Alternative names for primary hyperaldosteronism

Conn’s syndrome; Conn syndrome; primary aldosteronism; hyperaldosteronism

What is primary hyperaldosteronism?

Aldosterone is a hormone produced by the adrenal glands located just above each kidney. Aldosterone helps to control the amount of fluid in the body by affecting how much salt and water the kidney retains or excretes. Aldosterone production from the adrenal gland is regulated by another hormone called renin. Renin is produced by specialised cells in the kidney that detect when the body lacks salt. The kidney secretes renin which stimulates the adrenal glands to release aldosterone. The kidney detects an increase in aldosterone in the bloodstream and responds by retaining extra salt rather than excreting it in the urine. As the body regains the salt it needs, the level of renin in the bloodstream drops and therefore the amount of aldosterone in the blood also falls, meaning more water is excreted in the urine. This is an example of a feedback system.

Hyperaldosteronism refers to any state where there is excessive or inappropriate levels of aldosterone in the bloodstream. In primary hyperaldosteronism, aldosterone secretion is inappropriately high for the level of body salt and blood volume regardless of the renin level in the blood (which is usually suppressed). Secondary hyperaldosteronism occurs when the kidney produces too much renin. This is often seen in patients with chronic low blood volume such as in cardiac, liver or renal disease; the kidney mistakes the low blood supply for dehydration and produces excess renin.

What causes primary hyperaldosteronism?

Hyperaldosteronism may be due to either diffuse swelling/overgrowth (hyperplasia) affecting the adrenal gland, in one or both glands (much more commonly both); or, a small tumour within the gland (called an adrenal adenoma). In both cases, there is excessive secretion of aldosterone. These tumours are invariably small, benign, and do not spread or invade other areas in the way malignant tumours can.

Rarely, the condition is hereditary – so called glucocorticoid or dexamethasone-suppressible hyperaldosteronism. Rarer still, large adrenal carcinomas may secrete aldosterone. In all conditions, the feedback system fails and aldosterone secretion continues despite a low blood renin level.

What are the signs and symptoms of primary hyperaldosteronism?

Most people will not have disease-specific symptoms. The diagnosis is often made when people are incidentally found to have high blood pressure.

Patients with primary hyperaldosteronism are often diagnosed very late as the symptoms can be subtle. Most commonly, high blood pressure as a result of water and salt retention is found and a doctor will often suspect primary hyperaldosteronism if high blood pressure is not responding to multiple medications and/or if the patient is very young. About one-third of patients with primary hyperaldosteronism will also have a low blood level of potassium, which the kidney excretes in exchange for salt. Occasionally, this may cause symptoms such as cramps, weakness and excessive thirst.

How common is primary hyperaldosteronism?

The prevalence of hyperaldosteronism is debated. Initial studies reported that it probably affects 0.1–1% (1 in 1,000 to 1 in 100) of all patients with high blood pressure. However, with the wider use of screening tests in patients with high blood pressure, estimates of the prevalence have risen. Some studies suggest 5–10% of patients with high blood pressure have primary hyperaldosteronism; and in those patients whose blood pressure is resistant to drug therapy, it may be as high as 25%.

Adenomas are more frequent in women, and the diagnosis is most commonly made between the ages of 30 and 40.

Is primary hyperaldosteronism inherited?

The most common causes of hyperaldosteronism (adrenal hyperplasia and benign adrenal tumours) are not inherited. The rare form – glucocorticoid-suppressible hyperaldosteronism – is inherited as an autosomal dominant condition.

How is primary hyperaldosteronism diagnosed?

Primary hyperaldosteronism is suspected if a patient has high blood pressure that does not respond to medication (often three or four drugs used together) and/or if the patient is very young. Your doctor may be more suspicious if the potassium level in the blood is low. A strong history of high blood pressure and/or stroke in the family may also raise suspicion. Your doctor would normally refer you to an endocrinologist at this point, who will organise a blood test to check the levels of renin and aldosterone. To make this more accurate, your doctor may have to change the medications you already take as they can affect the results of this test. The blood test is most often performed at 9 a.m. in the sitting or lying position. In primary hyperaldosteronism, the aldosterone level is significantly raised, whilst the renin level is normally low. If the renin level is normal or high, it is likely that the patient has secondary hyperaldosteronism.

To confirm the diagnosis of hyperaldosteronism, a ‘salt challenge’ test may be carried out. In this test, aldosterone levels are checked after giving a salt solution drip directly into the bloodstream, or by increasing the amount of salt in the diet for a few days before rechecking aldosterone levels. In both cases, a normally healthy person’s aldosterone level should fall. If this does not happen, primary hyperaldosteronism is confirmed.

To find a cause, your doctor may organise a scan of the adrenal glands to look for a benign tumour or gland swelling. If there is doubt, a day-case radiology procedure can be performed under local anaesthetic using a fine cannula (narrow tube), to measure the amount of aldosterone in each of the veins coming from the two adrenal glands. A much higher level from one gland than the other suggests a tumour on one side (it could be so small that may not be actually visible in the scan). Newer imaging techniques such as methionine PET scan are also enabling doctors to localise small abnormalities that were not previously visible.

If glucocorticoid-suppressible hyperaldosteronism is suspected, the doctor may give you some synthetic corticosteroids ('steroids') to try and lower aldosterone levels, or may recommend genetic testing.

How is primary hyperaldosteronism treated?

It is recommended that adrenal tumours should be removed if the patient is considered fit enough for surgery. This is usually performed via keyhole surgery – a process called laparoscopic adrenalectomy – by an expert adrenal surgeon (usually an endocrine surgeon) in many hospitals and is usually very safe with few complications. In virtually all cases, potassium levels are normalised with successful surgery, and over 70% of patients have an improvement in blood pressure, with 50% of patients coming off blood pressure medication completely.

Surgery is usually not recommended if the cause is swelling of both glands, since this will have little impact on future blood pressure. Also, the adrenal glands produce other hormones that are very important to normal body functions. In these situations, medications that block the effect of aldosterone causing salt and water retention in the kidney can be used.

Are there any side-effects to the treatment?

The medication most commonly used to treat primary hyperaldosteronism (called spironolactone) can cause high blood potassium and low blood salt (hyponatraemia) as it blocks the action of aldosterone. It can affect periods in women and in men it can also cause impotence and enlargement of breast tissue, as it blocks the action of testosterone. Eplerenone is an alternative drug that works through the same mechanism as spironolactone but without the sex hormone side-effects; however eplerenone is much more expensive.

Pregnant women or those of child bearing age would usually not be offered spironolactone as it can have serious effects on the developing baby.

What are the longer-term implications of primary hyperaldosteronism?

The main consequence of primary hyperaldosteronism is high blood pressure, which leads to an increased risk of heart disease and strokes, as well as disease of the peripheral blood vessels, the eyes, and the kidneys. However, treatment for hyperaldosteronism can be very effective and is primarily aimed at reducing these long-term complications of high blood pressure. Patients who require long-term medication for this condition may need regular follow-up appointments with their doctor.