ADDISON DISEASE

Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It

causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal
crisis with cardiovascular collapse. Diagnosis is clinical and by finding elevated plasma ACTH
with low plasma cortisol. Treatment depends on the cause but generally includes hydrocortisone
and sometimes other hormones.
Addison disease develops in about 4/100,000 annually. It occurs in all age groups, about equally
in each sex, and tends to become clinically apparent during metabolic stress or trauma. Onset of
severe symptoms (adrenal crisis) may be precipitated by acute infection (a common cause,
especially with septicemia). Other causes include trauma, surgery, and Na loss from excessive
sweating. Even with treatment, Addison disease may cause a slight increase in mortality. It is not
clear whether this increase is due to mistreated adrenal crises or long-term complications of
inadvertent over-replacement.
Etiology
About 70% of cases in the US are due to idiopathic atrophy of the adrenal cortex, probably
caused by autoimmune processes. The remainder result from destruction of the adrenal gland by
granuloma (eg, TB, histoplasmosis), tumor, amyloidosis, hemorrhage, or inflammatory necrosis.
Hypoadrenocorticism can also result from administration of drugs that block corticosteroid
synthesis (eg, ketoconazole, the anesthetic etomidate). Addison disease may coexist with
diabetes mellitus or hypothyroidism in polyglandular deficiency syndrome. In children, the most
common cause of primary adrenal insufficiency is congenital adrenal hyperplasia, but other
genetic disorders are being increasingly recognized as causes.
Causes
The adrenal glands are small hormone-releasing organs located on top of each kidney. They are
made up of an outer portion, called the cortex, and an inner portion, called the medulla.
The cortex produces three hormones:

Glucocorticoid hormones (such as cortisol) maintain sugar (glucose) control, decrease

(suppress)immune response, and help the body respond to stress.

Mineralocorticoid hormones (such as aldosterone) regulate sodium and potassium

balance.

Sex hormones, androgens (male) and estrogens (female), affect sexual development and
sex drive.

Addison disease results from damage to the adrenal cortex. The damage causes the cortex to
produce hormone levels that are too low.
This damage may be caused by the following:

The immune system mistakenly attacking the adrenal glands (autoimmune disease)

Infections such as tuberculosis, HIV, or fungal infections

Hemorrhage into the adrenal glands

Tumors

Risk factors for the autoimmune type of Addison disease include other autoimmune
diseases:

Chronic thyroiditis

Dermatis herpetiformis

Graves' disease

Hypoparathyroidism

Hypopituitarism

Myasthenia gravis

Pernicious anemia

Testicular dysfunction

Type I diabetes

Vitiligo

Certain rare genetic defects may also cause adrenal insufficiency.

Pathophysiology
Mineralocorticoid deficiency: Because mineralocorticoids stimulate Na reabsorption and K
excretion, deficiency results in increased excretion of Na and decreased excretion of K, chiefly in
urine but also in sweat, saliva, and the GI tract. A low serum concentration of Na and a high
concentration of K result. Urinary salt and water loss cause severe dehydration, plasma
hypertonicity, acidosis, decreased circulatory volume, hypotension, and, eventually, circulatory
collapse. However, when adrenal insufficiency is caused by inadequate ACTH electrolyte levels
are often normal or only mildly deranged.

Glucocorticoid deficiency: Glucocorticoid deficiency contributes to hypotension and causes

severe insulin sensitivity and disturbances in carbohydrate, fat, and protein metabolism. In the
absence of cortisol, insufficient carbohydrate is formed from protein; hypoglycemia and
decreased liver glycogen result. Weakness follows, due in part to deficient neuromuscular
function. Resistance to infection, trauma, and other stress is decreased. Myocardial weakness and
dehydration reduce cardiac output, and circulatory failure can occur. Decreased blood cortisol
results in increased pituitary ACTH production and increased blood -lipotropin, which has
melanocyte-stimulating activity and, together with ACTH, causes the hyperpigmentation of skin
and mucous membranes characteristic of Addison disease. Thus, adrenal insufficiency secondary
to pituitary failure does not cause hyperpigmentation.
Symptoms
Symptoms of Addison disease include:

Chronic diarrhea, nausea, and vomiting

Darkening of the skin in some places, causing the skin to look patchy

Dehydration

Dizziness when standing up

Paleness

Extreme weakness, fatigue, and slow, sluggish movement

Mouth lesions on the inside of a cheek (buccal mucosa)

Salt craving

Weight loss with reduced appetite

Exams and Tests

Laboratory tests may show:

Increased potassium

Low blood pressure, especially with a change in body position

Low cortisol level

Low serum sodium

Low blood pH

Normal sex hormone levels

Additional laboratory tests may be ordered.

Other tests may include:

Abdominal x-ray

Abdominal CT scan

Treatment
Treatment with replacement corticosteroids will control the symptoms of this disease. These
medicines usually need to be taken for life.
Never skip doses of your medication for this condition because life-threatening reactions may
occur.
Your doctor may increase your dosage because of:

Infection

Injury

Stress

Surgery

During an extreme form of adrenal insufficiency, called adrenal crisis, you must inject
hydrocortisone right away. Treatment for low blood pressure is usually needed as well.
Some people with Addison disease are taught to give themselves an emergency injection of
hydrocortisone during stressful situations. Always carry medical ID (card, bracelet, or necklace)
that says you have adrenal insufficiency. The ID should also say the type of medicine and dosage
you need in case of an emergency.
Outlook (Prognosis)
With hormone therapy, most people with Addison disease are able to lead a normal life.
Possible Complications
Complications can occur if you take too little or too much adrenal hormone.
Complications also may result from the following related illnesses:

Diabetes

Hashimoto thyroiditis (chronic thyroiditis)

Hypoparathyroidism

Ovarian hypofunction or testicular failure

Pernicious anemia

Thyrotoxicosis

References
Robbins Basic Pathology
Harrisons Principle of Medicine, Ed, 18
Chaker AJ, Vaidya B. Addison disease in adults: diagnosis and management. Am J Med.
2010;123:409-413.
Guber HA, Farag AF. Evaluation of endocrine function. In: McPherson RA, Pincus MR,
eds. Henry's Clinical Diagnosis and Management by Laboratory Methods. 22nd ed.
Philadelphia, Pa: Elsevier Saunders; 2011:chap 24.
Stewart PM, Krone NP. The adrenal cortex. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg
HM, eds.Williams Textbook of Endocrinology. 12th ed. Philadelphia, Pa: Elsevier Saunders;
2011:chap 15.