Conn’s syndrome

What is Conn's syndrome?

The name goes back to the American physician Dr. Jerome Conn, who first described the disease in 1955. In medical terminology, it is also known as “primary hyperaldosteronism”. This term indicates that the cause of the disease is an excess of the hormone aldosterone. Aldosterone contributes significantly to the regulation of the body’s water and salt balance. Through its effect on special transporters in the kidneys, it promotes the excretion of potassium and inhibits the excretion of sodium and water.

While aldosterone levels in healthy people vary constantly in order to keep fluid volume and salt concentrations in the body within narrow limits, in Conn’s syndrome there is a constant excess of aldosterone. As an excessive amount of water and sodium is retained in the body as a result, an increase in the volume of fluid in the vascular system leads to high blood pressure, known as arterial hypertension. The additional increase in potassium excretion can also lead to low potassium levels in the blood, known as hypokalemia. In the long term, the disease favors the development of serious cardiovascular diseases such as heart attacks or strokes. Early treatment can prevent these complications. Effective medication and, for some patients, surgery are available for this purpose.

Conn’s syndrome – frequency and age

It is estimated that eight to twelve percent of all hypertensive patients (people with high blood pressure) suffer from Conn’s syndrome. Considering that almost one in six people in Switzerland suffers from high blood pressure, this means that at least 175,000 people in Switzerland are affected by Conn’s syndrome. This makes the disease the most common cause of so-called secondary forms of hypertension, i.e. those 15 percent of all forms of blood pressure that are based on a specific trigger. Far more frequently, namely in 85 percent of cases, no clear trigger can be identified. This is referred to as primary or essential hypertension. Conn’s syndrome occurs more frequently between the ages of 30 and 50, but can occur at any age. Women and men are affected about equally often.

Conn's syndrome: causes

Conn’s syndrome is caused by an overproduction of aldosterone in the adrenal glands. Depending on the underlying cause, the following subtypes of the disease are distinguished:

• An enlargement of both adrenal glands, known as bilateral adrenal cortical hyperplasia, can lead to an overproduction of aldosterone. It is the most common cause, accounting for around 60 percent of all cases.
• A benign tumor of the adrenal cortex, a so-called aldosterone-producing adenoma, is also a possible source of aldosterone and is the second most common cause, accounting for 40 percent of all cases. These tumors are usually found in only one of the two adrenal glands. This form of the disease is comparatively often associated with low potassium levels in the blood.

There are also much rarer causes, which each account for less than one percent of all cases:

• a very rare unilateral enlargement of the adrenal cortex, known as unilateral adrenal cortical hyperplasia
• an aldosterone-producing, malignant tumor of the adrenal cortex
• familial hyperaldosteronism, i.e. a very rare hereditary form caused by a genetic defect

Conn's syndrome: symptoms

In almost all cases, Conn’s syndrome leads to the development of permanent high blood pressure. This can hardly be distinguished from other forms of hypertension. High blood pressure resulting from primary hyperaldosteronism can often only be inadequately controlled despite taking several antihypertensive drugs. Very high blood pressure levels can cause symptoms such as fatigue, headaches, dizziness, ringing in the ears, nosebleeds, palpitations or a feeling of pressure on the chest. If Conn’s syndrome also leads to low potassium levels in the blood (up to 1/3 of all cases), muscle weakness or cramps, constipation and cardiac arrhythmia can occur. In many cases, however, primary hyperaldosteronism is asymptomatic and goes unnoticed for a long time. However, this disease is by no means harmless: Conn’s syndrome can also lead to serious secondary diseases of the cardiovascular system when it is silent.

Conn’s syndrome: Diagnosis with us

As the causes and consequences of secondary hypertension always affect several organ systems, its diagnosis and treatment require a comprehensive, multidisciplinary approach. At the USZ, all the disciplines involved (endocrinology, cardiology, angiology, nephrology, pneumology, internal medicine, radiology and visceral surgery) therefore work hand in hand under one roof. In most cases, high blood pressure, a persistently low potassium level in the blood or an adrenal gland nodule discovered by chance during other investigations lead to the suspicion of primary hyperaldosteronism.

Diagnostics consists of a multi-stage process. First, a blood test is carried out to look for Conn syndrome. If the result is positive, a second blood test is required to definitively confirm or rule out the disease. If primary hyperaldosteronism is diagnosed, further examinations are carried out to clarify which subtype of the disease is present. The differentiation of the respective subtype is an important prerequisite for the subsequent selection of a specific treatment.

Our daily endeavor is to always offer all those affected the best possible and most efficient diagnosis and treatment and at the same time to help develop these ourselves. The Hypertension Research Network (HYRENE) has dedicated itself to this goal. Several research groups at the USZ and the University of Zurich are working hard in this unique network to gain new insights into the field of hypertension and make them available to those affected.

Conn’s syndrome: blood tests

At the beginning of the investigations, the blood concentrations of aldosterone and another hormone called renin, which controls the release of aldosterone from the adrenal glands, are determined. The formation of the ratio of both hormone concentrations, the so-called aldosterone-renin quotient, serves as a screening test for Conn’s syndrome. If the quotient is above a defined limit value, it indicates the presence of primary hyperaldosteronism. If it is below this level, the disease is very probably ruled out. The increased quotient characteristic of Conn’s syndrome results from the fact that the blood concentration of aldosterone is very high, while that of renin is very low. However, as the screening test does not prove the presence of the disease, a confirmatory test must be carried out in any case.

Several tests are available here (for example the captopril test and the fludrocortisone suppression test). However, the so-called saline load test is used most frequently. In this test, a total of 2 liters of saline solution are administered via an infusion over 4 hours. The saline and volume load on the body leads to a rapid drop in the aldosterone concentration in the blood of healthy people. However, if Conn’s syndrome is present, the concentration of aldosterone is hardly affected, so that the hormone level remains high. If both tests, the screening test and the subsequent confirmation test, are abnormal, a diagnosis of primary hyperaldosteronism is made. It is important to note that in many cases a temporary switch from previously taken blood pressure medication to alternative preparations must be made before the tests in order to obtain meaningful results. This is due to the fact that some active ingredients in common blood pressure medications can falsify the measured values.

Examination of the adrenal gland with CT and MRI

Once the diagnosis of Conn’s sydrome is confirmed, either a computed tomography (CT) scan or magnetic resonance imaging (MRI) of the abdomen is performed to visualize the adrenal glands. Sectional images can be used to detect tumors of the adrenal glands or other abnormalities of the adrenal cortex. It should be noted that the detection of an adrenal tumor does not necessarily mean that it is the source of the aldosterone. Benign adrenal tumors that do not produce hormones (“hormone-inactive adenomas”) are not uncommon and increase in frequency with increasing age. Very small tumors of the adrenal glands (< 5 mm in size), which are sufficient to cause the disease, can be missed on imaging.

Adrenal vein blood sampling

In many cases, it makes sense to supplement the sectional imaging with blood sampling from the adrenal veins, a so-called adrenal vein catheter sampling. The examination usually takes place on an outpatient basis and serves to localize the source of aldosterone (unilateral versus bilateral). After local anesthesia, an interventional radiologist inserts a catheter into the inguinal vein and advances it to the draining blood vessels (veins) of the adrenal glands. Blood can now be taken from the left and right adrenal glands and the concentration of aldosterone measured. If there are relevant lateral differences, this indicates a unilateral aldosterone source, i.e. a unilateral aldosterone-producing adenoma. However, if the aldosterone concentration is approximately the same on both sides, it can be assumed that the disease is caused by bilateral adrenal cortical hyperplasia, i.e. an enlargement of the adrenal glands on both sides.

Conn's syndrome: early detection

Unfortunately, primary hyperaldosteronism is often discovered late despite its prevalence and its great importance for those affected. It is not uncommon for years or decades to pass before a diagnosis is made. Often there are only unspecific symptoms, if any, which do not give rise to any suspicion of the presence of this disease. The high blood pressure resulting from excess aldosterone is also often mistaken for “normal”, i.e. primary, high blood pressure for a long time. However, certain indications increase the probability of the presence of primary hyperaldosteronism and should therefore lead to an appropriate clarification:

• At least moderate high blood pressure with values >160/100 mmHg
• High blood pressure that is difficult to control despite taking several antihypertensive drugs
• Well-controlled blood pressure while taking four antihypertensive drugs
• High blood pressure and a low potassium level in the blood at the same time
• High blood pressure and a nodule (discovered by chance) in the adrenal gland
• High blood pressure and the simultaneous presence of sleep apnea syndrome (a syndrome that causes breathing to stop at night)
• Conn’s syndrome in first-degree relatives or a diagnosis of high blood pressure before the age of 30 in a family member

Course and prognosis of Conn’s syndrome

The course and prognosis of primary hyperaldosteronism depend largely on how early the disease is recognized and treated. The disease can potentially be cured by surgery. If surgery is not an option, effective, specific medication is available. If left untreated, primary hyperaldosteronism leads to serious secondary diseases and organ damage in the medium to long term (e.g. arteriosclerosis, heart attack, stroke, impaired kidney function). It is now known that high blood pressure resulting from Conn’s syndrome leads to complications earlier and more frequently than other forms of high blood pressure without treatment.

Treatment details

In principle, primary hyperaldosteronism can be treated with medication and surgery. Both concepts have proven to be very effective over decades. The success of treatment is assessed primarily on the basis of blood pressure control, the aldosterone/renin quotient and the potassium level in the blood. The decision for or against a particular therapy must always be made on a case-by-case basis. It is particularly dependent on the subtype of primary hyperaldosteronism. In addition, patient preference, concomitant diseases and the findings of cross-sectional imaging and laboratory tests are taken into account.