Addison's Disease: Exploring Adrenal Insufficiency

Understanding Addison's Disease

What Are The Adrenal Glands? 

The adrenal glands are a pair of small, triangular-shaped glands that sit on top of each kidney. They are part of the body’s endocrine system and make hormones that regulate many important functions in the body. The adrenal cortex (outer layer) makes glucocorticoids (cortisol), mineralocorticoids (aldosterone), and androgenic steroids. The adrenal medulla (inner layer) makes epinephrine (adrenaline) and norepinephrine (noradrenaline).

What is Addison’s Disease?  

Addison’s disease, also called adrenal insufficiency or hypoadrenalism, is a condition in which the adrenal glands don’t make enough hormones (cortisol, steroid hormones, aldosterone, adrenaline, and noradrenaline). 

According to the National Institute of Diabetes and Digestive and Kidney Diseases, Addison’s disease affects about 1 in 100,000 people in the U.S. 

It is, therefore, a rare disorder, but a serious one. The lack of adrenal hormones can be life-threatening. Treatment consists of replacing certain hormones (cortisol and aldosterone) with oral medication. In some cases, this syndrome may be accompanied by other genetic syndromes.

Symptoms of Addison’s Disease: What Does Addison’s Disease Cause?  

People with Addison’s disease may have the following symptoms due to lack of enough cortisol and aldosterone hormones:

• Extreme fatigue that gets slowly worse

• Loss of appetite and unintentional weight loss

• Skin discoloration (Patches of darkened skin, especially in skin creases, scars, and on the gums)

• Low blood pressure (which can cause lightheadedness, dizziness, and even fainting)

• Low blood sugar (hypoglycemia)

• Craving for salty foods

• Stomach pain, nausea, vomiting, diarrhea

• Muscle pain, muscle spasms, and joint pain

• Mood changes such as irritability or depression

• Loss of body hair

• Decreased libido (sexual drive)

• Abnormal menstrual periods

Can You Have Addison's Disease For Years Without Knowing?

Yes, you can have Addison’s disease for months or years without knowing. The symptoms of Addison’s disease develop very slowly and are nonspecific (they could be due to a range of other medical conditions). This causes many people with Addison’s disease to ignore them. But then a stressful event, such as a serious injury or illness, causes sudden worsening of existing Addison’s disease symptoms and further symptoms, prompting the person to seek medical care.

Addisonian Crisis or Acute Adrenal Failure

Sometimes, after a period of extreme mental or physical stress, such as the death of a loved one or a severe illness or injury, the symptoms of Addison’s disease develop very quickly and become life-threatening. This is called an Addisonian crisis or acute adrenal failure and it is a medical emergency. Seek emergency medical attention if you are experiencing severe symptoms such as:

• Severe weakness

• Severe abdominal pain, diarrhea, vomiting, and dehydration

• Lower back or leg pain

• Low blood pressure

• Confusion or restlessness

• Mental status changes, delirium, or loss of consciousness

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Causes and Risk Factors 

Primary Adrenal Insufficiency

Addison’s disease is also known as primary adrenal insufficiency; it is caused by damage to the adrenal cortex, preventing it from making enough hormones (cortisol, aldosterone, and steroid hormones). This type of adrenocortical insufficiency usually results from an autoimmune response, where the body’s immune system mistakenly attacks healthy tissues for unknown reasons. 

In addition to autoimmune Addison’s disease, other causes of primary adrenal gland failure include:

• Infections such as tuberculosis, repeated fungal infections, or human immunodeficiency virus (HIV)-related infections.

• Hemorrhaging (bleeding) into the adrenal glands.

• Metastasis (spread of cancer cells) from some other part of the body to the adrenal glands.

• Amyloidosis (abnormal buildup of amyloid protein in various organs).

• Adrenoleukodystrophy (a rare genetic disorder that affects the nervous system and adrenal glands).

• Surgical removal of the adrenal glands.

• Treatment with certain medications that can prevent the adrenal glands from making glucocorticoids, for example, etomidate (Amidate) and ketoconazole. 

• Medications that block the action of glucocorticoids, such as mifepristone (Korlym, Mifeprex).

• Cancer treatment with drugs called checkpoint inhibitors.

Secondary Adrenal Insufficiency  

As mentioned above, it is called primary adrenal insufficiency when the immune system attacks the adrenal glands (this is called autoimmune Addison). 

Secondary adrenal insufficiency occurs when the pituitary gland in the brain does not make enough of a hormone called adrenocorticotropic hormone (ACTH). ACTH tells the adrenal cortex to produce the hormone cortisol and other adrenal hormones. Non-cancerous pituitary tumors, inflammation, and surgery on the pituitary gland can prevent the pituitary gland from making enough ACTH, leading to secondary adrenal insufficiency. Read which medications are used to balance pituitary gland function.

Other causes of secondary adrenal insufficiency include suddenly stopping treatment with corticosteroid drugs, such as prednisone. These drugs are used to treat a wide range of medical conditions, including arthritis and asthma. If you stop taking steroid medicine suddenly after taking it for a long time, it can lead to adrenal insufficiency. This happens because the adrenal glands stop making cortisol when you are taking steroid medicines. That’s why it’s important to slowly taper (lower) the dose of steroid medicines. Learn about the side effects of prednisone.

Note: Primary and secondary adrenal insufficiency cause similar symptoms. However, secondary adrenal insufficiency is more likely to cause low blood sugar and less likely to cause low blood pressure, dehydration, and hyperpigmentation (dark patches of skin). 

Tertiary Adrenal Insufficiency

In healthy people, a part of the brain called the hypothalamus secretes corticotropin-releasing hormone (CRH). CRH stimulates the pituitary gland to secrete ACTH. ACTH tells the adrenal glands to secrete adrenal hormones. Tertiary adrenal insufficiency occurs due to a problem with the hypothalamus in the brain. A common cause is treatment with steroid medications or surgery to treat Cushing disease.

Risk Factors and Genetic Considerations  

Adrenal insufficiency (Addison’s disease) can affect anyone, but it is more common in women and people between 30 and 50 years of age.

Risk factors for developing Addison’s disease include:

• Surgery or diseases affecting the pituitary or adrenal glands. 

• Inherited genetic disorders that affect the adrenal glands (congenital adrenal hyperplasia).

• Other autoimmune diseases, such as type 1 diabetes, pernicious anemia, autoimmune thyroid disease, vitiligo, dermatitis herpetiformis, or myasthenia gravis.

• Traumatic brain injury.

Diagnosis of Addison's Disease  

Your health care provider can make a diagnosis of adrenal insufficiency (Addison’s disease) based on your symptoms, medical history, physical exam, and tests including:

• Blood tests to measure sodium, potassium, cortisol, ACTH, and antibodies for autoimmune disease.

• ACTH stimulation test to check if the adrenal glands respond by making cortisol after a shot of synthetic ACTH (ACTH is the pituitary hormone that tells the adrenals to make cortisol). Low levels of cortisol after the ACTH shot indicate a problem with the adrenal glands (primary adrenal insufficiency).

• Insulin-induced hypoglycemia test to check blood sugar and cortisol levels after a shot of insulin. This helps healthcare providers determine if problems with the pituitary gland are causing secondary adrenal insufficiency. In healthy people, a shot of fasting-acting insulin should lead to a drop in blood glucose and a rise in cortisol levels.

• Imaging tests such as a CT scan of the abdomen to look at the adrenal glands or a CT or MRI of the head to look at the pituitary gland.

Differential Diagnosis  

Addison’s disease can cause similar symptoms as many other medical conditions, including but not limited to:

• Hereditary myopathies

• Celiac disease

• Syndrome of inappropriate antidiuretic hormone (SIADH)

• Peutz-Jehgers syndrome

• Porphyria cutanea tarda

• Sarcoidosis

• Tuberculosis

• Histoplasmosis

• Eosinophilia

• Hyperkalemia

Blood tests and imaging tests can help healthcare providers differentiate between these conditions and diagnose Addison’s disease.

Treatment and Management  

Hormone Replacement Therapy  

Appropriate treatment for Addison's disease consists of hormone replacement therapy to replace the missing hormones in the body that the adrenal glands are not making. Doctors use the following medications for treating Addison’s disease:

• Replacement of the hormone cortisol with steroid medications such as prednisone (Rayos), methylprednisolone (Medrol), or hydrocortisone (Cortef). 

• Replacement of the hormone aldosterone with fludrocortisone acetate (Florinef).

The dose of your Addison’s medicine will need to be adjusted during pregnancy and periods of stress, such as when you are having surgery or are ill or injured. Also, if you have severe vomiting and can’t keep down medication, you may need to get corticosteroid shots.

Lifestyle Adjustments and Monitoring  

In addition to prescribed medications for Addison’s disease, your healthcare provider may recommend that you do the following:

• Eat a high-sodium (salt) diet, especially during strenuous exercise, hot weather, or if you have vomiting or diarrhea. Your doctor will tell you how much salt you should eat. 

• Take calcium and vitamin D supplements. 

• Wear a medical alert bracelet and carry a steroid emergency card to tell emergency medical personnel about the type of care you need in case of an adrenal crisis. 

• Keep extra medicine on hand because missing even one dose of your medicine can be dangerous. 

• Have a glucocorticoid injection kit available and know how to use it in emergencies. 

• Follow up regularly to check hormone levels and adjust medication doses. 

• Have annual screening for other autoimmune disorders. 

Emergency Treatment for Adrenal Crisis  

An Addisonian crisis is a medical emergency and needs to be treated in the hospital with intravenous (IV) fluids, glucose, and corticosteroids.

Living with Addison’s Disease  

People with Addison’s disease usually need to see their endocrinologist every 6-12 months for monitoring and adjustment of medication doses. Those who develop associated health conditions, such as type 1 diabetes or hypothyroidism (underactive thyroid gland), require treatment for these conditions. 

Prognosis: What Is The Life Expectancy of a Person With Addison's Disease?

People with Addison’s disease can have a normal life expectancy with proper management of the condition and taking medication on time. However, this is a potentially life-threatening condition, and an adrenal crisis can result in death if it is not recognized and treated with emergency medical care.

Coping Strategies: What is Life Like With Addison’s Disease? 

Most people with Addison's disease can lead normal lives if they take their medicine on time. However, it is common to have bouts of fatigue and other symptoms of Addison’s disease. So, it’s important to learn to manage periods of tiredness and low energy.

Coping strategies to prevent psychological stress, which can trigger an adrenal crisis, include self-care measures such as:

• Making time to relax. 

• Practicing deep breathing and other relaxation techniques.

• Focusing on the positives and finding joy in small things.

Other coping strategies include:

• Tell your family and friends that you have Addison's disease so that they know what to do in case of an Addisonian crisis.

• Always have spare medicine on hand and keep some at work and in your car.

• Carry double the medicine you’ll need while going away from home.

• Keep your medicine in carry-on luggage while traveling by air. 

• Carry your steroid injection kit and medical emergency card at all times.