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Cushing's syndrome

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What is Cushing's syndrome?

Cushing's syndrome is a rare condition that results from the body being exposed to too much of the hormone cortisol. This hormone is produced by the adrenal glands, and has many important roles in the human body; it regulates blood glucose (sugar), fat, carbohydrate and protein levels, inflammation, blood pressure, bone growth and mood. An excess of it can have unwanted effects.

About 1-2 people in every million have Cushing's syndrome. [1] [2] However, many more people overproduce cortisol and may have milder symptoms of Cushing's syndrome without being diagnosed as such.

Causes

Cushing's syndrome is caused by the body's tissues being exposed to too much cortisol over time. This can be the result of taking glucocorticoid medications, or of the body itself producing too much cortisol.

Medication

Glucocorticoids are substances that mimic the actions of cortisol. They are used by millions of people to treat a wide variety of inflammatory diseases, including lupus, asthma and others.

Overproduction of cortisol

The pituitary gland is a small gland in the brain. It produces the hormone adrenocorticotropin (ACTH), which regulates the production of cortisol from the adrenal glands that sit atop the kidneys. Therefore, problems in the pituitary gland and ACTH will cause problems in the adrenal gland and cortisol production.

ACTH and cortisol production. 

Pituitary adenoma

This is responsible for about 70% of cases of Cushing's syndrome. [3] An adenoma is a type of benign (not cancerous) tumor. The cells in the tumor secrete ACTH, which stimulates cortisol production. When Cushing's syndrome is due to a pituitary adenoma it is called 'Cushing's disease'.

Adrenal tumors

Adrenal tumors are usually benign, although they can be cancerous. The adrenal cells secrete cortisol into the blood.

Ectopic ACTH syndrome

This can be caused by a wide range of tumors (such as a small-cell carcinoma of the lung), which for some reason begin producing ACTH.

Familial Cushing's syndrome

An inherited tendency to develop one of any of the abovementioned tumors.

McCune-Albright syndrome

A rare genetic (but not inherited) disorder that is caused by mutations during early fetal development. This disorder affects the skin, bones and hormonal system. [4] Some people with this disorder can develop Cushing's syndrome.

Primary pigmented micronodular hyperplasia (PPNAD)

PPNAD is a rare genetic cause of Cushing's syndrome. It usually shows up at 10-20 years of age. [5]

Signs and symptoms

Cushing's syndrome is not easy to detect. Because the hormone cortisol is involved in several different biological processes in the body, overexposure to it can cause a wide variety of symptoms. Different people will experience different symptoms at different severities. As a result, people can experience symptoms of Cushing's syndrome for a long time before the diagnosis is made.

Cushing's syndrome can be suspected in people who have: [6]

Signs and symptoms of Cushing's syndrome include:

Methods for diagnosis

Your doctor will diagnose Cushing's syndrome by:

The tests are done to rule out other conditions with similar symptoms and to find out what is causing Cushing's syndrome, so that its cause can be treated.

Types of treatment

Treatment of Cushing's syndrome depends on its cause:

Medication regulation

If Cushing's syndrome is a side effect of taking glucocorticoid medication, your doctor may advise adjusting the type or dosage of the medication you are receiving, or taking additional medication to relieve the symptoms (see below).

Surgery

For tumors that are secreting cortisol, surgery can treat the problem. Chemotherapy or radiotherapy can also be used to treat certain tumors.

Cortisol replacement therapy

After surgery, cortisol replacement therapy may be needed, either for short-term or long-term treatment. Even if treatment is effective, it might take weeks until the body's hormone balance stabilizes.

Medication

In cases where surgery is not possible or not enough, medication to block the production or action of cortisol can be used.

Follow-up testing

Even after Cushing's syndrome has been successfully treated, there is a risk that it will return in time. Therefore, people who have been treated for Cushing's syndrome will often have follow-up tests in the following years to check for recurring signs and symptoms.

Potential complications and prognosis

If left untreated, Cushing's syndrome can lead to serious, life-threatening complications, including:

Prevention

It is not always possible to prevent Cushing's syndrome. You can lower your risk by being aware of the symptoms, especially if you are taking glucocorticoid medications in the long-term.
If you already have been diagnosed with Cushing's syndrome, you can manage your symptoms by getting enough physical activity, watching your weight and eating a healthy diet.

References

  1. Newell-Price, J. (2010). Etiologies of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.
  2. Stratakis, C.A. (2012). Cushing Syndrome in Pediatrics. Endocrinology and Metabolism Clinics of North America 41: 793–803.
  3. Biller, B.M.K., Swearingen, B. & Tritos, N.A. (2011). Management of Cushing disease. Nature Reviews Endocrinology 7: 279+.
  4. McCune-Albright syndrome. (2014, October 9). Genetics Home Reference. Accessed 17 October 2014, from link here
  5. Manipadam, M.T., Abraham, R., Sen, S., et al. (2011). Primary pigmented nodular adrenocortical disease. Journal of Indian Association of Pediatric Surgeons 16: 160–162.
  6. Bruno, O.D. (2010). Clinical features of Cushing’s Syndrome. In M. D. Bronstein (ed.), Cushing’s Syndrome. Totowa, NJ: Humana Press.
  7. Biller B.M.K. Swearingen B. & Tritos N.A. (2011). Management of Cushing disease. Nature Reviews Endocrinology 7: 279+.
  8. Causes and pathophysiology of Cushing’s syndrome. Accessed 16 October 2014 from link here syndrome?source=search_result&search=cushing%27s+syndrome&selectedTitle=5%7E150
  9. Choices N.H.S. (2013 May 20). Cushing’s syndrome - NHS Choices. Accessed 16 October 2014 from link here
  10. Cushing’s Disease. Accessed from link here
  11. cushing’s syndrome. Accessed 16 October 2014 from link here
  12. Cushing’s syndrome. Better Health Channel. Accessed 16 October 2014 from link here
  13. Cushing’s Syndrome. Text. Accessed 16 October 2014 from link here
  14. Cushing’s syndrome due to primary pigmented nodular adrenocortical disease. Accessed 16 October 2014 from link here
  15. Cushing’s syndrome in pregnancy. Accessed 16 October 2014 from link here
  16. Epidemiology and clinical manifestations of Cushing’s syndrome. Accessed 16 October 2014 from link here
  17. Establishing the cause of Cushing’s syndrome. Accessed 16 October 2014 from link here
  18. Manipadam M.T. Abraham R. Sen S. et al. (2011). Primary pigmented nodular adrenocortical disease. Journal of Indian Association of Pediatric Surgeons 16: 160–162.
  19. Marcello D. Bronstein. Cushing’s Syndrome - Pathophysiology Diagnosis and Treatment. Springer Science & Business Media 2010. Accessed from link here
  20. McCune-Albright syndrome. (2014a October 9). Genetics Home Reference. Accessed 17 October 2014 from link here
  21. McCune-Albright syndrome. (2014b October 9). Genetics Home Reference. Accessed 17 October 2014 from link here
  22. Medical therapy of hypercortisolism (Cushing’s syndrome). Accessed 16 October 2014 from link here
  23. Newell-Price J. (2010). Etiologies of Cushing’s Syndrome. In M. D. Bronstein (ed.) Cushing’s Syndrome. Totowa NJ: Humana Press. Accessed from link here
  24. Overactive Adrenal Glands/Cushing’s Syndrome | Johns Hopkins Medicine Health Library. Accessed 16 October 2014 from link here
  25. Overview of the treatment of Cushing’s syndrome. Accessed 16 October 2014 from link here
  26. Primary therapy of Cushing’s disease: Transsphenoidal surgery and pituitary irradiation. Accessed 16 October 2014 from link here
  27. Ragnarsson O. & Johannsson G. (2013). MANAGEMENT OF ENDOCRINE DISEASE: Cushing’s syndrome: a structured short- and long-term management plan for patients in remission. European Journal of Endocrinology 169: R139–R152.
  28. Service T.N.N.E. and M.D.I. Cushing’s Syndrome Page - National Endocrine and Metabolic Diseases Information Service. text. Accessed 16 October 2014 from link here
  29. Stratakis C.A. (2012). Cushing Syndrome in Pediatrics. Endocrinology and Metabolism Clinics of North America 41: 793–803.
  30. Tritos N.A. & Biller B.M.K. (2012). Advances in Medical Therapies for Cushing’s Syndrome. Discovery Medicine 13: 171–179.

10 Most frequently asked questions (FAQs)

What is Cushing's syndrome?
Cushing's syndrome happens when the body is exposed to too much of the hormone cortisol.
What are the symptoms of Cushing's syndrome?
Signs and symptoms of Cushing's syndrome include: fast, unexplained weight gain, usually concentrated in the upper body, but thin limbs and buttocks; rounded face (moon face) and a 'buffalo hump' of fat above the shoulders and around the neck; thin, fragile skin that bruises easily and purple-red lines or strips (striations), especially on the stomach, thighs, shoulders and upper arms; mood changes, irritability, anxiety, memory problems and poor concentration; sleep problems, insomnia; fatigue, weakness; thirst and frequent urination; in women, excess hair growth, menstrual changes, difficulty getting pregnant and diminished sex drive; in men, erectile dysfunction and decreased sex drive and fertility, and; in children, slow growth and bone weakness, leading to bone pain, back pain and other back problems.
What causes Cushing's syndrome?
Cushing's syndrome is caused by the body's tissues being exposed to too much cortisol over time. This can be the result of taking glucocorticoid medication (substances that mimic the actions of cortisol), or of the body producing too much cortisol, often as a result of a benign or cancerous tumor.
How is Cushing's syndrome diagnosed?
Your doctor will diagnose Cushing's syndrome by taking your family and medical history, noting any medication you are taking, giving you a physical examination, running laboratory tests including urine tests and blood tests, measuring hormone levels and, if any tumors are suspected, taking MRI or CT scans of the adrenal or pituitary glands.
How is Cushing's syndrome treated?
Treatment depends on its cause. If Cushing's syndrome is a side effect of taking glucocorticoid medication, your doctor may advise adjusting the type or dosage of your medication, or taking additional medication to relieve the symptoms. For tumors that are secreting cortisol, surgery can treat the problem. Chemotherapy or radiation therapy can also be used to treat certain tumors. Medication to block the production or action of cortisol can also be used.
Can Cushing's syndrome be cured?
Treatment of Cushing's syndrome is often effective.
Will Cushing's syndrome clear on its own?
Cushing's syndrome is not expected to clear on its own. Treatment is necessary in order to avoid complications.
Can Cushing's syndrome be prevented?
You can prevent the harm caused by Cushing's syndrome mostly by being aware of the symptoms, especially if you are taking glucocorticoid medication. If you have been treated for Cushing's syndrome, know that it may relapse, so follow-up examinations are recommended.
Will Cushing's syndrome keep coming back?
Cushing's syndrome can relapse. The risk varies according to the cause.
Is Cushing's syndrome serious?
If left untreated, Cushing's syndrome can lead to serious complications and may be life-threatening.

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About this article

Title: Cushing's syndrome

Author: Dr Idan Ben-Barak PhD, MSc, BSc (Med)

First Published: 13 Jul 2015

Last reviewed: 17 Jan 2022

Category: Information on Cushing's syndrome

Average rating: 4.7 out of 5 (1556 votes)

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