Medical therapy

Endocrine Society Reading Room | The limited efficacy of medical therapy in primary aldosteronism

Primary aldosteronism or primary hyperaldosteronism (PA) is the excessive production of aldosterone by the zona glomerulosa of the adrenal glands resulting in secondary hypertension. Although initially thought to be a rare cause of secondary hypertension with a prevalence of

PA syndrome can range from normotension with high aldosterone and low renin to resistant hypertension. The latter is more frequently detected because it sensitizes the search for low-renin hypertension. First-line therapeutic agents to treat this condition are mineralocorticoid receptor antagonists (MRAs) such as spironolactone and eplerenone or potassium-sparing diuretics such as amiloride.

Recent studies have shown that adrenalectomy may result in better outcomes and cardiovascular benefits than those obtained with pharmacological treatment alone. Surgical treatment is recommended for unilateral disease, but medical treatment remains the first line for bilateral disease.

Many previous studies have shown that pharmacological treatment in patients with PA leads to lower adherence to treatment due to secondary side effects (especially in men). A retrospective study by Tang et al., published in the Journal of the Endocrine Societyfocuses on the limited efficacy of pharmacological therapy of PA secondary to treatment side effects and the multiple limitations this implies on the cardiovascular health of patients.

The study methodology of 201 PA patients receiving medical treatment included as primary outcome the efficacy of medical treatment based on blood pressure control (BP 1 ng/ml/h) and serum potassium level (> 4.3 mmol/L with a median reference range of 3.5 to 5.0 mmol/L). Of the 155 patients who received long-term medical treatment, 59.2% achieved controlled blood pressure and 55.7% achieved normokalaemia.

One of the key aspects evaluated in this study was patient tolerance to medical treatment: 52.3% of patients experienced at least one side effect. Patients using spironolactone were more likely to experience side effects due to its anti-androgenic and gastrointestinal effects, which reduce treatment compliance. Other mineralocorticoid receptor antagonists, such as eplerenone, have been associated with a much lower rate of side effects; however, studies have shown that eplerenone is not as effective in treating PA because it is more expensive than spironolactone, requires double dosing, and is not FDA approved.

This study also reflects that the standard dosage for essential hypertension is not sufficient for patients with PA to achieve BP and biochemical control. Tolerated doses of medical therapy may not be adequate to ameliorate the cardiovascular effects caused by PA; therefore, affected patients require other interventions such as surgery (when possible), which leads to better blood pressure and biochemical control than pharmacological therapy.

Some of the limitations of the study include its retrospective design and moderate sample size, which may introduce some bias. Additionally, there was a difference in the algorithms used by clinicians to efficiently titrate drugs and continue to screen for BP and biochemical targets. Additionally, most of the patients in this study were taking spironolactone, so it cannot be compared effectively with other medications.

This study underscores the importance of educating clinicians about screening patients for PA, as many patients do not achieve their goals because they are not treated accordingly. Moreover, the need to subtype patients with PA will also benefit them if they receive adequate treatment. Furthermore, the study creates positive insight into the consideration of surgical therapy for patients with PA as a first-line treatment. Surgery has not only been proven to achieve goals, but ultimately reduces cardiovascular risk. The study concludes that new drugs in the research phase could change this paradigm.

Ricardo Villela, MD, works at the National University of Honduras and Ricardo Correa, MD, EdD, FACP, FACE, is Program Director, Endocrinology, Diabetes, and Metabolism at the University of Arizona at Phoenix and Phoenix Veterans Affairs Medical Center.

Read the study here and an interview with the lead author here.