Primary Aldosteronism and Mineralocorticoid Hypertension

1

What is the most common identifiable cause of resistant hypertension?

Resistant hypertension, defined as elevated blood pressure (BP) despite the concurrent use of three antihypertensive drug classes at maximum tolerated dose or controlled BP on four or more antihypertensive medications, affects approximately 15% of the hypertensive population. Primary aldosteronism (PA) is the most common secondary cause, accounting for up to 15% to 30% of the cases in a hypertension referral clinic setting. Even amongst the general hypertensive population, PA has a reported prevalence of 5% to 10%. PA is substantially under diagnosed due to lack of screening. One Italian study reported 992 diagnoses of PA during a 16-year period, corresponding to only 2% of the overall expected cases. Secondary analysis of the PATHWAY-2 study of resistant hypertension suggested that 25% of participants have previously undiagnosed aldosterone excess. The low detection rate is likely due to the lack of screening; only 7% of European primary care practitioners ever screened for PA using serum renin and aldosterone measurements and the rate of screening in the resistant hypertensive population was only 2% despite guidelines.

2

What patients should I evaluate for PA?

The Endocrine Society recommends screening for PA in patients with :

• Hypertension with BP greater than 150/100, resistant hypertension despite three agents, or controlled hypertension on four or more agents;

• Hypertension and spontaneous or diuretic-induced hypokalemia;

• Hypertension and adrenal incidentaloma;

• Hypertension and sleep apnea;

• Hypertension and a family history of early onset hypertension or cerebrovascular accident at a young age (younger than 40 years); or

• Hypertensive first-degree relatives of patients with PA.

Given the high prevalence of PA in both primary care and in referral centers, clinicians should have a low threshold to screen for PA. Several studies even found that PA was present in 3% to 6% of patients with newly diagnosed hypertension, suggesting that screening should be initiated before drug treatment or the development of resistant hypertension. A common misconception is that patients with PA present with hypertension at an early age. However, the average age of PA diagnosis is 50 to 60 years, so age alone should not be used to guide screening.

3

How often do patients with PA present without hypokalemia?

Only a minority of patients with PA (30%) present with hypokalemia; routine screening identifies even more patients with normokalemia. Thus most patients with PA are indistinguishable from patients with other forms of hypertension. Hypokalemia is more common in patients with aldosterone-producing adenoma than those with bilateral adrenal hyperplasia (affecting 50% and 20%, respectively).

4

What are the most common causes of PA?

The most common causes of PA are bilateral adrenal hyperplasia and unilateral aldosterone-producing adenoma, which account for 70% and 30% of cases, respectively. The most common form of familial hyperaldosteronism is glucocorticoid-remediable aldosteronism, although it accounts for only 1% of the overall PA cases. Sporadic mutations in the adenoma within a limited number of genes ( KCNJ5, CACNA1D, CACNA1H, ATP1A1, ATP1A3, and CTNNB1 ) are associated with the majority of aldosterone-producing adenomas, although genetic testing is not yet routinely performed.