Primary or secondary aldosteronism has been confirmed as a major underlying cause of resistant hypertension, following success in treating the condition with the mineralocorticoid receptor antagonist spironolactone.

A follow up of 269 patients with resistant hypertension participating in a trial of spironolactone found further evidence pointing to the hypertension being a salt-retaining state due to inappropriate aldosterone secretion.

In the study, substantial blood pressure reductions (around 20mmHg) were seen with spironolactone but not other antihypertensives, and the reductions in BP were predicted by aldosterone-to-renin ratio,

The spironolactone-related BP reductions were associated with significant decreases in markers of salt and water retention such as thoracic fluid content.

The study also showed that 25% of the patients had inappropriately high plasma aldosterone concentrations in the absence of high renin levels

The researchers said the findings provide strong evidence that the underlying mechanism in resistant hypertension was related to endocrine factors rather than haemodynamic changes such as vasodilation.

“We conclude that the mineralocorticoid receptor antagonist spironolactone is an effective treatment of resistant hypertension because resistant hypertension is commonly a salt-retaining condition probably due to inappropriate aldosterone secretion,” they wrote in Lancet Diabetes Endocrinology.

And by elucidating the mechanism, the researcher showed that other natriuretic drugs could be used in patients unable to tolerate spironolactone because of its anti-androgenic effects such as gynaecomastia.

“Physicians who are hesitant to prescribe spironolactone for hypertension, either because it is not a universally licensed indication, or because of anti-androgen-related intolerance, will be reassured by our additional finding that amiloride 10–20 mg achieved similar reductions in blood pressure as spironolactone, with similar, slight changes in electrolytes<’ they said.

The high levels of aldosterone might be due to zona glomerulosa aldosterone-producing adenomas, the researchers added.

The abnormal aldosterone secretion from such adenomas might not be detected with current thresholds for aldosteronism because levels would be reduced by antihypertensives acting on the renin-angiotensin system, the researchers said.

“Our findings should encourage debate about whether thresholds for diagnosis of primary aldosteronism should be reconsidered in patients presenting with resistant hypertension, and about the possibility of earlier diagnosis of primary aldosteronism to prevent development of resistant hypertension,” they concluded..