Addison’s Disease - Causes, Symptoms, Diagnosis, Treatment

Addison’s disease is an uncommon autoimmune disease, characterized by chronic and insufficient functioning of the outer layer of the adrenal gland. The adrenal glands are located atop each kidney and produce vital glucocorticoid hormones. Because of this chronic under-functioning of the adrenal glands, persons with Addison’s disease have a deficiency in the production of glucocorticoid hormones. Glucocorticoid hormones are involved in how the body utilizes and stores carbohydrates, protein, fat, and blood sugar.

The adrenal gland also plays a role in the immune response. A deficiency in glucocorticoid hormones causes an increase in the release of sodium and a decreased release of potassium in the urine, sweat, saliva, stomach, and intestines. These changes can cause low blood pressure and increased water excretion that can in some cases lead to severe dehydration.

Although there are many underlying factors in the development of adrenal insufficiencies, including the destruction of the adrenal cortex due to diseases such as tuberculosis, the growth of tumors, non-autoimmune diseases amyloidosis and adrenoleukodystrophy, and atrophy of the gland due to prolonged use of cortical steroids used in the treatment of other conditions and illnesses, most cases of Addison’s disease are thought to be autoimmune in nature.

Addison’s disease occurs when the adrenal glands do not produce enough (or any) of the hormones, cortisol, and aldosterone. These adrenal gland hormones are necessary for balancing water and energy in the body. Symptoms usually develop slowly over time and may include fatigue, loss of appetite, abdominal pain, and dark patches of skin. Sometimes symptoms occur suddenly causing a life-threatening condition called acute adrenal failure, also known as an acute adrenal crisis. Symptoms of an acute adrenal crisis include sudden weakness, pain, and fainting. The most common cause of Addison’s disease is an abnormal response of the body’s immune system. Injury to the adrenal gland can also cause Addison’s disease. Diagnosis is based on the symptoms, blood and urine tests that evaluate the adrenal function, and imaging studies. Treatment is focused on managing the symptoms and includes daily medications that replace the adrenal hormones. Treatment for an adrenal crisis may include int

Causes

Addison’s disease is caused by damage to your adrenal glands, resulting in not enough of the hormone cortisol and, often, not enough aldosterone as well. Your adrenal glands are 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 (medulla) produces adrenaline-like hormones. The outer layer (cortex) produces a group of hormones called corticosteroids. Corticosteroids include:

Glucocorticoids. These hormones, which include cortisol, influence your body’s ability to convert food into energy, play a role in your immune system’s inflammatory response and help your body respond to stress.
Mineralocorticoids. These hormones, which include aldosterone, maintain your body’s balance of sodium and potassium to keep your blood pressure normal.
Androgens. These male sex hormones are produced in small amounts by the adrenal glands in both men and women. They cause sexual development in men, and influence muscle mass, sex drive (libido) and a sense of well-being in both men and women.

Primary adrenal insufficiency

When the cortex is damaged and doesn’t produce enough adrenocortical hormones, the condition is called primary adrenal insufficiency. This is most commonly the result of the body attacking itself (autoimmune disease). For unknown reasons, your immune system views the adrenal cortex as foreign, something to attack and destroy. People with Addison’s disease are more likely than others to have another autoimmune disease as well.

Other causes of adrenal gland failure may include:

Tuberculosis
Other infections of the adrenal glands
Spread of cancer to the adrenal glands
Bleeding into the adrenal glands. In this case, you may have an addisonian crisis without any previous symptoms.

Secondary adrenal insufficiency

The pituitary gland makes a hormone called adrenocorticotropic hormone (ACTH). ACTH in turn stimulates the adrenal cortex to produce its hormones. Benign pituitary tumors, inflammation and prior pituitary surgery are common causes of not producing enough pituitary hormone.

Too little ACTH can lead to too little of the glucocorticoids and androgens normally produced by your adrenal glands, even though your adrenal glands themselves aren’t damaged. This is called secondary adrenal insufficiency. Mineralocorticoid production is not affected by too little ACTH.

Most symptoms of secondary adrenal insufficiency are similar to those of primary adrenal insufficiency. However, people with secondary adrenal insufficiency don’t have hyperpigmentation and are less likely to have severe dehydration or low blood pressure. They’re more likely to have low blood sugar.

A temporary cause of secondary adrenal insufficiency occurs when people who take corticosteroids (for example, prednisone) to treat chronic conditions, such as asthma or arthritis, stop taking the corticosteroids all at once rather than tapering off.

Last updated: 2020-12-24

Adrenal Glands – Causes

Symptoms

Addison’s disease symptoms usually develop slowly, often over several months. Often, the disease progresses so slowly that symptoms are ignored until a stress, such as illness or injury, occurs and makes symptoms worse. Signs and symptoms may include:

Extreme fatigue
Weight loss and decreased appetite
Darkening of your skin (hyperpigmentation)
Low blood pressure, even fainting
Salt craving
Low blood sugar (hypoglycemia)
Nausea, diarrhea or vomiting (gastrointestinal symptoms)
Abdominal pain
Muscle or joint pains
Irritability
Depression or other behavioral symptoms
Body hair loss or sexual dysfunction in women

Acute adrenal failure (addisonian crisis)

Sometimes the signs and symptoms of Addison’s disease may appear suddenly. Acute adrenal failure (addisonian crisis) can lead to life-threatening shock. Seek emergency medical treatment if you experience the following signs and symptoms:

Severe weakness
Confusion
Pain in your lower back or legs
Severe abdominal pain, vomiting and diarrhea, leading to dehydration
Reduced consciousness or delirium

In an addisonian crisis you will also have:

Low blood pressure
High potassium (hyperkalemia) and low sodium (hyponatremia)

Medical Terms	Other Names	Learn More: HPO ID
100% of people have these symptoms
Decreased circulating cortisol level	Low blood cortisol level	0008163
80%-99% of people have these symptoms
Abdominal pain	Pain in stomach [ more ]	0002027
Anorexia		0002039
Constipation		0002019
Diarrhea	Watery stool	0002014
Failure to thrive	Faltering weight [ more ]	0001508
Fatigue	Tired [ more ]	0012378
Hyperpigmentation of the skin	Patchy darkened skin	0000953
Increased circulating ACTH level	High blood corticotropin levels	0003154
Muscle weakness	Muscular weakness	0001324
Nausea and vomiting		0002017
Weight loss		0001824
30%-79% of people have these symptoms
Androgen insufficiency		0008226
Decreased circulating aldosterone level	Low blood aldosterone level	0004319
Decreased urinary potassium		0012364
Hyperkalemia	Elevated serum potassium levels	0002153
Hyperkalemic metabolic acidosis		0005976
Hyperuricemia	High blood uric acid level	0002149
Hyponatremia	Low blood sodium levels	0002902
Increased circulating renin level	Elevated blood renin level	0000848
Normocytic anemia		0001897
Renal salt wasting	Loss of salt in urine	0000127
5%-29% of people have these symptoms
Adrenal calcification		0010512
Adrenal hypoplasia	Small adrenal glands	0000835
Arthralgia	Joint pain	0002829
Celiac disease		0002608
Decreased female libido	Decreased female sex drive	0030018
Delayed puberty	Delayed pubertal development [ more ]	0000823
Dry skin		0000958
Generalized bone demineralization		0006462
Hashimoto thyroiditis		0000872
Hypercalcemia	High blood calcium levels [ more ]	0003072
Hypoglycemia	Low blood sugar	0001943
Hypoparathyroidism	Decreased parathyroid hormone secretion	0000829
Orthostatic hypotension	Decrease in blood pressure upon standing up	0001278
Premature ovarian insufficiency	Early menopause [ more ]	0008209
Salt craving		0030083
Seizure		0001250
Sparse axillary hair	Limited armpit hair [ more ]	0002215
Type I diabetes mellitus	Type 1 diabetes [ more ]	0100651
Vertigo	Dizzy spell	0002321
Vitiligo	Blotchy loss of skin color	0001045
1%-4% of people have these symptoms
Primary testicular failure		0008720
Thiamine-responsive megaloblastic anemia		0004860
Thymoma		0100522
Percent of people who have these symptoms is not available through HPO
Abnormality of skin pigmentation	Abnormal pigmentation [ more ]	0001000
Abnormality of the cardiovascular system	Cardiovascular abnormality	0001626
Adrenal insufficiency		0000846
Apnea		0002104
Autosomal recessive inheritance		0000007
Cyanosis	Blue discoloration of the skin	0000961
Feeding difficulties in infancy		0008872
Vomiting	Throwing up	0002013

When to see a doctor

See your doctor if you have common signs and symptoms of Addison’s disease, such as:

Darkening areas of skin (hyperpigmentation)
Severe fatigue
Unintentional weight loss
Gastrointestinal problems, such as nausea, vomiting and abdominal pain
Lightheadedness or fainting
Salt cravings
Muscle or joint pains

Diagnosis

A diagnosis of Addison’s disease is suspected based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. Often a diagnosis is made incidentally during a routine exam when a blood test shows low levels of sodium or high levels of potassium. A diagnosis may be confirmed through a variety of specialized tests including the ACTH stimulation test, insulin-induced hypoglycemia test, and x-ray examination.

The ACTH stimulation test measures the amount of cortisol in the blood. During this test, adrenocorticohormone (ACTH) is injected into the body, stimulating the production of cortisol. If the test fails to stimulate adequate cortisol production, it indicates that the adrenal glands are damaged or not functioning properly.

The insulin-induced hypoglycemia test may be used to determine if the symptoms of Addison’s disease are due to problems with the pituitary gland. This test measures blood sugar (glucose) levels before and after the injection of fast-acting insulin, which should lead to a drop in glucose and a rise in cortisol.

X-ray imaging techniques such as computed tomography (CT scan) of the abdomen may be taken to check the size of the adrenal glands and to detect other signs of disease such as calcification of the adrenal glands. During a CT scan, a computer and x-rays are used to create a film showing cross-sectional images of an organ’s tissue structure.

Treatment

The treatment of Addison’s disease is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Individuals with Addison’s disease are treated by replacing the deficient steroid hormones (cortisol and aldosterone). Cortisol is replaced by the drug hydrocortisone and aldosterone is replaced by the drug fludrocortisone. The dosage of these drugs is different for each individual and the dosage may be increased during infection, trauma, surgery and other stressful situations to prevent an acute adrenal crisis. Individuals should be encouraged to increase their salt intake in their diets.

An adrenal crisis demands immediate hormonal investigation and intravenous (injected directly into a blood vessel) administration of high-dose hydrocortisone and fluid (salt water) and electrolyte replacement; a short-term course of other drugs called vasopressors may be needed to maintain blood pressure. Affected individuals should carry a card or wear a tag stating that they have Addison’s disease.

Complications

Addisonian crisis

If you have untreated Addison’s disease, you may develop an addisonian crisis as a result of physical stress, such as an injury, infection or illness. Normally, the adrenal glands produce two to three times the usual amount of cortisol in response to physical stress. With adrenal insufficiency, the inability to increase cortisol production with stress can lead to an Addisonian crisis.

An addisonian crisis is a life-threatening situation that results in low blood pressure, low blood levels of sugar and high blood levels of potassium. You will need immediate medical care.

People with Addison’s disease commonly have associated autoimmune diseases.

References