haley Veterans Hospital Tampa, Florida 33612
Address correspondence to: Arunabha Ganguly, M.D., J. A. Haley Veterans Hospital, Research Service (151), Building 2, Room 208, 13000 Bruce B. Downs Boulevard, Tampa, Florida 33612.
To the editor:
The paper by Phillips et al. (1) in the December 2000 issue of JCEM describes the use of various tests including bedside testing in the evaluation of patients with primary aldosteronism. Among the tests used were the postural plasma aldosterone test and plasma 18-hydroxycorticosterone level, which have been previously reported to be useful in clinically differentiating between an aldosteronoma and bilateral adrenal hyperplasia. While the paradoxical fall in plasma aldosterone level in the presence of an aldosteronoma generally had been seen in the majority of patients with this entity in previous studies, surprisingly, it was observed only in a minority in this study. It has been evident increasingly that a subpopulation of aldosteronoma patients are responsive to angiotensin II by showing a rise in plasma aldosterone on assumption of erect posture (a normal response) from the supine position instead of a characteristic fall (seen in aldosteronoma). This group of patients apparently also does not produce (2) an excessive amount of 18-hydroxycortisol and 18-oxocortisol (two newly identified steroids), unlike the ACTH-responsive group does, and this and other findings have raised the possibility of different cellular origin of aldosteronomas (3). But, the normal postural aldosterone response in some patients with aldosteronoma is not always due to angiotensin II responsiveness, and most studies have not addressed this issue. In a significant proportion of such patients, the rise of plasma aldosterone during their postural response is attributable to coincidental or stress-related (due to venepuncture) increase in plasma cortisol levels (as probably was measured in this study, but not in many other studies reported). The authors of this report suggest that they may have had a large number of angiotensin II-responsive aldosteronoma patients included in their study. This is a possibility.
There could be other explanations, too. The original study (4), describing the value of postural response in patients with primary aldosteronism, had blood samplings taken 4 h apart (0800 h and 1200 h). The timing of the test is also crucial because the biggest difference related to ACTH is likely to be seen during such time points. The authors in this study have carried out the tests with blood sampling only 2 h apart (they have not given the time of samplings). The other possible confounding variable is the time frame of withdrawal of medications for these patients before the study. The effect of some medications such as spironlactone can linger a while causing some problem. The authors also have not described the assays used for the measurements of the steroids. Many investigators are now using direct assays with commercial kits (without separation or purification of the steroids). Although the kits are quite reasonable for clinical use, they may not be wholly suitable for investigative studies. I have some reservations about the commercial kits and the precision of the levels of plasma steroids measured with them. Nonspecific binding in individual plasma samples is quite unpredictable. In the earlier studies dealing with these tests, plasma steroids were measured by highly specific steroid assays (using a purification step) developed in research laboratories. Measurements of plasma steroids these days have become much more casual in many academic medical centers.
Incidentalomas can pose problems in the differentiation between aldosteronoma and bilateral hyperplasia. Although this investigative group is very experienced in the diagnosis of aldosteronism, in this paper, the authors do not describe the criteria of biochemical diagnosis they have used. Pathology or computed tomography scanning of their patients with aldosteronoma suggest that some of the patients with adenoma had either abnormality in their computed tomography scan of bilateral disease or nonclassical pathological findings (e.g. more than one adenoma). Unilateral adrenal hyperplasia can potentially be another confounding variable in the differentiation (5). Thus, it is likely that these patients studied do not represent the classic patients with aldosteronomas and may be different from them, as the authors do suggest. Finally, the blood pressure response to surgery and postoperative studies of renin-aldosterone could further help to corroborate the diagnosis of these patients, although they have not been reported.
Received February 26, 2001.
References
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