What is Addison Disease?
Addison’s disease, or autoimmune adrenalitis, is a condition where your body’s immune system attacks your own adrenal glands – a pair of small glands that sit on top of the kidneys. This condition is pretty rare and can be life-threatening in emergencies. It causes a drop in hormones like cortisol, aldosterone, and androgens, due to the damage of both adrenal glands. Addison’s disease typically shows up progressively as a deficiency in glucocorticoid hormones, followed by mineralocorticoid. However, it can also suddenly develop, usually in response to another illness. How it shows up largely depends on how quickly and extensively the adrenal function is affected.
Addison’s disease often takes a while to diagnose because the symptoms tend to appear slowly and subtly, and can get worse over time. This often makes it hard to identify early on. It’s important for doctors to stay alert for potential signs to avoid misdiagnosing it. In many instances, the condition is only diagnosed once the patient has an acute adrenal crisis–a situation where blood pressure drops sharply, and there are marked changes in blood sodium, potassium, and glucose levels.
The diagnosis is confirmed by tests showing low cortisol and aldosterone levels, high renin levels, and a weak cortisol response when ACTH, a hormone that stimulates the adrenal glands, is given. An adrenal crisis is a serious matter requiring immediate attention and treatment. For patients who have been stabilized with a diagnosis of Addison’s disease, they will need lifelong hormone replacement therapy. This therapy helps to keep their glucocorticoid and mineralocorticoid hormones at healthy levels.
What Causes Addison Disease?
Addison’s disease is a condition where the adrenal glands aren’t able to make enough hormones. There are two main types: primary and secondary adrenal insufficiency.
In primary adrenal insufficiency, also known as Addison’s disease, damage to the adrenal cortex is the root cause. This can be due to various reasons like auto-immunity, infections, bleeding, certain drugs, or infiltration into the adrenal glands.
The most common cause of Addison’s disease is the body’s immune system attacking the adrenal glands. This can be an isolated event or part of a larger syndrome where multiple glands are affected. Type 1 involves the parathyroid gland, Addison’s disease, and skin infections. Type 2 involves conditions like autoimmune thyroiditis, type 1 diabetes, and other autoimmune conditions. Addison’s disease may also occur together with celiac disease.
Several infections can also cause Addison’s disease, like sepsis, tuberculosis, cytomegalovirus, and HIV. In South America, a type of fungus called Blastomycosis is another common cause.
Additionally, severe bleeding in the adrenal glands can also trigger Addison’s Disease. This is often seen in conditions like DIC, trauma, meningococcemia, and cancerous growths. In children and those without spleens, adrenal crisis due to meningococcemia or Waterhouse-Friderichsen syndrome is common.
Infiltration into the adrenal gland is another cause and this often happens with conditions like hemochromatosis, amyloidosis, and metastases. Certain genetic disorders and the antiphospholipid antibody syndrome can also cause it.
Lastly, some medications might cause Addison’s disease because they obstruct the production of cortisol. For example, ketoconazole and etomidate can block the hormones needed to make cortisol.
On the other hand, secondary adrenal insufficiency happens when there’s a long-term use of steroids. Even though the adrenal glands are healthy, they don’t get the chemical signal from the pituitary gland to produce cortisol. But these glands can still produce aldosterone normally. So, it’s common to see symptoms after stopping the use of steroids. In this case, the problem lies either in the hypothalamus or the pituitary gland, hence only cortisol production is affected, not aldosterone.
Risk Factors and Frequency for Addison Disease
Addison’s disease is quite rare, affecting only .6 out of every 100,000 people each year. At any given time, the number of people with this disease ranges from 4 to 11 per 100,000 people. It usually shows up in adults between the ages of 30 to 50 and is more common in women. The most frequent type of Addison’s disease is the autoimmune type, which can be associated with other autoimmune conditions.
- Type I diabetes
- Hypoparathyroidism
- Hypopituitarism
- Pernicious anemia
- Graves’ disease
- Chronic thyroiditis
- Dermatitis herpetiformis
- Vitiligo
- Myasthenia gravis
Signs and Symptoms of Addison Disease
Addison’s disease is a medical condition that often comes on slowly and subtly, making it hard to diagnose early. This disorder can reveal itself through non-specific symptoms that get worse over time. It often gets misjudged, leading to improper diagnosis. This situation can escalate to an acute adrenal crisis, a severe phase where symptoms like low blood pressure, low sodium levels, high potassium levels, and low blood sugar appear. This acute phase can be triggered by stressful illnesses and events like infections, injuries, surgeries, and severe vomiting or diarrhea.
Addison’s disease can affect people of any age but is most commonly observed in a person’s 20s or 30s. Typical symptoms include severe tiredness, widespread weakness, weight loss, feeling sick, throwing up, abdominal pain, dizziness, rapid heart rate, and low blood pressure. Physical changes such as muscle wasting can also be observed. The condition may lead to a steady decline in health over weeks or months. Due to its wide range of symptoms, medical professionals have to stay alert while assessing patients for potential Addison’s disease, especially those with unexplained symptoms. An Addisonian crisis is a severe phase of this disease, with signs including extreme dehydration, confusion, resistant low BP, and shock. This phase is primarily seen in primary adrenal insufficiency.
In the case of Addison’s disease, it’s common to notice unusual pigmentation in the skin and the inner lining of body parts. This pigmentation can be seen all over the body and is more obvious on parts exposed to the sun and high-pressure areas. Medical professionals should look out for darkened skin folds in the palm, lining of the mouth, lips, especially the margins, elbows, fingers, back of the neck, area around the nipple and nails. This unusual skin color may seem like a tan or dark patches and is seen in almost all the patients with Addison’s disease. However, there are some exceptional cases of adrenal insufficiency with no skin discoloration, delaying diagnosis since this is a key telltale sign.
Remember, this unusual discoloration of the skin is not found in patients with secondary insufficiency as their levels of ACTH and MSH, two relevant hormones, are low. So, if a patient with Addison’s has high ACTH and MSH levels, they may develop more skin moles than normal. Women patients may also see lesser than usual hair in armpits and pubic area. Some even have patches of whitish skin, a condition called vitiligo.
Testing for Addison Disease
If your doctor suspects you have Addison’s disease, there are certain tests that can help confirm the diagnosis. These tests check for different levels of certain hormones in your body that can indicate if there is an issue with your adrenal glands. Here’s a breakdown of what these tests might look like:
Firstly, you’re likely to have a cortisol level test. A healthy body has higher levels of cortisol in the morning, so ideally this test would be done early in the morning. A level less than 3 mcg/dL likely indicates adrenal insufficiency, while a level more than 18 mcg/dL is usually normal and could rule out Addison’s disease.
Another test that could help determine whether the problem is located in your adrenal glands or in another part of your body that controls your adrenal glands is the ACTH stimulation test. In this test, cortisol and aldosterone secretion is stimulated rapidly. If your ACTH levels are high and still go up after stimulation but without a corresponding increase in cortisol, that could signal primary adrenal insufficiency. If your ACTH level is low and doesn’t respond to stimulation, this could indicate secondary adrenal insufficiency.
Besides cortisol, doctors also test your aldosterone and renin levels. Both of these hormones are often lacking in people who have primary adrenal insufficiency. High renin and low aldosterone levels might suggest adrenal cortex dysfunction.
Other lab findings could show signs that you have Addison’s disease, such as an abnormally high potassium level and low sugar, sodium and calcium levels in your blood.
Additional tests may include checking for antibodies that target your adrenal glands, meaning your body’s own immune system could be causing your adrenal glands to malfunction. Imaging studies could also be conducted to look for specific changes in your adrenal glands. For example, an MRI of the brain can show whether there’s a problem with the brain’s control over your adrenal glands. Other tests may be done to find out what’s causing your adrenal insufficiency.
Treatment Options for Addison Disease
Early detection is important for treating acute adrenal insufficiency, a severe hormonal emergency known as Addison crisis. This condition is life-threatening, so immediate treatment is vital. If not quickly recognized and treated, it may be fatal. A blood test should be taken for future measurements of ACTH and cortisol levels. If the ACTH level is high but cortisol is low, it means that there is primary adrenal insufficiency. The ACTH stimulation test can be used to measure cortisol when the initial tests don’t confirm the diagnosis. High plasma renin levels suggest a mineralocorticoid deficiency which is often accompanied by low aldosterone levels.
During the acute phase of treatment, it’s crucial to restore fluid levels with intravenous (IV) treatment using normal saline, correct low blood glucose (hypoglycemia) with dextrose, and replace missing hormones. Hydrocortisone is given immediately as the first hormonal treatment. Adults usually receive a 100 mg IV of hydrocortisone, which is then followed up every six hours over 24 hours with 50 to 100 mg. Children get a slightly lower dose. As the hydrocortisone treatment already has mineralocorticoid activity, additional mineralocorticoids aren’t needed during the acute phase. In the emergency department, dexamethasone can be used as it is long-lasting and doesn’t interfere with lab tests measuring cortisol. Prednisone and dexamethasone do not have mineralocorticoid activity. Blood sugar levels should be monitored and treated promptly.
In the maintenance phase, patients with stable Addison disease require life-long hormone replacement treatment. The goal is to maintain normal levels of glucocorticoid and mineralocorticoid. Common dosage regimens include 5 to 25 mg of hydrocortisone per day divided into two or three doses or 3 to 5 mg of Prednisone a day. Dosages should be adjusted based on the patient’s response and normalizing electrolyte levels. The dose should be as low as possible to control symptoms, and the patient should feel well. Plasma renin levels can be used to adjust the doses, not serum ACTH levels. In some cases, such as rifampin usage, which can increase glucocorticoid metabolism and inactivate cortisol, the glucocorticoid dose needs to be adjusted. Dexamethasone is not suitable for maintenance treatment because the dose is difficult to adjust and it increases the risk of the Cushing effect.
Fludrocortisone is given to keep plasma renin levels normal. An elevated PRA indicates that a higher dose of fludrocortisone is needed. The dose needs to be tailored to the degree of stress. Treating underlying issues like sepsis is important for the best outcome. A fludrocortisone dosage between .05 to .2 mg daily is generally given, with an 8 mg/m2/day hydrocortisone dose for children, divided into three or four doses.
In some cases, the treatment needs to be adjusted. In people with Addison disease, glucocorticoid doesn’t increase during stress. Therefore, during fever, infection, or other illnesses, the hydrocortisone dose should be increased. For patients taking rifampin, a higher dose of hydrocortisone is needed because rifampin speeds up the clearance of hydrocortisone. Thyroid hormone can increase the clearance of cortisol, possibly triggering an adrenal crisis. Correct levels of glucocorticoid can normalize thyroid-stimulating hormone.
For patients suffering from both diabetes insipidus and Addison disease, glucocorticoid treatment can worsen diabetes insipidus but prevents polyuria (excessive urination). A final thing to consider is that during the third trimester of pregnancy, the requirements for corticosteroids increase.
What else can Addison Disease be?
Adrenal crisis is a serious issue that can lead to shock, and it can be confused with many other conditions that cause similar symptoms. That’s why doctors need to carefully evaluate patients to diagnose it accurately. Here are some conditions that they often consider:
- Sepsis: Symptoms like weakness, fatigue, throwing up, low blood pressure, and shock could be the result of sepsis or adrenal insufficiency. The distinction can be made via a test that assesses how much cortisol (a hormone) your body produces in response to ACTH (another hormone), and by measuring the ACTH level itself.
- Shock: Shock from any cause coupled with a low level of cortisol in your blood might indicate adrenal insufficiency.
- Chronic Fatigue Syndrome: This condition causes persistent or recurring fatigue, which may resemble adrenal insufficiency. Tests assessing the level of cortisol after ACTH stimulation can differentiate between the two.
- Infectious Mononucleosis: The symptoms of fever, tiredness, and muscle ache can occur in both infectious mononucleosis and adrenal insufficiency. However, in infectious mononucleosis, there is typically a sore throat with a pus-like coating, and lab tests will show certain antibodies associated with the virus.
- Hypothyroidism: Like adrenal insufficiency, hypothyroidism (an underactive thyroid) can cause fatigue. However, it is commonly associated with weight gain. Measuring cortisol levels in your blood can differentiate between the two conditions.
In each case, examining the specific signs, symptoms, and test results can help doctors distinguish adrenal insufficiency from similar-looking conditions.
What to expect with Addison Disease
For Addison’s disease, the cure is a lifelong process that involves replacing two hormones: glucocorticoids and mineralocorticoids. Despite this, many patients with the condition lead an active lifestyle. However, the hormone replacement has to be precisely balanced to avoid giving too much or too little, which calls for regular check-ups. If the patient gets too much glucocorticoids, they might end up gaining weight, developing diabetes, and fragile bones. On the other hand, overdoing mineralocorticoids can lead to high blood pressure.
It’s important to note that about half of those with Addison’s disease may also get another autoimmune condition. For this reason, they should continue being monitored by their doctors. Also, it can be dangerous to give thyroid hormone replacements before giving glucocorticoids. This is because it may speed up cortisol clearance, thus triggering an adrenal crisis, which is an emergency condition. Therefore, it’s crucial to detect and handle an adrenal crisis promptly.
Possible Complications When Diagnosed with Addison Disease
Addison’s disease is a medical condition that can lead to several complications if not recognized and appropriately treated. If not treated, Addison’s disease can escalate into an adrenal crisis, which can cause intense low blood pressure, shock, low blood sugar, severe heart issues, and even death. Beyond these immediate crises, people with this illness have a higher risk of dying from infections, cancer, and heart disease. Unattended low blood sugar or hypoglycemia can also lead to serious health problems.
On the other side, if the treatment involves more than a person’s body needs, it can cause Cushing’s syndrome. In children, it may stunt growth. And for women with Addison’s disease, up to 10 percent can develop premature ovarian failure or a severe drop in ovarian function.
Another way to summarize these complications:
- Adrenal crisis leading to low blood pressure, shock, and low blood sugar
- Acute cardiovascular decompensation and death
- Increased risk of death due to infections, cancer, and heart disease
- Serious consequences from delayed recognition and treatment of low blood sugar
- Development of Cushing’s syndrome due to excessive glucocorticoid replacement
- Growth suppression in children
- 10% of women with Addison’s disease may experience premature ovarian failure or primary ovarian insufficiency
Preventing Addison Disease
People with Addison’s disease should be educated on how to manage and monitor their condition. This includes understanding their medication doses and the importance of following their treatment plan. For example, in stressful situations like having a fever, undergoing surgery, or dealing with stress, they might need to increase their steroid replacement doses.
They should also consider wearing a medical alert bracelet for emergencies. Additionally, self-care is crucial, which involves consuming enough sodium in their diet, keeping track of their weight, and monitoring their blood pressure.
