Hyperaldosteronism (Aldosteronism)

What aldosterone does

Aldosterone is made in the outer layer (cortex) of the adrenal glands, which sit on top of the kidneys. Normally it is part of the renin-angiotensin-aldosterone system:

1. When blood pressure or blood volume falls, the kidneys release renin.
2. Renin triggers production of angiotensin II, which tightens blood vessels and stimulates the adrenals.
3. The adrenals release aldosterone, which makes the kidneys retain sodium and water and excrete potassium.
4. Blood pressure and volume rise, and renin falls again.

High potassium also directly stimulates aldosterone. Too much aldosterone, for whatever reason, leads to excess salt and fluid, high blood pressure and potassium loss in the urine.

Primary vs secondary hyperaldosteronism

Primary hyperaldosteronism

Primary hyperaldosteronism, also called primary aldosteronism or Conn syndrome, is the most common hormonal cause of high blood pressure. It is found in roughly 5 to 10% of people with hypertension and in up to about 20% of those whose blood pressure stays high despite several medicines. Causes are:

• Bilateral adrenal hyperplasia: both glands are overactive. This accounts for about 60% of cases.
• Aldosterone-producing adrenal adenoma: a benign tumor in one gland, about 30 to 40%. This form can often be cured with surgery.
• Familial hyperaldosteronism: rare inherited forms, including one (type I) that responds to low-dose steroid treatment.
• Adrenal carcinoma: very rare.

Secondary hyperaldosteronism

Here the adrenals are working normally but are being pushed by high renin. Causes include:

• Renal artery stenosis: narrowing of an artery to the kidney, which the kidney senses as low pressure
• Heart failure, cirrhosis and nephrotic syndrome, in which the body senses low effective blood volume
• Diuretics and laxative misuse, vomiting or dehydration
• Pregnancy, a normal cause of raised renin and aldosterone
• Renin-secreting tumors of the kidney, which are rare
• Bartter and Gitelman syndromes, inherited salt-wasting kidney disorders

Symptoms

Many people have no symptoms other than high blood pressure. Symptoms of low potassium, present in only about a third of people with primary disease, include:

• muscle weakness, cramps or twitching
• tiredness
• passing large volumes of urine, including at night, and thirst
• palpitations or an irregular heartbeat
• tingling in the hands and feet
• headaches

Who should be tested

Testing for primary aldosteronism is recommended for people with:

• blood pressure above 150/100 mm Hg on repeated readings
• hypertension resistant to 3 drugs including a diuretic, or needing 4 or more drugs
• hypertension with low potassium, whether spontaneous or caused by diuretics
• hypertension with an adrenal mass found by chance on a scan
• hypertension with sleep apnea or atrial fibrillation
• hypertension with a family history of early-onset hypertension or stroke before age 40, or a relative with primary aldosteronism

The most recent Endocrine Society guidance goes further and recommends screening everyone with hypertension, because the condition is badly underdiagnosed.

Diagnosis

1. Screening: aldosterone-to-renin ratio

A morning blood test measures aldosterone and renin (as renin activity or concentration). A high ratio, with a low renin, suggests primary disease. Potassium should be corrected first. Some blood pressure drugs, especially spironolactone, eplerenone, diuretics, ACE inhibitors and ARBs, affect the result, so your doctor will advise whether any need adjusting before testing.

2. Confirmation

A suppression test checks whether aldosterone stays high when it should fall: an intravenous saline infusion, an oral salt-loading test with a 24-hour urine collection, or a captopril challenge. Some people with very clear results skip this step.

3. Finding the source

• CT scan of the adrenal glands looks for an adenoma or carcinoma.
• Adrenal venous sampling: a radiologist takes blood from the vein of each adrenal gland to see which side is producing excess aldosterone. It is needed before surgery, because small adrenal lumps are common and often unrelated.

For suspected secondary disease, tests focus on the cause: kidney artery imaging, heart and liver tests, and a review of medicines.

Treatment

Primary hyperaldosteronism

• Laparoscopic adrenalectomy: keyhole removal of the affected gland when one side is responsible. Potassium returns to normal in nearly everyone, and blood pressure improves in most people. About a third to half are able to stop all blood pressure medicines.
• Mineralocorticoid receptor antagonists: spironolactone or eplerenone block aldosterone's effect. They are the main treatment for bilateral disease or for people who do not want or cannot have surgery. Spironolactone can cause breast enlargement and tenderness in men; eplerenone causes this less often.
• Low-salt diet, regular exercise and other blood pressure medicines as needed.

Secondary hyperaldosteronism

Treatment targets the cause: opening or stenting a narrowed kidney artery in selected cases, treating heart failure or cirrhosis, and adjusting diuretics. Spironolactone and eplerenone are standard treatments in heart failure and in fluid buildup from cirrhosis, partly because they counter the excess aldosterone.

Complications

Aldosterone causes more harm than blood pressure alone would explain. Compared with people with similar blood pressure from other causes, people with primary aldosteronism have higher rates of stroke, heart attack, atrial fibrillation, heart failure and kidney damage. This is why diagnosing and treating it specifically matters.

Frequently asked questions

What is the difference between primary and secondary hyperaldosteronism?

In primary hyperaldosteronism the adrenal glands make too much aldosterone on their own, so renin is low. In secondary hyperaldosteronism a problem elsewhere, such as narrowed kidney arteries, heart failure or cirrhosis, raises renin, which then drives aldosterone up. The renin level separates the two.

What are the symptoms of hyperaldosteronism?

Most people have only high blood pressure, often hard to control. When potassium is low, there may be muscle weakness, cramps, tiredness, palpitations, thirst and frequent urination. Many people have normal potassium, so a normal potassium result does not rule it out.

Can hyperaldosteronism be cured?

Primary hyperaldosteronism caused by an adenoma in one adrenal gland can often be cured or greatly improved by removing that gland. Bilateral disease is controlled long term with spironolactone or eplerenone. Secondary forms improve when the underlying cause is treated.

How is hyperaldosteronism diagnosed?

It starts with a blood test of the aldosterone-to-renin ratio. If that is raised, a salt or saline suppression test confirms it. A CT scan and adrenal venous sampling then show whether one or both glands are responsible, which decides between surgery and medicine.

Does hyperaldosteronism cause weight gain?

It causes salt and water retention, which can add a little fluid weight, but it does not usually cause noticeable weight gain or visible swelling. Marked weight gain with high blood pressure suggests other causes, such as Cushing syndrome, which affects a different adrenal hormone.