Teitelbaum's Newsletter: Central Role of Hypothalamus

[Guest guest]

In Search of The Missing Link

Email Bulletin by Teitelbaum, MD

Summary:

Hypothalamic dysfunction can cause a cascade of problems that account

for

many, if not most of the abnormal findings seen in CFIDS/FMS.

Article:

There is an old story of the blind men who stumbled upon an elephant.

One

felt its trunk and believed it was a snake. Another felt its leg and

thought it was a tree trunk. Yet another, missing the elephant

entirely,

was certain nothing was there and told his friends they must be

crazy. This

seems to be the current state of affairs in our understanding of

CFIDS and

FMS (fibromyalgia).

We are lucky to be at a point where we have as many pieces of the

puzzle as

we do. Yet, the very abundance of seemingly unrelated pieces can be

confusing. Let's step back from the discordant details for a moment

and see

if they can help us see a bigger picture. (Although I like to think

that I

have a " bigger picture " of CFIDS/FMS, my guess is that I am the blind

man

feeling the left hind leg and thigh of the elephant!)

At the risk of getting too detailed, let's examine what information

we have

found, beginning with two assumptions that I believe to be true:

1. CFIDS/FMS are part of the same process in most cases.

2. CFIDS/FMS represent a common endpoint of a large number of possible

underlying triggers (i.e., many things can trigger the disease. Once

triggered, the process is similar and selfperpetuating regardless of

the

triggers and whether the triggers are gone). For example, an auto

accident

or viral syndrome can both trigger CFIDS/FMS in different people.

What Do We Know?

We know that several processes are common in CFIDS/FMS:

1. Disordered sleep.

2. Multiple hormonal dysfunctions.

3. Immune dysfunction.

4. Autonomic dysfunction with NMH (Neurally Mediated Hypotension).

5. Low body temperatures.

Things simplify a bit when one realizes that all of the above

processes are

controlled by the hypothalamus! When one examines the effects of and

symptoms caused by each of the above, the information we have learned

about

CFIDS/FMS begins to make more sense.

In Search Of the Missing LinkHypothalamic Dysfunction Effects of

Disordered

Sleep

A recent NIH conference on FMS focused on the role of disordered

sleep and

hypothalamic hormonal dysfunctions. By looking at sleep deprivation

research, several things stand out. Sleep deprivation can cause:

1. Immune dysfunction with multiple opportunistic infections.

2. Decreased metabolic activity, specifically in the hypothalamus,

limbic

system, and thalamus. This (as well as low estrogen) could account

for the

decreases in brain blood flow seen in the fascinating research done

by Jay

Goldstein, M.D.

3. Suppression of thyroid hormones (both T4 and T3).

4. Autonomic and temperature regulation dysfunction. When given the

choice,

sleep deprived test animals will often choose a higher room

temperature.

(Isn't it wonderful what science can test for?). Higher nighttime room

temperatures may further worsen sleep quality.

5. Marked hyperphosphatemiaDr. St. Amand postulates that a defect of

phosphate metabolism is important in FMS and has found that

guafenesin (and

other uric acid excreting agents) can improve symptoms. It is

possible the

sleep disorder triggers the phosphate defect. (Although I have been

told

that a recent controlled study by Dr.

did not find guafenesin to be beneficial, Dr. St. Amand feels

that

the study had critical design flaws. Personally, I have heard

beneficial

reports from enough patients who failed other " placebos/treatments " to

encourage me to study guafenesin further despite this one negative

study).

6. AIlodynia (when normally comfortable touch causes discomfort). It

is

postulated that in FMS this is caused by elevated substance p

secondary to

low brain serotonin levels. Low estrogen can also cause low serotonin

and

low acetylcholine. If sleep deprivation causes allodynia, might it

also

cause increased substance p and decreased serotonin? Evidence

suggests that

low acetylcholine function can contribute to CFIDS/FMS and a recent

study

also found that treating this with an acetylcholinesterase inhibitor

resulted in significant improvement in CFIDS symptoms (Galanthamine

Hydrobromide 10 mg three times a day for two months).

Effects Of Hypothalamic Hormonal Dysfunction

The hypothalamus is the master gland controlling most other glands in

the

body. Autoimmune injury can also damage the glands. Effects of the

hormonal

dysfunctions include:

1. Low thyroid : This can cause decreased metabolism with weight gain

and

low

body temperature (which can cause poor enzyme and metabolic function).

2. Low vasopressin (antidiuretic hormone) This causes decreased

ability to

hold onto fluid resulting in frequent urination and increased thirst.

Dehydration then occurs despite increased water intake. As

vasopressin is

also a stimulus for ACTH and adrenal function, low vasopressin could

also

result in decreased adrenal function. Both

dehydration and low cortisol can both increase the susceptibility to

NMH

(Neurally Mediated Hypotension).

3. Low growth hormone This causes low DHEA levels.

4. Decreased Cortisol this causes immune dysfunction and hypotension

and

the tendency to " crash " in stressful situations.

5. Low ovarian and testicular function Low estrogen can contribute to

the

decreased blood flow to specific areas in the brain that is seen in

CFIDS/FMS.

6. Low testosterone (in both males and females) can cause immune

dysfunction, although total testosterone levels are often normal, I

have

found that the active (free or unbound serum) testosterone levels are

usually low in the majority of men or women with CFIDS/FMS. In men,

bringing free testosterone levels back to midtohighnormal (with

testosterone injections) often dramatically improved symptoms after

two

months. (Caution: this, and the testosterone deficiency itself, may

lower

sperm counts).

7. Elevated ProlactinThe hypothalamus normally suppresses prolactin

production. It is not clear what role (if any) elevated prolactin

plays in

CFIDS. Excessive melatonin intake can also cause elevated prolactin

levels.

Lowering an elevated prolactin can improve symptoms.

8. Oxytocin is a hypothalamic neurotransmitter. Fletches, M.D.,

notes

that many CflDS/FMS patients improve with oxytocin therapy. At this

point,

though, it is not clear what, besides low estrogen, causes the

decreased

levels of multiple neurotransmitters.

Effects Of Immune Dysfunction

Although the causes of the immune dysfunction are not clear,

hypothalamic

dysfunction may play a role (as noted above).

The implications are that CFIDS ) patients also seem to have

opportunistic

infections (i.e., with organisms that usually do not cause illness in

most

people) and recurrent other infections. These infections can cause

CFIDS/FMS to persist. They include:

1. Chronic sinusitis 96 this can be bacterial or fungal.

2. Chronic prostatitis 96 Common in men with CFIDS (often subtle).

3. Bowel infections 96 A major player in CFIDS/FMSparasitic, fungal,

and

bacterial overgrowths (including Clostridia difficile) are common and

often

account for the " irritable bowel syndrome. " They can cause CFIDS/FMS

and

can cause the nutritional deficiencies (malabsorption) and the " leaky

gut "

with secondary food sensitivities and liver overload (the liver may

have to

detoxify many large molecules that should not have been absorbed

intact or

would normally have been broken down before absorption). Liver

overload,

combined with immune overactivation (part of the immune

dysfunctione.g.,

elevated interleukin levels) and decreased adrenal function, can

contribute

to the food, chemical/ environmental, and medication sensitivity .

This can

occur when the liver is overwhelmed and more' slowly metabolizes or

detoxifies these substances.

4. Rickettsia, mycoplasma, and other unusual organisms 96 Several

organisms

which are difficult to test for may both trigger and perpetuate

CFIDS/FMS

e.g., post polio syndrome, and post Lyme fatigue) .Doxycycline ( a

tetracycline antibiotic) given long term four to six weeks at a time

may

eradicate these, but may cause yeast over growth.

5. Viral infections 96 Some viruses can cause hypothalamic

suppression.

Although in most people this resolves when the virus goes away, in

CFIDS/FMS it may not. Because many patients get well without antiviral

treatments, I suspect the virus is long gone by several months after

the

illness begins, or is eliminated when the immune

suppression is treated and resolves.

Effects of Autonomic Dysfunction

The autonomic (sympathetic/ parasympathetic) nervous system is also

controlled by the hypothalamus Its malfunction can cause:

1. NMHNeurally Mediated Hypotension (diagnosed by tilttable testing).

2. Night and day sweats 96 The night sweats can disrupt sleep.

3. Nasal congestion with secondary fatigue and increased risk of

chronic

sinusitis.

Altered Temperature Regulation

Low body temperatures cause the body's energy and enzyme systems to

work

inefficiently ( enzyme function is very temperaturesensitive). Dr.

Denis

has found that if the body temperature is raised back to 98.6

(using

sustained release T3 thyroid hormorie not Synthroid) people often

feel much

better. He feels that stress or starvation (e.g., dieting) can

trigger low

T3 (a form of low thyroid with normal blood tests) and a

selfsustaining low

body temperature. Altered temperature regulation may also further

contribute to impaired sleep.

The Good News

As one can see, hypothalamic dysfunction can cause a cascade of

problems

that can account for many, if not most, of the abnormal findings seen

in

CFIDS/FMS, These processes can then perpetuate hypothalamic

suppression.

They also explain the multitude of symptoms seen in these illnesses.

Because of space limitation, I have not discussed symptoms. My

book " From

Fatigued to Fantastic " goes into the symptoms and effective treatment

of

CFIDS/FMS at length.

The good news is that everything I have discussed above is treatable.

The

trick is to sort out which problems are most active in each

individual and

to treat them all. Our recently completed placebocontrolled study,

Effective Treatment of Fibromyalgia and Chronic Fatigue Syndrome,

that we

recently submitted for publication demonstrates that CFIDS and

Fibromyalgia

can be effectively treated in most people by treating all the

underlying

processes simultaneously.

We certainly have much more to learn (I really do not think I have

defined

" the whole elephant " yet!). As we continue to integrate what we

learn, we

may begin to see the whole picture. Any thoughts?

Best wishes on your getting well!