255.4 - Disorders of Adrenal Glands, Addisons Disease (Corticoadrenal Insufficiency)
255.5 - Disorders of Adrenal Glands, Other Adrenal Hypofunction; Adrenal Medullary Insufficiency
279.4 - Autoimmune Disease, Not Elsewhere Classified; Autoimmune Disease NOS
Addison's disease (adrenal insufficiency) occurs when the outer layer of the adrenal gland, the cortex, is damaged, causing it to produce insufficient amounts of certain corticosteroid hormones that are essential for life. The three types of corticosteroids are androgens and estrogens, which affect sexual development and reproduction; glucocorticoid hormones such as cortisol, which maintain glucose regulation, suppress immune responses, and provide stress responses; and mineralocorticoid hormones such as aldosterone, which regulate sodium and potassium balance.
Adrenal insufficiency can occur for a variety of reasons. In 70% of cases of primary adrenal insufficiency, the body's immune system attacks and slowly destroys the adrenal glands (autoimmune disease). Tuberculosis, once the most common cause of Addison's disease, is responsible for only about 20% of cases of primary adrenal insufficiency. Since the appearance of acquired immunodeficiency syndrome (AIDS), tuberculosis is once again on the rise and a corresponding increase in Addison's disease caused by tuberculosis is expected. Less common causes of primary adrenal insufficiency include chronic infections, particularly fungal infections and viral infections (cytomegalovirus or CMV) associated with AIDS; amyloidosis; hemorrhage of the adrenal glands; and surgical removal of the adrenal glands. Waterhouse-Friderichsen syndrome is primary adrenal insufficiency that occurs due to adrenal gland hemorrhage during meningococcal infection.
In secondary adrenal insufficiency, the adrenal glands are healthy but the body fails to stimulate them to release hormones. This occurs when the pituitary gland, which is located at the base of the brain, fails to secrete adrenocorticotrophic hormone (ACTH), which normally stimulates the adrenal gland to release cortisol. Causes of secondary adrenal insufficiency include long-term use of steroids such as prednisone or surgical removal of pituitary tumors, either cancerous or non-cancerous. Less common causes are loss of blood flow to the pituitary gland, surgical removal of a portion of the pituitary gland, or surgical removal of the area of the brain called the hypothalamus.
Risk: Addison's disease tends to run in families. Individuals who take steroids over a long period of time and then develop a severe infection, injury, or undergo a surgical procedure are at increased risk of developing Addison's disease. It is slightly more common among women than men. It can appear at any age but is more often diagnosed in individuals between the ages of 30 and 50 (Odeke). Other conditions that may be associated with adrenal insufficiency include diabetes mellitus, hypoparathyroidism, hypopituitarism, pernicious anemia, testicular dysfunction, Graves' disease, chronic thyroiditis, and myasthenia gravis.
Incidence and Prevalence: Addison's syndrome is a rare disorder, with a prevalence of 40 to 60 cases per 1 million people in the US and Europe (Odeke).
History: In most cases of Addison's disease, symptoms appear gradually. Individuals often complain of progressively increasing weakness and fatigue, loss of appetite (anorexia), and unintentional weight loss. Many report dizziness or light-headedness especially when rising from a seated position. Abdominal pain, decreased tolerance to cold, hair loss (alopecia) particularly in women, and cravings for salty foods may also be reported. Nausea, vomiting, and chronic diarrhea occur in about 50% of cases. Women may report that their menstrual cycles have become irregular (dysmenorrhea) or stopped altogether (amenorrhea). Moodiness, irritability, or depression may be evident. In advanced cases, the individual may experience what is known as an Addisonian crisis characterized by abdominal pain; severe vomiting and diarrhea; hypotension; agitation, confusion and loss of consciousness.
Physical exam: Findings usually include low blood pressure (hypotension) that may worsen when the individual stands after sitting or lying down (orthostatic hypotension). The individual may be dehydrated. Skin changes are also commonly noted and include freckling and darkening of the skin. The skin darkening may resemble a deep tan but will be present even on parts of the body not exposed to the sun. The skin darkening may also be more visible on scars; pressure points, such as elbows, knees, and toes; lips; mucus membranes; and in skin folds.
Tests: The most specific test for Addison's disease is the ACTH stimulation test. In this test, blood is drawn to measure baseline levels of the hormones cortisol and aldosterone. Synthetic ACTH (Cortrosyn, cosyntropin, or Synacthen) is administered intravenously or by intramuscular injection. Blood is drawn again at 30 minutes to measure changes in the cortisol and aldosterone levels. In order to rule out the diagnosis of Addison's disease, there must be an increase in the baseline cortisol value by 7 mcg/dL or more, and the cortisol level must rise to 20 mcg/dL or more in 30 minutes (Odeke). In a healthy individual, the cortisol levels are higher after the injection of synthetic ACTH; in individuals with Addison's disease, there is little or no change in cortisol levels.
If an abnormal result is obtained, a variation of this test in which ACTH is given over a 2 to 3 day period may be conducted. Blood and/or urine samples are collected before and during this 2 to 3 day period. In this longer ACTH stimulation test, the cause of adrenal insufficiency can be determined. Primary adrenal insufficiency results in little or no cortisol production for the entire 72 hour period; secondary adrenal insufficiency, on the other hand, will show an adequate response by the second or third day. Elevated morning ACTH levels confirm a primary adrenal cause.
If the ACTH stimulation test is inconclusive, other tests may be conducted either to help confirm the diagnosis or help rule out other conditions. An insulin-induced hypoglycemia test evaluates the functioning of the pituitary gland and the hypothalamus. In this test, blood sugar (glucose) and cortisol levels are measured and then fast-acting insulin is given. The normal response is for glucose to fall and cortisol to rise, indicating a normal pituitary gland and hypothalamus.
Other blood tests that may prove helpful include a complete metabolic panel (CMP), a complete blood count (CBC) and a thyroid-stimulating hormone level (TSH). Individuals with Addison's disease generally have low sodium and cortisol levels, but high potassium, calcium, blood urea nitrogen (BUN), and creatinine levels. If the individual has not eaten prior to the blood test, there may be low blood sugar (hypoglycemia) and high ACTH levels.
When an autoimmune disease is the cause of adrenal dysfunction, adrenal antibodies may be present in the blood. An abdominal or chest x-ray may help reveal calcium deposits in the adrenal glands—a sign of tuberculosis infection. An abdominal CT may be performed to determine if the adrenal glands are smaller or larger than normal. Small adrenal glands may be a sign of autoimmune adrenal disease and larger than normal adrenal glands may be an indication of hemorrhage or infiltrative disease. Biopsies of the adrenal glands can rule out cancer.
In the rare instances of Addisonian crisis, potentially life-threatening low blood pressure (hypotension), low blood sugar (hypoglycemia), and high levels of potassium (hyperkalemia) may occur. Individuals experiencing Addisonian crisis require immediate hospitalization. Treatment will include immediate intravenous (IV) or intramuscular (IM) injections of steroids along with saltwater (saline) fluid replacements and sugar (glucose). Oral steroid medications may also be given.
Most cases of Addison's disease, however, do not require inpatient treatment. The goal of therapy is to replace the hormones that the body is not producing. Oral steroid medications are usually a combination of glucocorticoids and mineralocorticoids and are taken for the remainder of the individual's life. The individual is counseled to avoid dehydration by drinking plenty of fluids. An identification and medical instruction bracelet is often advised, and individuals are urged to carry injectable steroid medication for emergency use if medical care is not available.
Individuals with Addison's disease need to recognize the consequences of not closely following their medical regimen. Any stress such as illness, fever, hot and humid weather, profuse sweating, and even emotional stress can precipitate a sudden worsening of the condition and must be met with an increase in replacement hormones. Most individuals with Addison's disease are taught to give themselves an emergency injection of hydrocortisone in times of stress.
If an underlying disease, such as tuberculosis, is responsible, treatment of the underlying disease is important for recovery or resolution of symptoms.
With careful management, an individual with Addison's disease can live a full, relatively active life. However, illness, stress, and even general anesthesia for surgery can bring on an adrenal crisis necessitating special care and adjustments in replacement hormone dosages.
Untreated, Addison's disease is a progressive condition that can gradually result in severe abdominal pain, extremely low blood pressure, and kidney failure. Addisonian crisis must be treated immediately or coma and death can occur.
Illness, injury, or any type of stress can result in an Addisonian crisis, a potentially life-threatening condition that is managed with an increase of the hydrocortisone dose.
Other possible complications include extremely high fever (hyperpyrexia), psychotic reactions, accidental overdose of steroid medications and, rarely, a temporary paralysis due to low levels of potassium.
Additional complications related to the individual's underlying disease might also occur and will vary depending upon the particulars of that disease.
In most cases, work accommodations or restrictions are not necessary for individuals with Addison's disease. Taxing physical labor, such as working in hot humid environments or work that carries a great deal of stress, is unsuitable for an individual with Addison's disease. The particulars of the necessary accommodations vary significantly depending on the individual, severity of symptoms, individual's response to treatment, and job requirements.
If an individual fails to recover within the expected maximum duration period, the reader may wish to consider the following questions to better understand the specifics of an individual's medical case.
- Was diagnosis of Addison's disease confirmed through an ACTH stimulation test?
- Was the cause of the adrenocortical insufficiency, such as an autoimmune disorder, infection, tumor, or hemorrhage in the adrenal glands identified?
- Were underlying causes also addressed?
- Is individual on oral cortisol with or without fludrocortisone?
- Does current method of treatment appear to be effective?
- Has individual continued to experience any symptoms of adrenal crisis, such as vomiting, diarrhea, fever, confusion, low blood pressure, or dehydration?
- If current treatment is not effective, is individual a candidate for surgery or radiation therapy?
- Is individual on and able to maintain a diet high in fluids, carbohydrates, and protein?
- Would individual benefit from instruction in stress management techniques?
- Does individual wear an identification/medical instruction bracelet?
- Does individual carry injectable steroid medication for use in an emergency if medical care is not available?
- Were underlying causes, such as autoimmune disorders, infection, tumor, or tuberculosis resolved or brought under control?
- Does individual realize that Addison's disease is a lifelong condition that requires careful management, including avoiding stress and infection?
- Is individual able to adhere to oral therapy and dietary recommendations?
- Does individual attend regular follow-up visits with physician?
- Has individual experienced any complications related to the Addison's disease?
- Does individual have an underlying condition that may impact recovery?
Odeke, Slyvester, and Steven B. Nagelberg. "Addison Disease." eMedicine. Eds. Daniel Einhorn, et al. 25 Nov. 2003. Medscape. 14 Sep. 2004 http://emedicine.com/med/topic42.htm.