Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ONGOING

unilateral PA

1st line – unilateral laparoscopic adrenalectomy

Back
ONGOING
|
unilateral PA
|
surgical candidates
1st line – 

unilateral laparoscopic adrenalectomy

Unilateral adrenalectomy in carefully selected patients after a full workup provides a high chance of biochemical cure of primary aldosteronism (PA; 70% cured and 100% improved, as judged by postoperative fludrocortisone suppression testing​​), including cure of hypokalemia in all patients in whom it was present preoperatively.​​[107][115][116][117]​​ Hypertension is cured in 50% to 60% of fully worked-up patients, and improved in all remaining patients.​​​[115][116][117]​ Less than 20% of patients require equivalent or increased medication doses after surgery.​[104]

Almost always, the entire adrenal is removed - even when an apparent adenoma is seen on CT scanning or on visualization of the gland.

Laparoscopic adrenalectomy is associated with shorter hospital stays and fewer complications.[118]

Immediately before surgery, potassium supplementation should be withdrawn, aldosterone antagonists discontinued, and other antihypertensive therapy reduced, if appropriate.

Postoperative intravenous fluids should be given as normal saline without potassium chloride. A generous sodium diet should be recommended to avoid the hyperkalemia due to chronic contralateral adrenal gland suppression.[6] In rare instances, temporary fludrocortisone therapy may be required.

Successful removal of an aldosterone-producing adenoma during pregnancy has been rarely reported.[120] Although case reports suggest the optimal time for surgery is during the middle trimester, it is clearly preferable when possible to postpone surgery in patients found to have an aldosterone-producing adenoma during pregnancy until after delivery.

Consider – preoperative aldosterone antagonists

Back
ONGOING
|
unilateral PA
|
surgical candidates
Consider – 

preoperative aldosterone antagonists

Treatment recommended for SOME patients in selected patient group

For surgical candidates with severe hypertension and left ventricular hypertrophy (LVH) pre-surgery, spironolactone is the drug of first choice, with amiloride or eplerenone (in countries where available as a subsidized treatment for primary aldosteronism) reserved mainly for those who develop sex-steroid-related adverse effects.

Overtreatment can cause volume contraction with prerenal failure, raising creatinine levels and causing life-threatening hyperkalemia.

In patients with reduced renal glomerular function, concurrent administration of a low-dose potassium-wasting diuretic can be helpful to avoid hyperkalemia, but potassium and creatinine levels should still be carefully monitored.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Spironolactone can be associated with sex-steroid-related adverse effects, including gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[122] The incidence is dose-related. At 12.5 to 50 mg daily, the incidence of gynecomastia is approximately 10% to 15%.[107][123]

Primary options

spironolactone: 12.5 to 50 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 200 mg/day

Secondary options

amiloride: 2.5 to 15 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 40 mg/day

OR

eplerenone: 25 to 100 mg orally once daily or in 2 divided doses, maximum 100 mg/day

Consider – postoperative aldosterone antagonists

Back
ONGOING
|
unilateral PA
|
surgical candidates
Consider – 

postoperative aldosterone antagonists

Treatment recommended for SOME patients in selected patient group

Twenty percent of patients diagnosed with unilateral primary aldosteronism (PA) preoperatively show evidence of ongoing PA after surgery. If residual hypertension is due to aldosterone excess, it may respond well to aldosterone antagonist medication, but, as aldosterone levels have been reduced by surgery, caution is required.

Eplerenone (in countries where available as a subsidized treatment for PA) is another option for patients in whom spironolactone is poorly tolerated and where amiloride is unable to achieve sufficient aldosterone blockade. Normality of the ratio, which depends on renin becoming unsuppressed, is the best guide to whether or not adequate blockade of aldosterone is being achieved.

The lowest recommended dose should usually be used at introduction.

Overtreatment can cause volume contraction with prerenal failure, raising creatinine levels and causing life-threatening hyperkalemia.

In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia, but potassium and creatinine levels should still be carefully monitored.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Primary options

amiloride: 2.5 to 10 mg orally once daily or in 2 divided doses

OR

spironolactone: 12.5 to 25 mg orally once daily or in 2 divided doses

OR

eplerenone: 25 to 50 mg orally once daily or in 2 divided doses

1st line – aldosterone antagonists

Back
ONGOING
|
unilateral PA
|
not candidates for surgery
1st line – 

aldosterone antagonists

Indicated in patients with unilateral primary aldosteronism (PA) who prefer medical treatment or are not candidates for surgery.

Because of its less potent aldosterone antagonist action and its much lower propensity to induce adverse effects, amiloride may be the drug of first choice in many patients, particularly those with milder degrees of hypertension, biochemical disturbance, and target organ effects (e.g., echocardiographically demonstrated LVH).

Side-effects from amiloride are rare. Spironolactone can be associated with sex-steroid-related adverse effects, including gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[122] The incidence is dose-related. At 12.5 to 50 mg daily, the incidence of gynecomastia is approximately 10% to 15%.[107][123]

Amiloride and spironolactone can also be used in combination to minimize the dose of spironolactone and the risk of sex-steroid-related adverse effects.

Eplerenone (in countries where available as a subsidized treatment for PA) is another option for patients in whom spironolactone is poorly tolerated and where amiloride is unable to achieve sufficient aldosterone blockade. Normality of the ratio, which depends on renin becoming unsuppressed, is the best guide to whether or not adequate blockade of aldosterone is being achieved.

Overtreatment can cause volume contraction with prerenal failure, rising creatinine levels, and life-threatening hyperkalemia. In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia, but potassium and creatinine levels should still be carefully monitored.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Amiloride, spironolactone, and eplerenone have a slow onset of antihypertensive action. Benefit may not be apparent for 2 weeks, even months. If necessary, other antihypertensive agents with more rapid onset of action could be employed during this period, and then later reduced or withdrawn.

Primary options

amiloride: 2.5 to 15 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 40 mg/day

OR

spironolactone: 12.5 to 50 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 200 mg/day

OR

eplerenone: 25 to 100 mg orally once daily or in 2 divided doses, maximum 100 mg/day

bilateral PA (excluding familial hyperaldosteronism type I)

1st line – aldosterone antagonists

Back
ONGOING
|
bilateral PA (excluding familial hyperaldosteronism type I)
|
no adrenal lesion ≥2.5 cm
1st line – 

aldosterone antagonists

Lesions ≥2.5 cm should be considered for removal based on their malignant potential. Some centers use higher cutoffs of 3.0 cm or even 4.0 cm, but this increases the risk of missing a malignant lesion. CT should be repeated in 3 to 6 months and then annually to recognize growth which would suggest malignancy.

Because of its less potent aldosterone antagonist action and its much lower propensity to induce adverse effects, amiloride may be the drug of first choice in many patients, particularly those with milder degrees of hypertension, biochemical disturbance, and target organ effects (e.g., echocardiographically demonstrated LVH).

Side-effects from amiloride are rare. Spironolactone can be associated with sex-steroid-related adverse effects, including gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[122] The incidence is dose-related. At 12.5 to 50 mg daily, the incidence of gynecomastia is approximately 10% to 15%.[107][123]

Amiloride and spironolactone can also be used in combination to minimize the dose of spironolactone and the risk of sex-steroid-related adverse effects.

Eplerenone (in countries where available as a subsidized treatment for primary aldosteronism [PA]) is another option for patients in whom spironolactone is poorly tolerated and where amiloride is unable to achieve sufficient aldosterone blockade. Normality of the ratio, which depends on renin becoming unsuppressed, is the best guide to whether or not adequate blockade of aldosterone is being achieved.

Overtreatment can cause volume contraction with prerenal failure, rising creatinine levels, and life-threatening hyperkalemia. In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia, but potassium and creatinine levels should still be carefully monitored.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Amiloride, spironolactone, and eplerenone have a slow onset of antihypertensive action. Benefit may not be apparent for two weeks, even months. If necessary, other antihypertensive agents with more rapid onset of action could be employed during this period, and then later reduced or withdrawn.

Primary options

amiloride: 2.5 to 15 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 40 mg/day

OR

spironolactone: 12.5 to 50 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 200 mg/day

OR

eplerenone: 25 to 100 mg orally once daily or in 2 divided doses, maximum 100 mg/day

2nd line – laparoscopic adrenalectomy

Back
ONGOING
|
bilateral PA (excluding familial hyperaldosteronism type I)
|
no adrenal lesion ≥2.5 cm
2nd line – 

laparoscopic adrenalectomy

It is sometimes appropriate to consider the option of unilateral adrenalectomy in patients with bilateral forms of primary aldosteronism (PA) because both spironolactone and amiloride have been tolerated poorly even at low doses, or the dose of spironolactone required to control hypertension has produced adverse effects.

For rare patients with marked, bilateral adrenal hyperplasia and severe, bilateral PA (including those with severe forms of familial hyperaldosteronism type III), bilateral adrenalectomy (often in 2 stages, to gauge the effect of unilateral adrenalectomy first) may be required to control hypertension and biochemical manifestations of PA.[16][47]

The aim of adrenalectomy is to reduce the mass of adrenal tissue that is excessively and autonomously producing aldosterone, and thereby bring about improvements in BP levels and marked reductions in the doses of aldosterone antagonist medications required to control hypertension. BP responses under these circumstances are much less predictable than in patients with unilateral PA.

Laparoscopic adrenalectomy is associated with shorter hospital stays and fewer complications.[118]

Immediately before surgery, potassium supplementation should be withdrawn, aldosterone antagonists temporarily discontinued, and other antihypertensive therapy reduced, if appropriate.

Postoperative intravenous fluids should be given as normal saline without potassium. A generous sodium diet should be recommended to avoid the hyperkalemia due to chronic contralateral adrenal gland suppression.[6] In rare instances, temporary fludrocortisone therapy may be required. Plasma potassium levels should be monitored at least twice daily for the first 2 days.

Successful removal of an aldosterone-producing adenoma during pregnancy has been rarely reported.[120] Although case reports suggest that the optimal time for surgery is during the middle trimester, it is clearly preferable to postpone surgery in patients with PA during pregnancy until after delivery where possible.

Plus – pre- and postoperative aldosterone antagonists

Back
ONGOING
|
bilateral PA (excluding familial hyperaldosteronism type I)
|
no adrenal lesion ≥2.5 cm
Plus – 

pre- and postoperative aldosterone antagonists

Treatment recommended for ALL patients in selected patient group

It is highly desirable that hypertension and hypokalemia be controlled preoperatively. This usually involves treatment with an aldosterone antagonist. If not tolerated, other antihypertensive agents can be used.

Recommencement of aldosterone antagonist medication postoperatively can usually be deferred for several weeks. The lowest recommended dose should be used initially, and electrolyte and renal function carefully monitored.

Overtreatment can cause volume contraction with prerenal failure, rising creatinine levels, and life-threatening hyperkalemia. In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Spironolactone can be associated with sex-steroid-related adverse effects, including gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[122] The incidence is dose-related. At 12.5 to 50 mg daily, the incidence of gynecomastia is approximately 10% to 15%.[107][123]

Eplerenone (in countries where available as a subsidized treatment for primary aldosteronism) is another option for patients in whom spironolactone is poorly tolerated and where amiloride is unable to achieve sufficient aldosterone blockade. Normality of the ratio, which depends on renin becoming unsuppressed, is the best guide to whether or not adequate blockade of aldosterone is being achieved.

Primary options

amiloride: 2.5 to 15 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 40 mg/day

OR

spironolactone: 12.5 to 50 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 200 mg/day

OR

eplerenone: 25 to 100 mg orally once daily or in 2 divided doses, maximum 100 mg/day

1st line – unilateral laparoscopic adrenalectomy

Back
ONGOING
|
bilateral PA (excluding familial hyperaldosteronism type I)
|
adrenal lesion ≥2.5 cm
1st line – 

unilateral laparoscopic adrenalectomy

Lesions of this size should be considered for removal based on their malignant potential. Some centers use higher cutoffs of 3.0 cm or even 4.0 cm, but this increases the risk of missing a malignant lesion.

Laparoscopic adrenalectomy is associated with shorter hospital stays and fewer complications.[118] Open adrenalectomy may be required, however, in the case of very large lesions.

Immediately before surgery, potassium supplementation should be withdrawn, aldosterone antagonists discontinued, and other antihypertensive therapy reduced, if appropriate.

Postoperative intravenous fluids should be given as normal saline without potassium chloride. A generous sodium diet should be recommended to avoid the hyperkalemia due to chronic contralateral adrenal gland suppression.[6] In rare instances, temporary fludrocortisone therapy may be required.

Successful removal of an aldosterone-producing adenoma during pregnancy has been rarely reported.[120] Although case reports suggest that the optimal time for surgery is during the middle trimester, it is clearly preferable to postpone surgery in patients with primary aldosteronism during pregnancy until after delivery where possible.

Plus – pre- and postoperative aldosterone antagonists

Back
ONGOING
|
bilateral PA (excluding familial hyperaldosteronism type I)
|
adrenal lesion ≥2.5 cm
Plus – 

pre- and postoperative aldosterone antagonists

Treatment recommended for ALL patients in selected patient group

Where possible, hypertension and hypokalemia should be controlled preoperatively, ideally with an aldosterone antagonist.

Postoperatively, residual hypertension usually responds well to recommencement of aldosterone antagonist medication. This is usually deferred for several weeks. The lowest recommended dose should be used initially.

Overtreatment can cause volume contraction with prerenal failure, raising creatinine levels, and life-threatening hyperkalemia. In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Spironolactone can be associated with sex-steroid-related adverse effects, including gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[122] The incidence is dose-related. At 12.5 to 50 mg daily, the incidence of gynecomastia is approximately 10% to 15%.[107][123]

Eplerenone (in countries where available as a subsidized treatment for primary aldosteronism) is another option for patients in whom spironolactone is poorly tolerated and where amiloride is unable to achieve sufficient aldosterone blockade. Normality of the ratio, which depends on renin becoming unsuppressed, is the best guide to whether or not adequate blockade of aldosterone is being achieved.

Primary options

amiloride: 2.5 to 15 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 40 mg/day

OR

spironolactone: 12.5 to 50 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 200 mg/day

OR

eplerenone: 25 to 100 mg orally once daily or in 2 divided doses, maximum 100 mg/day

familial hyperaldosteronism type I

1st line – glucocorticoids

Back
ONGOING
|
familial hyperaldosteronism type I
|
adults
1st line – 

glucocorticoids

Glucocorticoids rapidly and effectively ameliorate hypertension.[13]​​[22]​​​​[44][45]​​[132]

The risk of Cushingoid adverse effects is minimal because the required doses are low.[133] However, patients should still be monitored for clinical development of Cushingoid features. Periodic dual energy-ray absorptiometry (DXA) bone scanning should be performed to monitor the development of osteoporosis.

Treatment should be avoided in children because of the potential to impair growth.

For pregnant patients, low-dose glucocorticoids have been used successfully to control hypertension. Prednisone and hydrocortisone are thought to be preferable to dexamethasone. Alternatives to glucocorticoids are any of the recognized pregnancy-safe antihypertensives.

Primary options

dexamethasone: 0.125 to 0.5 mg orally once daily

OR

prednisone: 2.5 to 5 mg orally once daily

2nd line – aldosterone antagonists

Back
ONGOING
|
familial hyperaldosteronism type I
|
adults
2nd line – 

aldosterone antagonists

Aldosterone antagonists are an alternative way to control hypertension in patients with familial hyperaldosteronism type I (FH-I).

They may be used in patients who wish to avoid or have been unable to tolerate glucocorticoid treatment, or in whom such treatment is otherwise contraindicated.

Because of its less potent aldosterone antagonist action and its much lower propensity to induce adverse effects, amiloride may be the drug of first choice in many patients, particularly those with milder degrees of hypertension, biochemical disturbance, and target organ effects (e.g., echocardiographically demonstrated LVH). Amiloride and spironolactone can also be used in combination to minimize the dose of spironolactone and the risk of sex-steroid-related adverse effects.

Eplerenone (in countries where available as a subsidized treatment for primary aldosteronism) is another option for patients in whom spironolactone is poorly tolerated and where amiloride is unable to achieve sufficient aldosterone blockade. Normality of the ratio, which depends on renin becoming unsuppressed, is the best guide to whether or not adequate blockade of aldosterone is being achieved.

Overtreatment can cause volume contraction with prerenal failure, rising creatinine levels, and life-threatening hyperkalemia. In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Spironolactone can be associated with sex-steroid-related adverse effects, including gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[122] The incidence is dose-related. At 12.5 to 50 mg daily, the incidence of gynecomastia is approximately 10% to 15%.[107][123]

Primary options

amiloride: 2.5 to 15 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 40 mg/day

OR

spironolactone: 12.5 to 50 mg orally once daily or in 2 divided doses, higher doses have been reported, maximum 200 mg/day

OR

eplerenone: 25 to 100 mg orally once daily or in 2 divided doses, maximum 100 mg/day

1st line – amiloride

Back
ONGOING
|
familial hyperaldosteronism type I
|
children (pre- and peripubertal)
1st line – 

amiloride

Although glucocorticoids are highly effective in controlling hypertension and hypokalemia (where present) in familial hyperaldosteronism type I (FH-I), they may impair growth in children and their use should therefore be avoided in that patient group.

Amiloride is a potassium-sparing diuretic and effective against hypertension and hypokalemia in patients with primary aldosteronism of all forms, including FH-I.[122] Although spironolactone is more effective in this respect than amiloride, its propensity to induce sex-steroid-related adverse effects and, in particular, to interfere with sexual development, renders its use in children undesirable.

Overtreatment with amiloride can cause volume contraction with prerenal failure, rising creatinine levels, and life-threatening hyperkalemia. In patients with reduced renal glomerular function, concurrent administration of a potassium-wasting diuretic in low dosage can be helpful to avoid hyperkalemia.​[6]

Hyperkalemia is more likely in patients who have renal dysfunction or are taking other potassium-retaining agents such as angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists, or nonsteroidal anti-inflammatory drugs (NSAIDs).

Primary options

amiloride: 2.5 to 7.5 mg orally once daily or in 2 divided doses

2nd line – eplerenone

Back
ONGOING
|
familial hyperaldosteronism type I
|
children (pre- and peripubertal)
2nd line – 

eplerenone

Eplerenone is a mineralocorticoid receptor antagonist that appears to be more selective for the receptor than spironolactone, and is, therefore, less likely to produce sex-steroid-related adverse effects such as gynecomastia and loss of libido, menstrual irregularities, and aggravation of breast fibrocystic change.[136] It may also be less likely to interfere with sexual development in children. Hence, it may be particularly suited for adult patients who have demonstrated intolerance to spironolactone because of sex-steroid-related adverse effects, or in children with primary aldosteronism (PA; including those with familial hyperaldosteronism type I). 

Eplerenone is already available and being used in clinical practice. However, indications for its use in different countries vary, and in some countries it is not approved for government-subsidized use in PA. Furthermore, data regarding its safety and efficacy in children with PA are lacking. Hence, it should remain a second-line option in this clinical context.

Primary options

eplerenone: consult specialist for guidance on dose

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer