Your body's network of hormone-producing organs, or its endocrine system, includes the adrenal gland, which makes several important hormones. One of these is cortisol, which called a stress hormone because it helps you respond to stress. Cortisol regulates your heart rate and blood pressure, keeps your blood glucose high enough to provide energy and modifies your immune system to prevent inflammation and other immune responses. Low cortisol can be caused by a problem in the adrenals themselves or in another part of the body.
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When the problem causing low cortisol develops in the adrenal gland itself, it's called primary adrenal insufficiency. This is a relatively rare condition, with between 30 and 117 cases reported per million people, according to an article in the August 2002 issue of "The Netherlands Journal of Medicine." The study also reports that 80 percent of cases result from an autoimmune condition, in which the immune system mistakenly produces substances called autoantibodies that attack the adrenal gland. The adrenals might also stop producing cortisol because an infection -- such as tuberculosis, human immunodeficiency virus or a fungal infection called histoplasmosis -- attacks the glands. Low cortisol may be present at birth, either due to an autoimmune problem or because the adrenals didn't develop properly. Rarely, other conditions such as cancer can destroy adrenal tissue and cause low cortisol, but this is extremely rare.
A pituitary hormone called adrenocorticotrophic hormone, or ACTH, regulates cortisol production by the adrenals. If ACTH is low, this causes low cortisol production, a condition called secondary adrenal insufficiency. If you take a cortisol-like medication, such as prednisone, it suppresses ACTH, and when you stop the drug, ACTH can remain low for some time. Other secondary causes include a pituitary injury that damages ACTH-producing cells, an inflammation in the pituitary or a genetic disorder that interferes with ACTH production.
A part of your brain called the hypothalamus also helps regulate cortisol production. It makes a substance called corticotrophin-releasing hormone, or CRH, which controls ACTH production by the pituitary. The hypothalamus alters its production of CRH by responding to the amount of cortisol in the blood, producing more when cortisol is low. In rare cases, the hypothalamus reacts incorrectly to cortisol levels and doesn't produce enough CRH, leading to low ACTH and, in turn, low cortisol production by the adrenals. Although the cause of this is unclear, it may involve an autoimmune condition in which autoantibodies injure brain cells that make CRH.
When to Be Concerned
Low cortisol production can be a complex problem that is often associated with low levels of other adrenal hormones, which have many roles in the body. If you experience a sense of fatigue that gradually worsens, a loss of muscle strength or poor appetite accompanied by weight loss, this could be due to a low cortisol level, especially if changes appear after a stress-producing incident such as an illness or an accident. See your doctor to discuss these changes and determine their cause.