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URL of this page: https://medlineplus.gov/genetics/condition/cushing-disease/

Cushing disease

Description

Cushing disease is caused by high levels of a hormone called cortisol, which leads to a wide variety of signs and symptoms. Cortisol has many functions, which include helping the body respond to stress. Cushing disease is a type of Cushing syndrome. As with Cushing disease, Cushing syndrome is caused by high levels of cortisol in the body. Because both conditions result from elevated cortisol levels, the signs and symptoms seen in people with Cushing disease are similar to those seen in people with Cushing syndrome.

People with Cushing disease may have rapid and unusual weight gain, particularly around the abdomen and face. Affected individuals may bruise easily and have purple stretch marks (striae) on the thighs and abdomen. Individuals with Cushing disease may also develop a hump on their upper back caused by changes in the amount and distribution of body fat.

Additional signs and symptoms of Cushing disease can include muscle weakness, fatigue, irregular menstruation, and thin and brittle bones that are prone to fracture (osteoporosis). Women with Cushing disease often have excessive hair growth (hirsutism) on the face, chest, and abdomen. People with Cushing disease are at increased risk of developing high blood pressure (hypertension) and diabetes. Affected individuals may also have a weakened immune system and an increased risk of infections.

Cushing disease can affect a person's thinking and mood. Affected individuals often report anxiety, irritability, and depression. This condition can also affect learning, concentration, and memory, leading to "brain fog."

People with Cushing disease are at an increased risk of developing life-threatening complications, which can include infections, heart disease, or stroke.

Cushing disease typically occurs alone (isolated). In rare cases, it may also be a feature of genetic syndromes that affect other parts of the body, such as multiple endocrine neoplasia 1 (MEN1) and familial isolated pituitary adenoma (FIPA).

Frequency

Cushing disease affects up to 2.4 in 1,000,000 people each year. The condition affects females more often than males. Cushing disease typically occurs between the ages of 20 and 50. However, children may also be affected.

Causes

Cortisol protects the body from stress, maintains blood glucose (also called blood sugar) levels, and turns off (suppresses) inflammation. Cortisol is produced by the adrenal glands, which are small glands located at the top of each kidney. Normally, the production of cortisol is triggered by the release of a hormone called adrenocorticotropic hormone (ACTH) from the pituitary gland, which is located at the base of the brain.

In people with Cushing disease, noncancerous (benign) pituitary gland tumors (also called adenomas) release too much ACTH. The extra ACTH causes the adrenal glands to release too much cortisol, which leads to the signs and symptoms of Cushing disease.

The cause of Cushing disease is often unknown. However, genetic changes in certain genes cause Cushing disease in up to 70 percent of affected individuals. Genetic changes that cause disease are called pathogenic variants. The pathogenic variants that cause Cushing disease are typically somatic, which means they are acquired during a person's lifetime and are present only in certain cells. The genes that are associated with Cushing disease often play a role in regulating the activity of hormones. 

In some people with Cushing disease, pituitary adenomas contain cells that have a pathogenic variant in the USP8 gene. Pathogenic variants in the USP8 gene are the most common genetic cause of Cushing disease.

The USP8 gene provides instructions for making an enzyme that helps regulate the breakdown (metabolism) of certain proteins, including proteins that are involved in important cell signaling pathways. The pathogenic variants in the USP8 gene that are associated with Cushing disease cause cells in the pituitary adenoma to produce a version of the protein that does not switch off properly. As a result, certain signaling proteins become overactive, causing cells within the adenoma to release too much ACTH.

Learn more about the gene associated with Cushing disease

Additional Information from NCBI Gene:

Inheritance

Isolated Cushing disease is typically sporadic, which means it occurs in people with no family history of the disorder.

When Cushing disease occurs as part of a genetic syndrome, it follows the inheritance pattern of that syndrome.

Other Names for This Condition

  • Corticotroph pituitary adenoma
  • Cushing’s disease
  • Pituitary ACTH hypersecretion
  • Pituitary corticotroph adenoma
  • Pituitary Cushing syndrome
  • Pituitary-dependent Cushing syndrome
  • Pituitary-dependent hypercortisolism

Additional Information & Resources

Genetic Testing Information

Genetic and Rare Diseases Information Center

Patient Support and Advocacy Resources

Clinical Trials

Catalog of Genes and Diseases from OMIM

Scientific Articles on PubMed

References

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