Aldosterone and Renin

Aldosterone and renin tests are used to evaluate whether the adrenal glands are producing appropriate amounts of aldosterone and to distinguish between the potential causes of excess or deficiency. Aldosterone may be measured in the blood or in a 24-hour urine sample, which measures the amount of aldosterone removed in the urine in a day. Renin is always measured in blood.

These tests are most useful in testing for primary aldosteronism, also known as Conn syndrome, which causes high blood pressure. If the test is positive, aldosterone production may be further evaluated with stimulation and suppression testing.

Both aldosterone and renin levels are highest in the morning and vary throughout the day. They are affected by the body’s position, by stress, and by a variety of prescribed medications.

A blood aldosterone test and a renin test are usually ordered together when someone has high blood pressure, especially if the person also has low potassium. Even if potassium is normal, testing may be done if typical medications do not control the high blood pressure or if hypertension develops at an early age. Primary aldosteronism is a potentially curable form of hypertension, so it is important to detect and treat it properly.

Aldosterone levels are occasionally ordered, along with other tests, when a healthcare practitioner suspects that someone has adrenal insufficiency or Addison disease. One of those tests, the aldosterone stimulation test, also called ACTH stimulation, tests aldosterone and cortisol to determine if someone has Addison disease, low pituitary function, or a pituitary tumor. A normal result is a cortisol increase and an increase in aldosterone after stimulation by ACTH.

The table below indicates the changes in renin, aldosterone, and cortisol that occur with different disorders.

Primary aldosteronism (Conn syndrome) is caused by the overproduction of aldosterone by the adrenal glands, usually by a benign tumor of one of the glands. The high aldosterone level increases reabsorption of sodium (salt) and loss of potassium by the kidneys, often resulting in an electrolyte imbalance. Signs and symptoms include high blood pressure, headache, and muscle weakness, especially if potassium levels are very low.

Lower than normal blood potassium (hypokalemia) in someone with hypertension suggests the need to look for aldosteronism. Sometimes, to determine whether only one or both adrenal glands are affected, blood may be taken from both of the adrenal veins and testing is done to determine whether there is a difference in the amount of aldosterone (and sometimes cortisol) produced by each of the adrenal glands.

Secondary aldosteronism, which is more common than primary aldosteronism, is caused by anything that leads to excess aldosterone, other than a disorder of the adrenal glands. It could be caused by any condition that decreases blood flow to the kidneys, decreases blood pressure, or lowers sodium levels. Secondary aldosteronism may be seen with congestive heart failure, cirrhosis of the liver, kidney disease, and toxemia of pregnancy (pre-eclampsia). It is also common in dehydration. In these conditions, the cause of aldosteronism is usually obvious.

The most important cause of secondary aldosteronism is narrowing of the blood vessels that supply the kidney, termed renal artery stenosis. This causes high blood pressure due to high renin and aldosterone and may be cured by surgery or angioplasty. Sometimes, to see if only one kidney is affected, a catheter is inserted through the groin and blood is collected directly from the veins draining the kidney (renal vein renin levels). If the value is significantly higher in one side, this indicates where the narrowing of the artery is present.

Low aldosterone (hypoaldosteronism) usually occurs as part of adrenal insufficiency. It causes dehydration, low blood pressure, a low blood sodium level, and a high potassium level. When infants lack an enzyme needed to make cortisol, a condition called congenital adrenal hyperplasia, this can decrease production of aldosterone in some cases.

The amount of salt in your diet and medications, such as over-the-counter pain relievers of the non-steroid class, diuretics, beta blockers, steroids, angiotensin-converting enzyme (ACE) inhibitors, and oral contraceptives can affect the test results. Some of these drugs are used to treat high blood pressure. Stress, exercise, and pregnancy can also affect the test results. Your healthcare provider will tell you if you should change the amount of sodium (salt) you ingest in your diet, your use of diuretics or other medications, or your exercise routine before aldosterone testing.

Licorice may mimic aldosterone properties and should be avoided for at least two weeks before the test because it can decrease aldosterone results. This refers only to the actual products of the licorice plant (hard licorice); most soft licorice and other forms of licorice sold in North America do not actually contain licorice. Check the package label if you are uncertain, or bring a package with you to ask the healthcare practitioner.

Aldosterone levels become very low with severe illness, so testing should not be done at times when someone is very ill.

You may be asked to arrive well before your testing time so you can remain in a lying or upright position long enough to establish that as your baseline testing position.

An aldosterone/renin ratio (ARR) is a screening test to detect primary aldosteronism in high-risk, hypertensive individuals. To determine the ratio, blood levels of aldosterone and renin are measured and a calculation is done by dividing the aldosterone result by the renin result. The ARR is considered the most reliable screening for primary aldosteronism, though it is not straightforward to interpret. Anything that could interfere with the test, such as medications, posture, sodium intake, and plasma potassium, needs to be taken into account before the test to avoid false positives or false negatives. Other tests, like suppression tests, are used to confirm the diagnosis after screening.

Aldosterone suppression tests are used to confirm a diagnosis of primary aldosteronism. There are a few different types of suppression tests:

• You may be instructed to follow a high-salt diet for three days, then have your aldosterone and sodium in your urine measured.
• You may have a saline (salt) solution administered through a vein (intravenous, IV) and then have your aldosterone level measured.
• You may follow a high-salt diet and be administered a synthetic corticosteroid called fludrocortisone, then have your aldosterone level measured.

In healthy people who are on a high-salt diet or who are administered saline or fludrocortisone, their aldosterone level will be suppressed.

The aldosterone stimulation test, also called ACTH stimulation, tests aldosterone and cortisol to determine if someone has adrenal insufficiency (Addison disease), low pituitary function, or a pituitary tumor. This test involves measuring aldosterone and cortisol before and after an injection of synthetic ACTH. A normal result is an increase in aldosterone and cortisol after stimulation by ACTH.

Bartter syndrome is a group of rare congenital disorders that affect the kidney’s ability to reabsorb sodium. People with Bartter syndrome lose too much sodium through the urine. This causes a rise in the level of the aldosterone and makes the kidneys remove too much potassium from the body. The syndrome is therefore associated with high levels of renin and aldosterone in the blood, increased blood pH (alkalosis), and high levels of potassium, calcium, and chloride in the urine.

The syndrome, which is usually diagnosed in early childhood, can be caused by mutations in at least one of five genes, and genetic testing can confirm a diagnosis. There are different types of Bartter syndrome, defined based upon which gene is the cause of the condition.

Signs and symptoms will vary depending on the type of Bartter syndrome. The antenatal form (appears before birth) can be life-threatening. The classical form found in infants and young children usually causes failure to thrive, constipation, muscle cramping and weakness as well as dehydration, increased urine production, and weakened bones.

The condition cannot be cured, but a few treatments are available, such as keeping an affected person’s blood potassium from being abnormally low through a potassium-rich diet or by taking supplements. While, with treatment, prognosis is good, those affected must be careful to maintain fluid and electrolyte balance. Kidney failure is a possible complication of Bartter syndrome. For more information, see The Bartter Site.