Cushing Syndrome: Getting Fatter???

Cushing's Syndrome

Cushing's syndrome is a hormonal disorder caused by prolonged exposure of the body's tissues to high levels of the hormone cortisol. Sometimes called "hypercortisolism," it is relatively rare and most commonly affects adults aged 20 to 50. An estimated 10 to 15 of every million people are affected each year.

What are the symptoms?
Symptoms vary, but most people have upper body obesity, rounded face, increased fat around the neck, and thinning arms and legs. Children tend to be obese with slowed growth rates.
Other symptoms appear in the skin, which becomes fragile and thin. It bruises easily and heals poorly. Purplish pink stretch marks may appear on the abdomen, thighs, buttocks, arms and breasts. The bones are weakened, and routine activities such as bending, lifting or rising from a chair may lead to backaches, rib and spinal column fractures.
Most people have severe fatigue, weak muscles, high blood pressure and high blood sugar. Irritability, anxiety and depression are common.
Women usually have excess hair growth on their faces, necks, chests, abdomens, and thighs. Their menstrual periods may become irregular or stop. Men have decreased fertility with diminished or absent desire for sex.

What causes Cushing's syndrome?
Cushing's syndrome occurs when the body's tissues are exposed to excessive levels of cortisol for long periods of time. Many people suffer the symptoms of Cushing's syndrome because they take glucocorticoid hormones such as prednisone for asthma, rheumatoid arthritis, lupus and other inflammatory diseases, or for immunosuppression after transplantation.
Others develop Cushing's syndrome because of overproduction of cortisol by the body. Normally, the production of cortisol follows a precise chain of events. First, the hypothalamus, a part of the brain which is about the size of a small sugar cube, sends corticotropin releasing hormone (CRH) to the pituitary gland. CRH causes the pituitary to secrete ACTH (adrenocorticotropin), a hormone that stimulates the adrenal glands. When the adrenals, which are located just above the kidneys, receive the ACTH, they respond by releasing cortisol into the bloodstream.

Cortisol performs vital tasks in the body. It helps maintain blood pressure and cardiovascular function, reduces the immune system's inflammatory response, balances the effects of insulin in breaking down sugar for energy, and regulates the metabolism of proteins, carbohydrates, and fats. One of cortisol's most important jobs is to help the body respond to stress. For this reason, women in their last 3 months of pregnancy and highly trained athletes normally have high levels of the hormone. People suffering from depression, alcoholism, malnutrition and panic disorders also have increased cortisol levels.
When the amount of cortisol in the blood is adequate, the hypothalamus and pituitary release less CRH and ACTH. This ensures that the amount of cortisol released by the adrenal glands is precisely balanced to meet the body's daily needs. However, if something goes wrong with the adrenals or their regulating switches in the pituitary gland or the hypothalamus, cortisol production can go awry.

Pituitary AdenomasPituitary adenomas cause most cases of Cushing's syndrome. They are benign, or non-cancerous, tumors of the pituitary gland which secrete increased amounts of ACTH. Most patients have a single adenoma. This form of the syndrome, known as "Cushing's disease," affects women five times more frequently than men.
Ectopic ACTH SyndromeSome benign or malignant (cancerous) tumors that arise outside the pituitary can produce ACTH. This condition is known as ectopic ACTH syndrome. Lung tumors cause over 50 percent of these cases. Men are affected 3 times more frequently than women. The most common forms of ACTH-producing tumors are oat cell, or small cell lung cancer, which accounts for about 25 percent of all lung cancer cases, and carcinoid tumors. Other less common types of tumors that can produce ACTH are thymomas, pancreatic islet cell tumors, and medullary carcinomas of the thyroid.

Adrenal Tumors Sometimes, an abnormality of the adrenal glands, most often an adrenal tumor, causes Cushing's syndrome. The average age of onset is about 40 years. Most of these cases involve non-cancerous tumors of adrenal tissue, called adrenal adenomas, which release excess cortisol into the blood.

Adrenocortical carcinomas, or adrenal cancers, are the least common cause of Cushing's syndrome. Cancer cells secrete excess levels of several adrenal cortical hormones, including cortisol and adrenal androgens. Adrenocortical carcinomas usually cause very high hormone levels and rapid development of symptoms.

Familial Cushing's SyndromeMost cases of Cushing's syndrome are not inherited. Rarely, however, some individuals have special causes of Cushing's syndrome due to an inherited tendency to develop tumors of one or more endocrine glands. In Primary Pigmented Micronodular Adrenal Disease, children or young adults develop small cortisol-producing tumors of the adrenal glands. In Multiple Endocrine Neoplasia Type I (MEN I), hormone secreting tumors of the parathyroid glands, pancreas and pituitary occur. Cushing's syndrome in MEN I may be due to pituitary, ectopic or adrenal tumors.

How is Cushing's syndrome diagnosed?
Diagnosis is based on a review of the patient's medical history, physical examination and laboratory tests. Often x-ray exams of the adrenal or pituitary glands are useful for locating tumors. These tests help to determine if excess levels of cortisol are present and why.
24-Hour Urinary Free Cortisol LevelThis is the most specific diagnostic test. The patient's urine is collected over a 24-hour period and tested for the amount of cortisol. Levels higher than 50–100 micrograms a day for an adult suggest Cushing's syndrome. The normal upper limit varies in different laboratories, depending on which measurement technique is used.
Once Cushing's syndrome has been diagnosed, other tests are used to find the exact location of the abnormality that leads to excess cortisol production. The choice of test depends, in part, on the preference of the endocrinologist or the center where the test is performed.

Dexamethasone Suppression TestThis test helps to distinguish patients with excess production of ACTH due to pituitary adenomas from those with ectopic ACTH-producing tumors. Patients are given dexamethasone, a synthetic glucocorticoid, by mouth every 6 hours for 4 days. For the first 2 days, low doses of dexamethasone are given, and for the last 2 days, higher doses are given. Twenty-four hour urine collections are made before dexamethasone is administered and on each day of the test. Since cortisol and other glucocorticoids signal the pituitary to lower secretion of ACTH, the normal response after taking dexamethasone is a drop in blood and urine cortisol levels. Different responses of cortisol to dexamethasone are obtained depending on whether the cause of Cushing's syndrome is a pituitary adenoma or an ectopic ACTH-producing tumor.
The dexamethasone suppression test can produce false-positive results in patients with depression, alcohol abuse, high estrogen levels, acute illness, and stress. Conversely, drugs such as phenytoin and phenobarbital may cause false-negative results in response to dexamethasone suppression. For this reason, patients are usually advised by their physicians to stop taking these drugs at least one week before the test.
CRH Stimulation TestThis test helps to distinguish between patients with pituitary adenomas and those with ectopic ACTH syndrome or cortisol-secreting adrenal tumors. Patients are given an injection of CRH, the corticotropin-releasing hormone which causes the pituitary to secrete ACTH. Patients with pituitary adenomas usually experience a rise in blood levels of ACTH and cortisol. This response is rarely seen in patients with ectopic ACTH syndrome and practically never in patients with cortisol-secreting adrenal tumors.

Direct Visualization of the Endocrine Glands (Radiologic Imaging)Imaging tests reveal the size and shape of the pituitary and adrenal glands and help determine if a tumor is present. The most common are the CT (computerized tomography) scan and MRI (magnetic resonance imaging). A CT scan produces a series of x-ray pictures giving a cross-sectional image of a body part. MRI also produces images of the internal organs of the body but without exposing the patient to ionizing radiation.

Imaging procedures are used to find a tumor after a diagnosis has been established. Imaging is not used to make the diagnosis of Cushing's syndrome because benign tumors, sometimes called "incidentalomas," are commonly found in the pituitary and adrenal glands. These tumors do not produce hormones detrimental to health and are not removed unless blood tests show they are a cause of symptoms or they are unusually large. Conversely, pituitary tumors are not detected by imaging in almost 50 percent of patients who ultimately require pituitary surgery for Cushing's syndrome.

Petrosal Sinus SamplingThis test is not always required, but in many cases, it is the best way to separate pituitary from ectopic causes of Cushing's syndrome. Samples of blood are drawn from the petrosal sinuses, veins which drain the pituitary, by introducing catheters through a vein in the upper thigh/groin region, with local anesthesia and mild sedation. X-rays are used to confirm the correct position of the catheters. Often CRH, the hormone which causes the pituitary to secrete ACTH, is given during this test to improve diagnostic accuracy. Levels of ACTH in the petrosal sinuses are measured and compared with ACTH levels in a forearm vein. ACTH levels higher in the petrosal sinuses than in the forearm vein indicate the presence of a pituitary adenoma; similar levels suggest ectopic ACTH syndrome.

The Dexamethasone-CRH TestSome individuals have high cortisol levels, but do not develop the progressive effects of Cushing's syndrome, such as muscle weakness, fractures and thinning of the skin. These individuals may have Pseudo Cushing's syndrome, which was originally described in people who were depressed or drank excess alcohol, but is now known to be more common. Pseudo Cushing's does not have the same long-term effects on health as Cushing's syndrome and does not require treatment directed at the endocrine glands. Although observation over months to years will distinguish Pseudo Cushing's from Cushing's, the dexamethasone-CRH test was developed to distinguish between the conditions rapidly, so that Cushing's patients can receive prompt treatment. This test combines the dexamethasone suppression and the CRH stimulation tests. Elevations of cortisol during this test suggest
Cushing's syndrome.
Some patients may have sustained high cortisol levels without the effects of Cushing's syndrome. These high cortisol levels may be compensating for the body's resistance to cortisol's effects. This rare syndrome of cortisol resistance is a genetic condition that causes hypertension and chronic androgen excess.
Sometimes other conditions may be associated with many of the symptoms of Cushing's syndrome. These include polycystic ovarian syndrome, which may cause menstrual disturbances, weight gain from adolescence, excess hair growth and sometimes impaired insulin action and diabetes. Commonly, weight gain, high blood pressure and abnormal levels of cholesterol and triglycerides in the blood are associated with resistance to insulin action and diabetes; this has been described as the "Metabolic Syndrome-X." Patients with these disorders do not have abnormally elevated cortisol levels.


How is Cushing's syndrome treated?
Treatment depends on the specific reason for cortisol excess and may include
surgery,
radiation,
chemotherapy or
the use of cortisol-inhibiting drugs.
If the cause is long-term use of glucocorticoid hormones to treat another disorder, the doctor will gradually reduce the dosage to the lowest dose adequate for control of that disorder. Once control is established, the daily dose of glucocorticoid hormones may be doubled and given on alternate days to lessen side effects.
Pituitary AdenomasSeveral therapies are available to treat the ACTH-secreting pituitary adenomas of Cushing's disease. The most widely used treatment is surgical removal of the tumor, known as transsphenoidal adenomectomy. Using a special microscope and very fine instruments, the surgeon approaches the pituitary gland through a nostril or an opening made below the upper lip. Because this is an extremely delicate procedure, patients are often referred to centers specializing in this type of surgery. The success, or cure, rate of this procedure is over 80 percent when performed by a surgeon with extensive experience. If surgery fails, or only produces a temporary cure, surgery can be repeated, often with good results. After curative pituitary surgery, the production of ACTH drops two levels below normal. This is a natural, but temporary, drop in ACTH production, and patients are given a synthetic form of cortisol (such as hydrocortisone or prednisone). Most patients can stop this replacement therapy in less than a year.
For patients in whom transsphenoidal surgery has failed or who are not suitable candidates for surgery, radiotherapy is another possible treatment. Radiation to the pituitary gland is given over a 6-week period, with improvement occurring in 40 to 50 percent of adults and up to 80 percent of children. It may take several months or years before patients feel better from radiation treatment alone. However, the combination of radiation and the drug mitotane (Lysodren®) can help speed recovery. Mitotane suppresses cortisol production and lowers plasma and urine hormone levels. Treatment with mitotane alone can be successful in 30 to 40 percent of patients. Other drugs used alone or in combination to control the production of excess cortisol are aminoglutethimide, metyrapone, trilostane and ketoconazole. Each has its own side effects that doctors consider when prescribing therapy for individual patients.
Ectopic ACTH SyndromeTo cure the overproduction of cortisol caused by ectopic ACTH syndrome, it is necessary to eliminate all of the cancerous tissue that is secreting ACTH. The choice of cancer treatment—surgery, radiotherapy, chemotherapy, immunotherapy, or a combination of these treatments—depends on the type of cancer and how far it has spread. Since ACTH-secreting tumors (for example, small cell lung cancer) may be very small or widespread at the time of diagnosis, cortisol-inhibiting drugs, like mitotane, are an important part of treatment. In some cases, if pituitary surgery is not successful, surgical removal of the adrenal glands (bilateral adrenalectomy) may take the place of drug therapy.
Adrenal TumorsSurgery is the mainstay of treatment for benign as well as cancerous tumors of the adrenal glands. In Primary Pigmented Micronodular Adrenal Disease and the familial Carney's complex, surgical removal of the adrenal glands is required.
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What could be deadlier than a Mental Illness

Dissociative Disorders

In dissociative disorders, one aspect of a person’s psychological makeup is dissociated (separated) from others. A commonality among most people diagnosed with these disorders is their susceptibility to trance states, hypnosis, and suggestibility. Hans Eysenck's research suggests as well that these are more likely to be nervous extraverts.

Dissocative amnesia is the “inability to recall important personal information, usually of a traumatic or stressful nature,” (DSM IV) but more than what we would characterize as ordinary forgetfulness. It is not due, of course, to a physical trauma, drug use, or a medical condition. Instead, it is due to the ability that these people have to focus away from certain memories that disturb them.
It has been increasingly common for people to report having forgotten childhood traumas, especially sexual abuse, while in the care of certain therapists. Recent researchers now believe that the “recovered memories” that these patients report are actually implanted in the minds of these very suggestable people by their over-enthusiastic therapists. It is still not known whether all recovered memories should be suspect or not, although memory research suggests that trauma is more typically remembered well, not poorly.

Fugue is amnesia accompanied by sudden travel away from a person’s usual haunts. Time away can range from a few hours to months. When these people return to normal, they often don’t remember what happened while they were away. A few adopt an entirely new identity while “on the road.”

Dissociative identity disorder -- formerly known as multiple personality -- involves someone developing two or more seperate “identities” that take over the person’s behavior from time to time. The "usual" personality doesn't remember what happens when an alternate personality takes over. Dissociative identity disorder is not the same as schizophrenia, but does have some similarities. In schizophrenia, voices and impulses are seen as coming from outside oneself, while in dissociative identity disorder, they are seen as coming from within, in the form of these alternate personalities.
One of the first cases to reach the public was the story of Eve White. Eve White (a pseudonym, of course), was a mild mannered woman with a domineering husband. She found herself waking up with garish makeup, hangovers, and other signs that she had been out carousing during the night. This alternate personality that took over occasionally was called Eve Black. Eventually, the two personalities were brought together, and Eve's story was made into a movie with actress Joanne Woodward called "The Three Faces of Eve." A second movie was much more popular: "Sybil." This was the true story of a woman who had been severely abused by her schizophrenic mother, and developed (supposedly) 26 personalities.
People with multiple personalities are usually easily hypnotized, making it likely that this disorder may be caused or at least aggravated by therapists, intentionally or unintentionally, much like recovered memories. It is looked upon with skepticism by many psychologists.
On the other hand, it may also be understood as a modern version of a fairly common occurance in the nonwestern, premodern world:

Spirit possession. In cultures where the powers of gods, ghosts, and demons are taken for granted, people sometimes feel possessed by these outside personalities. In more modern societies, lacking the possession explanation, people assume that the alternate personality is internal.


Depersonalization is the “persistent or recurrent feeling of being detached from one’s mental processes or body....” (DSM IV) Often the world seems odd as well, which is called derealization. Physical objects may seem distorted and other people may seem mechanical. Again, these people may be particularly easy to hypnotize, and the feeling can be induced even in normal people under hypnosis. Half of all adults may have experienced a brief episode of depersonalization or derealization in their lifetime, but it is most common in people who have suffered from abuse, the loss of a loved one, or have seen combat. It is also common under the influence of hallucinogens like LSD.


Dissociative trance disorder is an unofficial category often referred to by psychologists and psychiatrists working in premodern, nonwestern societies. Trance is a narrowing of one's attention so that some things (such as sight, movement, or even outer reality) are placed outside awareness. Cross-cultural therapist Richard Castillo, in his book Culture and Mental Illness, says that trance is "an adaptation with great individual and species survival value." It is not far from such non-pathological states as hypnosis and meditation.
Castillo gives numerous examples:
Amok is found in Malaysia and Indonesia. The word comes from the Sanskrit for "no freedom." It involves a person losing their sense of self, grabbing a weapon such as a machete, and running through the village slashing at people. Afterwards, they have no memory of what they have done and are typically excused from any damage, even if their actions resulted in someone's death!
Grisi siknis is found among teenage girls and yound women of the Miskito indians in Nicaragua. They also run wild with machetes, occasionally assaulting people or mutilating themselves. They have no memory of their actions.
Pibloktoq or arctic hysteria is found among polar eskimos. For anywhere from a few minutes to an hour, a person takes off their clothing and runs screaming through the snow and ice, as a response to a sudden fright.
Latah (in Malaysia) involves violent body movements, taking unusual postures, trance dancing, mimicking other people, throwing things, and so on.
"Falling out" (in the Bahamas) involves falling to the ground, apparently comatose, but hearing and understanding what is going on around you.
"Indisposition" (in Haiti) is a possession trance understood as a response to fear.
"Fits" (in India) is a seizure-like response by some women to family stress, curable by exorcism or by simply telling her husband to protect her from her inlaws!
In the west, these kinds of behaviors are often classified as impulse control disorders, along with trichotillomania, compulsive gambling, pyromania, and kleptomania (discussed with anxiety disorders). One of these - intermittent explosive disorder - is basically the same as running amok, and is commonly known as "going postal

Kaposi Sarcoma : Horror of AIDS

Definition of Kaposi's Sarcoma

Kaposi's sarcoma (KS) is a disease in which cancer cells are found in the tissues under the skin or mucous membranes that line the mouth, nose, and anus.
KS causes red or purple patches (lesions) on the skin and/or mucous membranes and spreads to other organs in the body, such as the lungs, liver, or intestinal tract.

Description of Kaposi's Sarcoma

consists of characteristic skin lesions that range from flat to raised purple plaques. These tumors have a rich network of small blood vessels, and red blood cells moving slowly through these channels lose their oxygen, changing from red to blue. The mixture of red and blue cells gives the KS lesion a characteristic purple color.
There are several forms of KS, based on cause rather than appearance. The "classic" Kaposi's sarcoma, found mainly in Mediterranean males and mid-European Jews, has always been rare. In the 1950s a large number of cases were found in Africa, and the incidence has dramatically increased since then. KS was later found to be a common result of an alteration of body immunity.

There are two circumstances under which this alteration takes place.

The first is when depression of the immune system is part of some treatment, for example in kidney or other organ transplants. To prevent the foreign organ from being rejected, powerful drugs are given to shut down the immune system.
The second circumstance is associated with Acquired Immune Deficiency Syndrome (AIDS).
Types Of Tumors
KS tumors are divided into three groups, based on appearance, with much overlap.
Nodular lesions are of varying size and thickness. They are purple and will at times have a halo of brown or yellow pigment around them.
Infiltrating lesions may be quite large, may be raised, or grow downward beneath the skin.
Lymphatic lesions can mimic other causes of swollen lymph nodes and may require a biopsy to rule out infection.
Under the microscope, all three types of KS appear similar. But three sub-types have been identified, all of which are treated much the same. The spindle cell variety is the slowest growing, the anaplastic is the most aggressive, and the mixed cell has a somewhat intermediate growth rate.

Causes and Risk Factors of Kaposi's Sarcoma

The epidemic KS, occurring as a disease that accompanies AIDS, is thought to have a cause - the virus named HIV (Human Immunodeficiency Virus). If given a blood test for HIV, nearly all patients with epidemic KS will show evidence of being infected.
Various ideas have been advanced to explain how this virus causes KS. One theory is that it causes a normal cell to become malignant either directly or by initiating a chain of events. Various agents that may be involved in such a change have been identified.
Yet another idea has to do with the body's T cells, some of which hunt for malignant cells that have developed spontaneously and kill them off before they can become cancers. The T cell is known to be infected with the virus and cannot kill the malignant cells.

Symptoms of Kaposi's Sarcoma

There are no general symptoms of early KS. In the epidemic form, KS may be the first sign of AIDS, or, the first lesion may follow an illness of months or years. During this time, the patient may have had non-specific symptoms such as fever, weight loss and sweating. Possibly there were other illnesses, such as lymphoma or tuberculosis, before the first KS lesion developed.
Once the disease occurs, symptoms relate to the site of involvement. Early and more advanced skin lesions are usually only mildly uncomfortable, although painful ulcers may occur.
Lesions in the gastrointestinal tract are very common but rarely cause significant symptoms. Early lesions in the lung have no symptoms either, but severe lung involvement produces a profound air hunger.

Treatment of Kaposi's Sarcoma

KS is not considered curable. Neither surgical removal of the first-detected lesion nor obtaining a complete remission of multiple sites with chemotherapy or other techniques results in cure. Long-term survival does occur both with or without treatment, however.
Survival in classic KS is usually years and sometimes decades. Some patients with AIDS-related KS are still alive after 10 years, though most survive only a few years and treatment decisions are usually aimed at palliation.
All forms of KS are sensitive to radiation therapy. Radiation is especially useful for lesions that are cosmetically disturbing, painful, involve the mouth extensively, block lymphatics, bleed, or protrude from the skin. Response rates are quite high and treatment is well tolerated.
Chemotherapy can be used in treatment but there is concern that aggressive treatment might further depress the immune system. The disease does respond to chemotherapy, both with single agents and combinations of drugs.
KS is one of the few tumors that responds to local injections of chemotherapy. Many anticancer drugs cause intense local damage if they are accidentally injected into tissue. This undesirable effect has been used in a positive way to treat skin lesions.
Biological therapy involves immunologic treatment of KS primarily with the interferons, mainly alpha. Other agents, especially interleukin-2 are being studied.