Screening for primary aldosteronism

Traditionally, a diagnosis of primary hyperaldosteronism is considered when a patient has hypokalemia, either spontaneous or caused by a diuretic. Patients with a low serum potassium level, low plasma renin activity, and a high plasma aldosterone level are likely to have primary aldosteronism. Of course, many patients with primary aldosteronism do not have all 3 components of this triad. The renin can be normal, particularly in patients with renal damage from uncontrolled hypertension; the aldosterone level can be normal because hypokalemia suppresses its secretion; and normokalemic hyperaldosteronism is increasingly recognized.

aldosterone-producing adenoma

idiopathic hyperaldosteronism

There are 2 major categories of primary aldosteronism: , characterized by unilateral secretion from an adrenal adenoma, and , characterized by bilateral secretion, usually from bilateral nodular hyperplasia. The diagnosis of aldosterone-producing adenoma is made with greater certainty because such abnormalities as asymmetry of adrenal vein aldosterone secretion, radiologic findings, and/or surgical pathology can be documented.

In contrast, idiopathic hyperaldosteronism is difficult to differentiate from the much more common low-renin essential hypertension. Rossi and colleagues hinge this distinction on the aldosterone/renin ratio (ARR). However, the ARR is a screening test, not a diagnostic test; reliance on the ARR alone will result in overdiagnosis of idiopathic hyperaldosteronism.¹ This might explain why Rossi and colleagues found 84% of subjects with idiopathic hyperaldosteronism to be normokalemic.

A high ARR is most likely indicative of idiopathic hyperaldosteronism in patients in whom clinical suspicion is enhanced by hypokalemia, severe or resistant hypertension, or radiologically evident nodular hyperplasia. The failure of salt loading to suppress aldosterone secretion also serves to confirm aldosterone hypersecretion. However, in normokalemic individuals, particularly in those with mild hypertension and minimally elevated or normal aldosterone levels, most patients with an elevated ARR probably have low-renin essential hypertension, not idiopathic hyperaldosteronism.

Several factors strengthen the case against relying on an arbitrary cutoff value for the ARR. First, some patients with a low renin level have a high ARR, even if the aldosterone level is normal. Second, fluctuations in aldosterone secretion and variability of the assay often affect the ratio. Third, the ARR can be misleading if the patient is taking antihypertensive drugs other than a calcium channel blocker and an alpha blocker, or both.

These limitations offer strong support for either a confirmatory test, such as salt loading, or perhaps more importantly, for integrating the ARR value with the clinical characteristics of the patient. Thus, in a patient with severe or refractory hypertension and unprovoked hypokalemia, a high ARR is virtually diagnostic, even without confirmatory testing. In a patient with spontaneous hypokalemia, an ARR slightly below the cutoff value should not be considered normal. In contrast, a normokalemic patient with mild hypertension who has an elevated ARR with minimal or no elevation of the aldosterone level is much more likely to have low-renin essential hypertension.

Because primary aldosteronism is more prevalent than was thought, particularly among patients with severe or refractory hypertension, it makes sense to use the ARR to screen more widely for primary aldosteronism, even in normokalemic patients.² However, to avoid overdiagnosis, if the clinical index of suspicion is low and the patient is normokalemic, a confirmatory test, such as salt loading, is indicated before assuming a diagnosis of primary aldosteronism.