Question:
Could you discuss in detail how you approach testing for and treating these problems in CFS and FM patients?

Dr. Holtorf: There is a mixture of underlying causes of Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM), and each underlying abnormality can trigger further problems. This results in a cascade of multiple physiologic abnormalities and a perpetuating vicious cycle. Successful treatment requires that this vicious cycle be addressed on multiple levels. This cascade of abnormalities [beginning with the "Genetic Predisposition" and then "Triggering Event of Physiologic Stress"] is graphically depicted below (see the site) - and a few of the abnormalities are also discussed.

Immune Dysfunction.

If a complete immune panel is done on CFS and FM patients, almost all have immune dysfunction, which often includes poor natural killer cell function and/or high RNAse-L activity.

Natural killer cell function.
These cells are very important in killing viruses and bacteria.
It is very difficult to eradicate chronic infections when these cells are not functioning well.

Antibiotics and antivirals do not work well and are often infective if the immune system is not stimulated as well. You are never able to kill all the infectious agents unless the body is able to clean up the residual left by the antibiotic or antiviral.

There are a number of methods to do this.
What we use depends on the infection present, but includes both natural and pharmaceutical antivirals, antibiotics, immune boosters and immune modulators. Growth hormone, thyroid and cortisol (adrenal hormone) are also very good immune enhancers.

... cortisol - low doses of cortisol for people who have adrenal insufficiency act as an immune enhancer. Large doses are immune suppressors. Your body normally increases cortisol in times of infection. Oxidative therapies, discussed below, can be very powerful. We customize the specific treatment for the patient.

RNase-L activity:
In response to infection, the body can produce an enzyme called RNase-L that breaks down the viral RNA to rid the body of the infection. When the infection is gone this enzyme is then turned off. In CFS, however, the presence of chronic infections can result in the stimulation of an abnormal “super” RNase-L enzyme that also breaks down the cell’s own RNA that is used to code for proteins and required for normal functioning.

The result is poorly functioning cells and an increase in cellular apoptosis (programmed cell death). Treatment consists of eradication of the chronic infection and immune modulators. The RNase-L activity test can be done by Redlabs USA (http://www.RedlabsUSA.com ). (No affiliation).

Coagulation Problems.

This is diagnosed with a specialized laboratory test that includes soluble fibrin monomer, prothrombin fragment 1 +2, fibrinogen and thrombin/antithrombin complex.

Defects are typically treated with heparin and vascular enzymes such as lumbrokinase and serapeptidase to stop the excessive production of soluble fibrin monomers and to help clean up the fibrin already laid down.

Eradication of chronic infections is also important, as there is often a chronic infection as the underlying stimulus of the abnormal activation of coagulation.

Low Thyroid

CFS and FM patients almost always have
low tissue levels of thryoid hormones due to hypothalamic and pituitary dysfunction and thyroid resistance, which has been documented in a number of studies.

Unfortunately, this hypothyroidism is missed 80% to 90% of the time because standard thyroid tests and TSH [thyroid-stimuating hormone] levels are usually normal, and this is what 90% of doctors are accustomed to using to diagnose low thyroid. Currently, the best method to diagnose low thyroid in these conditions is to look at the T3/reverseT3 ratio. [TSH causes the thyroid gland to produce two hormones: triiodothyronine (T3) and thyroxine (T4).]

When CFS and FM patients are treated with thyroid, they are almost always under-dosed because their pituitary dysfunction results in their TSH becoming quickly suppressed, which normally indicates too much thyroid.

Because these patients have pituitary dysfunction, one must not rely on the TSH, and not treat based on this parameter. In addition, due to the thyroid resistance, T4 preparations such as Synthroid and Levoxyl cannot provide adequate tissue levels of the active hormone. T4/T3 combinations such as Armour thyroid can be of benefit, but many patients also find that these preparations also do not provide adequate relief. Straight timed released T3 is often the best preparation to obtain adequate tissue levels.

Adrenal Insufficiency

Standard blood testing will almost always miss this deficiency.
Studies show that with sophisticated testing, close to 100% of CFS and FM have adrenal dysfunction and treatment can be very beneficial.

To diagnose, we typically use symptoms and a combination of blood sugar, free cortisol, and HgA1C%. Again, one must have a high clinical suspicion and not just think in terms of 'normal' and 'abnormal'. These normal levels are determined for healthy individuals, not the chronically ill, so the cortisol levels should be higher with this illness. 24-hour urine and saliva tests can be done, but these can also result in false positive and false negative results.

Growth Hormone Deficiency.

Many CFS and FM patients are low in growth hormone.
This hormone is produced in the pituitary, and with the documented pituitary dysfunction in CFS and FM, it is not unexpected that there is such a deficiency in these illnesses.

Treatment can sometimes make a tremendous impact and because the cost has come down significantly in recent years, it is a viable treatment for more patients. IGF-1 is the best indication for growth hormone levels, but again, one cannot use the standard laboratory normal ranges to diagnose.

Question:
Once you’ve determined which problems a CFS or FM patient has, do you prescribe both traditional and alternative treatments, or do you focus on a single method at a time?

Dr. Holtorf: In order to treat these diseases adequately, one must simultaneously use both traditional and so-called alternative treatments. If one treatment were used at a time it would take many years before the patient feels better. Many treatments can be withdrawn as the patient improves.

Question:
Please tell us a little bit about the Holtorf Medical Group, Inc: The Center for Hormone Imbalance, Hypothyroidism and Fatigue (http://www.HoltorfMed.com) where you practice.

Dr. Holtorf: I started the Holtorf Medical Group to concentrate on the treatment of complex endocrine dysfunction, hypothyroidism, fatigue, CFS and fibromyalgia. Eighty percent of our practice is for patients complaining of fatigue, with CFS and FM probably being the biggest part of the practice.

Question:
What are the biggest challenges you face with treating CFS and FM patients?

Dr. Holtorf: Although we have good success with CFS and FM, these are challenging cases that require doctors to spend significant time with the patient. It cannot be accomplished with seven-minute office visits.

Question:
What are the biggest successes you’ve experienced in treating CFS and FM?

Dr. Holtorf: Many of these patients are very sick and have given up.
It is so gratifying to get these patients back to having a life.
They are just so grateful. Many have been unable to work and/or have been on disability and now, following treatment, are happy, functional and productive.

Question:
Are you working on any promising new treatments at this time – either through research or through a trial and error process with your patients?

Dr. Holtorf: We are continually working on and implementing new treatments every day in practice. We have been using and refining many of the so-called “new” treatments for many years. For instance, Valcyte is considered a new, novel treatment for CFS, but we have been using it for 4 years, since it was first approved.

Question:
What are the most exciting developments you’ve seen recently in treatment options for CFS and FM?

Dr. Holtorf: Recent developments are taking place in a stepwise manner, but I do not believe it will be through the so-called ‘mainstream’ medicine one-drug cures. I think these are very treatable conditions, and advances will only continue to improve treatment.

I do believe, however, that the incidences of CFS and FM will significantly increase and at some point will be considered an epidemic because they are very poorly treated through the standard healthcare delivery system.

Kent Holtorf, M.D.,
on Effective Treatment of Chronic Fatigue Syndrome and Fibromyalgia
http://www.immunesupport.com/library/showarticle.cfm/id/4320
02-21-2003

Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM) are illnesses that often coexist and affect millions of Americans. Symptoms vary amongst individuals and commonly include severe fatigue, sleep disturbances, cognitive problems (commonly called ‘brain fog’), muscle pain and multiple infections. Unfortunately, many individuals and physicians continue to deny that these syndromes are legitimate diseases.

The medical literature is, however, very clear that these are legitimate diseases and individuals with these syndromes have measurable hypothalamic, pituitary, immune and coagulation dysfunction. These abnormalities then result in a cascade of further abnormalities, in which stress plays a role.

The pituitary and hypothalamic dysfunction results in multiple hormonal deficiencies that are often not detected with standard blood tests, and autonomic dysfunction, including neurally mediated hypotension.

The immune dysfunction, which includes natural killer cell dysfunction, results in opportunistic infections and yeast overgrowth, making the symptoms worse. Recent studies have shown that the coagulation dysfunction is usually initiated by a viral infection and has genetic predisposition. This abnormal coagulation results in increased blood viscosity (‘slugging’) and a deposition of soluble fibrin monomers along the capillary wall. This results in tissue and cellular hypoxia, resulting in fatigue, and decreased cognition (brain fog). Neurotransmitter abnormalities and macro and micro nutrient deficiencies have also been shown to occur with these disorders.

Gulf War Syndrome, which is almost identical to CFS and FM, was found to have a parallel cause. The cause was determined to be from multiple vaccinations under stressful conditions in susceptible individuals. These vaccines, which are viral mimics, resulted in the same coagulation cascade and the deposition of fibrin monomers, resulting in the same tissue hypoxia that occurs in FM and CFS. As a result, these multiple injections are being discontinued by the armed forces.

Current research suggests that many triggers can initiate a cascade of events, causing the hypothalamic, pituitary, immune and coagulation dysfunction. The most common initiating cause is a viral infection, which is very commonly Epstein-Barr Virus, Cytomegalovirus or HHV6. These are found in 80% of CFS and FM patients. Many people with these syndromes can pinpoint the onset of the disease(s) to a viral infection that never got better. Also, stress seems to be a contributing factor. Effective treatment, with 80 to 90 percent of individuals achieving significant clinical benefits, can be achieved by simultaneously treating the above problems that an individual is found to have.

The mix of treatments needed varies from patient to patient.
There are some abnormalities that are common. For instance, close to 100% of individuals with these syndromes have low thyroid. This is, however, usually not picked up on the standard blood tests because the TSH is not elevated in these individuals due to pituitary dysfunction. Many of these individuals will also have high levels of the anti-thyroid reverse T3, which is usually not measured on standard blood tests. In addition, the majority of individuals can also have a thyroid receptor resistance that is not detected on the blood tests. Consequently, thyroid treatment, especially with timed release T3, is effective for many patients. T4 preparations (inactive thyroid) such as Synthroid and Levoxyl do not work well for these conditions.

Adrenal insufficiency and growth hormone deficiency are also very common with these disorders, and supplementation with these hormones can often have profound effects. As with thyroid testing, these deficiencies are, unfortunately, usually not detected with the standard screen blood tests and require more specific testing.

When an individual is found to have one of the viruses discussed above, these can be treated with resulting improvement in symptoms. There are a number of drugs, including anti-viral medication, that are currently undergoing phase III clinical trials at clinics, including ours [Hormone and Longevity Medical Center], for FDA approval in the treatment of FM and CFS.

Although a concept that is sometimes uncomfortable and foreign to traditional medical styles of thinking, the need for multiple interventions is effective when an illness affects a critical control center (such as the hypothalamus), which impacts the multiple systems noted above. Unfortunately, there is not a single treatment that reverses hypothalamic dysfunction directly. Thus, this situation is different from illnesses that affect a single target organ and which can be treated with a single intervention.

For example, pituitary dysfunction itself often requires treatment with several hormones. This effect is multiplied in hypothalamic dysfunction, which affects several critical systems in addition to the pituitary gland. An integrated treatment approach based on simultaneously treating the above problems is significantly beneficial in CFS and FMS. Individuals with these devastating syndromes can “get their lives back” despite the fact that they were previously told, “There is nothing that can be done,” or “It is all in your head.”

Kent Holtorf, M.D.
Hormone and Longevity Medical Center
(310) 375-2705

Why Doesn’t My Doctor Know all of This?
http://www.hormoneandlongevitycenter.com/doctorsknowledge/

A question that is often raised by patients is “Why doesn’t my doctor know all of this?” The reason is that the overwhelming majority (all but a few percent) of physicians (endocrinologists, internists, family practitioners, rheumatologists, ect.) do not read medical journals. When asked, most doctors will claim that they routinely read medical journals, but this has been shown not to be the case.

The reason is multi-factorial, but it comes down to the fact that the doctors do not have the time. They are too busy running their practices. The overwhelming majority of physicians rely on what they learned in medical school and on pharmaceutical sales representatives to keep them “up-to-date” on new drug information. Obviously, the studies brought to physicians for “educational purposes” are highly filtered to support their product. ...

There is clear evidence and concern that published research is clearly tainted by whoever is the financial sponsor of the study. A study published in the Journal of Psychiatry (and later discussed in the May 2006 edition of Forbes magazine) states that the most important determinant of the outcome of the study is who paid for it. An analysis in the Archives of Internal Medicine reviewed 56 studies of painkillers and not once was the sponsor’s drug deemed inferior. In addition to reading the conclusion of the study, a physician must read the entire study and review the data with a critical eye, which is rarely done.

2007-04-27 Called Sharon Iglesias, siglesias@fibroandfatigue.com at 1-866-443-4276 for detail on testing. She noted that the doctors at the centers choose from over 800 tests and have the selected ones run at an onsite Quest lab before you leave. These generally include at least 12 viral tests, heavy metals, hormones, etc. Likely lab costs per patient can run between $1,005 and $2,000.

Appointments (are) tentatively set up as follows:
-- 24-Page Health Questionnaire, Copies of your Medical Records, To prepare for lab tests, please do not take thyroid medication the day of your appointment., For a morning appointment, do not eat, but you should drink plenty of water, visit fee is $390.00; if the Dr. orders any therapies, medication or supplements the cost will be in addition to the visit fee; Depending on what you agree to, it may cost an additional $ 150. or $200.; Depending on what the Therapies the doctor orders, you may be in the center for up to 2 hours more.

COSTS:
The first two appointments are each $390. 00 and you will spend about 50 minutes directly with the doctor. Follow up appointments are $199.00 and you will spend about 20-25 minutes with the doctor.

On your first visit the doctor will evaluate you, go over a 24 page questionnaire that we mail out to you ahead of time; he will address your sleep and pain issues. You have to sleep sufficiently in order to get better and you can’t sleep while you are in pain. He will address the mitochondrial (energy cells) at this time. He will also address IBS or other digestive problems if needed. The doctor will offer different therapies at this time and some supplements that can help you until we get your lab work back. We have IV’s for energy/nutrients; muscle and back stiffness and memory/concentration IV.

You can choose to have one of these on your first appointment in discussion with your doctor. They cost between $120-145, and we also have IV’s for viral infections if we later find you have a viral infection. After the doctor’s visit you will then get your lab work done.

Lab Testing: Female Patient
We test many of the hormones in your system - from sleep hormones such as melatonin to female hormones such as estrogen and progesterone. We also look at other hormone levels, such as human growth hormone and testosterone because women also need some testosterone. We evaluate your thyroid, adrenal and pituitary functions. We also perform viral and bacterial infection tests, where we look for 8 -10 different possible viral, bacterial, and fungal infections that you may have in your system that could be affecting your immunity. Our doctors perform very extensive blood testing. It’s not the basic testing that other doctors do where they draw 1-2 tests that look at pieces of the puzzle. It is 20-30 or more specialized blood tests to look at the big picture. We are very focused on finding out what is causing your symptoms.

Your second appointment is in 3 weeks.
It does take 3 weeks to get our labs results back because they do go to specialty labs. At this appointment the doctor will go over your labs and get you on an individualized treatment plan.

We treat with pharmacy grade neutraceuticals, a Compounding Pharmacy for plant based products and prescription medication, if we find you have viral infections. During your follow up appointments the doctor will address infections and unique etiologies such as neurotoxins and coagulation defects if needed.

SIX COMPONENTS OF CARE,

Stabilize the patient on the 1st visit. we address sleep, pain and cognition issues.
You spend 45 minutes with the physician.

Mitochondrial
Also on the 1st visit, we address mitochondrial enhancement- mitochondria are the energy producers of the cells. Mitochondrial dysfunction can be treated with nutrition via IV therapy and Nutraceuticals.

Your best course of treatment the physician recommends on the second visit, 3 weeks later, during another 45 minutes. They will review each lab test with you, relating it to your symptoms. They assist you in determining the next step in regaining balance with your hormones and continued enhancement of your immune system. The doctor will continue to modify your treatment to improve your sleep and comfort further.

The infectious Panel and additional panel of lab work that tests for 12 different viruses and bacteria that may have been thriving in your body for a long time. may be ordered, after the physician begins to treat the Immune System Dysfunction and Hormone Imbalances. These organisms can be treated with oral and IV therapy.

Coagulation defect or heavy metal toxicity
The physician may suspect additional unique etiologies such as the coagulation defect or heavy metal toxicity which can be treated with injection IV and oral therapy.

Maintenance plan.
It is our goal to get you to a maintenance plan where you come into the center every 3-6 months and when you may experience a flare up of your symptoms.

http://www.fmscommunity.org/fmslinks.htm

www.fmaware.org

www.fibroandfatigue.com