What causes Cushing’s syndrome?

What causes Cushing’s syndrome?

1. Exogenous Cushing's syndrome

The most common cause for excess cortisol in the body is due to the use of corticosteroid medications (mainly containing glucocorticoids) for a prolonged period of time. High doses taken regularly can lead to excess production of cortisol which is then released into the bloodstream and circulates the body. A cause that develops from outside the body is often termed 'exogenous Cushing’s syndrome'.

Corticosteroid medications are predominantly prescribed in the treatment of a variety of health conditions, treating inflammation. These medications are designed to function in much the same way as the body’s natural production system. Medication use includes the treatment of inflammatory conditions such as arthritis or lupus. These medications may also be prescribed following an organ transplant in an effort to assist the body in preventing rejection. Sometimes severe back pain or joint pain is also treated with high doses of injectable steroids.

Higher doses of corticosteroid medications are associated with elevated risk for Cushing’s syndrome. Doses usually stimulate higher amounts of cortisol production than is normally required by the body in order to treat certain medical conditions. This side-effect may result in Cushing’s syndrome if used for a prolonged period of time.

Lower dose medications, such as those used in inhalants for the treatment of asthma or in creams prescribed for skin conditions such as eczema, are not considered to have enough steroid content to cause a condition like Cushing’s syndrome.

2. Endogenous Cushing's syndrome

Less common, but still possible, is a natural malfunction resulting in overproduced amounts of cortisol in the body. Overproduction can occur in one or both adrenal glands or as a result of excess adrenocorticotropic hormones normally responsible for regulating cortisol amounts in the body.

Causes of this can be any one of the following:

  • Pituitary adenoma (pituitary gland tumour): Excess secretion of adrenocorticotropic hormone (ACTH) results in excess cortisol production and can lead to the development of benign (non-cancerous) tumours on the pituitary glands.
  • Ectopic ACTH-secreting tumours: A tumour (either benign or malignant / cancerous) may develop in an organ (such as the lungs, thyroid, pancreas or thymus gland) which does not normally produce adrenocorticotropic hormones (ACTH). Instead the tumour which develops may secrete ACTH in excess, stimulating cortisol production and resulting in Cushing’s syndrome.
  • Primary adrenal gland disease:  Cushing’s syndrome may also develop from excess cortisol that is stimulated by disorders or abnormalities of the adrenal glands. Adrenal adenoma or adrenal cortex tumours (adrenocortical carcinomas) are the most common of these conditions to cause this. These cancerous cells typically secrete excess adrenal cortical hormones (cortisol and adrenal androgens) resulting in very high hormone levels and a swift development of symptoms. An inherited tendency to develop tumours (of the adrenal tissue) on these endocrine glands which produce cortisol is being further researched. Cushing’s syndrome itself is not regarded as an inherited disease, however. Other abnormalities, such as benign, nodular enlargements of the adrenal glands can also sometimes occur, resulting in the development of the condition.

Other known causes which can influence cortisol levels include:

  • High stress levels (relating to an injury, surgical procedure, third-trimester pregnancy or an acute illness)
  • Mood disorders such as depression or a panic disorder (anxiety).
  • Malnutrition
  • Alcoholism
  • Athletic training
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