Adrenal Insufficiency
This article describes the causes, symptoms, signs and changes
seen in adrenal insufficiency as well as the tests and procedures
used for its diagnosis.
Posted by
Elaine Moore | Last updated: Mar 25, 2013
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Adrenal insufficiency is a condition that occurs when the adrenal glands produce inadequate amounts of the adrenal hormones cortisol, and sometimes, aldosterone. This condition can occur as a primary or secondary disorder, and it can have congenital or acquired origins. Primary conditions occur in less than 1 per 100,000 persons. Secondary conditions are more common. Adrenal insufficiency, which affects slightly more women than men, varies in severity, ranging from a subclinical or mild condition to an extreme, sometimes fatal, form, which is known as an Addisonian crisis. Most primary adrenal insufficiency is autoimmune in nature and caused by Addison's disease, which is described in a separate article, or as the result of infection. Primary conditions may also occur in patients with autoimmune polyglandular syndromes (APS). In these syndromes one or more other autoimmune conditions, including diabetes, hypoparathyroidism, autoimmune thyroid disease, and other endocrine and non-endocrine disorders, are also present. These syndromes, which are classified as types 1-4 APS, are also described in a separate article.
Autoimmune disease accounts for about 80 percent of all cases of primary adrenal insufficiency. Most other cases result from infection (with tuberculosis, cytomegalovirus, the HIV virus, fungi, and other infectious agents), or as a complication of various metabolic and genetic disorders such as adrenal hyperplasia and adrenoleukodystrophy, or as a sequelae to certain metastatic cancers. Also, in some bleeding disorders, such as antiphospholipid syndrome or in trauma, adrenal insufficiency may result from thrombosis or hemorrhage. Secondary conditions are related to both long and short-term use of corticosteroids (prednisone, prednisolone and others) or megesterol acetate. Other causes include high doses of medications used to lower cortisol levels in Cushing's syndrome or as a consequence of surgery for pituitary tumors. Patients who have been on long-term glucocorticoid therapy in the past may develop adrenal insufficiency later if they are subjected to acute stress, trauma, or infection. Secondary autoimmune conditions in APS Syndrome occur in about 50 percent of patients with primary or autoimmune adrenal insufficiency. In only about five percent of patients with other autoimmune conditions, particularly diabetes, does Addison's disease later occur.
The adrenal glands are situated directly above the kidneys. Different hormones are produced in the gland's different layers. In primary disorders, damage to the adrenal cortex, the outer layer of the adrenal glands, is responsible for inadequate hormone production of both cortisol and aldosterone. Cortisol helps regulate the immune response, helps the body use sugar and protein for energy and helps the body recover from infection and stress. Aldosterone helps regulate the body's fluid balance, ensuring that we have adequate amounts of water, salt, and potassium in the body.
Normally, the production and release of cortisol and aldosterone are regulated by the hypothalamus in the brain via the pituitary gland. When the hypothalamus, which is the master gland, recognizes that the cortisol level is low, it secretes a hormone known as corticotropin-releasing-hormone or CRH. CRH, in turn, prompts the pituitary gland to secrete a hormone called adrenocorticotropin or ACTH. ACTH, in turn, stimulates the adrenal glands to produce and release cortisol. Normally, when cortisol levels fall, the pituitary secretes more ACTH to help correct the problem, and ACTH levels are elevated
In secondary or central adrenal insufficiency, the hypothalamus fails to respond to low cortisol and doesn't release CRH, or the pituitary gland fails to recognize the hypothalamic signal or is otherwise unable to produce ACTH. Without these signals from the hypothalamus and pituitary glands, the adrenal cortex does not get the message or order to produce more cortisol. Consequently, cortisol levels fall. Steroids, which elevate blood cortisol levels, decrease ACTH levels. Seeing adequate cortisol in the blood, the hypothalamus stops secreting CRH, causing ACTH levels to fall. This disruption of the pituitary-hypothalamic-adrenal axis continues to be disrupted even when steroids are stopped. In some cases, this can occur after only two weeks of steroid use. Without adequate ACTH, cortisol production is limited.
