Cushing’s syndrome

Alternative Names: Itsenko-Cushing syndrome, hyperadrenocorticism or hypercorticism
Definition:
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

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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.

This pathology was described by Harvey Cushing in 1932.

Cushing’s syndrome is not confined to humans and is also a relatively common condition in domestic dogs and horses.

Treatments for Cushing’s syndrome can return your body’s cortisol production to normal and noticeably improve your symptoms. The earlier treatment begins, the better your chances for recovery.

Symptoms:
SymptomsMost people with Cushing syndrome will have:

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•Upper body obesity (above the waist) and thin arms and legs
•Round, red, full face (moon face)
•Slow growth rate in children

Skin changes that are often seen:
•Acne or skin infections
•Purple marks (1/2 inch or more wide) called striae on the skin of the abdomen, thighs, and breasts
•Thin skin with easy bruising

Muscle and bone changes include:
•Backache, which occurs with routine activities
•Bone pain or tenderness
•Collection of fat between the shoulders (buffalo hump)
•Thinning of the bones, which leads to rib and spine fractures
•Weak muscles

Woman with cushing syndrome often have:

•Excess hair growth on the face, neck, chest, abdomen, and thighs
•Menstrual cycle becomes irregular or stops

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Men may have:
•Decreased fertility
•Decreased or no desire for sex
•Impotence

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Other symptoms that may occur with this disease:
*Mental changes, such as depression, anxiety and irritability or changes in behavior
*Fatigue
*Headache
*High blood pressure
*Increased thirst and urination
*Muscle weakness
*Loss of emotional control
*Cognitive difficulties
*New or worsened high blood pressure
*Glucose intolerance that may lead to diabetes
*Headache
*Bone loss, leading to fractures over time

Iatrogenic Cushing’s syndrome (caused by treatment with corticosteroids) is the most common form of Cushing’s syndrome. The incidence of pituitary tumors may be relatively high, as much as one in five people, but only a minute fraction are 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

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. Although rare, Cushing’s syndrome can also be due to the use of medroxyprogesterone.

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

*In pituitary Cushing’s, a benign pituitary adenoma secretes ACTH. This is also 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.

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*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 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 free cortisol, is normal.

Pathophysiology:
The hypothalamus is in the brain and the pituitary gland sits just below it. The paraventricular 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 adenoma causes 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 of ACTH from a corticotrophic pituitary adenoma. This causes the blood ACTH levels to 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.

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. 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 may be 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 increase
S – Striae, Suppressed immunity
H – Hypercortisolism, Hypertension, Hyperglycemia, Hypercholesterolemia, Hirsutism
I – Iatrogenic (Increased administration of corticosteroids)
N – Noniatrogenic (Neoplasms)
G – Glucose intolerance, Growth retardation

Treatment:-
Most Cushing’s syndrome cases are caused by steroid medications (iatrogenic). Consequently, most patients are effectively treated by carefully tapering off (and eventually 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 ACTH and 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.

Lifestyle and home remedies:-

The length of your recovery from Cushing’s syndrome will depend on the severity and cause of your condition. Remember to be patient. You didn’t develop Cushing’s syndrome overnight and your symptoms won’t disappear overnight, either. In the meantime, these tips may help you on your journey back to health.

*Increase activities slowly. You may be in such a hurry to get your old self back that you push yourself too hard too fast, but your weakened muscles need a slower approach. Work up to a reasonable level of exercise or activity that feels comfortable without overdoing it. You’ll improve little by little, and your persistence will be rewarded.

*Eat sensibly. Nutritious, wholesome foods provide a good source of fuel for your recovering body and can help you lose the extra pounds that you gained from Cushing’s syndrome. Make sure you’re getting enough calcium and vitamin D. Taken together, they help your body absorb calcium, which can help strengthen your bones, counteracting the bone density loss that often occurs with Cushing’s syndrome.

*Monitor your mental health. Depression can be a side effect of Cushing’s syndrome, but it can also persist or develop after treatment begins. Don’t ignore your depression or wait it out. Seek help promptly from your doctor or a therapist if you’re depressed, overwhelmed or having difficulty coping during your recovery.

*Gently soothe aches and pains. Hot baths, massages and low-impact exercises, such as water aerobics and tai chi, can help alleviate some of the muscle and joint pain that accompanies Cushing’s syndrome recovery.

*Exercise your brain. If you’re recovering from any cognitive difficulties as a result of Cushing’s syndrome, mental exercises, such as math problems and crossword puzzles, may improve your brain function.

Coping and support:-
Support groups can be valuable in dealing with Cushing’s syndrome and recovery. They bring you together with other people who are coping with the same kinds of challenges, along with their families and friends, and offer a setting in which youe can share common problems.

Ask your doctor about support groups in your community. Your local health department, public library and telephone book and the Internet also may be good sources to find a support group in your area.

Prognosis:
Removing the tumor may lead to full recovery, but there is a chance that the condition will return.

Survival for people with ectopic tumors depends on the tumor type. Untreated, Cushing syndrome can be life-threatening.

Disclaimer: This information is not meant to be a substitute for professional medical advise or help. It is always best to consult with a Physician about serious health concerns. This information is in no way intended to diagnose or prescribe remedies.This is purely for educational purpose.

Resources:
http://en.wikipedia.org/wiki/Cushing’s_syndrome
http://www.mayoclinic.com/health/cushings-syndrome/DS00470
http://www.nlm.nih.gov/medlineplus/ency/article/000410.htm
http://www.bbc.co.uk/health/physical_health/conditions/cushing1.shtml

Cushing’s Syndrome


http://www.potbellysyndrome.com/documents/083EFB330BDDC27C6EEC8354AFFA139607633EB6.html
http://www.wrongdiagnosis.com/c/cushings_disease/book-diseases-7a.htm

http://www.nature.com/eye/journal/v20/n6/fig_tab/6701956f4.html

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