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Adrenal Insufficiency and Addison Disease

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What is adrenal insufficiency?

Adrenal insufficiency and Addison disease are hormonal or endocrine disorders caused by the body not producing enough of the adrenal hormones cortisol and aldosterone. The body regulates hormones through a signaling and feedback system, so this hormone imbalance can happen in a number of ways, possibly causing severe illness.

The feedbacks and signals that regulate hormone production involve signals sent between the hypothalamus and the pituitary gland in the brain and the adrenal glands located on top of each kidney. The adrenal glands are multi-layered and different layers produce hormones that control water and salt balances in the body and thus blood pressureFeedback system involving hypothalamus, pituitary, and adrenal glands.

For example, cortisol is produced and secreted by the adrenal cortex. Production of the hormone is regulated by the hypothalamus and the pituitary gland. When the blood cortisol level falls, the hypothalamus releases corticotropin-releasing hormone (CRH), which directs the pituitary gland to produce ACTH (adrenocorticotropic hormone). ACTH stimulates the adrenal glands to produce and release cortisol. In order for appropriate amounts of cortisol to be made, the hypothalamus and both the pituitary and adrenal glands must be functioning properly.

Without enough cortisol or aldosterone, people become weak and dehydrated, unable to maintain an adequate blood pressure or to respond properly to stress. 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 is produced by the adrenal cortex and manages the salt and potassium balance in the blood.

There are two different types of adrenal insufficiency and they depend on whether pituitary gland or adrenal dysfunction underlies hormone deficiencies.

  • Underactive or damaged adrenal glands cause Addison disease, also known as primary adrenal insufficiency. They affect cortisol and aldosterone amounts.
  • Decrease in the production of the pituitary hormone ACTH (adrenocorticotropic hormone) is at the root of secondary adrenal insufficiency. 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.

Addison disease affects about 1 to 4 people per 100,000 in the U.S. It is found in people 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, viralHIV, 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 (CAH), while 30% of the time adrenal damage is due to autoimmune disease, the inherited disease adrenoleukodystrophy, or less common causes.

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