Addison's Disease and Addisonian Crisis - Adrenal Insufficiency

Overview

Addison's disease is a rare disorder in which the adrenal glands fail to produce adequate amounts of certain hormones. The resulting low hormone levels impair a number of essential bodily functions.

The adrenal glands are small tissues located just above the kidneys. Normally, the outer part of the adrenal gland (adrenal cortex) produces hormones that regulate metabolism, maintain blood pressure, and support sexual reproduction. The inner part of the adrenal gland (adrenal medulla) produces hormones that help the body respond to high levels of stress.

In Addison’s disease, the adrenal cortex is damaged and becomes unable to produce adequate amounts of the following hormones:

  • Cortisol (termed a glucocorticoid hormone), which decreases inflammation, controls metabolism, and maintains blood sugar levels.
  • Aldosterone (termed a mineralcorticosteroid hormone), which helps maintain a stable blood pressure and proper blood levels of sodium and potassium.
  • Dehydroepiandrosterone (DHEA), which is involved in producing the sex hormones androgen and estrogen.

This disease can affect both males and females of any age. Most cases of Addison’s disease occur in adults age 30-50.

adrenal glands

Causes of Primary and Secondary Adrenal Insufficiency

Primary adrenal insufficiency

Addison’s disease is also known as primary adrenal insufficiency. This condition is caused by disorders that directly damage the adrenal cortex, including:

  • Immune system malfunction (autoimmune disease), the most common cause of Addison’s disease, in which the body mistakenly attacks the adrenal cortex
  • Infections, such as tuberculosis, that involve the adrenal glands
  • Cancer affecting the adrenal glands
  • Bleeding inside the adrenal glands.

Secondary adrenal insufficiency

Another type of adrenal gland dysfunction, secondary adrenal insufficiency, is caused by a problem outside of the adrenal glands themselves. Normally, the amount of cortisol produced by the adrenal glands is regulated by the hypothalamus and pituitary glands in the brain. The hypothalamus gland secretes corticotropin-releasing hormone (CRH), which triggers the pituitary gland to secrete adrenocorticotropic hormone (ACTH), which in turn stimulates the adrenal glands to produce cortisol. Secondary adrenal insufficiency occurs when there is a problem in the pituitary gland that lowers ACTH and cortisol. Secondary adrenal insufficiency can also be caused by long-term use of corticosteroid medication that suppresses adrenal gland production of cortisol.

Symptoms of the Disease and Addisonian Crisis

Usually the initial stage of Addison’s disease progresses slowly and produces vague symptoms that are often ignored until there is a stressful event, such as surgery or trauma, which causes the symptoms to worsen abruptly.

The most common signs and symptoms of Addison's disease include:

  • Fatigue
  • Weight loss
  • Muscle weakness
  • Low blood pressure
  • Dizziness
  • Darkening of the skin and mucous membranes (hyperpigmentation)
  • Nausea and vomiting
  • Craving salt
  • Headache
  • Sweating
  • Low blood sugar level
  • Loss of interest in sex (decreased libido)
  • Irregular or absent menstruation (amenorrhea)
  • Loss of pubic hair and body hair
  • Muscle twitching or seizures.

Untreated Addison’s disease can result in Addisonian crisis, a life-threatening illness associated with the following signs and symptoms:

  • Extremely low blood pressure
  • Severe pain in the back, abdomen or lower extremities
  • Severe vomiting
  • Diarrhea
  • Dehydration
  • Decreased level of consciousness and confusion.

Diagnosis

At the onset of Addison’s disease, the symptoms are often nonspecific, making the disease very difficult to diagnose.

The physical exam may show darkening of the skin and mucous membranes, signs of dehydration, and low blood pressure.

When a health care provider suspects a patient has Addison’s disease, a number of laboratory tests are used to confirm the diagnosis.

  • Low blood sodium level
  • High blood potassium level
  • Low blood sugar
  • Low sex hormone levels
  • Low blood cortisol levels
  • ACTH stimulation test, in which the patient receives an injection of ACTH. The normal adrenal response to ACTH is an increase in blood cortisol. However, in Addison’s disease, this increase is not observed.
  • CRH stimulation test. An injection of CRH normally causes an increase in both ACTH and cortisol but with Addison’s disease, the response is an increase in only ACTH without an increase in cortisol. In secondary adrenal insufficiency there is no increase in either ACTH or cortisol.
  • Ultrasound of the abdomen, a test that uses high-frequency sound waves, providing an image of the adrenal glands.
  • Tuberculosis (TB) skin test helps determine whether TB is causing the adrenal insufficiency.
  • Blood antibody levels are abnormal when the disorder is caused by an autoimmune disease.

Treatment

In Addison's disease, the basis of treatment is the replacement of the hormones that the adrenal glands are not producing. Treatment controls symptoms but does not cure the disease; life-long therapy is required. The hormone replacement therapy includes following:

  • Corticosteroid medication replaces low cortisol. Commonly used corticosteroids include prednisone, hydrocortisone, or dexamethasone.
  • Mineralocorticoid hormone (fludrocortisone acetate) replaces low aldosterone.
  • Androgen replacement medication treats low sex hormone levels.

Addisonian crisis is a life-threatening emergency that is fatal if not treated promptly. The following treatments are administered:

  • Hydrocortisone (an intravenous corticosteroid)
  • Intravenous fluids with sodium chloride and sugar (dextrose).

Preventing Addisonian Crisis

Currently, there are no known methods to prevent Addison’s disease. However, steps can be taken to prevent Addisonian crisis in people already diagnosed with the disease.

Immediately prior to undergoing any surgery, a person with Addison's disease should be treated with an intravenous injection of corticosteroid to support the blood pressure during the stress of the procedure and prevent Addisonian crisis. Also, during a major illness, the dose of corticosteroid needs to be increased. Patients are advised to wear a medical alert bracelet indicating their diagnosis of adrenal insufficiency and carry a dose of injectable corticosteroid in case of an emergency.

Sources

  • Carroll TB, Aron DC, Findling JW, Tyrrell B. Chapter 9. Glucocorticoids and Adrenal Androgens. In: Gardner DG, Shoback D. eds. Greenspan’s Basic & Clinical Endocrinology, 9e. New York, NY: McGraw-Hill; 2011.
  • Addison’s disease. Mayo Clinic website. http://www.mayoclinic.org/diseases-conditions/addisons-disease/basics/definition/con-20021340. Accessed December 29, 2014.
  • Adrenal Insufficiency and Addison’s Disease. National Endocrine and Metabolic Diseases Information Service (NEMDIS) website. http://endocrine.niddk.nih.gov/pubs/addison/addison.aspx. Accessed December 29, 2014.