Primary Hyperaldosteronism: Returning to the Limelight?

About 40 years ago, when renin activities were first being measured, the prevalence of low-renin hypertension was found to be about 20%.1 Some wondered whether these low-renin patients had primary aldosteronism (PA), which would explain the low renin levels in the presence of relatively normal aldosterone excretion.1 In the intervening years, the often fruitless search for an adrenal tumor, the lessthan-impressive amounts of aldosterone secreted by many low-renin patients, the infrequency of hypokalemia, the cumbersome workup and the increasing availability of better-tolerated oral antihypertensives has reduced the enthusiasm to pursue a diagnosis of primary aldosterone excess. Over time, PA gradually assumed a modest place on the list of secondary causes of hypertension. The growing popularity of the aldosterone-renin ratio in recent years to evaluate drug-resistant hypertension has brought aldosterone excess back into more common consideration in hypertension management.2 A large, recent study has stimulated interest further by showing that PA is likely underdiagnosed and may turn out to be one of the more common causes of secondary hypertension.3 This study, authored by Rossi and colleagues3 from Italy, reported the prevalence of PA in newly diagnosed hypertensive patients referred to hypertension centers to be 4.8%. The most impressive aspect of this study is the thoroughness of the evaluation and of the pursuit of biochemical and imaging support for the diagnosis. This was a prospective study investigating the prevalence of PA in 1125 newly diagnosed hypertensive patients. Diagnostic protocol included measurement of serum sodium, potassium, 24-hour urine, sitting plasma renin activity, and aldosterone at baseline and after 50 mg of captopril. In patients with a aldosterone-renin ratio >40 at baseline and/or >30 after captopril and/or probability of PA ≥50% had imaging tests and adrenal vein sampling or adrenocortical scintigraphy to identify underlying adrenal pathology. Of those patients, 4.8% had an aldosterone-producing adenoma and 6.4% had idiopathic hyperaldosteronism. Spontaneous hypokalemia was found in 9.6% of patients overall; however, it was observed in about one half of patients with an aldosterone-producing adenoma but only in 17% of those with idiopathic hyperaldosteronism. This study demonstrates the benefits of testing for PA in a referred hypertensive population, as the prevalence is fairly high. This enables the physician to use therapy to directly treat this cause of hypertension with an aldosterone antagonist. We believe that there are 2 important lessons from this study. The first is that when a patient does not respond to therapy with a thiazide diuretic or a calcium channel blocker and a second agent like an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker, we would consider screening for PA with plasma renin activity and a serum aldosterone level before the patient reaches “drug-resistant” status (3 medications). The second lesson is that a normal serum potassium level should not completely remove a PA diagnosis from the table. If evidence of renin suppression and aldosterone excess are present, it can be worthwhile to evaluate the patient further with imaging to assess for the presence of an adrenal adenoma. We typically consider imaging in people who are willing to have it removed if found, who are relatively newly diagnosed, or who have an unremarkable family history. Other times, we consider imaging on a case-by-case basis. Like the other adrenal form of hypertension, pheochromocytoma, a good dose of clinical suspicion is the first step.