Duncan Crow
Wholistic Consultant


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HGH Deficiency in Fibromyalgia (FM)



Robert Bennett's web site is www.myalgia.com

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Human Growth Hormone is the Treatment that Does the Most!

Bennett RM, Clark SC, Walczyk J. A randomized, double-blind, placebo-controlled study of growth hormone in the treatment of fibromyalgia. Am J Med 1998 Mar;104(3):227-31 Department of Medicine, Oregon Health Sciences University, Portland 97201, USA.

PURPOSE: The cause of fibromyalgia (FM) is not known. Low levels of insulin-like growth factor 1 (IGF-1), a surrogate marker for low growth hormone (GH) secretion, occur in about one third of patients who have many clinical features of growth hormone deficiency, such as diminished energy, dysphoria, impaired cognition, poor general health, reduced exercise capacity, muscle weakness, and cold intolerance. To determine whether suboptimal growth hormone production could be relevant to the symptomatology of fibromyalgia, we assessed the clinical effects of treatment with growth hormone.

CONCLUSIONS: Women with fibromyalgia and low IGF-1 levels experienced an improvement in their overall symptomatology and number of tender points after 9 months of daily growth hormone therapy. This suggests that a secondary growth hormone deficiency may be responsible for some of the symptoms of fibromyalgia.

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Fibromyalgia patients have dysfunctional Growth Hormone Release!

Bennett RM, Cook DM, Clark SR, Burckhardt CS, Campbell SM. Department of Medicine, Oregon Health Sciences University, Portland 97201, USA. Hypothalamic-pituitary-insulin-like growth factor-I axis dysfunction in patients with fibromyalgia. J Rheumatolo 1997 Jul; 24(7): 1384-9

OBJECTIVE: To investigate the serum levels of insulin-like growth factor-I (IGF-I) in patients with fibromyalgia (FM) compared to healthy controls and patients with other rheumatic diseases, and to explore possible etiologic mechanisms of low IGF-I levels inpatients with FM.

CONCLUSION: Many, but not all, patients with FM have low levels of IGF-I that cannot be explained by clinical associations. These results suggest that low IGF-I levels in patients with FM are a secondary phenomenon due to hypothalamic-pituitary-GH axis dysfunction.

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Disordered growth hormone secretion in fibromyalgia: a review of recent findings and a hypothesized etiology.

AUTHORS: Bennett RM

AUTHOR AFFILIATION: Dept. Medicine (L329A), Oregon Health Sciences University, Portland 97201, USA.

SOURCE: Z Rheumatol 1998;57 Suppl 2:72-6

CITATION IDS: PMID: 10025088 UI: 99149227

Growth hormone (GH) deficiency occurs in about 30% of fibromyalgia patients. Treatment of GH deficient fibromyalgia patients with recombinant growth hormone improves several clinical features, including the tender point count. Defective GH secretion in these patients appears to be due to increased somatostatin tone in the hypothalamus. An hypothesis is presented which relates dysfunctional GH secretion to the effects of intermittent hypercortisolemia on upregulating the density of beta-adrenergic receptors in the hypothalamus. The resulting augmentation of beta-adrenergic tone stimulates the release of somatostatin, thus, impairing GH secretion.

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The Growth Hormone (GH)-Releasing Hormone - GH - Insulin-like Growth Factor-1 Axis in Patients with Fibromyalgia Syndrome*

A. Leal-Cerro, J. Povedano, R. Astorga, M. Gonzalez, H. Silva, F. Garcia-Pesquera, F. F. Casanueva, and C. Dieguez

Department of Endocrinology (A.L.-C., R.A., H.S., F.G.-P.) and Reumatology (J.P., M.G.), Hospital Universitario "Virgen del Rocio", 15700 Sevilla; and Departments of Medicine (F.F.C.) and Physiology (C.D.), Complejo Hospitalario Universitario and Faculty of Medicine, University of Santiago, 15700 Santiago de Compostela Spain

Received September 30, 1998. Revised May 24, 1999. Accepted June 1, 1999.

Fibromyalgia (FM) is a painful syndrome of nonarticular origin, characterized by fatigue and widespread musculoskeletal pain, tiredness, and sleep disturbances, without any other objective findings on examination. Interestingly, some of the clinical features of FM resemble the ones described in the adult GH-deficiency syndrome. Furthermore, insulin-like growth factor (IGF)-1 levels are frequently reduced in patients with FM.

CONCLUSION: our data show that patients with FM exhibited a marked decrease in spontaneous GH secretion, but normal pituitary responsiveness to exogenously administered GHRH, thus suggesting the existence of an alteration at the hypothalamic level in the neuroendocrine control of GH in these patients. Furthermore, our finding of increased IGF-1 and IGFBP-3 levels after GH treatment, over 4 days, opens up the possibility of testing the therapeutic potential of hGH in patients with FM. (The Journal of Clinical Endocrinology & Metabolism 84: 3378-3381, 1999)

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Secretion of growth hormone in patients with chronic fatigue syndrome.

Growth Horm IGF Res 1998 Apr;8 Suppl B:127-9

Berwaerts J, Moorkens G, Abs R
Department of Endocrinology, Middelheim Hospital, Antwerp, Belgium.

PMID: 10990147, UI: 20443554

Decreased serum levels of insulin-like growth factor I (IGF-I) are common in patients with fibromyalgia, which is frequently associated with chronic fatigue syndrome (CFS).

Twenty patients with CFS (7 men, 13 women; age range, 30-60 years) and age- and sex-matched controls were tested for peak GH responses to insulin-induced hypoglycaemia and arginine administration. Nocturnal secretion of GH and serum levels of IGF-I were also measured. Serum IGF-I SDS (+/- SD) was significantly lower in patients with CFS than in controls (SDS, -0.39 +/- 1.07 vs 0.33 +/- 0.84; P = 0.02).

Patients with CFS also tended to have reduced nocturnal secretion of GH (area under the curve, 32.4 +/- 18.3 vs 62.7 +/- 43.7 microg/l/15 minutes; P= 0.06), but peak GH responses to insulin-induced hypoglycaemia and arginine administration did not differ significantly between the two groups. It is not clear whether the tendency for impaired spontaneous nocturnal GH secretion in patients with CFS is a cause or an effect of the condition.

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Growth Hormone Eases Fibromyalgia PainImproves Stiffness, Reduces Number of Tender Points

June 27, 2002 -- For anyone with fibromyalgia, effective treatment is elusive and the quest is frustrating. Research has shown that the illness may be due to low levels of growth hormone. And now, new research shows that growth hormone injections can relieve the pain and stiffness that comes with fibromyalgia.

Fibromyalgia is a chronic disorder that causes pain all over the body with muscle and joint stiffness. If affects mostly women and is diagnosed by identifying specific tender points on the body. These areas are particularly tender to touch - even to light touch. Although the definite cause of fibromyalgia is unknown, one theory is that it may be caused by below-normal levels of growth hormone. Growth hormone deficiency has been associated with low energy, muscle weakness, sensitivity to cold, weakened ability to remember and think, and other problems - many of which are seen in people with fibromyalgia.

This illness definitely has a hormone component, Alfonso Leal-Cerro, MD, tells WebMD. Leal-Cerro presented new findings at the annual meeting of The Endocrine Society. He is a professor of endocrinology at the Hospital Universitario Virgen del Rocio in Seville, Spain. "We had previously found that a high number of patients with fibromyalgia have low levels of insulin-like growth factor 1," he says. Growth hormone increases the level of insulin-like growth factor 1 (IGF-1) in the body. So Leal-Cerro and colleagues set out to see if giving growth hormone could help people suffering from fibromyalgia. Giving growth hormone should increase the levels of IGF-1.

Pharmacia donated the growth hormone that was used in the study, and one of the co-authors, Angels Ulied, is a staff researcher at Pharmacia in Barcelona, Spain. In this small study, he and colleagues followed 20 women with both fibromyalgia and low levels of IGF-1. Each woman received injections of either growth hormone or placebo. For six months, neither the women nor the researchers knew whether the women were receiving growth hormone or the placebo. Then, for the next 12 months, all the women were knowingly treated with growth hormone.

After six months of treatment, the women that received the growth hormone injections had significantly less morning stiffness and pain and fewer tender points than at the beginning of treatment. The women continued to see these benefits at 12 months. The placebo group had significantly less morning stiffness and fewer tender points but had no significant reduction in pain. Leal-Cerro said that he and colleagues are next planning to study treating fibromyalgia with an oral drug that increases production of growth hormone.

"Fibromyalgia is a frustrating disease for people who live with it, and they are desperate for effective treatment," Clifford J. Rosen, MD, tells WebMD. He was not involved in the study. "The people in the study were probably quite disabled with their disease, because their IGF-1 levels were quite low, and there is a body of literature that shows IGF-1 levels are lower in fibromyalgia than in the general population. This deficiency may contribute to the stiffness in fibromyalgia," says Rosen, staff endocrinologist at the University of Maine and St. Joseph's Hospital in Bangor, Maine. Rosen is the president-elect of the American Society of Bone and Mineral Research, and his research has focused on growth hormone, IGF-1, and the relation of these substances to bone growth. "However, I think it's too early to know if this is a feasible approach."

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(c) 2002 WebMD Inc.Hakkinen K, Pakarinen A, Hannonen P, et al. Effects of strength training on muscle strength, cross-sectional area, maximal electromyographic activity, and serum hormones in premenopausal women with fibromyalgia. J Rheumatol. 2002 Jun;29(6):1287-1295.

OBJECTIVE: To examine the effects of strength training on basal concentrations and acute responses of serum hormones, and their possible interrelationships with training induced muscle hypertrophy and strength gains of the knee extensor muscles in women with fibromyalgia(FM) and healthy controls.

CONCLUSION: Both the magnitude and timecourse of adaptations of the neuromuscular system to resistance training in women with FM were completely comparable to those taking place in healthy women. Basal levels of the anabolic hormones seem to be similar in women with FM compared to age matched healthy women. Observations recorded during the acute loading conditions might be considered an indication of the training induced adaptation of the endocrine system, showing that the acute GH response may become systematic after strength training in both women with FM and controls.

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Characterization of pituitary function with emphasis on GH secretion in the chronic fatigue syndrome.

Clin Endocrinol (Oxf). 2000 Jul;53(1):99-106.

PMID: 10931086 [PubMed - indexed for MEDLINE]

CONCLUSIONS: We observed a significant impairment of GH response during insulin-induced hypoglycaemia and a low nocturnal GH secretion in CFS patients. These changes did, however, not lead to different concentrations in serum IGF-I. The clinical expression of this inadequate GH secretion can thus be questioned, although the alteration in body composition may be related to this relative GH deficiency. Significantly increased prolactin and TSH levels were found when compared to controls. These findings give support to the hypothesis of a decreased dopaminergic tone in CFS. Further investigations are required in order to identify specific adaptations within the neurotransmitter system in CFS and to determine the clinical importance of the impaired GH homeostasis.

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ENDO: Fibromyalgia Responds to Growth Hormone Treatment

By Paula Moyer

Special to DG News

SAN FRANCISCO, CA -- June 20, 2002 -- Patients with fibromyalgia get relief from many of their symptoms when they are treated with growth hormone therapy.

"This illness definitely has an endocrine component," said Alfonso Leal-Cerro, MD, who presented these findings at the 84th annual meeting of the Endocrine Society.

"We had previously found that a high number of patients with fibromyalgia have low levels of insulin-like growth factor-1 [IGF-1]," explained Dr. Leal-Cerro, lead investigator on the study and professor of endocrinology at the Hospital Universitario Virgen del Rocio in Seville, Spain. "Therefore, we wanted to see if growth hormone administration would be effective at addressing their symptoms."

His team randomised 20 women with both fibromyalgia and IGF-1 lower than 125 ng/mL to injections of growth hormone (GH) or to placebo in a double-blind fashion. After six months, they entered an open label phase for 12 months. The treatment group received an initial GH dose of 0.13 mg/day (0.4 IU); the dose could be titrated up to .66 mg (2 IU) daily. The women assessed their morning stiffness and pain, andfibromyalgic tender points at baseline and at 3, 6, 9, and 12 months of treatment. Weight and waist-to-hip ratios were also obtained, and patients responded to a general quality-of-life questionnaire.

The treatment group had sustained elevations of IGF-1 levels throughout the study and reported significantly less morning stiffness and pain at six months than at baseline (p<0.02 and p<0.04, respectively). The treatment group also had fewer fibromyalgic tender points than controls (p<0.04). These results continued at 12 months (p<0.05 for stiffness, p<0.01 for pain, p<0.01 for tender points).

The placebo group had significantly less morning stiffness and fewer fibromyalgic tender points at six and 12 months than at baseline (p<0.05), but experienced no significant reduction in pain. The groups had no differences in weight, waist-to-hip ratios, or scores on the quality-of-life questionnaire.

The results suggest that a secondary growth hormone deficiency may be responsible for some symptoms of fibromyalgia, the investigators concluded. Dr. Leal-Cerro said that he and colleagues are next planning to study the efficacy of treating fibromyalgia with a GH secretagogue, which would be administered orally.

Pharmacia donated the growth hormone that was used in the study, and one of the co-authors, Angels Ulied, is a staff researcher at Pharmacia in Barcelona, Spain.

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Laurie Barclay, M.D.

NEW YORK

Source: Arthritis Rheum. 2002;46(5):1344-1350. Reviewed by Gary D. Vogin, MD

(MedscapeWire) May 06 — Growth hormone (GH) response to maximal exercise is impaired in patients with fibromyalgia, according to research reported in the May issue of Arthritis & Rheumatism. Normalization with pyridostigmine pretreatment suggests a defect in somatostatin tone, which may be related to the exhaustive stage of chronic stress.

"The results of this study indicate that GH deficiency is probably more common in fibromyalgia patients than was originally reported," senior author Robert Bennett, MD, MRCP, from Oregon Health Sciences University in Portland, says in a news release.

Fibromyalgia is thought to be a stress-related syndrome, linked to malfunctions of the hypothalamic, pituitary, and adrenal hormones, including GH.

In this study, 20 women with fibromyalgia and a control group of 10 healthy women exercised to volitional exhaustion, reaching maximum respiratory and pulse rate on a treadmill. One month later, testing was repeated 1 hour after pretreatment with pyridostigmine, which inhibits somatostatin secretion.

Without pyridostigmine pretreatment, 11 of the 20 patients with fibromyalgia had no exercise-induced increase in GH levels. After the administration of pyridostigmine, 19 of the 20 patients had a normal GH response to exercise.

The overall increase in GH was 8 times higher than without pretreatment and was similar to that seen in controls. Pyridostigmine alone did not stimulate GH secretion in patients with fibromyalgia, nor did it affect GH levels in controls. Even those fibromyalgia patients with normal insulin-like growth factor 1 levels had an impaired GH response to exercise.

"Recognition of defective GH secretion in fibromyalgia patients is of some practical relevance because GH replacement therapy was shown to benefit fibromyalgia patients in a 9-month placebo-controlled study," Bennett says.


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