Should primary aldosteronism be diagnosed among normotensive subjects during general health check-up and/or at general outpatient clinics?

The accepted prevalence worldwide of primary aldosteronism (PA) in unselected patients with hypertension was considered to be low in the past, perhaps about 2% or even <1%.¹ However, there have recently been reports suggesting higher values suggesting a prevalence of up to 10–15% among patients with hypertension.^{2, 3} Nevertheless, there have always been wide variations in the reported prevalence of hyperaldosteronism. When Conn first described the syndrome, he estimated that about 20% of hypertensives would have an adrenal adenoma,⁴ whereas most experts previously described PA in <1% of patients with mild-to-moderate essential hypertension and had assumed hypokalemia was only a selective marker for differentiating PA among hypertensives.^{5, 6, 7, 8, 9, 10, 11} Recent cross-sectional studies reported PA in >10% of hypertensive patients, in both general and specialty settings.^{12, 13, 14, 15, 16, 17, 18}

Moreover, the results of recent screening of hypertensive patients in Japan using the simultaneous measurements of the plasma aldosterone concentration (PAC) and plasma renin activity (PRA) or the aldosterone–renin ratio (ARR) have shown that PA is observed in 3.3–10% of hypertensive patients and is the most frequent cause of secondary hypertension.^{19, 20, 21, 22, 23} However, the prevalence of this disease among normotensive and mildly hypertensive patients has not yet been estimated.

In this issue, Ito et al.²⁴ provides data showing that the prevalence of PA as could be assessed in his study was at least 6.8% in prehypertensive patients, 3.3% in stage 1 hypertensive patients, and 3.1% in stage 2 hypertensive patients. They screened a total of 292 adult subjects with hypertension or prehypertension based on a PAC (ng per 100ml) to PRA (ng ml⁻¹ hr⁻¹) ratio (ARR) above 20 and confirmed by captopril suppression test. Ito's study suggests a high prevalence of PA among prehypertensive and stage 1 hypertensive Japanese patients.²⁴ They concluded that significant numbers of prehypertensive individuals may have subclinical forms of this disease.

There have been several case reports, describing PA without hypertension,^{25, 26, 27, 28, 29, 30, 31} although the reason for the absence of hypertension has not been clarified in any of the cases of normotensive PA reported. It is suggested that a short duration of hyperaldosteronemia could explain normotension in those patients. Thus, it is recommended that we should note the presence of normotensive PA at the general health check-up or general outpatient clinics, in order to prevent cardiovascular events, induced by hyperaldosteronemia, which may easily occur in the near future. It is well known that PA is a disease caused by autonomic hypersecretion of aldosterone because of the adrenocortical lesions, associated with increased urinary potassium excretion, and organ disorders (cerebral hemorrhage, cerebral infarction, myocardial infarction, cardiomegaly, arrhythmia, renal insufficiency and so on.) due to excessive aldosterone.^{32, 33, 34} When the patient with normotensive PA can physically tolerate and wishes to undergo surgical treatment, determination of whether aldosterone hypersecretion is bilateral or unilateral, and, if unilateral, which adrenal gland is responsible by adrenal venous sampling (AVS), is also necessary, like as the cases with hypertensive PA.^{35, 36, 37} Thus, it is suggested that we need to enthusiastically treat normotensive PA after detecting the laterality of adrenal lesions by AVS, although we should statistically analyze whether or not surgical treatment for the subclinical form of PA, such as nermotensive PA induces better prognosis for long periods of life.

In conclusion, it is suggested from the data presented by Ito et al.²⁴ that the prevalence of PA is at least 6.8% in prehypertensive patients. Thus, prehypertensive individuals should be screened for the subclinical form of PA in order initiate early diagnosis and treatment to prevent future risks.