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Further information on hypercortisolism as relates to the disorder of Pseudo Cushing's:

http://www.geocities.com/timjosling/csrpseudo.html

Specific segments...

Pseudo Cushing's Syndrome

Pseudo Cushing's Syndrome, sometimes known as psychological Cushing's syndrome, is a medical condition consisting of high Cortisol levels without any obvious physical cause.

In spite of the damaging effects of high cortisol levels this condition is almost universally untreated.

The patient is offered exhortations to reduce stress levels and so forth. Evidence is now growing that a better approach is possible.

Cortisol

Cortisol is a hormone produced by the adrenal glands. It is used by your body to moderate the body's response to stress. It is essential to life. Without cortisol, any stress would kill you. Addison's disease, a lack of cortisol caused by failure of the adrenal gland, is fatal unless treated by cortisol replacement medication.

Cortisol is part of the body's 'fight or flight' response to stress. The other part of the 'fight or flight' response to stress occurs when the hypothalamus signals the adrenal glands to output adrenaline and noradrenaline. These are the hormones that increase heart rate and blood pressure and that make you sweat when you are under stress.
Functions of Cortisol

Cortisol has many functions...

* It reeduces the level of immune response to disease, preventing auto-immune diseases and shock.
* It signals your body to burn protein for energy, and also in many people makes them hungry which is another way to increase the availability of energy.
* It reduces inflammation. This is why cortisol variants are commonly used as medications, for example in asthma and for skin complaints. Transplant patients and people with auto-immune conditions and allergies use it to reduce inflammation and immune over-reaction.
* In many other respects it moderates the body's response to stress, but these are not important for this discussion.

Adverse Effects of Cortisol

Excessive levels of cortisol are known to produce numerous effects. Not all the effects are felt in all people however.

1. Glaucoma and cataracts.
2. Central Serous Retinopathy.
3. High blood pressure particularly during stress.
4. Obesity.
5. Loss of muscle tone.
6. Reduced immune function; susceptibility to infection and cancer.
7. High cholesterol.
8. High levels of cortisol and its associated hormones are picked up by receptors in the brain and produce increased levels of anxiety and feelings of stress.
9. Damage to the hippocampus, a brain area associated with memory, particularly spatial memory.
10. Osteoporosis. This condition of loss of bone mass is very serious because it is often a broken bone that finally leads to the death of elderly people.
11. Stunted growth in children, as is commonly seen in asthmatics treated with cortisol derived medication.
12. Depression. A high proportion of depressed people have high cortisol levels.

Regulation of cortisol

Cortisol levels are controlled by a three level feedback process, with input from the hypothalamus. The hypothalamus is the body's stress detector.

The hypothalamus produces CRF. This stimulates the pituitary to produce ACTH. In turn the ACTH stimulates the adrenal gland to produce cortisol.

In response to high levels of cortisol the hypothalamus reduces its output of CRF and the pituitary reduces its output of ACTH. This causes the adrenal glands to reduce cortisol output. In this way cortisol levels are regulated.

However the down regulation of CRF can be overridden by the hypothamalus in the presence of stress, particularly physical stress.

Cortisol levels are cyclic, at two levels.

On a daily basis output is highest at wake-up time, and lowest at about midnight. The low level at night may be to allow the body to perform repair and growth activities that are impeded by cortisol. In healthy people, the daily variation is very wide. As people age, the daily fluctuation tends to reduce, and the average level tends to rise.

Cortisol levels also fluctuate over a period of hours, again quite widely. This is why blood tests for cortisol are largely useless because it you may pick a high or low moment.

In addition the cortisol level goes up in response to stress. Stress is any form of physical or psychological stress. The hypothalamus is your body's stress detector and receives input from a wide variety of organs, sense systems, and brain regions. The following are considered as stress by the hypothalamus: illness including tooth decay, pain, fatigue, psychological stress, physical or emotional conflict, excessive exercise, hunger, dehydration, thirst, jet lag and loss of blood.
Causes of High Cortisol Levels

The main cause of high cortisol levels is the use of prescribed cortisol derived medications. These are extensively used to treat inflammation.

Common examples are asthma and inflammatory skin conditions. Cortisol medications have a valuable role to play in treating excessive inflammation where this is life threatening or where short term treatment is needed to prevent inflammation from causing damage. This cortisol is prescribed to reduce the damage from sun spots, where the inflammatory response to the burn can cause additional damage to the eyes. However in my opinion cortisol derived medications are over used, and patients are often not made aware of possible side effects.

Cortisol is naturally high in situations of high stress, such as illness. Continued psychological stress can also raise levels, though after a while the body tends to reduce levels back towards normal.

Certain diseases of the hypothalamus, pituitary and adrenal glands can cause high levels of cortisol. The most common cause is a tumour. These illnesses are known as "Cushing's disease" or "Cushing's Syndrome" depending on the location of the tumour. These conditions are quite rare.

If the high cortisol is not due to an identified physical cause, it is called "pseudo-Cushing's syndrome". This is an unfortunate term, because the high cortisol is still very real.

It is true that in pseudo Cushing's syndrome the levels do not get as high as they can in tumour induced Cushing's, which can kill you. However the damage is still very real.

Excessive alcohol consumption raises cortisol levels. This is a common cause of pseudo Cushing's syndrome.

Another cause is associated with psychological symptoms. High cortisol levels are associated with depression and anxiety. It has always been assumed that the depression and anxiety caused the high cortisol levels via the hypothalamus, which is supposed to interpret the depression and anxiety as a form of stress.

Illness, abuse or neglect in childhood also cause chronically increased levels of cortisol throughout life. A sign of this is stunted growth.
Testing Cortisol Levels

It is important to have a test before trying any treatments. Otherwise you will never know if the treatments are effective.

There are two problems with testing cortisol levels.

First, levels in the blood fluctuate on an hourly and daily basis. This means that blood tests are useless for diagnosing high cortisol level, unless you have frequent blood tests over a period of 24 hours (excluding 12mn to 6 am). In some cases blood tests are useful to determine why the level is high, but I would not recommend having a blood test as a screening test.

As a result, the only useful screening tests is a 24 hour urine cortisol test. You collect urine for 24 hours precisely and the total cortisol derivatives produced gives an indication of the level.

The second problem is that cortisol levels vary widely in normal circumstances, depending on the level of stress. For example in AIDS patients and other people with chronic infections, levels are high. The 'normal' levels therefore cover a wide range, but if your level is always in the high normal range this level is likely to harm you.

Ideally, you should have it tested after a bad week, due to illness or stress, and also after a good week - for example after a relaxing weekend away. That way you will get an indication of you levels fluctuate during common life events.

If you have the test only at the end of a long relaxing holiday you may get a falsely low reading.

Note that patients often ask for a test for Cushing's disease. This illness causes high cortisol levels. However it is very rare and almost all the symptoms are more commonly cause by other complaints. Most GPs will have had many people tested for Cushing's, but few or no actual cases.

So you may get some resistance from your GP. You need a medical authorisation to have the test.

Psychological Cushing's

One form of pseudo Cushing's syndrome mentioned above is associated with psychological markers.

These psychological markers include high levels of anxiety and subjective stress levels. Depression is also very strongly linked to high cortisol levels.

A form of personality, called the "type A personality" is associated with high cortisol levels. The popular impression of the type A person is of a high flying businessman. Actually a type A person is better described as highly conscientious, anxious, meticulous, methodical, reliable, organised, punctual and susceptible to illness.

Previously it was thought that the psychological condition caused the high cortisol. However recent evidence suggests the contrary:

1. Psychological techniques have been found to be somewhat ineffective in reducing cortisol levels in these circumstances. If the real problem were psychological, you would expect psychological techniques to be effective.
2. A Swedish study found that there is a genetic link to high cortisol levels, affecting about 14% of the population.
3. Receptors in the brain have been shown to pick up CRF, ACTH and cortisol levels and researchers have been able to turn subjects' perceived stress levels up and down by disabling these receptors.

There is an unfortunate tendency among some GPs to dismiss anything that cannot be diagnosed or explained as psychological. In many cases an organic cause of the problem is later found.

The brain receptor studies provide a mechanism for high stress hormone levels to produce the type A personality. If your body over-reacts to any stress, and this makes you feel anxious and tense, you are likely to try and avoid stress. Thus is a type A person born: never late to the airport because they find it too stressful to be late.

Causes of Psychological Cushing's

As mentioned above it appears many people have a genetic predisposition to high cortisol levels.

In addition life circumstances can lead to high cortisol levels. Stress in early childhood such as illness or abuse or neglect has been shown to lead to a chronic life long hyper reactivity to any form of stress, which leads to high levels of cortisol in adulthood.

In addition chronic stress of any kind will produce high cortisol levels and the frequent accompanying symptoms of anxiety, depression and heightened feelings of psychological stress. This will occur regardless of whether the stress is physical or psychological.

Anti-depressants have been shown to reduce cortisol levels. However these often have adverse side effects, and many are addictive.

Other drugs exist to control cortisol levels or its impact on the body. But unfortunately these drugs cause levels of CRF and ACTH to increase, as a result of the body's feedback mechanisms. So they are not used unless absolutely necessary.

Many people with high cortisol levels do use anti-depressants and anti-anxiety medications.

While Cushing's Syndrome and Cushing's Disease are more rare than Pseudo Cushing's or simple hypercortisolism, they are disorders of sufficient concerns that if one has a hypercortisol condition that they should always request that their Endo follow through with appropriate testing to insure whether or not they may have one of those two, CD or CS....

CD is a disorder where the HPA Axis breakdown is occurring at the Pituitary gland and that an offending tumor exists there - almost always - benign - that is sending the "more and more and more" signals; while CS is a disorder where the HPA Axis dysfunction is at the adrenal level - usually - with a tumor of the adrenal gland - usually benign but sometimes not - causing that "more and more and more" message to be sent, on a rare occasion CS will be due to a small-cell ACTH-secreting cancer somewhere in the body that is causing that message to be sent... treatment of preference is to locate and surgically remove the offending tumor.

Larry