What is Hypoaldosteronism?
Hypoaldosteronism is a condition where your body doesn’t make enough or can’t properly use the hormone aldosterone. This hormone is created in a part of your adrenal glands called the ‘zona glomerulosa’. Sometimes, your body may try to compensate for the lack of aldosterone by making more of it. In these cases, we refer to the condition as ‘pseudo-hypoaldosteronism’.
Researchers have made significant strides in understanding how aldosterone is produced, how it’s released, and how it acts on the parts of the body it targets. Understanding these basics are essential to discern how things can go wrong in related diseases. The zona glomerulosa, the outermost layer of your adrenal glands, is unique because it has the critical genes and enzymes needed to make aldosterone. It doesn’t have the machinery to make another important hormone, cortisol.
Other hormones and compounds play minor roles, but potassium and a compound called angiotensin II are the main controllers of aldosterone. The renal-aldosterone-angiotensin system is an important feedback loop that helps regulate sodium, potassium, water, fluid outside cells, and blood pressure. If blood flow drops, cells in a part of your kidneys called the macula densa will make an enzyme named renin. Renin turns a protein from your liver into angiotensin I. An enzyme then changes it into angiotensin II, which tells your body to make and release more aldosterone.
There are special sodium channels in certain kidney cells that are influenced by aldosterone. They’re made of three parts and are controlled by aldosterone at a genetic and non-genetic level. The channels allow for passive movement of sodium in the body. The receptors for aldosterone are not just located in the kidneys, but also in the colon, sweat glands, salivary glands, airways, eyes, and other tissues.
Both cortisol and aldosterone can bind to the same receptor. But usually, aldosterone dominates receptor binding because an enzyme in the kidney changes cortisol into an inactive form, called cortisone.
What Causes Hypoaldosteronism?
There are several instances where a hormone called aldosterone, produced by adrenal glands, can malfunction or fail to work properly. These problems can either stem from an issue with the production or release of aldosterone, or a resistance to aldosterone in the body.
A) Aldosterone might not be produced properly due to several reasons, such as:
– Being born extremely premature (before 28 weeks) can lead to immature aldosterone-making enzymes.
– There are also two specific genetic conditions called aldosterone synthase deficiency I and II which can impact production.
– Serious illnesses or recovery from adrenal gland surgery can hinder its production as well.
– Some drugs can also cause a decrease in aldosterone production if used for a long time and then suddenly stopped.
B) Sometimes, aldosterone is produced but it’s not released properly:
– This can be due to a decrease in other hormones, known as renin or Ang II, which are necessary for aldosterone production.
– It can also be congenital (since birth) or acquired (developed later in life due to conditions like kidney disease, diabetes, nerve damage, sickle cell disease, or HIV).
– Certain medications like NSAIDs, COX-2 inhibitors, ACEI/ARBs can also cause this problem.
C) Another problem can be aldosterone resistance, where the body doesn’t respond effectively to aldosterone:
– This could be genetic, resulting in conditions known as Autosomal dominant pseudohypoaldosteronism (PHA AD) and Autosomal recessive pseudohypoaldosteronism (PHA AR).
– It could also be acquired due to urinary tract infection, obstructive uropathy (blockage in urinary flow).
– Certain medicines or after having a transplant can lead to aldosterone resistance too.
Sometimes, problems with aldosterone could be a sign of a more extensive adrenal gland failure that hasn’t yet shown up. Both birth defects and conditions that develop later in life can result in this kind of adrenal gland failure, such as congenital adrenal hyperplasia (CAH), adrenal hypoplasia (AHC) or acquired adrenal destruction. This discussion won’t delve further into these conditions.
Risk Factors and Frequency for Hypoaldosteronism
Congenital hyperaldosteronism (HA), specifically autosomal dominant pseudohypoaldosteronism type I, is not common. It affects less than 1 in 80,000 people and can be more common in certain ethnic groups due to genetic factors.
However, acquired causes of hyperaldosteronism are more typical. These are often seen in hospitalized patients, children with type 1 diabetes or sickle cell disease, and adults with type 1 and 2 diabetes. Older adults who are on numerous medications that can affect their hormones are also more prone.
Another situation where hyperaldosteronism can occur is after an adrenalectomy (removal of one or both adrenal glands) for Conn syndrome. In fact, about 5% of patients experience this.
- It’s common to see high levels of potassium in the blood, a condition known as hyperkalemia, in patients who have had an organ transplant.
- Blood potassium levels can rise further after the use of certain medicines, specifically calcineurin inhibitors.
- The occurrence of hyperkalemia in these patients is estimated to be between 40-70%.
Signs and Symptoms of Hypoaldosteronism
Children with a form of Pseudohypoaldosteronism (PHA) called PHA AD usually have a milder disease that affects only the kidneys. They may get better as they grow up. However, children with another type of PHA, called PHA AR, generally have a more severe disease. It not only affects the kidneys but also extends to their sweat and salivary glands. These children often have frequent respiratory infections, skin rashes, eye problems like blocked meibomian (oil) glands, and may have breathing difficulties right after birth. An increase in amniotic fluid during pregnancy (polyhydramnios) could indicate the presence of PHA AR. These children do not get better as they grow and may need frequent hospital visits and intricate care.
Another type of PHA, called PHA III, can be cured. The cure takes place once the child’s urinary tract infection or urinary obstruction gets better. There are also rare syndromes with inborn abnormalities that include high aldosterone (HA) as a part.
In adults, taking a detailed medical history will help to identify any medicines that may be causing the high levels of aldosterone. Life-threatening heart rhythm problems due to high potassium have occasionally been reported in patients treated with a common blood thinner, heparin.
Medical professionals need to be extra cautious and suspect HA among patients who are hospitalized, seriously ill, or have diabetes, kidney diseases from various causes, sickle cell disease, and HIV. This can help in early recognition and treatment of high aldosterone.
Patients who have undergone an operation to remove one adrenal gland for a condition called Conn’s syndrome, can have lowered levels of a hormone called ZG in the normal gland for an extended period. Risk factors associated with this condition include higher age, history of long-lasting high blood pressure, large size of adrenal tumor, kidney function before and after surgery, and usage of nonsteroidal anti-inflammatory drugs (NSAIDs) before surgery.
Testing for Hypoaldosteronism
Doctors can diagnose a baby’s salt-wasting crisis by testing a blood sample taken before treatment starts. This is important to prevent the treatment from affecting test results. The sample is divided into two parts.
The first part is used to check levels of various substances in the blood like aldersterone (a hormone involved in salt regulation), 17 hydroxyprogesterone (a chemical involved in producing hormones), and renin (a protein that helps control blood pressure). These initial tests can provide guidance for what additional tests may be needed.
The second part of the blood sample is kept for further confirmatory tests. This could include testing the levels of cortisol and ACTH, two hormones involved in the body’s stress response. Blood and urine analysis may also be used to test aldosterone and 18 OHC levels, components which tell doctors about the potential synthesis deficiencies that could be present in the baby.
Yet, in babies with extremely high aldosterone levels, there could be a misleading phenomenon called the ‘hook effect’; it could be misunderstood as aldosterone synthase deficiency. But if the tests are repeated after taking a series of diluted samples, it could be revealed if the baby actually has very high aldosterone levels, which might indicate the condition called PHA.
Further confirmatory tests like blood potassium level and kidney function are important too. Even molecular genetic tests that allow for gene sequencing can be beneficial.
Therefore, early and thorough testing can help doctors better understand what’s happening to a baby’s body, give an accurate diagnosis, and initiate the optimal treatment as soon as possible.
Treatment Options for Hypoaldosteronism
Hyperaldosteronism (HA) is a medical condition where the body produces too much aldosterone, a hormone that helps maintain the balance of salt and water in the body. In infants and children with two particular diseases – ALD synthase deficiency and PHA AD – HA can cause a dangerous situation called a salt-wasting crisis, where the body loses too much salt. This condition is treated with fluids and salt (NaCl). Before confirming that the child has HA, they are typically treated with a hormone therapy using a drug called hydrocortisone. This drug helps stabilize the child during their critical condition.
If subsequent tests show that their hormone levels are normal, the hydrocortisone treatment can be stopped once the child is stable. Then they are usually given an oral medication called fludrocortisone, which helps control their salt and water balance. Infants and young children may require a larger dosage of this drug due to their increased resistance.
However, fludrocortisone isn’t effective for treating PHA. In those cases, they’ll need sodium bicarbonate and other treatments to control the levels of potassium in their blood. Some severe cases may require a procedure like peritoneal dialysis. Other drugs like thiazides and indomethacin can also help manage certain symptoms of PHA AD.
PHA AR is a severe condition that affects multiple organs and requires a significant amount of salt replacement. Carbenoxolone, a specific drug, may be useful for treating this condition because it enhances the body’s response to aldosterone.
In a condition called Conn Syndrome, a drug named spironolactone is used to manage blood pressure should be stopped at least three days prior to surgery. After the surgical procedure of removing the adrenal gland (adrenalectomy), patients are managed with fludrocortisone. They might also need extended therapy until their adrenal functions recover.
People who have had a kidney transplant and are being treated with a certain class of drugs named calcineurin inhibitors might face high potassium levels in blood due to HA. They usually respond well to low doses of fludrocortisone.
In type 4 RTA, fludrocortisone can help to reduce high levels of potassium in the blood. However, caution is necessary as this drug can cause certain side effects such as fluid overload and worsening of heart failure. It’s critical to review and potentially discontinue certain medications during this treatment.
What else can Hypoaldosteronism be?
Hypoaldosteronism, or a lack of the hormone aldosterone, can be confused with various other conditions that affect the adrenal gland (a small gland located above the kidneys). Understanding the differences between these health issues is important to ensure the correct diagnosis.
For example, Congenital Adrenal Hyperplasia (CAH) may cause female infants to have ambiguous genitalia (unclear physical sex characteristics) and both sexes to exhibit high levels of a hormone called 17 OHP. Addison’s disease, which commonly affects older children and adults, is usually accompanied by decreased levels of a hormone called cortisol and increased ACTH (another hormone), and may present serious symptoms and hyperpigmentation (darkened areas of skin).
On the other hand, infants with a condition called congenital adrenal hypoplasia (AHC) typically experience salt-wasting (loss of sodium through urine) and hyperpigmentation; with cortisol deficiency appearing later on. If cortisol deficiency is suspected, a cosyntropin stimulation test may be performed to confirm it.
Also, a condition characterized by a deficiency of cholesterol side-chain cleaving enzymes affects all three adrenal axes (the three hormone systems controlled by the adrenal gland). This condition may result in salt-wasting, low cortisol and ambiguous genitalia in male infants.
Decreased aldosterone (ALD) levels and increased levels of a hormone called PRC are indicative of ALD synthase deficiency. A similar condition known as pseudohypoaldosteronism (PHA) displays very high PRC and ALD levels; both conditions are also characterized by low sodium, high potassium, and acidosis (too much acid in body fluids).
In ALD synthase deficiency, a hormone known as 18 OHC can be low to normal in type 1 and increased in type 2, whereas the level of a substance called tetrahydro-aldosterone (THA, a metabolite of aldosterone) can be decreased in type 1 and low to normal in type 2.
A definitive way to diagnose biosynthetic defects causing hypoaldosteronism is by a process known as gene sequencing.
An index called aldosterone contralateral suppression index (CSI) aids in diagnosing Conn Syndrome before surgery. Patients with a CSI less than 0.47 are at risk for prolonged adrenal suppression and need close monitoring of potassium levels after unilateral adrenalectomy (the removal of one adrenal gland).
In critically ill patients, hypoaldosteronism might not cause significant issues due to high cortisol levels that make up for the absence of aldosterone.
Some conditions may cause low aldosterone levels due to retention of sodium, high blood pressure, low potassium levels, suppressed PRC, and fluid volume expansion. Examples include Liddle syndrome and mineralocorticoid excess syndrome due to inhibition of an enzyme called 11 beta HSD2. Gordon syndrome causes high blood pressure along with high potassium levels, hyperchloremic acidosis (too much chlorine and acid in body fluids), and suppressed renin (a hormone) due to fluid volume expansion.
What to expect with Hypoaldosteronism
The outlook is promising for children with ALD synthase deficiency and PHA AD if these conditions are spotted and treated early. Many kids can eventually stop taking their medications, and some even outgrow their condition as they age. On the other hand, older kids who aren’t treated adequately may experience slow growth or failing to thrive. But if treated appropriately, they can grow normally and even catch up in growth over time.
However, patients with PHA AR typically don’t see an improvement and will need careful monitoring. Those with PHA III will be cured after their primary kidney infection or blockage is resolved.
Managing medications that cause HA diligently can greatly reduce the disease’s impact on patients. Most patients with HA who’ve had their adrenal glands removed due to Conn syndrome recover swiftly, although some at high risk may need continuous monitoring.
Possible Complications When Diagnosed with Hypoaldosteronism
Patients being treated for HA might face some issues if they take too much fludrocortisone. These can include the body holding onto too much water, low potassium levels, and the body not producing enough PRC, which can even lead to a condition called congestive heart failure.
Other less dangerous but still impactful side effects encompass constipation caused by increased water and salt absorption in the colon, weight gain due to the body retaining more fluid, and weakness in the muscles due to a lack of potassium. Medicine dosage should be adjusted to ensure the right levels of PRC.
Lack of proper treatment can result in poor growth in children. If the diagnosis of infants with serious disease is delayed, this increases the chance of fatality.
In summary:
- Too much fludrocortisone may lead to the body retaining excess fluid
- Lead to low potassium levels
- Suppress PRC production, which could lead to congestive heart failure
- Other side-effects include constipation due to increased water and salt absorption
- Weight gain due to fluid retention
- Muscle weakness due to low potassium
- Inadequate treatment can hinder children’s growth
- Delayed diagnosis in infants with severe disease can result in increased mortality
Preventing Hypoaldosteronism
If your child has been born with congenital causes of high aldosteronism (HA) – a condition that causes high blood pressure and low potassium levels, it’s crucial to understand the nature of the disease, how regularly to substitute salt in their diet, and how to properly provide them with their medication. Parents should be aware of the signs that indicate an overdose, and the importance of regular check-ups with the doctor. Remember, all this information should be explained to you in simple, easy-to-understand language.
Individuals with Conn’s Syndrome, a medical condition where your body produces too much of a hormone called aldosterone, should be taught about the potential risk of low aldosterone levels after their surgery. For patients with type 4 Renal Tubular Acidosis (RTA) – a kidney condition that causes the buildup of acid in your body, it’s necessary to be educated about the dangers of using common, over-the-counter painkillers like Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). This is important as these could negatively affect their condition. Helping to understand how their medical condition interacts with common medications can prevent potential issues.
