Causes of Cushing’s Disease

Cushing’s disease occurs when benign — non-cancerous — tumors called adenomas form in the brain’s pituitary gland, triggering the excessive production of adrenocorticotropic hormone (ACTH). Sustained high levels of this hormone signal the adrenal glands, which sit atop the kidneys, to overproduce cortisol, leading to a wide variety of physical, hormonal, and psychological symptoms.

Symptoms emerge because cortisol plays key roles in numerous bodily processes. These include regulating salt and sugar levels, maintaining adequate blood pressure, managing inflammation, controlling respiration, converting food into energy, and even forming memories. Many of these effects are all involved in the body’s complex stress response. For this reason, cortisol often is referred to as “the stress hormone.”

Genetic mutations have been found to cause Cushing’s disease in only a few cases. These mutations generally affect genes that regulate hormone activity. Most are somatic mutations, meaning that a person acquires them over a lifetime, rather than inheriting them.

Cushing’s disease vs. Cushing’s syndrome

Cushing’s disease is a subset of the broader Cushing’s syndrome, which encompasses all hypercortisolism disorders — meaning those characterized by excess cortisol. The syndrome can be triggered by external (exogenous) or internal (endogenous) factors.

Tumors

Endogenous Cushing’s syndrome comprises all forms of the syndrome, including Cushing’s disease, in which the body’s own overproduction of cortisol is the reason why hormone levels rise above healthy limits. In most cases, this is triggered by the presence of a tumor.

Cushing’s disease is the most common form of endogenous Cushing’s syndrome, accounting for approximately 70% of all cases. In addition to pituitary tumors, other benign and malignant tumors that form in other organs that normally do not produce ACTH, such as the thyroid, thymus, lungs, or pancreas, might — in rare cases — trigger the hormone’s overproduction, and consequently that of cortisol, too.

Benign tumors on the adrenal cortex — the outer region of the adrenal glands — also can trigger the overproduction of cortisol. Cancerous tumors can  accomplish this, too, although they occur much less frequently than benign ones.

Medications

Exogenous Cushing’s syndrome occurs when too much cortisol is introduced in the body. This is typically associated with long-term use of corticosteroid medications. These medications often are used to treat various inflammatory disorders of the lungs, skin, and joints, as well as certain types of cancers, and even to prevent transplant rejection.

Genetics

An uncommon familial form of Cushing’s syndrome also exists, in which people inherit a predisposition toward developing tumors on one or more endocrine glands, which are specialized structures that produce and release hormones into the bloodstream.

 

Last updated: May 13, 2021

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