Elsevier

The Lancet

Volume 371, Issue 9628, 7–13 June 2008, Pages 1921-1926
The Lancet

Articles
Prevalence of primary hyperaldosteronism in resistant hypertension: a retrospective observational study

https://doi.org/10.1016/S0140-6736(08)60834-XGet rights and content

Summary

Background

Results of several studies published since 1999 suggest that primary hyperaldosteronism (also known as Conn's syndrome) affects more than 10% of people with hypertension; however, such a high prevalence has also been disputed. Experts generally agree that resistant hypertension has the highest prevalence of primary hyperaldosteronism, on the basis of small studies. We aimed to assess the prevalence of primary hyperaldosteronism in a large group of patients with resistant hypertension.

Methods

Patients with resistant hypertension (blood pressure >140/90 mm Hg despite a three drug regimen, including a diuretic) who attended our outpatient clinic were assessed for primary hyperaldosteronism. Serum aldosterone and plasma renin activity were determined and their ratio was calculated. Patients with a positive test (ratio >65·16 and aldosterone concentrations >416 pmol/L) underwent salt suppression tests with intravenous saline and fludrocortisone. Diagnosis of primary hyperaldosteronism was further confirmed by the response to treatment with spironolactone.

Findings

Over 20 years, we studied 1616 patients with resistant hypertension. 338 patients (20·9%) had a ratio of more than 65·16 and aldosterone concentrations of more than 416 pmol/L. On the basis of salt suppression tests, 182 (11·3%) patients had primary hyperaldosteronism, and response to spironolactone treatment further confirmed this diagnosis. Hypokalaemia was seen only in 83 patients with primary hyperaldosteronism (45·6%).

Interpretation

Although the prevalence of primary hyperaldosteronism in patients with resistant hypertension was high, it was substantially lower than previously reported. On the basis of this finding, we could assume that the prevalence of primary hyperaldosteronism in the general unselected hypertensive population is much lower than currently reported. Thus, the notion of an epidemic of primary hyperaldosteronism is not supported.

Funding

None.

Introduction

In the decades after Jerome Conn's initial description of the condition,1 the prevalence of primary hyperaldosteronism—increased aldosterone secretion from the adrenal glands—has remained an unresolved issue.2, 3 Conn himself suggested that as many as 20% of people with hypertension could have this disorder; however, the ability to confirm this theory was hindered by the scarcity of widely available assays for renin and aldosterone determination.

For more than three decades primary hyperaldosteronism was thought to be a rare disease, diagnosed only in academic institutions by interested clinicians; studies of unreferred patients supported a prevalence of around 1%.4, 5, 6, 7 By contrast, several studies published since 1999 suggest that the prevalence of primary hyperaldosteronism is about 10% of the population of patients with hypertension.8, 9, 10, 11, 12, 13

The aldosterone to renin ratio (ARR) can be used as the screening test for primary hyperaldosteronism. However, its use is accompanied by a high percentage of false positive results, especially in patients taking β blockers, mainly due to methodological problems in accurate detection of low renin concentrations. Thus, a confirmatory salt suppression test is needed for an accurate diagnosis. From all available tests, the acute 4-h intravenous saline loading14 and the 4-day fludrocortisone administration15 seem to be the most reliable and offer accurate diagnosis of primary hyperaldosteronism.

Although there is still debate, most researchers agree that resistant hypertension is the condition with the highest probability of primary hyperaldosteronism detection.2, 3, 16, 17 The true prevalence of resistant hypertension is unknown. Although some studies estimated the prevalence as between 2·9% and 13%,18 other observational studies and outcome trials have suggested that up to 30% of patients with hypertension could be resistant to therapy.19

The aim of our study was to contribute the 20-year data of our clinic, reporting the prevalence of primary hyperaldosteronism in a large white population of patients with resistant hypertension.

Section snippets

Methods

We did a retrospective, observational study at the Hypertension Clinic of the Second Propedeutic Department of Internal Medicine, in Thessaloniki, Greece. The study was done in accordance with the principles of the Helsinki declaration and the procedures followed were in accordance with institutional guidelines. The study was approved by the Hospital Ethics Committee and all patients gave written informed consent.

The study included all consecutive patients with resistant hypertension that

Results

Over 20 years, 1616 patients with truly resistant hypertension were studied in our Department. The baseline characteristics of the patients are shown in table 1. Hypokalaemia was detected in 311 (20·5%) patients with resistant hypertension.

A positive test, defined as the combination of a high aldosterone to plasma renin activity ratio (more than 65·16) and serum aldosterone concentrations of more than 416 pmol/L was seen in 338 patients (20·9%)—ie, one in five patients with resistant

Discussion

Although the ARR was positive in about 20% of patients with resistant hypertension, after three confirmatory tests the diagnosis of primary hyperaldosteronism was confirmed only in about half, resulting in a prevalence of 11·3% of the total study population. Thus, only one in ten patients with resistant hypertension was finally diagnosed as having primary hyperaldosteronism. If we take into account that resistant hypertension is seen in 10–30% of people with hypertension19, 22 and primary

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