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پیوند های ویژه

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Adrenal Insufficiency&Addison's Disease

?What is it

Adrenal insufficiency is a condition characterized by inadequate production of the adrenal hormones cortisol and aldosterone. The adrenal glands are small organs located on top of each kidney. They consist of an inner layer called the adrenal medulla and an outer layer called the adrenal cortex. Each layer produces several different hormones that control many body systems. Hormone production is regulated by interactions between the hypothalamus, the pituitary gland, and the adrenal glands. If any part of their signaling and feedback system is not working, it can cause major disruptions and illness within the body. Primary adrenal insufficiency, also called Addison's disease, affects the levels of both cortisol and aldosterone. It is caused by underactive or damaged adrenal glands. Secondary adrenal insufficiency is the result of a pituitary dysfunction and typically affects only cortisol production.

Cortisol is a glucocorticoid hormone, produced by the adrenal cortex. Among its many roles, cortisol affects the metabolism of carbohydrates, proteins, and fats, affects glucose levels in the blood, acts as an anti-inflammatory agent, and helps the body react to stress. Aldosterone, a mineralocorticoid hormone that is also produced by the adrenal cortex, manages the salt and potassium balance in the blood. Without enough of these two hormones, the body becomes weak and dehydrated, unable to maintain an adequate blood pressure or to respond properly to stress.

Addison's disease affects about 1 to 4 people per 100,000 in the U.S. It is found in patients of all ages and affects both males and females equally. Symptoms of insufficiency may not emerge until about 80% to 90% of the adrenal cortex has been destroyed.

In the U.S., about 70% of primary adrenal insufficiency in adults is due to an autoimmune process. About 30% of the time, the adrenal damage is due to other causes, such as: tuberculosis, a common cause in areas of the world where tuberculosis is more prevalent; bacterial, viral and fungal infections; adrenal hemorrhage; and the spread of cancer into the adrenal glands. Rarely, it may be due to a genetic abnormality of the adrenal glands. In children, about 70% of cases are caused by a congenital disease termed congenital adrenal hyperplasia, while 30% of the time adrenal damage is due to autoimmune disease, another inherited disease termed adrenoleukodystrophy, or less common causes.

Secondary adrenal insufficiency is due to a decrease in the production of the pituitary hormone ACTH (adrenocorticotropic hormone). ACTH is a pituitary messenger - it tells the adrenal cortex to produce cortisol. If there is insufficient ACTH, due to pituitary damage, a pituitary tumor, or some other cause, then cortisol production is not stimulated. Secondary adrenal insufficiency can also arise when corticosteroid therapy (such as prednisone, which may be given to relieve inflammation in conditions such as rheumatoid arthritis) is abruptly halted. These treatments suppress natural cortisol production, and it can take several weeks or months for normal production to resume. With secondary adrenal insufficiency, aldosterone production is usually not affected

Signs and symptoms


The
symptoms associated with adrenal insufficiency are often vague and nonspecific. They may emerge slowly, first appearing during times of stress, then increasing in intensity over a period of several months. Symptoms may include:

  • Abdominal pain
  • Decreased body hair
  • Dehydration with Addison’s disease
  • Diarrhea or constipation
  • Dizziness and fainting
  • Fatigue
  • Hyperpigmentation with Addison’s disease - dark patches of skin, especially in the folds of the skin; sometime black freckles on the forehead and face and/or discoloration around areas such as the nipples, lips, and rectum
  • Joint and muscle aches
  • Low blood pressure
  • Hypoglycemia
  • Muscle weakness
  • Salt craving with Addison’s disease
  • Vomiting
  • Weight loss

Sometimes, however, the signs and symptoms of adrenal insufficiency may appear suddenly. About 25% of the time, adrenal insufficiency is diagnosed during an adrenal crisis (also called an Addisonian crisis). This crisis may be caused by a period of increased stress, trauma, surgery, or a severe infection. If left untreated it can be fatal. In an adrenal crisis, the signs and symptoms may include:

  • Kidney failure
  • Loss of consciousness
  • Low blood pressure
  • Severe pain in the lower back, abdomen or legs
  • Severe vomiting and diarrhea, leading to dehydration
  • Shock
  • Tests

  • Symptoms such as hyperpigmentation, weakness, low blood pressure, and salt cravings may cause a doctor to suspect adrenal insufficiency, especially if these symptoms appear to worsen during periods of stress. Laboratory tests are used to determine whether adrenal insufficiency is present, to distinguish between primary and secondary insufficiencies, and to try to determine the underlying cause of the condition. Tests are also ordered to evaluate a patient’s electrolyte balance, glucose level, and kidney function. During an adrenal crisis, they are ordered to determine the severity of the imbalances and to monitor the effectiveness of treatment.
    • Laboratory Tests
      Cortisol. Levels normally vary in the blood, peaking in the early morning. If the adrenal gland is either not functioning normally or not being stimulated by ACTH, then cortisol levels will be consistently low. Cortisol levels are used, along with ACTH and ACTH stimulation tests, to help diagnose adrenal insufficiency.
    • ACTH. ACTH is a pituitary hormone that signals the adrenal glands to produce cortisol. This test is primarily ordered as a baseline test to evaluate whether or not the pituitary is producing appropriate amounts of ACTH. In a patient with adrenal insufficiency, low ACTH levels indicate secondary adrenal insufficiency, while high levels indicate primary adrenal insufficiency (Addison’s disease). The ACTH test is often ordered along with the ACTH stimulation test.
    • ACTH stimulation test. This test involves measuring the level of cortisol in a patient’s blood before and after an injection of synthetic ACTH. If the adrenal glands are functional, cortisol levels will rise in response to the ACTH stimulation. If they are damaged or non-functional, then their response to ACTH will be minimal. This rapid screening test may be ordered along with a baseline ACTH test and, if abnormal, may be followed with a 1 to 3 day prolonged ACTH stimulation test to help differentiate between primary and secondary adrenal insufficiency.
    • Aldosterone. Blood or urine aldosterone levels are measured to help diagnose Addison’s disease - to determine whether the adrenal gland is producing aldosterone. If the levels are low, it is another indication that the patient may have a primary adrenal insufficiency.
    • Electrolytes. Electrolytes (Sodium, Potassium, Chloride and Carbon dioxide) are measured to help detect and evaluate the severity of an existing electrolyte imbalance and to monitor the effectiveness of treatment. Electrolytes may be affected by many conditions; with Addison’s disease the sodium, chloride, and carbon dioxide levels are often low, while the potassium level may be very high.
    • BUN and Creatinine are tests done to monitor kidney function.
    • Glucose levels may be very low during an adrenal crisis. Glucose may be ordered in order to help monitor a patient during a crisis.
    • Occasionally used tests
      Insulin-induced hypoglycemia test. Occasionally, a doctor will order this test to assist in the detection of adrenal insufficiency. Glucose and cortisol levels are measured at predetermined intervals after an injection of insulin is used to stress the pituitary gland. In healthy people, blood glucose levels fall and cortisol concentrations increase. In those with adrenal insufficiency, cortisol levels will remain low and glucose levels will fall, then recover slowly.
    • Renin. Renin activity is elevated in primary adrenal insufficiency because a lack of aldosterone causes increased renal sodium losses. This lowers blood sodium levels and decreases the amount of fluid in the blood (which lowers blood volume and pressure), which in turn stimulates renin production by the kidney.
    • 21-hydroxylase autoantibodies are sometimes ordered as part of the diagnostic process when autoimmune Addison’s disease is suspected. They are considered a good marker of autoimmune Addison's disease but are not widely used at this time.
    • Non-Laboratory Tests
      X-rays may be used to look for
      calcification on the adrenal cortex that may be due to a tuberculosis infection.
    • CT (computerized tomography) or MRI (magnetic resonance imaging) scans are sometimes used to look at the size and shape of the adrenal glands and the pituitary. The adrenal glands can be enlarged with infections and cancers. With autoimmune diseases and secondary adrenal insufficiency, the adrenal glands are often normal or small in size.
    • Treatments

    • There are treatments available for primary adrenal insufficiency but no cure. If the condition is due to an infection, the affected person may regain some adrenal function when the infection resolves. Even when people have extensive and permanent damage to their adrenal cortex, however, they should be able to live healthy, relatively normal lives by replacing the missing hormones and observing a few precautions.
      • In the case of secondary adrenal insufficiency, it is very rare for a patient to respond to treatment if the cause is pituitary damage or disease. However, if the underlying condition can be resolved, such as if the insufficiency is due to corticosteroid therapy, cortisol production may eventually resume. Treatment for secondary insufficiency also involves hormone replacement

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