Pretend your lab test uses two standard deviations to diagnose a “shoe problem.” One hundred people go to the mall and their shoe sizes are measured. From these one hundred people, a normal shoe size range is established of 4 to 13. If you picked up a pair of shoes from a pile of shoes in this normal range that happened to be a size 12, they might—or might not—fit your foot. If your feet measure a size 12, for example, they fit just perfect.14 However, if your feet measure a size 5, you are in trouble—even though the normal range derived from the standard deviation would not indicate so. Of course, you would insist that the shoes did not fit because they didn’t feel right on your feet.
Like shoes, hormone levels are not “one size fits all.” Because of this, treatment needs to be based predominantly on symptoms, using the blood tests only as one more piece of information. The goal in CFS/FMS management is to restore optimal function while keeping labs in the normal range for safety. Using this information, let’s look at each gland, how to tell if there is a malfunction, and how to optimize function. Let’s begin with the adrenal gland—your “stress handler.”
The Adrenal Glands
The adrenal glands, which sit on top of the kidneys, are actually two different glands in one. The center of the gland makes epinephrine (also known as adrenaline—for the adrenaline “junkies” out there) and is under the control of the autonomic nervous system. Although it is known that this part of the nervous system is also on the fritz in chronic fatigue patients—contributing to such symptoms as hot and cold sweats, neurally mediated hypotension, and panic attacks—it is not understood whether or how this ties into the adrenals’ ability to make adrenaline in CFS/FMS. More likely, adrenaline deficiency is a central brain problem.
The outer part of the adrenal gland, the cortex, also makes many important hormones. These include:
Cortisol. The adrenal glands increase their production of cortisol in response to stress. Cortisol raises blood sugar and blood pressure levels, and moderates immune function, in addition to playing numerous other roles. If the cortisol level is low, the person has fatigue, low blood pressure, hypoglycemia, poor immune function, an increased tendency to allergies and environmental sensitivity, and an inability to deal with stress.
Dehydroepiandrosterone sulfate (DHEA-S). Although its mechanism of action is not clear, DHEA is the most abundant hormone produced by the adrenal cortex. If it is low, you will feel poorly. DHEA-S levels normally decline with age, but appear to drop prematurely in chronic fatigue patients. Patients often feel much better when their DHEA-S levels are brought to the mid-normal range for a twenty-nine-year-old.
Aldosterone. This hormone helps to keep salt and water balanced in the body.
Estrogen and testosterone. These hormones are produced in small but significant amounts by the adrenals as well as by the ovaries and testicles.
SYMPTOMS OF ADRENAL I NSUFFICIENCY
If your adrenal glands are underactive, what might you be experiencing? Low adrenal function can cause, among other symptoms:
Fatigue
Recurrent infections
Difficulty shaking off infections
Poor response and “crashing” during stress
Achiness
Hypoglycemia (low blood sugar with irritability when hungry)
Low blood pressure and dizziness upon first standing
Hypoglycemia deserves special mention. Many people with CFS/FMS sometimes become shaky and nervous, then dizzy, irritable, and fatigued. These people often feel better after they eat sweets, which improves their energy and mood for a short period of time. Because of this, these people often crave sugar, not realizing that it makes their blood sugar level initially shoot back up to normal, which is what makes them feel better, but then makes it continue shooting up beyond normal. The body responds to this by driving the sugar level back down below normal again. The effect, energy-wise, is like a roller coaster.
Dr. Jefferies has noted—and again, my experience confirms his finding—that most people with hypoglycemia have underactive adrenal glands. This makes sense because the adrenal glands’ responsibilities include maintaining blood sugar at an adequate level during stress. Sugar is the only fuel that the brain can use. When a person’s blood sugar level drops, he or she feels anxious, irritable, and then tired.
CAUSES OF ADRENAL I NSUFFICIENCY
About two-thirds of chronic fatigue patients appear to have underactive adrenal glands.1 One reason may be that the hypothalamus does not make enough corticotrophin-releasing hormone (CRH), which is the brain’s way of telling the adrenals that more cortisol is needed. I suspect that many people also have adrenal exhaustion. Hans Selye, one of the first doctors to research stress reactions, found that if an animal becomes severely overstressed, its adrenal glands bleed and develop signs of adrenal destruction before the animal finally dies from the stress.
If you think back to your biology classes in high school, you may remember something called the fight-or-flight response. This is a physical reaction that occurs during times of stress. During the Stone Age, when a caveman met an animal that wanted to eat him, the caveman’s adrenal glands activated multiple systems in his body that prompted him to either fight or run. This reaction helped the caveman survive. In those days, however, people probably had a couple of weeks or months to recover before facing the next major stress.
In today’s society, people often experience stress reactions every few minutes. For example, when driving to work, a woman is delayed because of heavy traffic. While sitting behind the wheel, she frets about the consequences of her walking into the office late. Every time she hits a red light or pulls up behind a car that has slowed down, her adrenal glands’ fight-or-flight reaction goes off again. When she finally arrives at work, she finds her boss waiting for her, which triggers the reaction once more. During the day, the woman may also have to deal with stresses such as angry customers or difficult coworkers. Her husband or children may phone, forcing her to deal with family stresses. If the woman is ill—suffering from CFS, for example—she has another major stress. The different problems associated with CFS, such as poor sleep, infections, and pain, put more stress on her adrenal glands.
I suspect that many people suffer adrenal exhaustion, but without the destruction that Dr. Selye saw in his experimental animals. With the kinds of stresses common in modern society, a person’s adrenal test may initially show hormonal levels that are actually higher than usual (but possibly still inadequate to deal with the degree of stress), since the adrenal glands increase hormonal output to deal with the many burdens placed on your body. Over time, this may exhaust the adrenal reserve—that is, the adrenals’ ability to increase hormone production in response to stress. At this point the hormone levels may then drop to overtly deficient levels. This is why some studies show low adrenal hormone levels and others show normal levels.2
Treating inadequate adrenal function when it is present is critical if your CFS/fibromyalgia is to resolve. A study published in the Annals of the New York Academy of Sciences discussed the evidence for hypothalamic-pituitary-adrenal (HPA) axis insufficiency in CFS and FMS. The study concluded: “Our group has established [that] the impaired activation of the hypothalamic-pituitary-adrenal axis is an essential neuroendocrine feature of this condition.”3 In addition, in endocrinologist William Jefferies’s experience (and in mine as well), people with either low hormone production or a low reserve often respond dramatically to treatment with a low dose of adrenal hormone.4, 5
Dr. Jefferies’s opinion is that everyone who has unexplained, disabling chronic fatigue should be given a low-dose trial of adrenal hormone.5 Although Dr. Jefferies may well be on the mark, I tend to use this treatment first only on patients whose symptoms, in combination with lab tests, are suggestive of inadequate adrenal function. Most people are able to improve their adrenal function using the natural remedies that I discuss on Chapter 4? 91, especially when used in combination with very low doses of natural prescription hydr
ocortisone.
PROBLEMS WITH ADRENAL TESTING
Although the adrenal glands make several kinds of hormones, the lab tests for these glands use the production of cortisol as their marker. However, unlike other lab tests, which measure against the two standard deviations we discussed, cortisol levels are only considered low in approximately one out of a hundred thousand people. Most people show morning cortisol levels of approximately 18 to 20 mcg/dl. However, a cortisol level of 10, half of what most people run, 8, or even 6.1 is considered totally normal. To technically have adrenal insufficiency, your morning cortisol needs to be less than six. Shockingly, insufficiency at a level of 5.9 is considered life-threatening. The method of evaluation goes from “normal” to deadly in just .01 mcg/dl. Unfortunately, the lab machine is only accurate within 3 to 4 mcg/dl. In fact, I’ve seen a 4 mcg/dl variation on two cortisol levels accidentally done on the same tube of blood. This rigid interpretation of test results doesn’t make sense to me, and it certainly does not make sense when it comes to taking care of patients.
Not all blood tests are created equal, however, and the HPA axis has a sluggish response to stimulation as well. It has been shown that even the test considered to be more sensitive—the ACTH (cortrosyn) stimulation test—misses the majority of CFS/FMS patients that have adrenal deficiency. When a combination of stimulation tests is used, however, close to 100 percent of these individuals need adrenal support.
FURTHER EVIDENCE SUPPORTING THE NEED TO TREAT ADRENAL PROBLEMS DESPITE NORMAL BLOOD TESTS
For those of you who have a bit more of a technical bent, let’s discuss some of the evidence that:
adrenal axis dysfunction is shown to be present in many CFS/fibromyalgia patients6–34, 48 despite normal cortisol levels
when a combination of stimulation tests is used, such as the metyrapone test, or when more sophisticated analysis is used, close to 100 percent of these individuals have documented adrenocortical dysfunction38–44 and
treatment with low-dose cortisol has been shown to be safe, appropriate, and effective in these patients. 4, 5, 11, 15, 16, 30, 35
A study in the American Journal of Psychiatry measuring urine hormone levels in 121 consecutive patients with CFS found low twenty-four-hour cortisol levels in all of the CFS patients. The authors conclude: “Urinary free cortisol was significantly lower in the subjects with chronic fatigue syndrome regardless of the presence or absence of current or past comorbid psychiatric illness…. From whatever cause, low-circulating cortisol is associated with fatigue; furthermore, raising cortisol levels can reduce fatigue in chronic fatigue syndrome. Thus, this study provides further evidence that adrenocortical dysfunction in chronic fatigue syndrome, whatever the etiology and whether primary or secondary, may be one piece of the multifactorial jigsaw underlying the production of symptoms in chronic fatigue syndrome.”37
Another study, published in the Journal of Endocrinological Investigation, performed a combination of stimulation tests on FMS patients. The researchers found that more than 95 percent of these patients had hypothalamic-pituitary-adrenal (HPA) axis dysfunction.9 They state: “The etiology and pathophysiology of this disease [are] not fully understood but the current data [suggest] that the PFS [primary fibromyalgia syndrome] is not a primary disease of muscle. In contrast, an increasing amount of evidence suggests that the central stress axis, the HPA axis, seems to play an important role in the development of PFS [fibromyalgia].”9
The inability of the adrenal glands to respond adequately to stress is important. For example, cortisol levels normally increase with pain, but it has been shown that patients with CFS/FMS either cannot appropriately increase cortisol production in response to pain or that the patients’ inability to increase cortisol causes the increased pain. A study published in the journal Arthritis and Rheumatism showed a strong relationship between cortisol levels and pain in individuals with CFS and FMS, and that low cortisol levels alone explained 38 percent of the variation in pain upon waking. The authors conclude: “The results of this study indicate that pain symptoms in women with FMS are associated with low cortisol concentrations during the early part of the day…. These data support the hypothesis that HPA axis function is associated with symptoms in FMS and accounts for the substantial percentage of pain symptom variance during the early part of the day.”45
In addition to what was found in Professor Jefferies’s decades of experience and in my studies, a placebo-controlled study was published in The Lancet in which patients with chronic fatigue syndrome were treated with low-dose hydrocortisone (5 to 10 milligrams/day), thus increasing their cortisol levels, or placebo. The study found significant improvements in those treated with low-dose hydrocortisone versus those treated with placebo, and 28 percent improved to normal levels. The authors concluded: “This study shows that low-dose hydrocortisone results in significant reduction in self-rated fatigue and disability in patients with chronic fatigue syndrome…. The degree of disability was reduced with hydro-cortisone treatment, but not with placebo.”16 This also supports the effectiveness and appropriateness of raising cortisol levels through supplementation.
Another study, published in JAMA, also found significant improvement in fatigue scores with hydrocortisone replacement, but these researchers used excessive dosing of 25 to 35 milligrams of cortisol, which resulted in mild adrenal suppression and marked worsening of sleep.51 Therefore, I limit patients to a maximum of 20 milligrams/day, as this dose has been shown to be quite safe. 11, 17, 46, 47
TREATING ADRENAL INSUFFICIENCY
People with hypoglycemia, which in CFS/FMS is most often caused by inadequate adrenal function, can treat low-blood-sugar symptoms by cutting sugar and caffeine out of their diets; having frequent, small meals; and increasing their intake of protein while decreasing carbohydrates. It’s best to avoid white flour and sugar and to substitute complex carbohydrates such as whole grains and vegetables. Fruit—not fruit juices, which contain concentrated sugar—can be eaten in moderation, about one to two pieces a day, depending on the type of fruit. If you get irritable, eat something with protein. For quick relief, put a quarter to half a teaspoon of sugar (or even just one or two Tic Tacs) under your tongue at the same time. This is enough to quickly raise your blood sugar level but not enough to put you on a sugar “roller-coaster ride.”
More directly, treating the underactive adrenal problem with low doses of adrenal hormone usually quickly banishes the symptoms of low blood sugar. I like to begin with natural hydrocortisone such as Cortef (by prescription at most pharmacies) or, better yet, sustained-release hydrocortisone from a compounding pharmacy. This immediately gives your body the support that your adrenal glands are unable to give, and may help you feel much better quickly. The added cortisol also takes some of the strain off your adrenals so that they can heal.
If you and your doctor decide that treating the problem with natural hydrocortisone is not in your best interest, there are also many natural things you can take that can both help to support your adrenal glands and naturally raise your body’s cortisol level.
NATURAL ADRENAL SUPPORT
Below are several things that can help your adrenal glands heal:
Adrenal glandulars supply the raw materials that your adrenal glands need to heal. It is critical, however, that you get them from reputable companies (I recommend Enzymatic Therapy) so that the purity and potency are guaranteed and so that you can be sure they come from cows that are not at risk of transmitting infections.
Vitamin C is crucial for adrenal function. Your body’s highest levels of vitamin C are found in the adrenal glands and brain tissues, and the urinary excretion of vitamin C is increased during stress. Optimizing vitamin C intake by taking 500 to 1,000 milligrams a day also helps immune function.
Pantothenic acid, a B vitamin, also supports adrenal function, and pantothenic acid deficiency causes shrinking of your adrenal glands. Optimal levels are approximately 100 to 150 milligrams daily, although some physicians use even higher
levels for adrenal support.
Licorice slows the breakdown of adrenal hormones in your body, helping to maintain optimal levels. There is no licorice in licorice candies in the United States because of this, as too much licorice can raise cortisol levels too high. Another beneficial effect of the licorice is that it helps in the treatment of indigestion, and it is even as effective as the prescription heartburn medication Tagamet. Do not take licorice if you have high blood pressure, as too much licorice can cause excess adrenal function and worsen high blood pressure. You can safely take 200 to 400 milligrams a day of a licorice extract standardized to contain 5 percent glycyrrhizic acid.
Chromium also helps decrease the symptoms of low blood sugar. Take 200 micrograms a day.49
If you’d rather not take these natural remedies separately, or just to simplify the supplementation, you can take Adrenal Stress End, which I helped the Enzymatic Therapy Company develop. Take one to two capsules in the morning. If symptoms recur in the afternoon, add another capsule at lunch. Adrenal Stress End, combined with the Energy Revitalization System vitamin powder, supplies everything noted above, as well as many other nutrients that will help support adrenal function. You can also put together your own supplement program using these and any of the other supplementation recommendations in this book.
Toxicity of Cortisone
Adrenal hormones are essential for life. Without them, a person dies. But, as with any hormone, too much can be dangerous, and any cortisol supplementation should be closely monitored by your CFS/FMS specialist. In the early studies using adrenal hormones, the researchers had no idea what dose was normal and what was toxic. When they gave injections of the hormone to arthritis patients, the patients’ arthritis went away, and they felt better. However, they gave patients many times more than the normal amount, and many patients became toxic and died. Because of this, the researchers became frightened and avoided using adrenal hormones whenever possible. Medical students were taught to avoid adrenal hormones unless no other treatment choices existed.
From Fatigued to Fantastic! Page 11