Hormonal Fatigue
There’s nothing like a little bit of adrenaline from your adrenal glands to jumpstart your day. Cortisol is another hormone secreted by the adrenals that can also be alerting. It’s an anti-inflammatory steroid to help your tissues heal under all sorts of stressful situations. Ordinarily, your morning adrenaline and cortisol levels are much higher than in the evening. Otherwise, they would keep you awake at bedtime.
With fibromyalgia, your body is not fully energized, and your brain has trouble falling asleep. This leaves you in a state of limbo. You seldom feel like you have enough get up and go in the morning, yet you are wired-but-tired in the evening. Part of the reason for this chronic out of sync feeling is due to a disruption of the normal secretion pattern for cortisol and adrenaline. But that is not all. Your immune and metabolic responses to stress are also partly to blame.
Stress Responses
Trauma, infections, starvation, overexertion, and lack of sleep are all stressful to your body. These situations rapidly trigger your immune system into action to contain tissue damage. Insulin is a hormone secreted from the pancreas to help your cells to draw in glucose from the bloodstream. It’s a process that enables you to bounce back quickly from short-term stressors.
To prevent your immune system from going overboard, you have two other processes designed to keep your body functions in check. One is your hypothalamic-pituitary-adrenal (HPA) system that releases a series of hormones, ending with the secretion of cortisol from the adrenal glands. Not only does cortisol improve morning alertness, it also counters the effects of inflammatory cytokines that increase pain and fatigue.
Pain is a stressor that activates your entire HPA system. It responds by pouring out elevated amounts of hormones, but the process seems disrupted in people with fibromyalgia. Although the corticotrophin-releasing hormone (CRH) from the hypothalamus is doubled in the spinal fluid of fibromyalgia patients, the pituitary responds with surprisingly normal levels of ACTH. Worse yet, the cortisol level needed for morning alertness is lower in people with fibromyalgia, according to a study by Roberto Riva, Ph.D., of Sweden.1
The second process responding to stress is the sympathetic branch of your nervous system. Studies in fibromyalgia patients show the noradrenaline-transmitting nerves of the sympathetic system are dominant. As you can see from the diagram, noradrenaline works to get the adrenal glands to kick in. However, adrenaline secretion from the adrenals is lower than normal in fibromyalgia patients.2
While your body’s two main stress response systems show signs of being hyper-active (elevated CRH and increased sympathetic drive), the result is an underactive adrenal response.
Adrenal Hormones
Why would people with fibromyalgia produce low cortisol levels despite normal ACTH production from the pituitary? “A desensitization of the adrenal glands to ACTH might be possible,” says Riva. By desensitization, he means that the adrenals are not as responsive as they should be. Riva adds that the reduced cortisol production is commonly referred to as adrenal fatigue.
Riva looked to see if the low morning cortisol levels were simply a result of chronic pain or if they might be related specifically to fibromyalgia. He found people with regional pains in the neck and shoulder area produced ample amounts of cortisol, more so than the healthy controls. So, pain by itself doesn’t necessarily cause the HPA system to stop working properly. Yet, prolonged elevations in cortisol are not healthy, so over time (perhaps years), the HPA system may undergo changes that contribute to your symptoms.
Even your sympathetic system, which is super-charged and disrupting your sleep, isn’t able to get your adrenal glands to secrete enough adrenaline. When fibromyalgia patients are put through a stressful challenge of exhaustive exercise, their adrenals produce dramatically less adrenaline than healthy control subjects.3
Low adrenaline is another sign your adrenal glands are exhausted and your body is ill-equipped to handle stressful challenges. But poor adrenal function is just part of your problem. Your immune response to cortisol and your body’s metabolic reaction to stress are also not working properly.
Immune Reaction
The quick response of your immune system to resolve any type of threat (such as injury or infection) is necessary for survival. During this process, your immune system pumps out all types of cytokine chemicals. One is interleukin-6 (IL-6). This cytokine is known for its ability to increase the availability of nutrients to the tissues to promote healing. IL-6 accomplishes this by activating the release of insulin to break down fat stores and increase blood glucose.
Injection of IL-6 in healthy subjects leads to activation of the HPA system, increased cortisol production, breakdown of fat stores, and greater energy expenditure.4 It is a favorable response to any short-term challenge to the body. But what happens when the threat outlives its usefulness and becomes chronic in nature, such as the pain of fibromyalgia?
Although fibromyalgia patients may not have elevated levels of cortisol, their bodies respond to this hormone with an overproduction of IL-6, according to Andrea Geiss, Ph.D., and her team in Germany.5 Geiss subjected fibromyalgia patients and healthy subjects to a brief pain stimulus to look at cortisol and IL-6 production. For each molecule of cortisol produced by the adrenals, twice the amount of IL-6 was produced by the fibromyalgia group. In addition, the IL-6 levels remained elevated in the fibromyalgia patients for more than nine hours.
“Reduced cortisol levels are associated with increased pain and fatigue ratings in fibromyalgia patients,” says Geiss. She adds, these symptoms are made worse by an enhanced production of IL-6 in response to pain. “Although the fibromyalgia patient’s adrenaline levels remained low before and after pressure pain stimulation,” Geiss says noradrenaline was higher at both test points.
Daily Activity
A variety of situations make cortisol, noradrenaline and adrenaline levels fluctuate throughout the day. Measuring these substances at one point in time doesn’t explain what happens in fibromyalgia patients day after day. A German team followed a group of fibromyalgia patients for two weeks.6 Their goal was to explore the link between cortisol levels, sympathetic system activity, physical activity, and measures of fatigue.
Lower morning cortisol levels corresponded to feeling more physically fatigued. Measures of sympathetic activity did not correlate with fatigue. So, cortisol may have a greater influence on your level of exhaustion. When looking at activity levels, days with greater physical activity predicted higher fatigue ratings the next day.
“Our findings underline the fact that patients with fibromyalgia might find it hard to begin and adhere to exercise programs,” write the study authors. They point out patients likely benefit from such programs, but physical exhaustion can impede one’s ability to exercise.
Treatment
Treating the physical fatigue of fibromyalgia is not easy. You can’t simply take cortisol, nor can you take glucocorticoids because they suppress immune functions. Various supplements may help (see Diet & Nutrition), but probably not as much as you would like.7 Here are two possibilities:
• Coenzyme Q10 (300-400 mg/day)
• Acetyl L-Carnitine (500 mg – 3/day)
Improving the balance of friendly bacteria living in the gut may be another option, but more research is needed. Fibromyalgia patients have an imbalance in the number of unfriendly bacteria that reside in their gut. These bacteria can prompt the release of immune cytokines (like IL-6) into the bloodstream. Studies investigating the role of gut bacteria in fibromyalgia and potential treatments are ongoing. For more details, see the article on Gut Influences.
Staying in Rhythm
Most of the systems in your body operate on a cyclic pattern; it’s called a circadian rhythm. Take your sleep-wake cycle as an example. The body is used to sleeping during the nighttime and being awake during the day. The pineal gland in the brain secretes melatonin at the same time each night, which sets your body’s internal clock. Cortisol and other hormones operate in a rhythmic fashion, which is based on this internal clock.
Many fibromyalgia patients say adhering to a sleep-wake schedule helps them fall asleep at night and function better during the day. There are no research studies to show this is the case. However, jet-lag is well documented. When people travel by plane to dramatically different time zones, they feel “out of sync” for a day or two. Perhaps if you keep a rigid schedule, it may increase morning cortisol and reduce daytime fatigue.
Summing Up Fatigue
There are many sources of your fatigue. Your brain’s hypothalamus and your sympathetic system are both urging your adrenals to pour out cortisol and adrenaline. Yet your adrenal glands are insensitive to these demands. Even when you exercise, your body does not produce as much adrenaline as it should (which may explain why exercise is not invigorating for you). Worse yet, your immune system over-reacts to your body’s cortisol by pumping out IL-6. This cytokine chemical has the potential to disrupt sleep and enhance pain. But this is just half the picture because there are also metabolic consequences (see the article on Altered Metabolism).
1. Riva R, et al. Psychoneuroendocrinology 37(2):299-306, 2012.
2. Adler GK, et al. Am J Med 106:534-43, 1999.
3. Giske L, et al. Eur J Pain 12:351-60, 2008.
4. Straub RH, et al. Clin Exp Rheumatol 29(suppl 68):S23-S31, 2011.
5. Geiss A, et al. Psychoneuroendocrinology 37(5):671-84, 2012.
6. Doerr JM, et al. J Psychosom Res 93:55-61, 2017.
7. Barnish M, et al. Nutrients 15:2154, 2023.