Norman M Kaplan's1
cautions over an epidemic of primary aldosteronism refer to the role of ARR ratios as diagnostic criteria for primary aldosteronism; the possible selection bias; and the difficulty to accept that most of these new hyperaldosteronism cases are normokalaemic.
As in all endocrine physiological axis assessment, the diagnostic criteria for primary aldosteronism need a two-stage process: screening test and confirmatory test. At present, the plasma ARR activity ratio is recognised as a reliable screening tool for diagnosis of primary aldosteronism.1—5
The current accumulated experience shows that ARR value higher than 25 suggests a pathological disorder (given the low limit for plasma renin in 0·3 ng mL−1
and aldosterone is expressed as ng/dL).1—5
We agree with Kaplan that this measurement is the logical initial test. However, the hallmark to confirm an autonomous aldosterone pathological production still remains the response to manoeuvres that normally suppress the axis. The diagnosis of autonomous aldosterone production can be confirmed by oral sodium loading, acute intravenous volume expansion with isotonic saline, captopril test, or the fludrocortisone suppression test.
We communicated the prevalence of primary aldosteronism in unselected essential hypertensives by use of an ARR activity ratio as the screening test and following a strict confirmatory fludrocortisone suppression test during an oral sodium loading.2
44 of 305 patients had this ratio higher than 25, and in 29 (10%) we confirmed the diagnoses. All patients with primary aldosteronism had aldosterone concentrations higher than 9 ng/dL; at lower concentrations the confirmatory test was always negative, independent of the ratio value. We noted only one adrenal nodule and five bilateral adrenal enlargements. All of our patients responded to aldosterone antagonist.
Three other studies have been done in the past year with similar protocols. Those and our study grouped 2140 unselected hypertensive patients from different populations, and showed a prevalence of primary aldosteronism close to 7% (range 4·6—9·5).2—5
Idiopathic hyperaldosteronism was also more frequent than unilateral adenoma and the rate of hypokalaemia was low.
The main drawback of study is the difficulty in determining the gold standard diagnostic criteria. A major problem in assessment of the renin-angiotensin-aldosterone system is that, although patients with aldosterone-producing adenoma have autonomous aldosterone production, those with bilateral hyperplasia may retain some feedback suppression; the disorder could be missed if a strict suppression test is used.
These data suggest that we probably need to redefine the concept of primary aldosteronism. We postulate that primary aldosteronism is a continuous pathological disorder in which a high ARR value represents an abnormal regulation of the renin-angiotensin-aldosterone system.