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Cushing’s Disease

What is Cushing’s disease?

Cushing’s disease refers to a serious condition caused by long-term exposure of the body to an excess amount of hormone cortisol 1. This condition mostly occurs when the pituitary gland releases too much adrenocorticotropic hormone (ACTH). Cushing’s disease refers to a form of Cushing’s syndrome. Other potential forms of Cushing’s syndrome include ectopic Cushing’s syndrome, exogenous Cushing syndrome, and Cushing syndrome caused by an adrenal tumor. Cushing syndrome, sometimes known as hypercortisolism, a condition that develops by the use of oral corticosteroid medication.

The excess level of cortisol hormone develops Cushing’s syndrome. Cortisol usually plays a variety of roles and affects all tissues and organs in the body. Cortisol helps to regulate blood pressure, reduces inflammation, and helps to maintain the normal function of the heart and blood vessels. Usually, the pituitary gland regulated the production of cortisol in the body. Several diseases like pituitary adenoma, ectopic ACTH syndrome, adrenal tumors, and familial Cushing’s syndrome acts as an underlying cause of Cushing’s disease 2.

Cushing’s syndrome mostly affects adults ages between 20 to 50 years and more prevalent in females, accounts for 70% of total cases 3. An estimated prevalence rate of Cushing’s disease comprises 10 to 15 persons per million population. Primary adenomas refer to the most common cause of Cushing’s disease. The signs and symptoms of Cushing’s disease may vary according to the level of cortisol hormone. Some patients with Cushing’s disease may develop large pituitary tumors.

Other common signs and symptoms of Cushing’s disease include weight gain, high blood pressure, short-term memory, excess hair growth in women, moon face, fatigue, extra fat around the neck, irritability, poor concentration, etc. Less common signs and symptoms of Cushing’s disease also include insomnia, acne, recurrent infection, balding in women, depression, cognitive difficulties, Diabetes mellitus, erectile dysfunction, weak bones, etc.

How to Diagnose Cushing’s disease?

Diagnosis of Cushing’s disease involves reviewing patient’s history and laboratory tests to determine the existence of excessive levels of cortisol. Patients suspected of Cushing’s disease must initially appear to have excess cortisol production combined with an elevated 24 hours urinary excretion of cortisol. To access the physical features of Cushing’s syndrome, doctors compare the old and recent photographs of the facial and body appearance to reveal the classic changes associated with this disorder. Diagnosing Cushing’s disease comprises a multidisciplinary process involving physicians,radiologists, surgeons, endocrinologists, and chemical pathologists. Doctors can perform the following tests to determine the excess level of cortisol 4:

  1. ACTH blood test: This test helps to measure the plasma adrenocorticotropic hormone (ACTH) concentration.
  2. Dexamethasone suppression test: Technicians use 2 dexamethasone suppression tests (DSTs) to determine the plasma cortisol level. A plasma cortisol level above 50 nmol/L confirms Cushing’s disease.
  3. ACTH stimulation test: This involves the administration of corticotropin-releasing hormone or another agent to differentiate Cushing’s disease from ectopic ACTH secretion.
  4. Urinary free cortisol test: This 24-hour urinary cortisol test measures the excess cortisol excreted by the kidneys into the urine.

Other tests like late-night salivary cortisol test, inferior petrosal sinus sampling, and imaging tests also help to diagnose Cushing’s disease in a patient.

How do Doctors Treat Cushing’s disease?

Treatment of Cushing’s disease depends on the underlying cause of excess cortisol. Based on the underlying cause, the surgeons will evaluate the condition and determine the best treatment protocol for the patient. The treatment protocol may include surgery, radiation, chemotherapy, or the use of cortisol-inhibiting drugs to combat the excess production of cortisol 5.

  1. Surgery: Surgical resection of the ACTH-secreting pituitary adenoma refers to the first line of treatment of Cushing’s disease. This surgery involves the removal of the tumor via transsphenoidal surgery (TSS), which will not leave a visible scar.
  2. Medication: Several medications like ketoconazole, mitotane, mifepristone, metyrapone, etc. help to inhibit cortisol production. These agents considered as a second–line course of treatment.
  3. Radiation therapy: This option performed after unsuccessful transsphenoidal surgery. Additionally, bilateral adrenalectomy also provides an immediate reduction of cortisol level and helps to control hypercortisolism.


  1. Steffensen, C., Bak, A. M., Zøylner Rubeck, K. & Jørgensen, J. O. L. Epidemiology of Cushing’s syndrome. Neuroendocrinology 92, 1–5 (2010).
  2. Buliman, A., Tataranu, L. G., Paun, D. L., Mirica, A. & Dumitrache, C. Cushing’s disease: a multidisciplinary overview of the clinical features, diagnosis, and treatment. J. Med. Life 9, 12–18 (2016).
  3. Castinetti, F., Morange, I., Conte-devolx, B. & Brue, T. Cushing ’ s disease. ??? 7, 1 (2012).
  4. Santos, A. et al. Quality of Life in Patients With Cushing’s Disease. Front. Endocrinol. (Lausanne). 10, 1–10 (2019).
  5. Sharma, S. T., Nieman, L. K. & Feelders, R. A. Cushing’s syndrome: Epidemiology and developments in disease management. Clin. Epidemiol. 7, 281–293 (2015).



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