Adrenal insufficiency and Addison's Disease: Function of Adrenal Hormones, Symptoms, Causes, Diagnosis and Treatment

Addison's disease is an endocrine, or hormonal, disorder that occurs when the adrenal glands do not produce enough of certain hormones. This is also known as adrenal insufficiency.

Updated: June 16, 2022

Addison's disease is an endocrine, or hormonal, disorder that occurs when the adrenal glands do not produce enough of certain hormones. This is also known as adrenal insufficiency. The adrenal glands are located just above the kidneys.
Adrenal insufficiency can be primary or secondary. Mostly Addison's disease occurs for primary adrenal insufficiency, when the adrenal glands are damaged and cannot produce enough of the adrenal hormone cortisol. The adrenal hormone aldosterone may also be produced too little and often in insufficient levels.
Secondary adrenal insufficiency occurs when the pituitary gland fails to produce enough adrenocorticotropin (ACTH) hormone that stimulates the adrenal glands to produce the hormone cortisol. Pituitary gland is a pea-sized gland at the base of the brain. Cortisol production drops as a result of low ACTH. Eventually, the adrenal glands can shrink due to lack of ACTH stimulation. Secondary adrenal insufficiency is much more common than Addison's disease.
Addison's disease can occur in any age groups and affects both sex. It can be life-threatening if left untreated. Treatment for Addison's disease involves hormone replacement therapy in which hormones are taken to replace the insufficient amounts being made by your adrenal glands. This can provide almost the same beneficial effects produced by your naturally made hormones.

Function of Adrenal Hormones:

Adrenal hormones, such as cortisol and aldosterone, play key roles in the functioning of the human body, such as regulating blood pressure; metabolism and the body's response to stress. In addition, the body uses the adrenal hormone dehydroepiandrosterone (DHEA) to make androgens and estrogens hormones.


Cortisol belongs to the class of hormones called glucocorticoids, which affect almost every organ and tissue in the body. The most important job of cortisol is to help the body respond to stress. In addition to this, cortisol also helps

  • maintain blood pressure and heart and blood vessel function
  • slow the immune system's inflammatory response, that is how the body recognizes and defends itself against bacteria, viruses, and substances that appear foreign and harmful
  • regulate metabolism

The amount of cortisol produced by the adrenal glands is precisely balanced in a healthy person. Cortisol is regulated by the hypothalamus and the pituitary gland. A trigger hormone called corticotropin-releasing hormone (CRH) will be released by hypothalamus, which signals the pituitary gland to produce ACTH. ACTH stimulates the adrenal glands to produce cortisol. Cortisol then signals back to both the pituitary gland and hypothalamus to decrease these trigger hormones after a balanced amount.


Aldosterone belongs to the class of hormones called mineralocorticoids which helps maintain blood pressure and the balance of sodium and potassium in the blood. This hormone is also produced by the adrenal glands. When aldosterone production is too low, the body loses too much sodium and retains too much potassium.
The decrease of sodium in the blood can lead to a drop in both blood volume and blood pressure. Too little sodium in the body also can cause a condition called hyponatremia. Symptoms of hyponatremia include feeling confused and fatigued and having muscle twitches and seizures.
Too much potassium in the body can lead to a condition called hyperkalemia which can cause irregular heartbeat, nausea, and a slow, weak, or an irregular pulse.


Dehydroepiandrosterone is another hormone produced by adrenal glands. DHEA is used by the body to make the sex hormones, androgen and estrogen. The adrenal glands may not make enough DHEA with adrenal insufficiency. Healthy men derive most androgens from the testes where as a healthy women and adolescent girls get most of their estrogens from the ovaries. The symptoms from DHEA insufficiency in women and adolescent girls include loss of pubic hair, dry skin, a reduced interest in sex, and depression.

Symptoms of Adrenal insufficiency and Adrenal crisis:

The most common symptoms of adrenal insufficiency are

  • chronic, or long lasting, fatigue
  • muscle weakness
  • loss of appetite
  • abdominal pain
  • weight loss

Other symptoms of adrenal insufficiency can include

  • nausea
  • vomiting
  • diarrhea
  • low blood pressure that drops further when a person stands up, causing dizziness or fainting
  • craving salty foods
  • irritability and depression
  • headache
  • sweating
  • hypoglycemia, or low blood sugar
  • irregular or absent menstrual periods
  • body hair loss or sexual dysfunction in women

Hyperpigmentation or darkening of the skin, can occur in Addison's disease. However this will not be there for secondary adrenal insufficiency. This darkening is most visible on scars, skin folds, lips, pressure points such as the elbows, knees, knuckles, and toes, and mucous membranes such as the lining of the cheek.
Until a stressful event, such as surgery, a severe injury, an illness, or pregnancy, causes the symptoms to worsen, these can be ignored as the progress is very slow.

Adrenal Crisis:

Sudden, severe worsening of adrenal insufficiency symptoms is called adrenal crisis. If the person has Addison's disease, this worsening can also be called an Addisonian crisis or Acute adrenal failure. Sometimes symptoms appear for the first time during an adrenal crisis. But most of the time symptoms of adrenal insufficiency become serious enough that people seek medical treatment before an adrenal crisis occurs.

Symptoms of adrenal crisis include:

  • sudden, severe pain in the lower back, abdomen, or legs
  • severe vomiting and diarrhea
  • dehydration
  • low blood pressure
  • loss of consciousness
  • High potassium (hyperkalemia) and low sodium (hyponatremia)

Left untreated, an adrenal crisis can be fatal.

Causes of Adrenal insufficiency :

Cause of primary adrenal insufficiency:

Addison's disease occurs when your adrenal glands are damaged, producing insufficient amounts of the hormone cortisol and often aldosterone as well. These glands are located just above your kidneys. As part of your endocrine system, they produce hormones that give instructions to virtually every organ and tissue in your body.
Your adrenal glands are composed of two sections. The interior called medulla produces adrenaline-like hormones and the outer layer called cortex produces a group of hormones called corticosteroids, which include glucocorticoids, mineralocorticoids and androgens. Some of the hormones such as the glucocorticoids and the mineralocorticoids produced by the cortex are essential for life.
Primary adrenal insufficiency or Addison's disease occurs when the cortex is damaged and doesn't produce its hormones in adequate quantities. Autoimmune disorder is the most common cause of Addison's disease. This happens when the body's immune system attacks the body's own cells and organs. In autoimmune Addison's, which mainly occurs in middle-aged females, the immune system gradually destroys the adrenal cortex. Primary adrenal insufficiency occurs when at least 90 percent of the adrenal cortex has been destroyed resulting in insufficient cortisol and aldosterone.
Other causes of adrenal gland failure may include:

  • Tuberculosis and other bacterial infections, such as Neisseria meningitidis, which is a cause of meningitis, and fungal infections
  • Other infections of the adrenal glands
  • Spread of cancer to the adrenal glands
  • Bleeding into the adrenal glands, which may present as adrenal crisis without any preceding symptoms.
  • amyloidosis, a serious, though rare, group of diseases that occurs when abnormal proteins, called amyloids, build up in the blood and are deposited in tissues and organs
  • surgical removal of the adrenal glands
  • genetic defects including abnormal adrenal gland development, an inability of the adrenal glands to respond to ACTH, or a defect in adrenal hormone production
  • medication-related causes, such as from anti-fungal medications and the anesthetic etomidate, which may be used when a person undergoes an emergency intubation. Intubation is the placement of a flexible, plastic tube through the mouth and into the trachea, or windpipe, to assist with breathing

Cause of secondary adrenal insufficiency:

Adrenal insufficiency can also occur if your pituitary gland is not functioning properly. The pituitary gland makes a hormone called adrenocorticotropic hormone (ACTH), which stimulates the adrenal cortex to produce its hormones. Even though your adrenal glands aren't damaged, there will be insufficient production of hormones normally produced by your adrenal glands because of inadequate production of ACTH by pitutary gland. This condition is called as secondary adrenal insufficiency.
Stoppage of corticosteroid medication is another more common cause of secondary adrenal insufficiency which is temporary. Corticosteroids are often prescribed to treat inflammatory illnesses such as rheumatoid arthritis, asthma, and ulcerative colitis. In this case, the prescription doses produces more hormone than those normally achieved by the glucocorticoid hormones created by the body. The adrenal glands produce less of their natural hormones when corticosteroids are taken for prolonged periods. The adrenal glands may be slow to restart their production of the body's glucocorticoids once the prescription doses of corticosteroid are stopped. Therefore prescription corticosteroid doses should be reduced gradually over a period of weeks or even months to give the adrenal glands time to regain function and prevent adrenal insufficiency. The adrenal glands might not begin to function normally for some time even with gradual reduction. This is because you can not predict when the adrenal glands will regain its function. So a person who has recently stopped taking prescription corticosteroids should be watched carefully for symptoms of secondary adrenal insufficiency.
Surgical removal of the ACTH-producing tumors of the pituitary gland is another cause of secondary adrenal insufficiency. Usually these noncancerous tumors causes Cushing's syndrome which is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of cortisol. The source of extra ACTH is suddenly gone when the tumors are removed and a replacement hormone must be taken until the body's adrenal glands are able to resume their normal production of cortisol. As the time to time to regain its normal function is unpredictable, a a person who has had an ACTH-producing tumor removed and is going to stop his or her prescription corticosteroid replacement hormone should be watched carefully for symptoms of adrenal insufficiency.
Secondary adrenal insufficiency may also occurs when there is some changes in pituitary gland, either decreases in size or stops producing ACTH. These changes can result from

  • tumors or an infection in the pituitary
  • loss of blood flow to the pituitary
  • radiation for the treatment of pituitary or nearby tumors
  • surgical removal of parts of the hypothalamus
  • surgical removal of the pituitary

Diagnosis of adrenal insufficiency:

Adrenal insufficiency can be difficult to diagnose in its early stage. After reviewing the medical history and symptoms of a a person it can be suspected by a doctor.
A diagnosis of adrenal insufficiency is confirmed through hormonal blood and urine tests. These tests are done to determine cortisol levels and to find out the exact cause. Imaging studies of the adrenal and pituitary glands are done to help determine the cause.

Hormonal Blood and Urine Tests:

Blood test:

Measuring your blood levels of sodium, potassium, cortisol and ACTH gives your doctor an initial indication of adrenal insufficiency.

ACTH stimulation test:

The ACTH stimulation test is the most commonly used test for diagnosing adrenal insufficiency. This test involves measuring the level of cortisol in your blood before and after an injection of synthetic ACTH. ACTH signals your adrenal glands to produce cortisol. The normal response after an ACTH injection is a rise in blood and urine cortisol levels. However, people with Addison's disease or longstanding secondary adrenal insufficiency have little or no increase in cortisol levels.

CRH stimulation test:

A CRH stimulation test can help determine the cause of adrenal insufficiency when the response to the ACTH test is abnormal. This test involves measuring the level of cortisol in your blood before and after an injection of synthetic CRH. Blood is taken before and 30, 60, 90, and 120 minutes after the injection.
People with Addison's disease respond by producing high levels of ACTH, but no cortisol where as people with secondary adrenal insufficiency do not produce ACTH or have a delayed response. As CRH will not stimulate ACTH secretion if the pituitary is damaged, so it points to the pituitary as the cause for no ACTH response. A delayed ACTH response points to the hypothalamus as the cause.

Diagnosis during Adrenal Crisis:

During adrenal crisis, a reliable diagnosis is not possible. However, measurement of blood ACTH and cortisol during the crisis is often enough to make a preliminary diagnosis. The test should be done before corticosteroids is given for treatment.
Low blood sodium, low blood glucose, and high blood potassium are some of the other symptoms of adrenal crisis. An ACTH stimulation test can be performed to help make a specific diagnosis once the crisis is controlled.
After diagnosis of adrenal insufficiency the following tests can be done to look at the adrenal glands and find out the exact cause. The disease may be related to TB, or any antibodies associated with autoimmune Addison's disease.

Ultrasound of the abdomen:

A device called a transducer is used by ultrasound procedure, that bounces safe, painless sound waves of organs to create an image of their structure. Abnormalities in the adrenal glands, such as enlargement or small size, nodules, or signs of calcium deposits, which may indicate bleeding can be seen in the images.

Tuberculin skin test:

A tuberculin skin test measures how a patient's immune system reacts to the bacteria that cause TB. A special TB blood test can be done to test whether a person has TB infection. In this condition the TB bacteria live in the body without making the person sick. Other tests such as a chest x-ray and a sample of sputum can be done to diagnose TB disease. In this condition TB bacteria are actively attacking a person's lungs and making the person sick.

Antibody blood tests:        

The blood test can detect antibodies associated with autoimmune Addison's disease.
After detection of secondary adrenal insufficiency, the following tests can be done to obtain a detailed view of the pituitary gland and assess how it is functioning.

Computerized tomography (CT) scan:

CT scans use a combination of x-rays and computer technology to create images. This test can check the size of your adrenal glands and look for other abnormalities that may give insight to the cause of the adrenal insufficiency.

Magnetic resonance imaging (MRI):

MRI machines use radio waves and magnets to produce detailed pictures of the body's internal organs and soft tissues without using x-rays. MRIs are more advance then CT scan and can be used to produce a three-dimensional (3-D) image of the hypothalamus and the pituitary gland to find out if an abnormality is present.

Treatment of Adrenal insufficiency:

Hormone replacement therapy is the treatment to correct the levels of steroid hormones your body isn't producing. The dose of each medication is adjusted to meet the needs of the patient.
Cortisol is replaced with a corticosteroid, such as hydrocortisone, prednisone, or dexamethasone, taken orally one to three times each day, depending on which medication is chosen. These can be given both as oral medications and injections.
For aldosterone deficiency, oral doses of a mineralocorticoid hormone, called fludrocortisone acetate (Florinef) can be used as replacement, which should be taken once or twice daily. As people with secondary adrenal insufficiency normally maintain aldosterone production, they do not require aldosterone replacement therapy.
An ample amount of sodium is recommended, especially during heavy exercise, when the weather is hot or if you have gastrointestinal upsets, such as diarrhea. A temporary increase in your dosage will also be suggested by your doctor if you are facing a stressful situation, such as an operation, an infection or a minor illness.
During adrenal crisis, low blood pressure, low blood glucose, low blood sodium, and high blood levels of potassium can be life threatening. Standard therapy involves immediate IV injections of corticosteroids and large volumes of IV saline solution with dextrose, a type of sugar. This treatment is quite effective in rapid improvement. When the patient can take liquids and medications by mouth, the amount of corticosteroids is decreased until a dose that maintains normal hormone levels. If aldosterone is deficient, oral doses of fludrocortisone acetate should be given to the person regularly.

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