Testing, Diagnosing, and Treating Primary Aldosteronism: A Leading Cause of Hard-to-Treat Hypertension

Silas Culver, MD, is an adult endocrinologist and basic science researcher. As a clinician, he treats patients with general endocrine disorders, including diabetes, thyroid, adrenal, and bone disease. His research interests include obesity and its role in kidney disease, high blood pressure, and diabetes.

Hypertension is extremely common and has serious health implications.  High blood pressure affects as many as 1.39 billion adults worldwide and is estimated to lead to over 10 million deaths each year.(1)  While most of these individuals have primary hypertension, a term for hypertension not due to an underlying medical condition, a significant number of patients do have a secondary cause for their high blood pressure.  One such condition that often goes undiagnosed is an excess of the hormone aldosterone known as primary aldosteronism (PA).  Historically called Conn’s Syndrome, PA affects as many as 5-10% of all patients with hypertension and is a leading cause of hard to treat or “resistant” hypertension.(2)  High levels of aldosterone are also more harmful to the kidney and heart than primary hypertension alone.  In addition, PA is highly treatable, highlighting the importance of identifying patients with this condition.

What causes Primary Aldosteronism?

Aldosterone is produced in the adrenal glands, two hormone producing organs located just above the kidneys.  Aldosterone’s primary function is to signal the kidneys to retain sodium, which ordinarily helps support normal blood pressure.  Aldosterone production in healthy individuals is closely regulated by hormonal signals from the kidney.  However, groups of adrenal cells can escape this regulation and begin to make excess aldosterone, giving rise to PA.  These groups of cells often form benign tumors known as adrenal adenomas that can be seen on a CT scan or MRI.  However, some clusters of cells can also be too small to be seen with these scans.  Excess aldosterone production can involve just one adrenal gland or both.  Greater sodium retention in response to aldosterone leads the body to hold onto fluid, raising blood pressure, while also increasing the loss of potassium in the urine as the kidney exchanges sodium for potassium.  As a result, some affected individuals also develop low potassium levels although many patients maintain normal potassium. 

Who should be tested?

While it is reasonable to screen most patients with new hypertension for PA, there are certain groups of patients who especially warrant evaluation.  Specifically, patients who require multiple medications to control their blood pressure or who have uncontrolled hypertension despite multiple medications are at high risk for PA.  The same is true for patients with hypertension and a history of low potassium.  The rising number of patients obtaining CT scans and MRIs in recent years has also increased the incidental discovery of adrenal nodules.  While not all nodules make hormones, patients with both hypertension and an adrenal nodule should undergo evaluation for PA as well. There are also genetic forms of PA that can run in families, so individuals with a family history of PA who develop hypertension or suffer a stroke at an early age should be tested.

How is PA diagnosed?

Testing for PA is most often performed by doctors specializing in hormones, known as endocrinologists.  However, some kidney doctors (nephrologists), heart doctors (cardiologists), surgeons, and primary care doctors will also perform these tests.  Initial testing usually involves blood tests for levels of aldosterone as well as the kidney hormone that regulates aldosterone, known as renin.  Higher levels of aldosterone along with low renin suggest that aldosterone is being produced independently by the adrenal.  Some patients will also require further confirmatory testing to make the diagnosis of PA.  In these tests, the patient undergoes a procedure, such as increasing oral salt intake or injecting IV saline, that should normally reduce aldosterone production.  If aldosterone levels remain high during these tests, this indicates PA.  Once a diagnosis of PA is made, the physician may order an additional test known as adrenal venous sampling (AVS) to determine whether the increased aldosterone is coming from one or both adrenal glands.  During AVS, a catheter is used to sample blood coming from each of the adrenal glands so that the aldosterone levels can be measured and compared.

What is the treatment?

For patients with excess aldosterone production in just one adrenal gland, the preferred treatment is usually surgical removal of the involved gland, as this can cure the patient.  Medication can be used instead in patients who cannot or do not wish to have surgery, as well as individuals in whom both adrenal glands are making excess aldosterone.  These medications work by blocking the action of aldosterone in the kidney and other organs.  Successful treatment, whether by medication or surgery, improves blood pressure control, maintains normal potassium levels, and reduces risk for heart and kidney complications.

Conclusion

PA is an important and relatively frequent cause of hypertension that unfortunately goes unrecognized in many patients.  Fortunately, it is very treatable through surgery or medication.  Studies are ongoing at the University of Virginia and other medical centers across the country attempting to find both easier methods for identifying patients with PA and for determining which mode of therapy is best for each individual patient.  The hope is that improved awareness among patients and physicians combined with better diagnosis and treatment options will decrease the impact of this all-to-common condition.

1.          Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, Ramirez A, Schlaich M, Stergiou GS, Tomaszewski M, Wainford RD, Williams B, Schutte AE. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension 2020;75(6):1334–1357.

2.          Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WFJ. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2016;101(5):1889–1916