Primary Aldosteronism in Diabetic Subjects With Resistant Hypertension

Response to Ng et al.

We reported that hypertension affects nearly 70% of patients with type 2 diabetes at our institution and that 45% of them require three or more antihypertensive agents (1). Despite the multidrug approach, one-third of patients do not achieve the recommended blood pressure goal of <130/80 mmHg. These findings led us to investigate the prevalence of primary hyperaldosteronism (PHA), the most common cause of endocrine hypertension, in diabetic patients with resistant hypertension. We found that 14% of diabetic patients with resistant hypertension had biochemical evidence of PHA. Thus, select patients with diabetes should be screened for PHA, and this in turn may lead to improvement in cardiovascular outcomes.

We acknowledge the viewpoints of Ng et al. (2), and we agree that it would be of great therapeutic relevance to know whether there are long-term differences between subjects with essential hypertension and those with PHA as it relates to cardiovascular injury and mortality. More than 80% of patients with type 2 diabetes have features of metabolic syndrome, and 40–70% of patients with surgically treated aldosterone-producing adenomas have long-term hypertension (3). Thus, we hypothesize that the early diagnosis and treatment of PHA in diabetic patients with resistant hypertension may afford them even better cardiovascular outcomes.

As Ng et al. outlined, we also agree that further investigations should be done related to screening and diagnosis of PHA in patients with type 2 diabetes. There are currently no studies to guide appropriate cutoff values for plasma aldosterone (PAC) or plasma renin activity for screening patients with diabetes or obesity. Similarly, there is no uniform acceptance of a best test to confirm diagnosis of PAH. The screening PAC–to–plasma renin activity ratio cutoff of >30 ng · ml⁻¹ · h⁻¹ and post–sodium load PAC cutoff of ≥5.0 ng/dl were arbitrarily selected from previously published diagnostic ranges noted in the general population (4,5).

Historically, most cases of PHA have been attributed to unilateral aldosterone-producing adenomas; however, we now know that the majority of PHA cases are most likely attributable to bilateral adrenal hyperplasia (5,6). Medical management with aldosterone antagonists is the treatment of choice for patients with bilateral adrenal hyperplasia. Independent of the antihypertensive effects, aldosterone blockade has been shown to improve potassium balance and decrease mortality in heart failure cases (7). Two-thirds of our study cohort had bilateral disease, and we are currently evaluating response to medical management as it relates to long-term renal and cardiovascular outcomes.

In conclusion, PAH is common in diabetic patients with resistant hypertension. Our study indicates that diabetic subjects with poorly controlled hypertension on three or more antihypertensive drugs should be screened for aldosteronism. Research is needed to better establish optimal diagnostic cutoffs and the true prevalence of PAH in patients with and without diabetes.