What is Conn Syndrome (Primary Hyperaldosteronism)?
Conn syndrome, named after JW Conn who first identified it in 1955, is a medical condition seen in a patient with high blood pressure and an adrenal gland tumour that produced excessive amounts of a hormone called aldosterone. This condition usually leads to high blood pressure, low potassium levels, and reduced renin in the blood. Over time, similar cases involving exaggerated aldosterone production have been identified, regardless if a tumour existed or not. Today, the condition is often referred to as primary hyperaldosteronism, encompassing all such cases.
Diagnosing Conn syndrome might be challenging, but it’s important due to its potential to cure high blood pressure through surgery or medication. However, it’s crucial to differentiate between a type of tumour called an aldosteronoma and a condition called idiopathic adrenal hyperplasia. Aldosteronomas are typically removed surgically, while idiopathic adrenal hyperplasia is treated with medication. It’s also necessary to know that certain conditions can cause high aldosterone levels. These include inherited diseases, renin-responsive tumours, ectopic secretion (hormone production in unusual locations like the kidneys and ovaries), and adrenal gland cancers.
What Causes Conn Syndrome (Primary Hyperaldosteronism)?
: This syndrome can occur due to several factors like adrenal gland enlargement, benign tumors in the adrenal gland, adrenal cancer that secrets a hormone called aldosterone (a rare occurrence), or a condition called familial hyperaldosteronism. Certain gene changes have been linked to the lesser seen cases of the disease.
Familial hyperaldosteronism has different types. Type 1 happens when there’s a mix up between the CYP11B2 and CYP11B1 genes, which dictate the production of certain enzymes and hormones. Instead of being regulated by RAS, it becomes regulated by another hormone called ACTH.
Type 2 of familial hyperaldosteronism adopts an autosomal dominant pattern, meaning you only need the gene from one parent to develop the disorder. It doesn’t react to a drug called dexamethasone and may possibly be linked to a specific region on chromosome 7.
Type 3 is caused by changes or mutations in a specific gene called the KCNJ5 gene. Different mutations can cause varying disease severity.
Changes in three other genes, which are responsible for creating certain membrane proteins, can trigger increased aldosterone production. A single letter change (c.-2G>C) in the NR3C2 gene has been associated with increased activation of RAS and high blood pressure in the wider population. In most cases, these conditions originate from a specific layer of the adrenal glands and often involves significant growth of glandular tissue.
Risk Factors and Frequency for Conn Syndrome (Primary Hyperaldosteronism)
Primary hyperaldosteronism is the leading cause of secondary high blood pressure, affecting around 6% to 20% of adults who have high blood pressure. This percentage increases for those with resistant high blood pressure. In general, when people with high blood pressure were continuously monitored, about 10% had this condition. But, the number jumped to 30% when a particular screening method, which checks the ratio of aldosterone to renin hormones, was used in everyday healthcare.
- The main cause of this condition is an aldosterone-producing adenoma or non-cancerous tumor, which accounts for 50% to 60% of cases.
- The rest are due to idiopathic or bilateral adrenal hyperplasia, which basically means the adrenal glands are unusually enlarged without a known cause.
- It’s also important to note that this condition is about twice as common in women compared to men.
Signs and Symptoms of Conn Syndrome (Primary Hyperaldosteronism)
Often, people suffering from Conn syndrome don’t show any symptoms. But when they do, they might experience fatigue, muscle weakness, cramps (due to loss of potassium), headaches, and heartbeat irregularities. Other symptoms include excessive thirst and frequent urination due to low potassium levels causing a certain type of diabetes called nephrogenic diabetes insipidus.
Many individuals with Conn syndrome are diagnosed when doctors notice persistently low potassium levels and high blood pressure. Some may exhibit severe heart rhythm disturbances after being put on water pills for high blood pressure. Others might be diagnosed when their high blood pressure doesn’t respond to treatment.
- High blood pressure
- Bloated abdomen
- Ileus (a type of bowel obstruction) associated with low potassium levels
- Symptoms related to high blood pressure, such as heart murmurs, altered mental status, and eye damage (retinopathy)
It’s important to note that Conn syndrome doesn’t cause swelling due to fluid build-up because the body naturally eliminates extra sodium (a condition called spontaneous natriuresis).
Testing for Conn Syndrome (Primary Hyperaldosteronism)
If a patient with high blood pressure also has low levels of potassium, it could point to a condition called primary hyperaldosteronism. However, not all patients with this condition show low potassium levels; in fact, up to 38% of them may have normal levels, particularly those who have an uncommon kind of adrenal gland overgrowth or a genetic predisposition for the disease.
When a doctor conducts blood tests on these patients, they often find low potassium, high sodium, and a condition called metabolic alkalosis, all resulting from the hormone aldosterone affecting certain parts of the kidney. The patient may also excrete a higher-than-normal amount of potassium in their urine.
A higher ARR can indicate primary hyperaldosteronism, but the specific cut-off points vary because testing methods and ways of interpreting results differ. Even though a high ARR might suggest primary hyperaldosteronism, doctors still need to run additional tests to confirm the diagnosis. However, there’s no standardized best test in the medical community for confirming primary hyperaldosteronism, leading different healthcare providers to use different tests.
Once doctors have established that the patient’s body is producing aldosterone when it shouldn’t be, they need to investigate whether the patient might have a certain kind of hormonal gland tumor. A CT scan is an effective way of doing this but it doesn’t always produce an accurate diagnosis.
The doctor will likely follow up with more tests, keeping in mind that the best method depends on the patient’s individual situation. It’s important to know when the hormone levels peak and when they dip, as these details can help distinguish between different types of hyperaldosteronism.
In general, these tests should be performed on patients with certain types of high blood pressure and those with a family history of early-onset hypertension or certain types of strokes or brain conditions. Additionally, any patient suspected of having secondary hypertension should also be tested.
Treatment Options for Conn Syndrome (Primary Hyperaldosteronism)
The goals of treating diseases linked to the overproduction of aldosterone, a hormone that helps balance salt and water in the body, are to normalize blood pressure, electrolyte levels, and aldosterone levels. The treatment method depends on what’s causing the problem. For patients with a noncancerous tumor on one adrenal gland, a surgery to remove it can cure high blood pressure in 30-60% of cases. However, for patients with idiopathic hyperaldosteronism, a condition where both adrenal glands have become overactive, the cure rate drops to about 19% even after one or both adrenal glands are removed. The standard treatment for these patients is drug therapy, primarily involving medicines that block the effect of aldosterone, such as spironolactone and eplerenone, or other drugs that help spare potassium from being eliminated by the body, like amiloride.
Before surgery, patients need to be medically optimized to lower their blood pressure and minimize surgical risks. Aldosterone-blocking drugs such as eplerenone and spironolactone are typically used as they have been shown to have survival benefits. Spironolactone is often preferred as it not only lowers blood pressure but also helps maintain normal potassium levels and fluid volume in the body. For a small group of patients who have excessive aldosterone production due to the presence of glucocorticoids, low-dose corticosteroids can help control blood pressure.
Surgery may not be the best option for some patients, especially those who are very weak and have multiple other health issues. Also, those diagnosed with bilateral adrenal hyperplasia, a condition where both adrenal glands are overactive, are usually managed through drug therapy. In cases where only one adrenal gland is affected, surgery to remove the gland is often the preferred choice. Prior to surgery, patients are usually treated with spironolactone for 4-6 weeks. Nowadays, surgery to remove the adrenal gland, called laparoscopic adrenalectomy, is often performed using minimally invasive techniques.
The results of treatment can vary. Following surgery, normal blood pressure is achieved in about two-thirds of patients, but it can take 6-12 months for the blood pressure to fully stabilize. However, after five years, only about half of the patients maintain their normal blood pressure. Additionally, those who did not respond to spironolactone before surgery are often prone to continue having high blood pressure even after undergoing surgery.
What else can Conn Syndrome (Primary Hyperaldosteronism) be?
When a doctor is trying to diagnose Conn syndrome, there are several other conditions they need to consider because they can cause similar symptoms. These include:
- High blood pressure (Hypertension)
- A condition where the body’s fluids are too alkaline (Metabolic alkalosis)
- Narrowing of arteries supplying blood to the kidneys (Renal artery stenosis)
- Very high blood pressure that can damage the body (Malignant hypertension)
- High blood pressure during pregnancy (Preeclampsia)
- Consuming too much licorice
- Gitelman syndrome, a kidney disorder
- Bartter syndrome, another type of kidney disorder
- Cancer of the adrenal gland (Adrenal carcinoma)
The doctor would have to take into account these possibilities and perform necessary tests to make a correct diagnosis.
What to expect with Conn Syndrome (Primary Hyperaldosteronism)
Conn syndrome, if not treated, can lead to severe health complications and even death. The main health issues related to this condition are high blood pressure and low levels of potassium in the blood. Low potassium levels can cause heart rhythm problems, which can be life-threatening.
Possible Complications When Diagnosed with Conn Syndrome (Primary Hyperaldosteronism)
Complications usually stem from chronic high blood pressure, or hypertension, which could lead to severe health problems such as heart attack, stroke, or heart failure. Additionally, high blood pressure can damage the eyes (retinopathy) and kidneys (end-stage renal disease). Conn syndrome, a specific hormonal disorder, can also bring about complications post surgery.
Common complications:
- Heart attack
- Stroke
- Heart failure
- Eye damage (Retinopathy)
- Significant kidney damage (End-stage renal disease)
- Complications post Conn Syndrome surgery
Recovery from Conn Syndrome (Primary Hyperaldosteronism)
Following surgery, it’s crucial to keep a close eye on blood pressure for several months. Some patients may experience high levels of potassium in their blood, which could require treatment with water pills. A diet low in salt is advised, particularly as it helps to control high blood pressure.
