In Search of The Missing Link: Hypothalamic Dysfunction and Chronic Fatigue Syndrome/Fibromyalgia Syndrome
By Jacob Teitelbaum, MD •
May 24, 2000
Hypothalamic dysfunction can cause a cascade of problems that account for many, if not most of the abnormal findings seen in CFIDS/FMS.
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 self-perpetuating 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 Link-----Hypothalamic 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
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 hyperphosphatemia-Dr. 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.
Bennett 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
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 mid-to-high-normal (with testosterone injections) often dramatically improved symptoms after two months. (Caution: this, and the testosterone deficiency itself, may lower sperm counts).
7. Elevated Prolactin-The hypo-thalamus 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. Jorge 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 – this can be bacterial or fungal.
2. Chronic prostatitis – Common in men with CFIDS (often subtle).
3. Bowel infections – A major player in CFIDS/FMS-parasitic, 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 dysfunction-e.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 – 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
5. Viral infections – 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. NMH-Neurally Mediated Hypotension (diagnosed by tilt-table testing).
2. Night and day sweats – 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 temperature-sensitive). Dr. Denis Wilson 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 self-sustaining 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 placebo-controlled 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!
From Fatigued to Fantastic! Newsletter .Vol. 1, Issue 1, 3rd Printing Feb. 1997 (Rev. 12/99)
||Discuss This Article
|Posted by: marian keaney
Nov 16, 2010
I have found this research useful and very informative, and hope to discuss it in detail with my consultant. causedbeenproblematic for years now. disordered sleep and low body temperature have caused enormous problems in my personal and professional life.I am grateful for your resesrch which i hope to discuss in more detail larer. Best wishes. marian.