Conn’s Syndrome – Types, Complications and Risk factors

Definition

Conn’s Syndrome means the adrenal glands produce too much of the steroid hormone aldosterone, which helps regulate sodium and potassium excretion. The adrenal glands are two small triangular glands, one on top of each kidney. This condition, also called primary aldosteronism, results from overproduction of aldosterone by one or both adrenal glands. Overproduction of aldosterone by both glands, noncancerous masses in one adrenal gland or, very rarely, cancerous tumors, can cause overproduction of aldosterone.

Primary aldosteronism usually manifests with high blood pressure and low potassium levels in the blood. Left unchecked, high blood pressure raises your risk for complications including heart attack and stroke, while low potassium can cause heart rhythm irregularities.

Types of Conn’s Syndrome

There are two types of hyperaldosteronism, known as primary and secondary hyperaldosteronism. While they have similar symptoms, their causes are different.

Primary hyperaldosteronism

Primary hyperaldosteronism is caused by a problem with one or both adrenal glands. It’s sometimes referred to as Conn’s syndrome. Some people are born with overactive adrenal glands. Others might have it due to: a benign tumor on
one of the adrenal glands, adrenocortical cancer, which is a rare aldosteroneproducing cancerous tumor, glucocorticoid-remediable aldosteronism, a type of aldosteronism that runs in families and other types of inheritable issues that affect the adrenal glands.

Secondary hyperaldosteronism

Secondary hyperaldosteronism is caused by something outside the adrenal glands. It’s usually related to reduced blood flow to your kidneys. Several things can cause this, including: a blockage or narrowing of the renal artery, chronic liver disease, heart failure and diuretic medications.

Epidemiology

In between 6% and 20% of adult hypertensive patients, and more frequently in those with resistant hypertension, primary hyperaldosteronism is the most frequent cause of secondary hypertension. When identical patients with hypertension were assessed, the prevalence of 10% was reported. When the aldosterone to renin ratio (ARR) was utilised as a screening technique in general practise, the prevalence rose to 30%. 50% to 60% of cases have an aldosterone-producing adenoma, and the remaining 20% have bilateral or idiopathic adrenal hyperplasia. It affects women nearly twice as often as it does males.

Pathophysiology of Conn’s Syndrome

Primary hyperaldosteronism is caused by aldosterone-producing adenomas, bilateral idiopathic adrenal hyperplasia, aldosterone-producing adrenal carcinoma, and familial aldosteronism. The increased amount of aldosterone potentiates renal sodium reabsorption and water retention, and potassium excretion. The increased sodium reabsorption by the kidneys results in plasma volume expansion which is the primary initiating mechanism for hypertension. This may induce tissue inflammation and heightened sympathetic drive, with subsequent development of fibrosis in vital organs, such as heart, kidneys, and vasculature. As a result, this may lead to the development of chronic kidney disease, atrial fibrillation, stroke, ischemic heart disease, and congestive heart failure.

Besides the elevation in sodium, patients often develop hypokalemia and metabolic alkalosis. Nearly 1/5th of patients with Conn syndrome have impairment in glucose tolerance which is due to the inhibitory effects of hypokalemia on insulin secretion.

Causes of Conn’s Syndrome

Conn’s Syndrome occurs when the adrenal glands release too much aldosterone.

Primary hyperaldosteronism is due to a problem of the adrenal glands themselves. Most cases are caused by a noncancerous (benign) tumor of the adrenal gland.

Secondary hyperaldosteronism is due to a problem elsewhere in the body that causes the adrenal glands to release too much aldosterone. These problems can be with:

• Genes
• Diet
• Medical disorders such as with the heart, liver, kidneys, or high blood pressure

The condition mostly affects people 30 to 50 years old and is a common cause of high blood pressure in middle age.

Symptoms of Conn’s Syndrome

Most often, patients have higher than normal blood pressure. Blood tests help to tell if high blood pressure is from Conn’s Syndrome or something else. The usual treatment for high blood pressure doesn’t generally help treat hyperaldosteronism.

The abnormal electrolyte levels often seen with too much aldosterone lead to signs such as:

• Lack of muscle strength
• Frequent voiding
• Nighttime voiding
• Headache
• Increased thirst
• Pins and needles feeling
• Eyesight problems
• Paralysis that comes and goes
• Muscle twitching and cramps

The severity may depend on the degree of the electrolyte abnormality.

Risk factors

Most primary aldosteronism is considered sporadic (unrelated to family genetics). A risk factor for PA is anything that increases the risk of developing PA.

Not everyone with a family member with PA will develop it, but if there are other indicators for screening, familial hyperaldosteronism can be considered.

There are four forms of familial hyperaldosteronism (FH): types I-IV. If FH is suspected based on a family history, a genetic counselor can help determine the risk for a familial disorder and order appropriate genetic testing.

Complications of Conn’s Syndrome

Complications are often related to the underlying chronic hypertension that can cause acute myocardial infarction, stroke and heart failure.

Most important, hypertension can also lead to retinopathy and end-stage renal disease.

The surgery for Conn syndrome can also lead to complications.

Diagnosis

Primary hyperaldosteronism is diagnosed by measuring the blood levels of aldosterone and renin (a hormone made by the kidney). To best measure these hormones, blood samples should be drawn in the morning. In primary hyperaldosteronism, the aldosterone level will be high while renin will be low or undetectable. The potassium level may be low or normal. If these tests are positive, then patients may have another test to confirm the diagnosis. These tests try to lower the amount of aldosterone produced either by giving a medication or giving extra salt through the diet or an intravenous fluid. If the aldosterone level is high and the renin level is low after these tests, the diagnosis is confirmed. Some medications, especially blood pressure medications, can interfere with these tests. Your physician will review your medications and decide if any need to be stopped for 4 to 6 weeks prior to testing. In general, patients with a long-standing history of hypertension or difficult to control hypertension should be screened for hyperaldosteronism.

PAC:PRA ratio

This blood test is a screening test, meaning that it is performed if hyperaldosteronism is suspected but not yet diagnosed. A high ratio of PAC to PRA suggests primary hyperaldosteronism, but additional testing may be needed to confirm the diagnosis.

Captopril Suppression Test

This blood test measures the body’s response to captopril, a medication used to treat high blood pressure. Results of this test can confirm whether a person has primary hyperaldosteronism.

24-hour Urinary Excretion of Aldosterone Test

Patients eat a high-salt diet for five days, and then undergo urine tests during a 24-hour period. If the level of aldosterone in the urine is high, such results can confirm that a patient has primary hyperaldosteronism.

Saline Suppression Test

In this test, the patient receives a salt solution through an IV. A blood test then measures the patient’s levels of aldosterone and renin. Primary hyperaldosteronism can be confirmed if the level of aldosterone in the blood remains high and renin is low after this salt loading.

Localization

For patients with proven primary hyperaldosteronism, the next step is to figure out if this is unilateral or bilateral disease. This is critical because the treatment for each is different. A computed tomography (CT or CAT) scan or magnetic resonance imaging (MRI) scan will be done to see if there is a tumor in either adrenal gland. If the patient is younger than 40 years old and there is a tumor in only one adrenal (especially if it is between 1 and 2 cm), then the patient may go directly to treatment.

If the patient is older than 40 and/or there is either no tumor seen or tumors in both adrenals, then the patient will have a special test called selective venous sampling. In this test, a surgeon or radiologist will draw blood directly from the veins draining both adrenal glands to determine if one or both are making too much hormone. Significantly higher hormone levels on one side only clinches the diagnosis of unilateral disease. Selective venous sampling is usually done as an outpatient procedure.

Treatment

Treating hyperaldosteronism focuses on reducing your aldosterone levels or blocking the effects of aldosterone, high blood pressure, and low blood potassium. There are several ways to do this, depending on what’s causing your hyperaldosteronism.

• Medication – We might prescribe a mineralocorticoid receptor antagonist, such as spironolactone. This type of medication blocks the effects of aldosterone on your body, such as high blood pressure and low blood potassium. You may still need to take additional medications to help manage your blood pressure.
• Surgery – If you have a tumor on one of your adrenal glands, we will refer you to a doctor who may be able to remove the affected gland. Following the procedure, called an adrenalectomy, you’ll likely notice a gradual decrease in blood pressure.  As you heal, we will regularly monitor your blood pressure to determine whether it’s time to change your blood pressure medication. Eventually, you may be able to stop taking it completely.

Lifestyle changes

In addition to medication and surgery, there are several lifestyle changes you can make to provide additional health benefits and help counteract the effects of too much aldosterone.  These include:

Eating a healthy diet: Following a balanced diet that helps you maintain a healthy weight can reduce your blood pressure. Start by choosing fresh, unprocessed foods to reduce your salt intake. Try incorporating elements of the DASH diet, which is designed for people with high blood pressure. In addition, many blood pressure medications work better when combined with a healthy diet. A diet lower in salt is often key in hyperaldosteronism.

Exercising: Consistent exercise, even just a 30-minute walk a few times a week, can help to reduce blood pressure.

Reducing alcohol and caffeine: Caffeine and alcohol can both increase your blood pressure. Some blood pressure medications are also less effective when taken with alcohol.

Quitting smoking: Smoking cigarettes constricts your blood vessels, which increases your heart rate and can raise blood pressure. Smoking also increases your risk of heart attack and stroke, even without high blood pressure.

Prevention of Conn’s Syndrome

There is no known way to prevent it, but it is advisable to keep blood pressure low. For this, it is important to lead a healthy lifestyle:

• A balanced and healthy diet
• Appropriate weight
• Exercise regularly
• Don’t smoke, and limit alcohol and caffeine intake