What is it?
Conn’s syndrome is another name for primary hyperaldosteronism and may also be referred to as aldosteronism. The condition was named by Jerome Conn who first described a tumour of the adrenal glands that produced excess aldosterone. It is a disease of the outer layer of the adrenal glands called the adrenal cortex. The adrenal glands are small triangular organs which sit on top of the kidneys. The glands are part of the endocrine system, a group of glands that produce and secrete hormones that act on and regulate many body functions. Aldosterone is a hormone that plays an important role in maintaining blood volume, pressure and the concentration of sodium and other electrolytes. The amount of aldosterone produced is normally regulated by renin, an enzyme made in the kidneys. When renin levels increase due to low blood pressure, reduced flow of blood to the kidneys or to sodium deficiency, aldosterone increases and when renin decreases, aldosterone decreases.
In Conn’s syndrome, very large amounts of aldosterone are produced by one or more adrenal tumours which are usually not cancerous (benign), sometimes the gland just increases in size (hyperplasia) and sometimes the reasons are unknown (idiopathic). Only rarely is the cause a cancerous adrenal tumour. Regardless of the cause, increased aldosterone can most commonly lead to low blood levels of potassium (hypokalaemia), increased blood pH (alkalosis), and hypertension. Very rarely, increased aldosterone will lead to high blood levels of sodium (hypernatraemia). Conn's syndrome is the most common cause of secondary hypertension (that is hypertension caused by something other than the working of the heart or blood vessels). Sometimes increased aldosterone will lead to frequent need for urination (polyuria), increased thirst, muscle weakness and cramps, temporary paralysis, headaches, and tingling.
Diagnosing Conn’s syndrome is important because it represents one of the few causes of hypertension that are potentially curable. Although anyone can develop primary hyperaldosteronism, it is most commonly seen in adults between the ages of 30 and 50 and is more common in women than men. It can sometimes be difficult to diagnose as patients may have variable symptoms or no symptoms at all. Suspicion of Conn’s syndrome may be raised in patients who are resistant to the usual ways of treating high blood pressure (hypertension). The presence of hypokalaemia in a person with hypertension suggests the need to look for primary hyperaldosteronism and the reason for an increase production of aldosterone. Not all patients have hypokalaemia.
Secondary aldosteronism is when the adrenal glands themselves are not driving the production of aldosterone, when this happens it is not called Conn’s syndrome. It can occur as a result of anything that increases renin levels, such as decreased blood flow to the kidneys, low blood pressure, or low sodium levels in the urine. The most important cause is narrowing of the blood vessels that supply the kidney, this is called renal artery stenosis. Other causes of secondary hyperaldosteronism include congestive heart failure, cirrhosis, kidney disease, and pre-eclampsia.
The goal when looking for Conn’s syndrome is for tests to understand where the aldosterone is coming from. The conclusions made from these tests may then help decide whether surgery is likely to be beneficial or the condition can be treated with drugs.
Laboratory Tests
Electrolytes, usually blood sodium, potassium and sometime chloride and bicarbonate may be measured to look for an electrolyte imbalance. If an imbalance is seen, then the doctor may give the patient spironolactone, a drug that blocks the action of aldosterone, to see if balance is restored. Hypertension is treated according to NICE guidelines with diuretic drugs, beta-blockers, inhibitors of angiotensin converting enzyme (ACE), calcium channel blockers alone or in combinations according to ethnicity, gender and age. Doctors will frequently request blood renin tests along with aldosterone tests in blood samples or in a 24-hour urine collection to help diagnose primary hyperaldosteronism and to monitor the effectiveness of treatment. The ratio of aldosterone to renin is used as an early test for primary hyperaldosteronism. If aldosterone is high and renin levels are low, then the ratio will be significantly increased and primary hyperaldosteronism is likely to be present.
If hyperplasia or an aldosterone-producing tumour is suspected, but not seen using normal procedures, then a doctor may request confirmatory tests during a hospital admission. Oral sodium loading or saline infusion should be used with caution in patients with uncontrolled hypertension. Fludrocortisone suppression or a captopril challenge tests are used in specialist centres. It will be necessary for drug treatment to be discontinued. Primary hyperaldosteronism is indicated by an elevated aldosterone/renin ratio at 08.00h. A low renin activity that shows little or no increase after 30 min of mobility also supports autonomous aldosterone secretion. To aid the distinction between hyperaldosteronism due to adrenal adenoma and that due to bilateral adrenal hyperplasia, it may be helpful to consider the plasma aldosterone concentrations at 08.00h and 12.00h. In normal subjects and patients with adrenal hyperplasia the aldosterone rises on standing. If cortisol values between 08.00h and 12.00h show a decrease due to normal diurnal rhythm, an elevated aldosterone level at 08.00h decreasing by 50% or more at 12.00h is suggestive of an adenoma or GRA.
Adrenal venous sampling is a definitive confirmatory test. In this procedure, blood is collected from the vein that carries blood away from each adrenal gland. A catheter will be inserted into a vein in the thigh and moved up inside a large vein in the back to the the adrenal veins. The correct location is seen by imaging. The adrenal vein blood samples from each side are tested for aldosterone (sometimes cortisol is also measured and an aldosterone/ cortisol ratio calculated) and then the results from the two adrenal glands compared. If they are significantly different, then it is likely that an adenoma is present in the gland with the highest aldosterone concentration.
Non-Laboratory Tests
- Blood pressure measurement - often the first indicator of possible primary hyperaldosteronism
- CT (computed tomography) scan or MRI (magnetic resonance imaging) are used to locate adrenal tumours. Determining large adrenal glands (hyperplasia) can be tricky because the size of normal adrenal glands varies a lot from one person to the next.. The interpretation of the scan can also be complicated as benign adrenal tumours are relatively common, especially as people become older. Many of these benign tumours do not produce aldosterone or other hormones and are found during investigations for other reasons.
The goal of treatment of Conn’s syndrome is to lower blood pressure to normal or near normal levels, decrease blood aldosterone levels, and resolve any electrolyte imbalance. The treatment used will depend on the cause of the excess aldosterone production. If it is due to a single benign adrenal tumour (Conn's syndrome), then the affected gland may be surgically removed. In many cases, this operation will remove the hypertension and other symptoms, but in other cases further treatment will be necessary to control blood pressure. If the primary hyperaldosteronism is due to a cancerous tumour (rare), then organs next to the adrenal gland will need to be looked at during surgery and may need to be removed.
If the cause of the primary hyperaldosteronism cannot be discovered (idiopathic) or appears to be due to hyperplasia in both adrenals, then surgery is not usually recommended. The patient’s condition will be treated with spironolactone (which blocks the action of aldosterone) and one or more blood pressure drug therapies.
Patients should consult with their doctors and, when necessary, with an endocrinologist (a specialist in the endocrine system).