Growth hormone in fibromyalgia.
Growth hormone is one of the numerous chemical mediators of the hypothalamic-pituitary-adrenal axis (HPAA,) a very complex system that governs many functions, including the immune response to stress.
Various abnormalities of the HPAA have been implicated in fibromyalgia, including abnormalities in the production and release of growth hormone. Some research has suggested that the level of growth hormone is consistently low in about one-third of those with fibromyalgia.
Other research (including the publication summarized below) suggests that average growth hormone levels might often be normal, but that most of those with fibromyalgia have diminished release of growth hormone in response to exercise. In fact 153 out of 165 fibromyalgia patients (93%) were found to have deficient growth hormone release in response to strenuous exercise.
So it seems fibromyalgia is often associated with a significant defect in the regulation of growth hormone. Growth hormone may be chronically low in some and low in response to exercise in nearly all.
What symptoms could result from growth hormone defect?
It’s reasonable to suspect that such a growth hormone defect might be responsible for many symptoms of fibromyalgia. Growth hormone deficiency has been linked to weight gain, diminished energy, depressed mood, sleep disturbance, impaired thinking, poor memory, reduced exercise capacity, stiffness, muscle weakness, and cold intolerance – all of which are common in fibromyalgia.
How might a growth hormone defect result in symptoms?
If a growth hormone defect is at least partly to blame for the symptoms of fibromyalgia, the question is – why? How might diminished growth hormone release in response to exercise worsen the symptoms of fibromyalgia? More generally, why is growth hormone deficiency associated with all of the above listed symptoms?
The answer – it appears – is that growth hormone release in response to stress (e.g. exercise) limits the production of inflammatory cytokines. So a defective growth hormone response results in the excess production of pro-inflammatory cytokines.
Growth hormone deficiency may be only one of several means (albeit an important one) by which excess pro-inflammatory cytokine production leads to the onset or worsening of fibromyalgia symptoms.
Why does low growth hormone result in more pain for those with fibromyalgia?
Science: Low growth hormone release after exercise results in higher pro-inflammatory cytokine (PIC) levels.
Conclusion: Deficient growth hormone results in greater pain because it leads to an increase in PICs.
Evidence connecting low growth hormone to elevated cytokines.
The publication summarized below investigated the connections between exercise, growth hormone, cytokines and fibromyalgia symptoms. The researchers, having noted the connection between the HPAA system and the immune system, and that the symptoms of growth hormone deficiency seem to mimic those of “sickness syndrome” (which is known to result from excess production of pro-inflammatory cytokines,) hypothesized that serum cytokine levels and fibromyalgia symptom severity would be higher in patients who had deficient growth hormone release after exercise.
Their findings generally confirmed that hypothesis. Defective growth hormone response to exercise was found to be associated with elevated resting levels of some inflammatory cytokines and levels of pain, as follows.
Symptoms were more severe in those with defective growth hormone response.
Only one-third of those with a defective growth hormone response were able to work outside the home, vs over 85% of those with a normal growth hormone response to exercise. While work status is only an indirect measure, the inability to work outside the home suggests greater symptom severity.
Those with growth hormone defect had more pain and more tender points at baseline (before exercising.)
Higher cytokine levels.
At baseline (pre-exercise) those with a defective growth hormone response to exercise were found to have substantially higher IL-1, IL-6 and IL-8. No difference in IL-10 (an anti-inflammatory cytokine) was noted, and no difference was observed in TNF-alpha (another pro-inflammatory cytokine that has previously been linked in some studies to fibromyalgia.)
In addition, physical endurance during exercise was found to correlate with resting levels of IL-1, IL-6 and IL-8 (actually a ‘negative’ correlation, since higher cytokine levels predicted lower exercise endurance.)
Finally, IL-8 levels varied directly in response to the extent of growth hormone defect. IL-8 has previously been shown to be elevated in fibromyalgia and several studies have shown that IL-8 levels are predictive of pain in fibromyalgia. This study seems to confirm that IL-8 may be of special significance in relation to fibromyalgia.
Is a growth hormone defect the cause of fibromyalgia?
Probably not, because a growth hormone defect cannot explain many of the symptoms of fibromyalgia. Also, while growth hormone defect may be very common among those with fibromyalgia, some patients show no evidence of growth hormone defect.
Of interest, the summarized study found that those with defective growth hormone release had an average duration of illness more than 6 years longer than those with normal growth hormone function. This may explain, in part, the sometimes progressive nature of fibromyalgia. It has been observed that, even where symptom severity does not worsen over time, patients with fibromyalgia of longstanding duration may respond less favorably to medications. Perhaps one reason fibromyalgia patients become more difficult to treat over time is because the defect in growth hormone response becomes more pronounced?
It is more likely, as suggested above, that the symptoms of growth hormone deficiency occur as a result of the effect on pro-inflammatory cytokines. And since these same inflammatory cytokines also feed back on the HPAA, the relationship between growth hormone and inflammatory cytokines in fibromyalgia might define a vicious cycle – each worsening the other.
If so, then an effective treatment might be one that interrupts that vicious cycle, either by reducing the impact (or production) of pro-inflammatory cytokines, or by supplementing the growth hormone deficiency.
Could growth hormone be a good treatment for fibromyalgia?
Human growth hormone administration (it must be injected) to healthy adults has been shown to increase muscle mass, reduce fat and increase bone density. Treatment is expensive, requires a prescription, and has only been approved in the US as an adjunct therapy for those with HIV/AIDS related muscle wasting.
Nonetheless, several researchers have investigated the possibility of using growth hormone as a treatment for fibromyalgia.
While further investigation is required, initial evidence suggests that growth hormone may be an effective treatment for fibromyalgia, at least for those patients with severe symptoms who show evidence of growth hormone defect.
Preliminary Evidence of Increased Pain and Elevated Cytokines in Fibromyalgia Patients with Defective Growth Hormone Response to Exercise.
Summary of the Abstract
Fibromyalgia symptoms seem to be affected by dysfunction of the hypothalamic-pituitary-hormonal axes and the immune response system.
It has been observed that fibromyalgia symptoms such as widespread pain, insomnia, fatigue, stiffness and even depression are related to abnormal levels of growth hormone. These symptoms are similar to those described as “sickness behavior” – which is believed to result from excess production of pro-inflammatory cytokines.
Cytokine levels and fibromyalgia symptom severity were investigated in two groups, those with a normal growth hormone response to exercise, and those with a deficient growth hormone response to exercise.
Levels of IL-1, IL-6, IL-8, IL-10, and TNF-alpha were measured in 24 participants, half with a normal growth hormone response and half with an abnormal response to exhaustive exercise. The fibromyalgia impact questionnaire was used to determine fibromyalgia severity.
Growth hormone dysfunction was found to be associated with increased pain, a higher tender point count, and a greater elevation in pro-inflammatory cytokine levels, including IL-1, IL-6, and IL-8.
The results of this investigation suggested that a defective growth hormone response to exercise may be associated with increased levels of pro-inflammatory cytokines and pain severity in fibromyalgia patients.