What is Primary Hyperaldosteronism?
Primary hyperaldosteronism (PA) is a medical condition that often goes unnoticed but can cause high blood pressure. Typically, it’s expected to find this condition in individuals who have high blood pressure along with low potassium levels. However, in most cases, patients don’t have low potassium levels. The top two causes of PA are adenomas that produce aldosterone (small, benign tumors in the adrenal gland), and the overactivity of the adrenal gland area called the “zona glomerulosa”.
Some forms of PA can be passed down in families, and these are divided into three types: Type I, Type II, and Type III familial hyperaldosteronism. To make an initial diagnosis, doctors often use a blood test that measures the ratio of aldosterone (a hormone that regulates blood pressure) to plasma renin activity (a protein involved in blood pressure control) in the morning. If the ratio is over 20 to 1, it means the adrenal gland is producing too much aldosterone.
Where possible, removing the affected adrenal gland through a surgery called adrenalectomy, is the best treatment for those who have the disease in just one adrenal gland. However, individuals who are not well suitable for surgery or have overactivity in both adrenal glands, can use medication to block the effects of aldosterone and manage high blood pressure.
What Causes Primary Hyperaldosteronism?
The most common reason for primary hyperaldosteronism, a condition where the adrenal glands make too much of the hormone aldosterone, is due to growths known as aldosterone-producing adenomas. Other causes can include adrenal cancer that produces aldosterone, abnormal aldosterone secretion from the kidneys or ovaries, and bilateral zona glomerulosa hyperplasia, a condition where certain cells in the adrenal gland grow excessively.
Family history can also play a role in causing this condition. Type I, known as glucocorticoid-remediable hyperaldosteronism, occurs when a hybrid gene is formed. This gene contains parts of two different enzymes, 11B-hydroxylase, which is normally regulated by a hormone called ACTH, and aldosterone synthase. As a result of this gene formation, ACTH ends up stimulating aldosterone synthase, leading to increased production of aldosterone.
The reasons behind Type II are unclear; however, it is linked to a gene found on 7p22 (band 11q13), and findings typically show either excessive growth or adenomas in tissues.
Type III occurs due to a mutation in a gene called KCNJF, which is in charge of coding potassium channels. This mutation leads to increased availability of calcium ions in certain adrenal gland cells, resulting in increased aldosterone production.
Risk Factors and Frequency for Primary Hyperaldosteronism
Primary hyperaldosteronism is a global medical issue and there’s no sign that it’s more prevalent in some areas than others. Women tend to have more cases of aldosterone-producing adenomas, a type of this disease, than men. Research also suggests that people of African origin or African Americans might exhibit a higher occurrence, especially in the variant of the disease known as idiopathic adrenal hyperplasia.
Signs and Symptoms of Primary Hyperaldosteronism
Primary hyperaldosteronism is a suspected diagnosis when a young person experiences high blood pressure that is difficult to control, even with three different kinds of blood pressure medications, including a water pill. This condition may also be indicative if the individual has a family history of early high blood pressure or of having a stroke at a young age. Symptoms might include serious muscle weakness, heart palpitations, fatigue, or muscle cramps, all of which could be a result of low potassium levels. Others may experience excessive thirst and urination due to a type of water imbalance caused by low potassium levels.
It was once believed that low potassium levels were a common sign of primary hyperaldosteronism, but recent estimates suggest less than 37 percent of patients with this condition will have low potassium. Patients who consume appropriate amounts of sodium could be more likely to suffer from low potassium. This is because as more sodium is delivered to certain tubes in the kidneys due to increased sodium intake, this leads to more potassium being expelled due to heightened levels of aldosterone, a hormone. Therefore, even if a patient does not display low potassium levels, the diagnosis could still be considered when a patient is resistant to blood pressure medication, or has low potassium levels upon starting a low dose of a water pill.
- Young patients experiencing high blood pressure that’s hard to control with medication
- Family history of early high blood pressure or stroke
- Severe muscle weakness
- Heart palpitations
- Fatigue
- Muscle cramps (due to low potassium levels)
- Excessive thirst and urination
Physical examinations won’t directly indicate a diagnosis of primary hyperaldosteronism. However, too much blood pressure can strain the heart, leading to an enlarging of the heart’s main pumping chamber and creating a certain heart sound. Chronic high blood pressure can cause effects throughout the body, including heart failure, protein in urine (a possible sign of kidney damage), changes in the retina due to high blood pressure, sound caused by narrowed blood vessels in the neck, symptoms of stroke, muscle weakness, and changes in mental status due to high blood pressure affecting the brain.
Testing for Primary Hyperaldosteronism
The Endocrine Society suggests certain patients might need to be checked for a condition called primary hyperaldosteronism. Such patients include those who have high blood pressure that doesn’t get better even with three different medications and those who lose potassium because they are taking a type of medicine called a diuretic. Also, if you have high blood pressure and someone in your family had a stroke at an early age, or you have a family member who has primary hyperaldosteronism, you might need to be checked.
Doctors think you might have primary hyperaldosteronism if you are younger and have high blood pressure, low potassium, and your blood pressure doesn’t get better with treatment. To check, your doctor might ask you to have a blood test in the morning to check two things in your blood called aldosterone and renin. If the ratio of aldosterone to renin is more than 20 to 1, then it suggests that the problem might be in your adrenal gland. Your doctor might also ask you to have other tests: swallowing a sodium pill, having a saline infusion, taking a drug called fludrocortisone, or taking a drug called captopril. These tests are expected to lower aldosterone levels in your blood, but if you have primary hyperaldosteronism, these levels might not drop. After confirming primary hyperaldosteronism, your doctor will ask you to have an adrenal CT scan to see if your adrenalin gland is healthy. You might also have to give a blood sample from your adrenal vein.
One of the best ways to check for primary hyperaldosteronism is to measure two things – cortisol and aldosterone – in your adrenal and peripheral veins before and after a medication called ACTH is given to you. These measurements can tell if an adenoma (non-cancerous tumor) is present. If only one adenoma is found, doctors usually go for a surgery called laparoscopic adrenalectomy. However, if surgery is not an option for you, medication is the way forward. If the origin of the problem is in both adrenal glands, then medication is usually given.
Treatment Options for Primary Hyperaldosteronism
The main treatment for primary hyperaldosteronism, a condition where the adrenal glands produce too much of the hormone aldosterone, is a type of minimally invasive surgery called laparoscopic resection. This procedure is used to remove adenomas, which are small, benign tumors. This approach often corrects low potassium levels (hypokalemia) in the body. However, high blood pressure may still continue in up to 65% of patients after the surgery.
Surgery is usually recommended for patients who have a condition where only one of the adrenal glands is producing too much aldosterone. After the affected adrenal gland is surgically removed, nearly all patients experience resolved hypokalemia and some improvement in controlling their blood pressure.
If the patient can’t have surgery or if both adrenal glands are overproducing aldosterone (a condition known as bilateral adrenal hyperplasia), they may be treated with certain drugs such as spironolactone or eplerenone, which block the actions of aldosterone (known as mineralocorticoid antagonists). A study showed that spironolactone was more effective than eplerenone in helping control blood pressure in patients with primary hyperaldosteronism.
Another drug that might be helpful is amiloride, which blocks sodium channels in the body. Other drugs for controlling blood pressure can be continued as needed. For patients who can’t have surgery, spironolactone is often used as the first choice of drug treatment.
What else can Primary Hyperaldosteronism be?
In patients who have high blood pressure that refuses to drop despite treatment, there are other possible underlying conditions that doctors will look into. These include narrowing of the kidney arteries, high levels of aldosterone hormone due to other causes, certain types of tumors and low blood supply to the kidneys. Excessive consumption of licorice can also cause blood pressure issues because it can affect how the kidneys process the hormone cortisol. When there’s too much cortisol, it can act like another hormone that can raise blood pressure.
There are also some genetic diseases that look like primary hyperaldosteronism, a condition in which the adrenal glands produce too much of the hormone aldosterone. These include:
- Chrétien syndrome: This is a rare disease caused by too much POMC hormone from a type of tumor called pituitary adenoma. This leads to a specific type of high blood pressure.
- Gitelman syndrome: This disease affects the function of the salt transporter in kidney cells, leading to loss of salt from the body and a secondary increase of aldosterone.
- Liddle syndrome: This is a genetic condition that makes kidney cells too active in absorbing salt, which leads to high blood pressure. However, levels of aldosterone and another hormone, renin, are low in this condition.
What to expect with Primary Hyperaldosteronism
Research indicates that people with primary hyperaldosteronism, a condition where the adrenal glands produce too much of the hormone aldosterone, face more health risks because of persistent high blood pressure. This continuous high blood pressure can increase the chances of heart disease, including conditions like coronary artery disease, stroke, and congestive heart failure (a condition where the heart can’t pump blood well) related to an enlarged left heart chamber.
Furthermore, other studies suggest that these individuals have a greater risk of heart rhythm problems due to consistent low potassium levels, a condition known as hypokalemia.
Individual studies have shown that surgical removal of the adrenal gland, known as adrenalectomy, leads to improved health outcomes by significantly reducing high blood pressure and hypokalemia. This has been compared to individuals using medical therapy along.
Possible Complications When Diagnosed with Primary Hyperaldosteronism
: Patients with primary aldosteronism, a particular kind of hormonal disorder, have an increased risk of heart-related issues. These individuals usually have a larger left heart ventricle and reduced performance of the ventricle, compared to individuals with other forms of high blood pressure. High blood pressure, also known as hypertension, may lead to conditions like stroke, irregular heartbeats, and heart attack.
In a study, 54 patients with primary aldosteronism were compared to a control group with similar age, gender, Body Mass Index (BMI), and duration of hypertension. Some patients received treatment through medication, while others underwent surgery to remove a growth in their adrenal gland. The study found that the aldosteronism patients had more heart-related problems before the treatment. However, after the treatment, there was no high risk of heart-related issues. Patients were followed up for approximately seven years, and the occurrence of heart attack, surgery to increase blood flow to the heart, sustained irregular heartbeats, or stroke was almost the same across all groups.
Patients with primary aldosteronism are more likely to have metabolic syndrome, a group of condition that raises the risk of heart disease, stroke, and type 2 diabetes.
These patients also have high levels of aldosterone (a hormone that regulates blood pressure) in their blood. This can result in more filtration in the kidneys and increased kidney blood flow, which can lead to a higher amount of albumin (a protein) in the patients’ urine. A case study with 50 patients found that patients with primary aldosteronism had higher filtration rates and more albumin in their urine compared to patients with regular high blood pressure. However, after six months of treatment, these patients showed significant reduction in albumin in the urine and reduced filtration rates – an indication that kidney function had returned to normal.
In addition, a separate study found that the incidence of previous strokes was higher in people with primary aldosteronism (12.9%) compared to those with regular high blood pressure (3.4%). This study compared a total of 124 patients with primary aldosteronism and 465 patients with primary hypertension, all of whom had similar ages, genders, and an average blood pressure of 175/107.
Preventing Primary Hyperaldosteronism
Patients need to learn about the usual signs of a condition called primary hyperaldosteronism. This condition is related to the adrenal glands – the parts of your body that produce a variety of hormones. The family medical history is crucial, specifically the instances of high blood pressure or stroke among close relatives. If you are diagnosed with hyperaldosteronism, it’s crucial to regularly take your prescribed medication, as this is the main treatment option other than surgery.
If you are diagnosed with essential hypertension, which is high blood pressure without a specific medical cause, particularly at a young age, and if the medications are not working well, it is important to talk about this with your primary care doctor. Make sure to stick to your treatment plan and keep a log of your blood pressure readings. This information can assist your doctor in investigating further to discover other possible factors causing your high blood pressure.
