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Apollo Hospitals, and Apollo Medical College, Hyderabad, IndiaMacquarie University, Medical School, Sydney, NSW AustraliaUniversity of Texas Southwestern Medical School, Dallas, TX, USA
Although most hypertensive patients have “primary” hypertension, 5–10% have “secondary” hypertension, which has an identifiable underlying cause. Unlike primary hypertension, secondary hypertension can be managed rationally by reversing its causative mechanism(s).
A not-so-uncommon cause of secondary hypertension is primary aldosteronism, which can be treated easily by offsetting the aldosterone excess. Primary aldosteronism affects about 5% of patients with hypertension and >10% of those with resistant hypertension, making it an important cause of reversible hypertension.
Notably, primary aldosteronism is associated with serious complications, extensive cerebro-cardiovascular disease, severe target organ damage beyond the degree of hypertension, and sudden death. Patients with primary aldosteronism experience direct cardiotoxic effects of both hypertension and aldosterone, increasing the risk for complications and worsening their prognosis.
Thus, the diagnosis of primary aldosteronism is critical. However, numerous estimates suggest that primary aldosteronism remains largely underdiagnosed at present.
The earliest biochemical aberration triggered by primary aldosteronism is spontaneous hypokalemia, which should be its first warning sign. Although primary aldosteronism diagnosis rests on demonstrating aldosterone overproduction, hypokalemia is its best initial indicator. The sequential examination for primary aldosteronism begins with the finding of hypokalemia, a simple test. Although “normokalemic” and “normotensive” primary aldosteronism exist, most patients eventually develop hypokalemia and hypertension.
The ACC/AHA guidelines recommend screening for primary aldosteronism in adults with resistant hypertension or hypokalemia.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
However, Hundemer and colleagues recently reported depressingly low rates of screening for aldosterone excess (1.6%) in hypertensive patients with hypokalemia.
Even when hypokalemia was noted on more than five occasions, only 4.8% of patients were screened for primary aldosteronism. A formidable number of patients with hypokalemia and a potentially curable form of hypertension slipped through the cracks!
In my experience, even when patients with suspected primary aldosteronism are referred to specialists, the reason is often “resistant” hypertension, not hypokalemia. This inertia to take hypokalemia seriously and the gross inattention to hypokalemia in clinical practice, despite clear clinical guidelines, is a disgrace to the healthcare system. Hence, medical professionals globally must attach importance to (low) potassium levels in patients with hypertension and take hypokalemia more seriously, so that primary aldosteronism — a curable form of hypertension with potentially deadly ramifications — is not missed.
Although specialty care has a downstream role, the causes of secondary hypertension — including primary aldosteronism — should first be suspected at the point-of-care level. Unexplained hypokalemia (of any degree) should trigger further work-up, beginning with the aldosterone-to-renin ratio (ARR) and simple biochemical tests. A simple screen through ARR can confirm a biochemical diagnosis of primary aldosteronism. Subsequently, radiological imaging can be performed to identify unilateral or bilateral adrenal pathology.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
Nothing is more expensive eventually than a missed opportunity to cure a serious and reversible disease (although this does not justify needless diagnostic tests). In my opinion, a one-time test such as ARR can indicate curable hypertension and is cost-effective. While recommending ARR as part of the initial battery of tests for hypertension is debatable, obtaining ARR values in primary care for hypertensive patients with unexplained hypokalemia is justified.
The larger question is, how do we unify guideline recommendations and practice patterns? I believe that primary aldosteronism should be suspected at the community practice level, and ARR should be recommended for patients with spontaneous or unexplained hypokalemia in the primary care setting. Hence, the guidelines offered by specialty organizations could be more useful if offered directly for primary care physicians.
Perhaps it is time to consider downgrading primary aldosteronism from a rare categorical disease to a common syndrome. The management of primary aldosteronism evolves through multiple phases (Figure 1). The first step in this journey is attention to hypokalemia. Looking the other way borders on negligence, if not malpractice. Physician, heal thyself!
Figure 1Phases in the management of primary aldosteronism
Acknowledgement: The author thanks Ms. Madhavi Latha Nagaraj for secretarial assistance and Ms. Nicola Ryan and Ms. Zeba Khatri for their editorial help, corrections, and references verification in assembling this commentary.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
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