Addison Disease

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Addison Disease

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Addison disease (or Addison’s disease) is adrenocortical insufficiency due to the destruction or dysfunction of the entire adrenal cortex. It affects glucocorticoid and mineralocorticoid function. The onset of disease usually occurs when 90% or more of both adrenal cortices are dysfunctional or destroyed.

Thomas Addison first described the clinical presentation of primary adrenocortical insufficiency in 1855 in his classic paper, On the Constitutional and Local Effects of Disease of the Supra-Renal Capsules.^[1]

The diagnosis of adrenocortical insufficiency rests on the assessment of the functional capacity of the adrenal cortex to synthesize cortisol. This is accomplished primarily by use of the rapid adrenocorticotrophic hormone (ACTH) stimulation test (Cortrosyn, cosyntropin, or Synacthen).^[2]

In acute adrenal crisis, where treatment should not be delayed in order to do the tests, a blood sample for a random plasma cortisol level should be drawn prior to starting hydrocortisone replacement.

Other tests performed in the diagnosis of Addison disease include the following:

Imaging studies include the following:

Corticosteroid drugs are used for replacement therapy in Addison disease and secondary adrenocortical insufficiency.^{[3, 4]}Hydrocortisone sodium succinate or phosphate is the drug of choice for daily maintenance in these conditions and in the treatment of acute adrenal crisis.

In patients in acute adrenal crisis, intravenous (IV) access should be established urgently, and an infusion of isotonic sodium chloride solution should be begun to restore volume deficit and correct hypotension. Some patients may require glucose supplementation. The precipitating cause should be sought and corrected where possible.

United States

The prevalence of Addison disease is 40-60 cases per 1 million population.

International

The occurrence of Addison disease is rare. The reported prevalence in countries where data are available is 39 cases per 1 million population in Great Britain and 60 cases per 1 million population in Denmark. A study by Olafsson and Sigurjonsdottir found the prevalence of primary adrenal insufficiency in Iceland to be 22.1 per 100,000 population.^[5] A study by Hong et al found the prevalence of primary adrenal insufficiency in Korea to be 4.17 per 1 million population.^[78]

Morbidity and mortality associated with Addison disease usually are due to failure or delay in making the diagnosis or a failure to institute adequate glucocorticoid and mineralocorticoid replacement.^[6]

If not treated promptly, acute addisonian crisis may result in death. This may be provoked either de novo, such as by adrenal hemorrhage, or in the setting of an acute event superimposed on chronic or inadequately treated adrenocortical insufficiency.

With slow-onset chronic Addison disease, significant low-level, nonspecific, but debilitating, symptomatology may occur.

Even after diagnosis and treatment, the risk of death is more than 2-fold higher in patients with Addison disease. Cardiovascular, malignant, and infectious diseases are responsible for the higher mortality rate.^[7]

White and Arlt examined the prevalence of and risk factors for adrenal crisis in patients with Addison disease, utilizing a survey of Addison patients in the United Kingdom, Canada, Australia, and New Zealand. The authors’ results indicated that approximately 8% of patients diagnosed with Addison disease require annual hospital treatment for adrenal crisis. In addition, the investigators concluded that exposure to gastric infection is the most important risk factor for adrenal crisis in the presence of Addison disease; diabetes and/or asthma^[8]concomitant with Addison disease also increase the risk, according to White and Arlt.^[9]

A study by Chantzichristos et al indicated that in patients with type 1 or 2 diabetes, those who also have Addison disease have a higher mortality rate than do those with diabetes alone. Over a median follow-up period of 5.9 years, the mortality rate for diabetes patients with Addison disease was 28%, compared with 10% for those without Addison disease. The increase in the estimated relative overall mortality risk was 3.89 for the Addison disease patients compared with the other group. Although cardiovascular deaths accounted for the highest mortality rate in both groups, the death rate from diabetes complications, infectious diseases, and unknown causes was greater in the patients with Addison disease than in those with diabetes alone.^[10]

Addison disease is not associated with a racial predilection.

Idiopathic autoimmune Addison disease tends to be more common in females and children.

The most common age at presentation in adults is 30-50 years, but the disease could present earlier in patients with any of the polyglandular autoimmune syndromes, congenital adrenal hyperplasia (CAH), or if onset is due to a disorder of long-chain fatty acid metabolism.

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George T Griffing, MD Professor Emeritus of Medicine, St Louis University School of Medicine

George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, International Society for Clinical Densitometry, Southern Society for Clinical Investigation, American College of Medical Practice Executives, American Association for Physician Leadership, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical and Translational Research, Endocrine Society