Primary aldosteronism

Primary aldosteronism (excess production of aldosterone) is usually caused by an aldosterone-secreting adenoma (Conn syndrome). The features of primary aldosteronism are elevated blood pressure, hypokalaemia (present in about 50% of cases), aldosterone excess and suppressed plasma renin activity.

A plasma aldosterone-to-renin ratio is the initial screening test for suspected primary aldosteronism. An elevated aldosterone-to-renin ratio is a positive result; refer patients with an elevated aldosterone-to-renin ratio to a specialist for further tests to confirm the diagnosis.

The aldosterone-to-renin ratio is susceptible to interference by many blood pressure–lowering drugs, as well as nonsteroidal anti-inflammatory drugs (NSAIDs)—the effects of common drugs on aldosterone, renin, and aldosterone-to-renin ratio are shown in Effect of common drug classes on aldosterone-to-renin ratio. Patients are often taking one or more blood pressure–lowering drugs before a diagnosis of primary aldosteronism is considered. The initial aldosterone-to-renin ratio can be performed while the patient is taking a blood pressure–lowering drug, but expert advice is recommended to interpret the result, with consideration of the effect of the drug. For example, beta blockers increase the aldosterone-to-renin ratio, so a normal aldosterone-to-renin ratio in a patient taking a beta blocker makes the diagnosis of primary aldosteronism unlikely.

Blood pressure–lowering drugs that do not affect the aldosterone-to-renin ratio include diltiazem, verapamil, prazosin and hydralazine. Hydralazine can cause reflex tachycardia; this can be prevented by starting verapamil before the hydralazine.

Table 1. Effect of common drug classes on aldosterone-to-renin ratio
[NB1] [NB2]
Effect on aldosterone	Effect on renin	Effect on aldosterone-to-renin ratio	False-positive or false-negative screening result for primary aldosteronism
beta blockers centrally acting antiadrenergic drugs (methyldopa, clonidine) nonsteroidal anti-inflammatory drugs (NSAIDs)
↓	⇊	↑	false positive
angiotensin converting enzyme inhibitors angiotensin receptor blockers
↓	⇈	↓	false negative
all diuretics
↑	⇈	↓	false negative
dihydropyridine calcium channel blockers
↓ or neutral	↑	↓	false negative
Note: NB1: Hypokalaemia can suppress aldosterone and cause a false-negative result for primary aldosteronism; ensure the patient is potassium replete before testing. NB2: The impact of the effect of these drugs on the interpretation of the result depends on the aldosterone-to-renin ratio threshold used, which varies among centres.

Primary aldosteronism caused by an aldosterone-secreting adenoma (Conn syndrome) is usually treated with adrenalectomy.

If adrenalectomy is contraindicated or the patient has bilateral adrenal hypersecretion, an aldosterone antagonist is first-line treatment. An aldosterone antagonist is also used in preparation for an adrenalectomy. Use:

spironolactone 25 mg orally, once daily. Adjust dose according to blood pressure, serum potassium concentration and plasma renin concentration. primary aldosteronism spironolactone

Spironolactone also blocks androgen receptors, which can lead to gynaecomastia and erectile dysfunction in males. If these adverse effects occur, amiloride is a suitable alternative. Use:

amiloride 5 mg orally, twice daily. Adjust dose according to blood pressure and serum potassium concentration. primary aldosteronism

Eplerenone rarely causes gynaecomastia or erectile dysfunction. It can be considered instead of spironolactone, but at the time of writing, it is not approved by the Australian Therapeutic Goods Administration (TGA) for treating primary aldosteronism¹.

Familial dexamethasone-suppressible primary aldosteronism is an uncommon variant of primary aldosteronism. Usual treatment is low-dose dexamethasone, spironolactone or amiloride.

¹ See the Therapeutic Goods Administration website for current information.Return