Growth Hormone Perturbations in Fibromyalgia: A Review

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Objective

Fibromyalgia (FM) is a syndrome characterized by chronic widespread pain, fatigue, disrupted sleep, depression, and physical deconditioning. In this article, we review the literature on the normal activity of the hypothalamic-pituitary-growth hormone-insulin-like growth factor-1 (HP-GH-IGF-1) axis and its perturbations in FM subjects.

Methods

Studies included in this review were accessed through an English language search of Cochrane Collaboration Reviews. Keyword MeSH terms included “fibromyalgia,” “growth hormone” (GH), or “insulin-like growth factor-1” (IGF-1).

Results

Twenty-six studies enrolling 2006 subjects were reviewed. Overall, low levels of IGF-1 were found in a subgroup of subjects. Growth hormone stimulation tests often revealed a suboptimal response, which did not always correlate with IGF-1 levels. No consistent defects in pituitary function were found. Of the 3 randomized placebo controlled studies, only 9 months of daily injectable recombinant GH reduced FM symptoms and normalized IGF-1.

Conclusions

These studies suggest that pituitary function is normal in FM and that reported changes in the HP-GH-IGF-1 axis are most likely hypothalamic in origin. The therapeutic efficacy of supplemental GH therapy in FM requires further study before any solid recommendations can be made.

Section snippets

GH Control in Healthy Individuals

GH is most clearly understood as a promoter of linear growth in children. It is a 191-amino-acid polypeptide hormone synthesized and secreted in a pulsatile manner by the anterior pituitary gland. GH enhances amino acid uptake and accelerates transcription and translation of mRNA, thus increasing protein synthesis. The following 2 hypothalamic hormones with opposing physiologic effects regulate GH secretion: (1) GHRH, a hypothalamic hormone consisting of 44 amino acids stimulates the secretion

Clinical Features

GH is necessary for the attainment of a normal adult height. GH deficiency (GHD) in children invariably results in significant growth retardation (31). There are many causes of childhood GHD, most are related to rare mutations of genes involved in GH and GHRH synthesis and their receptors (31). An interesting form of reversible GHD in children is called “psychosocial dwarfism” (32). This occurs in children coming from a hostile/abusive environment and is reversed by transfer to a supportive and

Patients and Methods

Studies included in this review were accessed through an English language search of Cochrane Collaboration Reviews (MEDLINE, CINAHL, EMBASE, PubMed, Healthstar, Current Contexts, Web of Science, PsychInfo, and Science Citation Indexes). Keyword MeSH terms included “fibromyalgia,” and “growth hormone” or “insulin-like growth factor 1”and resulted in 61 hits through December 2005. Additionally, 7 other articles were found through a hand search of journals, conference proceedings, and

Subjects

Overall, the 26 studies enrolled 2006 subjects (1262 FM women, 31 FM men, 89 female disease controls, 12 male disease controls, 583 female healthy controls, and 29 male healthy controls). Disease controls most commonly had CFS, osteoarthritis, rheumatoid arthritis, hypothyroidism, inflammatory rheumatic diseases, or myofascial pain syndrome. All subjects were adults and most were white, though often race or ethnicity was not disclosed.

Design, Methods, and Primary Outcome Measures

Three studies are randomized controlled treatment trials;

Discussion

In the past 2 decades, the diagnosis of FM has become more widely accepted as a legitimate clinical disorder due largely to objective findings of disordered central pain processing and sleep. GHD and FM patients share many of the same symptoms (Table 2) and these similarities led to the original investigations on the HP-GH-IGF-1 axis in FM patients (114, 115). As described in this review article, the disordered HP-GH-IGF-1 axis and its link to FM symptoms have now generated a respectable body

Acknowledgments

The authors express their gratitude to Dianne G. Adams, MPH for valuable assistance in preparing the manuscript. This work was supported by NIH/NINR Grant R01 NR008150-01.

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