Adrenal Insufficiency

Adrenal insufficiency is a disorder where the adrenal glands cannot make enough of certain essential hormones that keep your body working properly. While this is a rare condition, with proper treatment most people can lead normal, active lives.

Table of contents

• What is adrenal insufficiency?
• The adrenal glands and their location
• Types of adrenal insufficiency
• What adrenal hormones do
• What causes this condition
• Signs and symptoms
• Adrenal crisis: A medical emergency
• Who is affected
• How doctors diagnose adrenal insufficiency
• Treatment and hormone replacement
• Managing illness and stress
• Ongoing care and monitoring

What is adrenal insufficiency?

Adrenal insufficiency is a disorder that occurs when the adrenal glands don’t make enough of certain hormones^[1]. These small but vital glands produce hormones that are essential for life. Without proper treatment, adrenal insufficiency can affect your body’s ability to respond to stress and maintain other essential life functions^[1].

The condition is also known as hypocortisolism or adrenocortical hypofunction^[6]. When it affects the adrenal glands directly, it is called primary adrenal insufficiency or Addison’s disease^[1].

Addison’s disease, Primary adrenal insufficiency, Hypocortisolism, Adrenocortical hypofunction

The adrenal glands and their location

• Adrenal glands
• Kidneys
• Pituitary gland
• Hypothalamus

The adrenal glands are two small, triangle-shaped glands located just above the kidneys^[1]. They are part of your endocrine system, which is the network of glands that make hormones^[7]. Despite their small size—described as pea-sized—these glands have a crucial job in keeping your body functioning correctly^[4].

The outer layer of the adrenal glands is called the cortex. This is where important hormones like cortisol and aldosterone are made^[2]. In adrenal insufficiency, the adrenal cortex does not make enough of these essential hormones^[19].

Types of adrenal insufficiency

There are three main types of adrenal insufficiency, depending on where the problem starts in the body^[1].

Primary adrenal insufficiency, often called Addison’s disease, occurs when the adrenal glands themselves are damaged and can’t make enough hormones^[1]. This type affects both cortisol and aldosterone production. In developed countries like the United States, the most common cause is autoimmune disease, meaning the body’s defense system mistakenly attacks and destroys the adrenal glands^[2].

Secondary adrenal insufficiency is much more common than primary adrenal insufficiency^[2]. This type starts in the pituitary gland, a small gland at the base of the brain^[1]. The pituitary makes a hormone called adrenocorticotropin (ACTH), which tells the adrenal glands to make cortisol. If the pituitary doesn’t make enough ACTH, the adrenal glands don’t make enough cortisol. Over time, the adrenal glands can shrink and stop working^[1]. People with secondary adrenal insufficiency usually still produce aldosterone, so they have fewer problems with low blood pressure and salt balance than people with primary disease^[2].

Tertiary adrenal insufficiency starts in the hypothalamus, a small area of the brain near the pituitary^[1]. The hypothalamus makes corticotropin-releasing hormone (CRH), which tells the pituitary to make ACTH. When the hypothalamus doesn’t make enough CRH, the pituitary gland doesn’t make enough ACTH, and in turn, the adrenal glands don’t make enough cortisol^[1].

What adrenal hormones do

The adrenal glands make two main types of hormones: cortisol and aldosterone^[1].

Cortisol is sometimes called the “stress hormone” because it helps your body respond to stress^[1]. This hormone is essential for life^[7]. Cortisol has many important jobs in your body. It helps control blood pressure, controls blood glucose (also called blood sugar), reduces inflammation, and helps control metabolism^[1]. Cortisol also helps your body respond to the stress of illness, injury, or surgery^[7]. Your body naturally produces more cortisol during times of stress, but people with adrenal insufficiency cannot do this^[4].

Aldosterone helps maintain the balance of sodium (salt) and potassium in your blood^[1]. This balance affects the balance of sodium (salt) and potassium in your blood, which in turn controls the amount of fluid your kidneys remove as urine. This affects blood volume and blood pressure^[7].

What causes this condition

The most common cause of adrenal insufficiency overall is the use of glucocorticoid medications, such as prednisone, hydrocortisone, or dexamethasone, to treat other illnesses^[2]. These medications can be taken by mouth, given through a vein or muscle, or used as inhaled or topical preparations^[10]. When people take these medicines for several weeks or longer, their body senses that cortisol is present and the pituitary produces less ACTH. This can lead to suppression of the body’s own cortisol production^[10].

For primary adrenal insufficiency (Addison’s disease), the most common cause is autoimmune disease^[2]. In this condition, the body’s immune system attacks and destroys the adrenal cortex. Other causes of primary adrenal insufficiency include bleeding in the glands, infections, genetic or inherited diseases, and surgical removal of the adrenal glands^[2].

Secondary adrenal insufficiency can be caused by problems with the pituitary gland^[2]. Some causes may be temporary, while others may be permanent. Permanent causes include pituitary tumors, pituitary surgery, or radiation damage to the pituitary^[2].

Signs and symptoms

With adrenal insufficiency, the damage to your adrenal glands usually happens slowly over time, so symptoms appear gradually^[7]. The disease may develop so slowly that people who have it might ignore the symptoms at first^[3]. Symptoms vary from person to person^[7].

Early symptoms of adrenal insufficiency can affect you in various ways. The most common symptom is extreme tiredness, also called fatigue, that steadily gets worse^[3][7]. Other common symptoms include:

• Dizziness or fainting when standing after sitting or lying down, due to low blood pressure^[3]
• Muscle weakness^[3]
• Upset stomach, nausea, vomiting, or diarrhea^[3]
• Pain in the stomach area^[3]
• Loss of appetite and unintentional weight loss^[3][7]
• Muscle cramps, widespread pain, or joint pain^[3]
• A craving for salty food^[7]
• Low blood sugar^[7]

Other symptoms can cause changes in how you look. These include body hair loss and areas of darkened skin, especially on scars and skin creases and on the gums^[3]. These darkened patches may be harder to see on Black or brown skin^[3]. Children with primary adrenal insufficiency may appear unusually tanned or have darkened skin creases, gums, and scars^[5].

Women with adrenal insufficiency may have abnormal menstruation (periods), lose body hair, and have a decreased sexual drive^[7].

Adrenal crisis: A medical emergency

In some cases, symptoms can come on quickly and cause a life-threatening event called an adrenal crisis or acute adrenal failure^[7]. This can happen after an injury, during a severe illness, or during times of intense stress^[7]. An adrenal crisis is a medical emergency. If it’s not treated, it can lead to shock and death^[7].

Common causes of adrenal crisis include sudden onset of diarrhea or vomiting, a rise in body temperature above 38°C (about 100°F), or a significant accident or injury^[4]. For some people, significant psychological stress such as bereavements or witnessing trauma can also trigger a crisis^[4].

Symptoms of an adrenal crisis include extreme weakness, sudden and severe pain in your lower back, belly, or legs, feeling restless, confusion, and very low blood pressure^[7]. During an illness, if you experience sudden onset of vomiting and cannot keep your cortisol pills down, you need immediate medical attention to prevent an adrenal crisis^[8].

Who is affected

Addison’s disease is rare. In the United States, it affects about 1 in 100,000 people^[7]. In the United States and Western Europe, the estimated prevalence is one in 20,000 people^[13].

Addison’s disease can affect people of all age groups, but it’s most common in people 30 to 50 years old^[7]. People who have certain autoimmune diseases are at higher risk of developing the autoimmune form of Addison’s disease. These conditions include Type 1 diabetes, pernicious anemia, Graves’ disease, chronic thyroiditis, vitiligo, and myasthenia gravis^[7].

People who have autoimmune polyendocrine syndrome, a rare inherited condition in which the immune system mistakenly attacks many tissues and organs, are much more likely to have Addison’s disease^[7].

How doctors diagnose adrenal insufficiency

Diagnosis is made through assessment by your endocrine team of your general health and well-being^[4]. Your doctor will talk with you about your medical history and your symptoms^[12].

If your doctor is concerned about adrenal insufficiency after reviewing your symptoms and medical history, they may check blood levels of cortisol and other hormones^[2]. A blood test can measure blood levels of sodium, potassium, cortisol, and ACTH^[12]. A blood test can also measure proteins called antibodies related to Addison’s disease caused by autoimmune disease^[12].

When adrenal insufficiency is suspected, the main test used to confirm the diagnosis is called an ACTH stimulation test or cosyntropin stimulation test^[13]. This test involves a morning in a day unit to have blood taken before and after an injection of synthetic ACTH^[4]. The test measures the level of cortisol in the blood before and after the injection^[12]. The results will enable your doctor to assess if there is any adrenal insufficiency^[4].

Your doctor may also order imaging tests. A CT scan of the stomach area can check the size of the adrenal glands and look for other issues^[12]. An MRI of the pituitary gland can spot damage that may cause secondary adrenal insufficiency^[12].

Treatment and hormone replacement

Treatment for adrenal insufficiency involves taking lab-made hormones to replace the ones that your body isn’t making^[3]. Your doctor will prescribe hormone medicines to replace the hormones that your adrenal glands aren’t making^[8].

Cortisol replacement is done with a corticosteroid medicine. The most common medicine is hydrocortisone, which you take two or three times a day by mouth^[8]. Doses typically range from 15 to 25 mg daily for hydrocortisone^[4]. Less often, doctors prescribe prednisone, which is taken once daily, with doses typically from 3 to 5 mg^[4]. Sometimes dexamethasone may be prescribed in situations when oral therapy is not tolerated^[13]. Treatment should be adjusted to the lowest dose that relieves symptoms^[13].

Aldosterone replacement is needed for people with primary adrenal insufficiency (Addison’s disease). The medicine used is called fludrocortisone, which you take once daily^[8]. People with secondary adrenal insufficiency usually make enough aldosterone, so they don’t need to take this medicine^[8]. Treatment should be adjusted to keep the level of a substance called plasma renin activity in the upper normal range^[13].

Once treatment is started, you should always carry an alert such as a medical alert card or bracelet^[4]. The alert should say that you have adrenal insufficiency, list your medicines, and state how much you need in an emergency^[6].

Treatment for adrenal crisis includes immediate injections of corticosteroids given through a vein (IV) and large amounts of IV saline (a salt solution) with dextrose (a type of sugar) added^[8].

Managing illness and stress

During normal health, when you become ill or suffer injuries, the body produces increased levels of cortisol to help survive those stresses^[4]. Since people with adrenal insufficiency cannot produce their own cortisol, they need to know when to provide an increased cortisol level during stressful times or during illness^[4]. This is known as following “sick day rules”^[4].

You’ll need higher doses of your medicine during times of physical stress^[8]. You will need to increase your dose if you have a high fever^[8]. Common situations that require increased doses include vomiting or diarrhea, needing bed rest or antibiotics, having a fracture or other significant physical trauma, or having a fever^[17].

For people taking hydrocortisone, the general guidance is to increase your daily dose to at least 40 mg, divided into 2 to 4 doses^[17]. If your usual dose is more than 20 mg, then double it rather than increasing it to 40 mg^[17]. For people taking prednisolone, increase your daily dose to 8 to 10 mg daily as 1 to 2 doses^[17].

You should increase your dose for 48 hours. If you are feeling better, go back to your usual dose. If you don’t feel better after 48 hours, continue to take the increased dose and speak to your doctor for more advice^[17].

If you’re having any type of surgery that uses general anesthesia, you may need treatment with IV corticosteroids and saline^[8]. If you have a severe injury, you may need a higher “stress” dose of corticosteroids right after the injury and while you recover^[8].

Ongoing care and monitoring

Your doctor will adjust the dose of each medicine to meet your body’s needs^[8]. Regular monitoring for signs of getting too little or too much medicine is essential during follow-up appointments^[20].

Patient education is a key feature of managing this condition^[20]. With proper management and continuous patient education, people with adrenal insufficiency can have an unrestricted life with minimal disability^[20]. With treatment, most people with adrenal insufficiency can have a normal, active life^[1].

Doctors should remain alert for the development of other autoimmune disorders in patients with Addison’s disease^[13]. Up to 50% of patients with autoimmune Addison’s disease develop another autoimmune disorder during their lifetime^[13].