Conn’s syndrome; Conn syndrome; primary aldosteronism; 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. The adrenal glands produce aldosterone in response to another hormone called renin. Renin is produced by specialised cells in the kidney that detect when the body lacks salt; renin released by the kidney signals 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 are 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.
Hyperaldosteronism may be due either to diffuse swelling/overgrowth (hyperplasia) affecting either, but much more commonly both, of the adrenal glands; 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.
The diagnosis is made as a secondary cause of high blood pressure; specific symptoms are often few.
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. 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. A common scenario is the development of a low potassium level when drugs such as thiazide diuretics are used to treat what was initially thought to be essential hypertension.
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 the plasma aldosterone/plasma renin ratio as a screening test in patients with hypertension, estimates of the prevalence have risen. Some studies suggest 5–10% of patients with high blood pressure have primary aldosteronism; 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.
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.
Primary hyperaldosteronism is suspected if a patient has high blood pressure that does not respond to medication (often three or four drugs used together). 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 will 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.
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.
It is recommended that adrenal tumours should be removed if the patient is considered fit enough for surgery. This is performed via keyhole surgery – a process called laparoscopic adrenalectomy – 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.
The medication most commonly used to treat primary hyperaldosteronism (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; 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.
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.
Last reviewed: Feb 2017