Cushing qyndrom

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Cushing's syndromeFrom Wikipedia, the free encyclopediaJump to: navigation, searchMergefrom.svg

It has been suggested that Cushing's disease be merged into this articleor section. (Discuss)Cushing's syndrome

Classification and external resourcesICD-10 E24.ICD-9 255.0MedlinePlus 000410eMedicine article/117365MeSH D003480

Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone (ACTH) or CRH [1]

Cushing's disease refers to one specific cause of the syndrome, a tumor (adenoma

) in the pituitary gland that produces large amounts of ACTH, which in turn elevates cortisol. It is the most common cause of Cushing's syndrome, responsible for 70% of cases[2]

This pathology was described by Harvey Cushing in 1932.[3][4] the syndrome is also called Itsenko-Cushing syndrome, hyperadrenocorticism or hypercorticism)

Cushing's syndrome is not confined to humans and is also a relatively common condition in domestic dogs and horses.Contents[hide]

* 1 Signs and symptoms

* 2 Causeo 2.1 Exogenous vs. endogenouso 2.2 Pseudo-cushing's syndrome

* 3 Pathophysiology* 4 Diagnosis

o 4.1 Mnemonic* 5 Treatment* 6 Epidemiology* 7 References* 8 External links

Signs and symptoms

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). A common sign is the growth of fat pads along the collar bone and on the back of the neck (buffalo hump) and a round face often referred to as a "moon face". Other symptoms include hyperhidrosis (excess sweating), telangiectasia (dilation of capillaries), thinning of the skin (whichcauses easy bruising and dryness, particularly the hands) and other mucous membranes, purple or red striae (the weight gain in Cushing's syndrome stretches theskin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or cause hair to become extremely dry and brittle. In rare cases, Cushing's can cause hypercalcemia, whichcan lead to skin necrosis. The excess cortisol may also affect other endocrine s

ystems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence, amenorrhoea/oligomenorrhea and infertility due to elevations in androgens. Patients frequently suffer various psychological disturbances, ranging from



euphoria to psychosis. Depression and anxiety are also common.[5]

Other striking and distressing skin changes that may appear in Cushing's syndrome include facial acne, susceptibility to superficial dermatophyte and malasseziainfections, and the characteristic purplish, atrophic striae on the abdomen.[6]:500

Other signs include polyuria (and accompanying polydipsia), persistent hypertension (due to cortisol's enhancement of epinephrine's vasoconstrictive effect) andinsulin resistance (especially common in ectopic ACTH production), leading to hyperglycemia (high blood sugar) and insulin resistance which can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosisnigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation,This is due to Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Pro-opiomelanocortin (POMC). Cortisol can also exhibit mineralcorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, gastrointestinal dis

turbances, opportunistic infections and impaired wound healing (cortisol is a stress hormone, so it depresses the immune and inflammatory responses). Osteoporosis is also an issue in Cushing's syndrome since, as mentioned before, cortisol evokes a stress-like response. Consequently, the body's maintenance of bone (andother tissues) becomes secondary to maintenance of the false stress response. Additionally, Cushing's may cause sore and aching joints, particularly in the hip,shoulders, and lower back.Cause

There are several possible causes of Cushing's syndrome.Exogenous vs. endogenous

Hormones that come from outside the body are called exogenous; hormones that com

e from within the body are called endogenous.

The most common cause of Cushing's syndrome is exogenous administration of glucocorticoids prescribed by a health care practitioner to treat other diseases (called iatrogenic Cushing's syndrome). This can be an effect of steroid treatment of a variety of disorders such as asthma and rheumatoid arthritis, or in immunosuppression after an organ transplant. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Although rare, Cushing's syndrome can also be due to the use of medroxyprogesterone [7][8]

Endogenous Cushing's syndrome results from some derangement of the body's own system of secreting cortisol. Normally, ACTH is released from the pituitary glandwhen necessary to stimulate the release of cortisol from the adrenal glands.

* In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This isalso known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome.

* In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors,hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.

* Finally, tumors outside the normal pituitary-adrenal system can produce ACTH that affects the adrenal glands. This final etiology is called ectopic or par

aneoplastic Cushing's syndrome and is seen in diseases like small cell lung cancer.



Pseudo-cushing's syndrome

Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cortisol level to be elevated. However, the total free cortisol, which is the active hormone in the body, as measured by a 24 hour urine collection for urinary fre

e cortisol, is normal.[9]Pathophysiology

The hypothalamus is in the brain and the pituitary gland sits just below it. Theparaventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropin (ACTH). ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on the pituitary, which decreases the amount of ACTH released from the pituitary gland. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. One of the causes of Cushing's syndrome

is a cortisol secreting adenoma in the cortex of the adrenal gland. The adenomacauses cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low. Cushing's disease refers only to hypercortisolism secondary to excess production ofACTH from a corticotrophic pituitary adenoma. This causes the blood ACTH levelsto be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because a tumor causes the pituitary to be unresponsive to negative feedback from high cortisol levels.

Cushing's Syndrome was also the first autoimmune disease identified in humans.[10]Diagnosis

When Cushing's syndrome is suspected, either a dexamethasone suppression test (administration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offer equal detection rates.[11] Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, high cortisol would be indicative of Cushing's syndrome because there is an ectopic source of cortisol or ACTH (e.g.: adrenal adenoma) that is not inhibited by the dexamethasone. A novel approach, recently cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which maybe equally sensitive, as late night levels of salivary cortisol are high in Cushingoid patients. Other pituitary hormone levels may need to be ascertained. Performing a physical examination to determine any visual field defect may be necessary if a pituitary lesion is suspected, which may compress the optic chiasm causing typical bitemporal hemianopia.

When any of these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (the incidental discovery of harmless lesions). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the ACTH levels in various veins in the body by venous catheterization, working towards the pituitary (petrosal sinus sampling) is necessary.Mnemonic

C - Central obesity, Cervical fat pads, Collagen fibre weakness, Comedones (acne

)U - Urinary free cortisol and glucose increaseS - Striae, Suppressed immunity



H - Hypercortisolism, Hypertension, Hyperglycaemia, HirsutismI - Iatrogenic (Increased administration of corticosteroids)N - Noniatrogenic (Neoplasms)G - Glucose intolerance, Growth retardationTreatment

Most Cushing's syndrome cases are caused by steroid medications (iatrogenic). Co

nsequently, most patients are effectively treated by carefully tapering off (andeventually stopping) the medication that causes the symptoms.

If an adrenal adenoma is identified it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTHand normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.

In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone)

but they are of limited efficacy.

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation.This clinical situation is known as Nelson's syndrome.[12]Epidemiology

Iatrogenic Cushing's syndrome (caused by treatment with corticosteroids) is themost common form of Cushing's syndrome. The incidence of pituitary tumors may berelatively high, as much as one in five people,[13] but only a minute fractionare active and produce excessive hormones.

Adults with the disease may also have symptoms of extreme weight gain, excess hair growth in women, high blood pressure, and skin problems. In addition, they may show:

* muscle and bone weakness* osteoporosis* diabetes mellitus* hypertension* moodiness, irritability, or depression* sleep disturbances* menstrual disorders such as amenorrhea in women and decreased fertility in

men* baldness* hypercholesterolemia

References

1. ^ Kumar, Abbas, Fausto. Robbins and Cotran Pathologic Basis of Disease, 7th ed. Elsevier-Saunders; New York, 2005.

2. ^ Schwartz's principles of surgery, 8th edition, p 14553. ^ Cushing HW. (1932). "The basophil adenomas of the pituitary body and the

ir clinical manifestations (pituitary basophilism).". Bulletin of the Johns Hopkins Hospital 50: 137–95.

4. ^ "Dr. Cushing Dead; Brain Surgeon, 70. A Pioneer Who Won Fame as Founder

of New School of Neuro-Surgery. Discovered Malady Affecting Pituitary Gland. WasNoted Teacher and Author". New York Times. October 8, 1939. http://select.nytimes.com/gst/abstract.html?res=F30915F73C5A177A93CAA9178BD95F4D8385F9. Retrieved 2



010-03-21. "Dr. Harvey Williams Cushing, international authority on brain surgery and neurology, who for his ..."

5. ^ Yudofsky, Stuart C.; Robert E. Hales (2007). The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences (5th ed.). American Psychiatric Pub, Inc.. ISBN 1585622397.

6. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseasesof the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.

7. ^ Siminoski, K; Goss, P; Drucker, DJ (1989). "The Cushing syndrome inducedby medroxyprogesterone acetate.". Annals of internal medicine 111 (9): 758–60. PMID 2552887.

8. ^ Merrin, PK; Alexander, WD (1990). "Cushing's syndrome induced by medroxyprogesterone.". BMJ (Clinical research ed.) 301 (6747): 345. doi:10.1136/bmj.301.6747.345-a. PMC 1663616. PMID 2144198. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1663616.

9. ^ C. W. Burke (1969). "The effect of oral contraceptives on cortisol metabolism". J Clin Pathol 3: 11–18. doi:10.1136/jcp.s1-3.1.11. PMC 1436049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1436049.10. ^ The History of Cushings Disease: a controversial tale, J R Soc Med. 1991June; 84(6): 363–366

11. ^ Raff H, Findling JW (2003). "A physiologic approach to diagnosis of theCushing syndrome". Ann. Intern. Med. 138 (12): 980–91. PMID 12809455. http://www.annals.org/cgi/pmidlookup?view=long&pmid=12809455.12. ^ Nelson DH, Meakin JW, Thorn GW (1960). "ACTH-producing pituitary tumors

following adrenalectomy for Cushing syndrome". Ann. Intern. Med. 52: 560–9. PMID 14426442.13. ^ Ezzat S, Asa SL, Couldwell WT, et al. (2004). "The prevalence of pituita

ry adenomas: a systematic review". Cancer 101 (3): 613–9. doi:10.1002/cncr.20412.PMID 15274075.Cushing's syndromeFrom Wikipedia, the free encyclopediaJump to: navigation, searchMergefrom.svg

It has been suggested that Cushing's disease be merged into this article

or section. (Discuss)Cushing's syndromeClassification and external resourcesICD-10 E24.ICD-9 255.0MedlinePlus 000410eMedicine article/117365MeSH D003480

Cushing's syndrome is a hormone disorder caused by high levels of cortisol in the blood. This can be caused by taking glucocorticoid drugs, or by tumors that produce cortisol or adrenocorticotropic hormone (ACTH) or CRH [1]

Cushing's disease refers to one specific cause of the syndrome, a tumor (adenoma) in the pituitary gland that produces large amounts of ACTH, which in turn elevates cortisol. It is the most common cause of Cushing's syndrome, responsible for 70% of cases[2]

This pathology was described by Harvey Cushing in 1932.[3][4] the syndrome is also called Itsenko-Cushing syndrome, hyperadrenocorticism or hypercorticism)

Cushing's syndrome is not confined to humans and is also a relatively common condition in domestic dogs and horses.Contents[hide]

* 1 Signs and symptoms* 2 Cause



o 2.1 Exogenous vs. endogenouso 2.2 Pseudo-cushing's syndrome

* 3 Pathophysiology* 4 Diagnosis

o 4.1 Mnemonic* 5 Treatment* 6 Epidemiology

* 7 References* 8 External links

Signs and symptoms

Symptoms include rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). A common sign is the growth of fat pads along the collar bone and on the back of the neck (buffalo hump) and a round face often referred to as a "moon face". Other symptoms include hyperhidrosis (excess sweating), telangiectasia (dilation of capillaries), thinning of the skin (whichcauses easy bruising and dryness, particularly the hands) and other mucous membranes, purple or red striae (the weight gain in Cushing's syndrome stretches the

skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs or breasts, proximal muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth), baldness and/or cause hair to become extremely dry and brittle. In rare cases, Cushing's can cause hypercalcemia, whichcan lead to skin necrosis. The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, inhibited aromatase, reduced libido, impotence, amenorrhoea/oligomenorrhea and infertility due to elevations in androgens. Patients frequently suffer various psychological disturbances, ranging fromeuphoria to psychosis. Depression and anxiety are also common.[5]

Other striking and distressing skin changes that may appear in Cushing's syndrome include facial acne, susceptibility to superficial dermatophyte and malasseziainfections, and the characteristic purplish, atrophic striae on the abdomen.[6]

:500

Other signs include polyuria (and accompanying polydipsia), persistent hypertension (due to cortisol's enhancement of epinephrine's vasoconstrictive effect) andinsulin resistance (especially common in ectopic ACTH production), leading to hyperglycemia (high blood sugar) and insulin resistance which can lead to diabetes mellitus. Insulin resistance is accompanied by skin changes such as acanthosisnigricans in the axilla and around the neck, as well as skin tags in the axilla. Untreated Cushing's syndrome can lead to heart disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpigmentation,This is due to Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Pro-opiomelanocortin (POMC). Cortisol can also exhibit mineralcorticoid activity in high concentrations, worsening the hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, gastrointestinal disturbances, opportunistic infections and impaired wound healing (cortisol is a stress hormone, so it depresses the immune and inflammatory responses). Osteoporosis is also an issue in Cushing's syndrome since, as mentioned before, cortisol evokes a stress-like response. Consequently, the body's maintenance of bone (andother tissues) becomes secondary to maintenance of the false stress response. Additionally, Cushing's may cause sore and aching joints, particularly in the hip,shoulders, and lower back.Cause

There are several possible causes of Cushing's syndrome.Exogenous vs. endogenous

Hormones that come from outside the body are called exogenous; hormones that come from within the body are called endogenous.



The most common cause of Cushing's syndrome is exogenous administration of glucocorticoids prescribed by a health care practitioner to treat other diseases (called iatrogenic Cushing's syndrome). This can be an effect of steroid treatment of a variety of disorders such as asthma and rheumatoid arthritis, or in immunosuppression after an organ transplant. Administration of synthetic ACTH is also possible, but ACTH is less often prescribed due to cost and lesser utility. Althou

gh rare, Cushing's syndrome can also be due to the use of medroxyprogesterone [7][8]

Endogenous Cushing's syndrome results from some derangement of the body's own system of secreting cortisol. Normally, ACTH is released from the pituitary glandwhen necessary to stimulate the release of cortisol from the adrenal glands.

* In pituitary Cushing's, a benign pituitary adenoma secretes ACTH. This isalso known as Cushing's disease and is responsible for 70% of endogenous Cushing's syndrome.

* In adrenal Cushing's, excess cortisol is produced by adrenal gland tumors,

hyperplastic adrenal glands, or adrenal glands with nodular adrenal hyperplasia.

* Finally, tumors outside the normal pituitary-adrenal system can produce ACTH that affects the adrenal glands. This final etiology is called ectopic or paraneoplastic Cushing's syndrome and is seen in diseases like small cell lung cancer.

Pseudo-cushing's syndrome

Elevated levels of total cortisol can also be due to estrogen found in oral contraceptive pills that contain a mixture of estrogen and progesterone. Estrogen can cause an increase of cortisol-binding globulin and thereby cause the total cor

tisol level to be elevated. However, the total free cortisol, which is the active hormone in the body, as measured by a 24 hour urine collection for urinary free cortisol, is normal.[9]Pathophysiology

The hypothalamus is in the brain and the pituitary gland sits just below it. Theparaventricular nucleus (PVN) of the hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropin (ACTH). ACTH travels via the blood to the adrenal gland, where it stimulates the release of cortisol. Cortisol is secreted by the cortex of the adrenal gland from a region called the zona fasciculata in response to ACTH. Elevated levels of cortisol exert negative feedback on the pituitary, which decreases the amount of ACTH released from the pituitary gland. Strictly, Cushing's syndrome refers to excess cortisol of any etiology. One of the causes of Cushing's syndromeis a cortisol secreting adenoma in the cortex of the adrenal gland. The adenomacauses cortisol levels in the blood to be very high, and negative feedback on the pituitary from the high cortisol levels causes ACTH levels to be very low. Cushing's disease refers only to hypercortisolism secondary to excess production ofACTH from a corticotrophic pituitary adenoma. This causes the blood ACTH levelsto be elevated along with cortisol from the adrenal gland. The ACTH levels remain high because a tumor causes the pituitary to be unresponsive to negative feedback from high cortisol levels.

Cushing's Syndrome was also the first autoimmune disease identified in humans.[10]

Diagnosis

When Cushing's syndrome is suspected, either a dexamethasone suppression test (a



dministration of dexamethasone and frequent determination of cortisol and ACTH level), or a 24-hour urinary measurement for cortisol offer equal detection rates.[11] Dexamethasone is a glucocorticoid and simulates the effects of cortisol, including negative feedback on the pituitary gland. When dexamethasone is administered and a blood sample is tested, high cortisol would be indicative of Cushing's syndrome because there is an ectopic source of cortisol or ACTH (e.g.: adrenal adenoma) that is not inhibited by the dexamethasone. A novel approach, recentl

y cleared by the US FDA, is sampling cortisol in saliva over 24 hours, which maybe equally sensitive, as late night levels of salivary cortisol are high in Cushingoid patients. Other pituitary hormone levels may need to be ascertained. Performing a physical examination to determine any visual field defect may be necessary if a pituitary lesion is suspected, which may compress the optic chiasm causing typical bitemporal hemianopia.

When any of these tests are positive, CT scanning of the adrenal gland and MRI of the pituitary gland are performed to detect the presence of any adrenal or pituitary adenomas or incidentalomas (the incidental discovery of harmless lesions). Scintigraphy of the adrenal gland with iodocholesterol scan is occasionally necessary. Very rarely, determining the ACTH levels in various veins in the body b

y venous catheterization, working towards the pituitary (petrosal sinus sampling) is necessary.Mnemonic

C - Central obesity, Cervical fat pads, Collagen fibre weakness, Comedones (acne)U - Urinary free cortisol and glucose increaseS - Striae, Suppressed immunityH - Hypercortisolism, Hypertension, Hyperglycaemia, HirsutismI - Iatrogenic (Increased administration of corticosteroids)N - Noniatrogenic (Neoplasms)G - Glucose intolerance, Growth retardationTreatment

Most Cushing's syndrome cases are caused by steroid medications (iatrogenic). Consequently, most patients are effectively treated by carefully tapering off (andeventually stopping) the medication that causes the symptoms.

If an adrenal adenoma is identified it may be removed by surgery. An ACTH-secreting corticotrophic pituitary adenoma should be removed after diagnosis. Regardless of the adenoma's location, most patients will require steroid replacement postoperatively at least in the interim as long-term suppression of pituitary ACTHand normal adrenal tissue does not recover immediately. Clearly, if both adrenals are removed, replacement with hydrocortisone or prednisolone is imperative.

In those patients not suitable for or unwilling to undergo surgery, several drugs have been found to inhibit cortisol synthesis (e.g. ketoconazole, metyrapone)but they are of limited efficacy.

Removal of the adrenals in the absence of a known tumor is occasionally performed to eliminate the production of excess cortisol. In some occasions, this removes negative feedback from a previously occult pituitary adenoma, which starts growing rapidly and produces extreme levels of ACTH, leading to hyperpigmentation.This clinical situation is known as Nelson's syndrome.[12]Epidemiology

Iatrogenic Cushing's syndrome (caused by treatment with corticosteroids) is themost common form of Cushing's syndrome. The incidence of pituitary tumors may be

relatively high, as much as one in five people,[13] but only a minute fractionare active and produce excessive hormones.



Adults with the disease may also have symptoms of extreme weight gain, excess hair growth in women, high blood pressure, and skin problems. In addition, they may show:

* muscle and bone weakness* osteoporosis* diabetes mellitus

* hypertension* moodiness, irritability, or depression* sleep disturbances* menstrual disorders such as amenorrhea in women and decreased fertility in

men* baldness* hypercholesterolemia

References

1. ^ Kumar, Abbas, Fausto. Robbins and Cotran Pathologic Basis of Disease, 7th ed. Elsevier-Saunders; New York, 2005.

2. ^ Schwartz's principles of surgery, 8th edition, p 14553. ^ Cushing HW. (1932). "The basophil adenomas of the pituitary body and their clinical manifestations (pituitary basophilism).". Bulletin of the Johns Hopkins Hospital 50: 137–95.

4. ^ "Dr. Cushing Dead; Brain Surgeon, 70. A Pioneer Who Won Fame as Founderof New School of Neuro-Surgery. Discovered Malady Affecting Pituitary Gland. WasNoted Teacher and Author". New York Times. October 8, 1939. http://select.nytimes.com/gst/abstract.html?res=F30915F73C5A177A93CAA9178BD95F4D8385F9. Retrieved 2010-03-21. "Dr. Harvey Williams Cushing, international authority on brain surgery and neurology, who for his ..."

5. ^ Yudofsky, Stuart C.; Robert E. Hales (2007). The American Psychiatric Publishing Textbook of Neuropsychiatry and Behavioral Neurosciences (5th ed.). American Psychiatric Pub, Inc.. ISBN 1585622397.

6. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseasesof the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.

7. ^ Siminoski, K; Goss, P; Drucker, DJ (1989). "The Cushing syndrome inducedby medroxyprogesterone acetate.". Annals of internal medicine 111 (9): 758–60. PMID 2552887.

8. ^ Merrin, PK; Alexander, WD (1990). "Cushing's syndrome induced by medroxyprogesterone.". BMJ (Clinical research ed.) 301 (6747): 345. doi:10.1136/bmj.301.6747.345-a. PMC 1663616. PMID 2144198. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1663616.

9. ^ C. W. Burke (1969). "The effect of oral contraceptives on cortisol metabolism". J Clin Pathol 3: 11–18. doi:10.1136/jcp.s1-3.1.11. PMC 1436049. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1436049.10. ^ The History of Cushings Disease: a controversial tale, J R Soc Med. 1991June; 84(6): 363–36611. ^ Raff H, Findling JW (2003). "A physiologic approach to diagnosis of the

Cushing syndrome". Ann. Intern. Med. 138 (12): 980–91. PMID 12809455. http://www.annals.org/cgi/pmidlookup?view=long&pmid=12809455.12. ^ Nelson DH, Meakin JW, Thorn GW (1960). "ACTH-producing pituitary tumors

following adrenalectomy for Cushing syndrome". Ann. Intern. Med. 52: 560–9. PMID 14426442.13. ^ Ezzat S, Asa SL, Couldwell WT, et al. (2004). "The prevalence of pituita

ry adenomas: a systematic review". Cancer 101 (3): 613–9. doi:10.1002/cncr.20412.PMID 15274075.

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Cushing qyndrom