Introduction to Fibromyalgia and Growth Hormone
Robert Bennett, MD, FRCP
It is not uncommon for physicians who are unfamiliar with
the complexity of the fibromyalgia syndrome to view the patients'
symptoms as due to a hormonal deficiency. The fatigue, mental
sluggishness and muscle pain of hypothyroidism are reminiscent
of fibromyalgia complaints. In general routine endocrine tests
are normal in fibromyalgia . Perhaps the most striking
"endocrine" finding in fibromyalgia is its predominance
in women . However there is no obvious relation to life-time
changes in estrogen secretion, as FM occurs in teenagers 
as well as post-menopausal females , and estrogen replacement
does not alleviate the symptoms of FM . A current paradigm
to explain the complexity of fibromyalgia symptomatology proposes
that it is a "stress related syndrome" in which
a disordered hypothalamic-pituitary-adrenal (HPA) axis acts
as a final common pathway linking fibromyalgia to other "stress-related"
somatic and psychiatric syndromes [6-8] . There are close
links between the HPA and the HP-growth hormone (GH) axis.
For instance corticotrophin releasing hormone (CRF) stimulates
the release of hypothalamic somatostatin, which in turn, acts
to restrain the pituitary secretion of GH. In this review
the evidence for disturbances in GH secretion and their postulated
link to a disordered HPA axis in fibromyalgia patients are
The physiology of the hypothalamic-pituitary-growth
The growth hormone - IGF-1 axis is subject to exquisite regulation
by multiple internal physiological variables and external
cues . Growth hormone is the only pituitary hormone that
is under the influence of both stimulatory and inhibitory
hypothalamic hormones. The normal pulsatile secretion of GH
depends on the tonic balance of stimulatory growth hormone
releasing hormone (GHRH) and inhibitory somatostatin (SRIF)
Under normal circumstances the production of GH occurs only
when the secretion of GHRH takes place in the setting of low
levels of somatostatin tone . Thus the regulation of GH
secretion is dependent on the relative amounts of GHRH and
somatostatin that are released from the hypothalamus into
the hypothalamic-hypophyseal portal venous system. GH secretion
has a diurnal pattern of secretion that is linked to stages
3 and 4 of the sleep cycle [13;14] , but this association
is less evident with increasing age.
Furthermore intentional sleep deprivation almost totally abolishes
GH production . The increased pulsatile GH secretion that
occurs during deep sleep (stages 3 and 4) is postulated to
be a result of reduced hypothalamic somatostatin tone combined
with increased GHRH release. There is an exponential decline
in the daily GH-secretion rate as a function of age, such
that every 7 years of advancing age beyond age 18-21 results
in an approximately 50% decline. There are negative correlations
between the daily GH-secretion rate and body mass index (BMI).
For each increase in BMI of 1.5 kg/m2, there is a 50% decrease
in the amount of GH secreted per day. Studies, using GHRH
stimulation and pyridostigmine( to reduce somatostatin tone),
point to combined defects in GHRH release and somatostatin
excess as being involved in the GH deficiency that often accompanies
obesity. At puberty, and throughout adulthood, gonadal steroid-hormone
concentrations in blood positively influence the intensity
of GH secretion. The major mediator of most GH related anabolic
activity is insulin related growth factor-1 (IGF-1).
Insulin related growth factor-1 is secreted mainly by the
liver in response to GH release. It has a half-life of about
21 hours and does not exhibit much diurnal variation, its
plasma level is considered to reflect the integrated pulses
of GH hormone secretion over the previous 48 hours.
Adult Growth hormone deficiency
Growth hormone deficiency in adults has been associated with
a miscellany of symptoms that are similar to those described
by fibromyalgia patients: low energy [17-20] , poor general
health , reduced exercise capacity , muscle weakness
, cold intolerance , impaired cognition , dysthymia
 and decreased lean body mass Consequences of adult GH
Furthermore GH is important in maintaining muscle homeostasis
, and it was theorized that sub-optimal levels might be
a factor in the impaired resolution of muscle microtrauma
in FM patients [27;28] . The treatment of GH deficiency in
adults has been reported to improve quality of life and energy
level [24;29] , reduce pain , improve depression ,
enhance self esteem , improve cholesterol and LDL levels
, enhance cognitive psychometric performance , augment
stroke volume , and improve exercise capacity and muscle
strength [22;22;34] .
Diagnosis of adult growth hormone deficiency
Low levels of IGF-1 are usually indicative of significant
adult GH deficiency , but it is not a very sensitive test
marker and will miss up to 60% of GH deficient patients aged
over 40. The currently favored test to diagnose adult GH deficiency
is the stimulated GH response to a combination of GHRH and
an inhibitor of somatostatin tone such as pyridostigmine,
arginine, clonidine or insulin Endocrinologists generally
consider the insulin tolerance test (ITT) to be the most useful
test to evaluate the overall GH secretion in subjects with
possible hypopituitary disease . However, ITT is not suitable
in elderly or in patients with cardiovascular disease or seizure
disorders. Furthermore the GH response to ITT maybe normal
in "physiologic" GH deficiency, as it measures the
overall capacity of the stress-axis rather than the physiological
secretion of GH. A comparison of ITT, pyridostigmine plus
GHRH (PD + GHRH) test, the clonidine plus GHRH (CLO+GHRH)
test, and insulin-like growth factor I (IGF-I) in diagnosing
GH deficiency has recently been reported . The peak GH
response was significantly higher during the PD+GHRH test
than during the ITT. IGF-I levels were subnormal in only 42%
of the patients. It was recommended that adults with suspected
GH deficiency and a normal IGF-I level should undergo two
different stimulation tests. In patients with a subnormal
IGF-I value, a single stimulation test would suffice to confirm
the presence of GH deficiency.
Growth hormone deficiency in fibromyalgia patients
It has been known for 25 years that FM patients have an abnormal
sleep pattern involving stages 3 and 4 of non REM sleep .
As GH is secreted predominantly during stages 3 and 4 of non-REM
sleep, it was originally hypothesized that FM patients may
have impaired GH secretion [38;39] . IGF-1 levels are abnormally
low in some fibromyalgia patients. In an analysis of IGF-1
levels in 500 female FM patients and 152 age matched non-FM
subjects the mean IGF-1 level in the FM patients was 137±58
ng/ml versus 216±86 ng/ml in controls (P = 0.00000000001)
. Eighty-five percent of the FM patients had IGF-1 levels
below the 50th percentile of the control population and 56%
fell below the 20th percentile. As IGF-1 levels fall progressively
with age the results were plotted as an IGF-1 versus age -
shown as the regression plot with the 99% confidence limits
of the mean. However there was also a considerable overlap
of the 2 populations as shown in the respective Gaussian distribution
(From Bennett et al, J.Rheumatol. 24:1384-1389, 1997)
The main graph shows the individual IGF-1 levels in 500 patients
with fibromyalgia (stippled circles) plotted against age.
The solid line is the regression mean for 152 control patients,
comprising both healthy blood donors and patients with other
rheumatic diseases. The 2 dotted lines represent the 99% confidence
limits of the mean. The inset graph shows the Gaussian distributions
for the fibromyalgia and control populations.
Growth hormone treatment in fibromyalgia patients
There is only one study to date that has reported on the
use of GH replacement therapy in FM patients with low levels
of IGF-1 . In this study 50 fibromyalgia patients were
enrolled in a 9 month, double blind, placebo controlled trial.
There was a prompt increase in IGF-1 levels within the first
month in all patients receiving GH injections which was sustained
throughout the 9 month trial. The placebo group showed no
such increase. Only the GH treated group achieved a significant
improvement between baseline and finish. There was a significant
improvement of the GH treated group compared to the placebo
group. No unexpected adverse reactions occurred in the GH
treated group. Carpal tunnel symptoms occurred in 28% GH patients
at some time during the treatment period; only 1 control patient
had such symptoms. Carpal tunnel symptoms were managed by
reducing the GH dose. No patients were experiencing carpal
tunnel symptoms at the end of the study. Although no patient
had a complete remission of symptoms, several patients on
GH experienced an impressive improvement in their functional
ability and 2 "disabled" patients returned to work.
In general there was a lag of about 6 months before patients
started to note improvement. All patients who experienced
improvement on GH suffered a reversion of symptoms over a
period of 1 to 3 months after stopping GH treatment.
A preliminary study of supplemental GH therapy in patients
with chronic fatigue syndrome has reported somewhat similar
encouraging results .
There have been concerns about elevated IGF-1 levels being
associated with an increased risk of some cancers [47-50]
. However GH therapy aims to normalize, not increase IGF-1
levels. It is possible that the low IGF-1 levels associated
with aging have a protective effect on the development of
some cancers; if this notion is correct normalization of IGF-1
levels could put some patients at increased risk of developing
cancer. On the other hand adult GH deficiency is associated
with an increased mortality due to accelerated atherosclerotic
cardiovascular disease [29;51;52].
As fibromyalgia affects 2-4% of all adults, it must be a
major contributing factor to many cases of adult GH deficiency,
with consequences for an impaired quality of life, increased
morbidity and sometimes mortality. Unfortunately GH therapy
is very expensive and is beyond the means of most fibromyalgia
patients and the budgets of most third party payers. The decision
to treat fibromyalgia patients with GH supplementation must
await confirmatory long-term studies of its efficacy/side
effects profile. Hopefully a better understanding of the pathophysiological
basis for GH deficiency in fibromyalgia will yield novel approaches
for treating GH deficient fibromyalgia patients that is more
physiological than daily GH injections.
Possible causes of GH deficiency in fibromyalgia patients
The complexity of the GH response has already been noted.
Low IGF-1 levels in fibromyalgia patients are unlikely to
be due to an anatomical cause (e.g. a pituitary tumor or infarction).
Rather it seems most likely that the problem is a "physiologic
GH deficiency". Some evidence for this notion was provided
by a study in which fibromyalgia patients were exercised to
volitional exhaustion on a treadmill; this is a standard test
of GH secretion. Unlike healthy controls, fibromyalgia patients
were unable to mount a GH response to exercise - despite reaching
an anaerobic threshold (an indication of an adequate exercise
workload). However, when fibromyalgia patients were given
pyridostigmine one hour prior to exercising, they were able
to mount a reasonable GH response . As pyridostigmine
is known to reduce somatostatin (somatostatin) tone in the
hypothalamus , this result is compatible with the notion
that GH deficiency in fibromyalgia is a potentially reversible
problem that has a physiologic basis - i.e. increased hypothalamic
The effects of HPA axis dysregulation secretion are postulated
to be relevant to GH deficiency in fibromyalgia [55;56] Rheumatologists
are familiar with the growth retardation that occurs in some
children with JRA or SLE, who have been treated with long-term
corticosteroids. This stunting is due to the inhibitory effect
of iatrogenic hypercortisolemia on GH secretion . Cortisol
inhibits GH production through the mechanism of an increased
density of b-adrenergic receptors -- with resulting stimulation
of adenyl cyclase and somatostatin release .
CRF is the major mediator of the HPA / sympathetic response
to both physical and psychological stressors. Neeck has hypothesized
that a stress induced increase in CRF is the common denominator
linking the disturbed HPA axis and reduced GH secretion in
fibromyalgia . The critical link being the observation
that CRF increases hypothalamic somatostatin tone [60;61].
However it seems difficult to reconcile the well described
association of hyper-cortisolemia and defective GH production
with the HPA defect described in fibromyalgia - namely a hypo-cortisolemic
response to stressors. This apparent paradox may be a result
of the diverging consequences of acute versus chronic stressors.
Hans Selye envisaged 3 stages to the stress response in his
description of the "general adaption syndrome" :
(i) an alarm reaction that originates in the brain and spreads
to the pituitary with an increased production of ACTH stimulating
the adrenal cortex to secrete cortisol, (ii) after more prolonged
exposure to the stressor, a second stage develops in which
there is increasing secretion of corticosteroids; this is
a regulatory physiological response promoting survival processes
while inhibiting non-essential processes, (iii) in the third
stage an "exhaustion" occurs characterized by a
progressive decline in cortisol production with increased
vulnerability to stress related illnesses. The first 2 stages
of the general adaption syndrome are mediated by the stress-induced
secretion of CRF . However, prolonged CRF secretion eventually
down regulates the density of CRF-1 receptors in the paraventricular
nucleus of hypothalamus . Thus in the face of persistent
CRF secretion its physiological effects on cortisol secretion
ultimately become blunted . Maybe the sub-population of
fibromyalgia patients with defective neuroendocrine and sympathetic
stress responses has reached this "third stage"
of Selye's general adaption syndrome?
There are several other examples of human "stress related"
disorders that exhibit an impaired cortisol secretion, namely:
chronic pelvic pain syndrome , chronic fatigue syndrome
, post traumatic stress disorder  and over-training
syndrome . All these conditions are characterized by an
increase in central HPA function with a paradoxical blunting
of the adrenal cortisol response. Thus it appears that fibromyalgia
is just one of several other chronic disorders, that are characterized
by a hypoactive stress response in terms of HPA axis and a
reduced sympathetic responses [59;68-70].
Currently it is not possible to arrive at any definitive conclusions
as to the link between HPA axis dysfunction and GH deficiency
in fibromyalgia. Nevertheless, the presence of a clinically
significant GH deficiency in a sub-population of fibromyalgia
patients now seems well established. Understanding its links
with chronic stress may provide some insights into mechanisms
whereby environmental stressors and developmental factors
interact with inherited susceptibility to modify gene expression
and ultimately generate symptoms ;[68;72] 40;58; .
It is simple, scientific logic...
As your growth hormone DECREASES,
the rate at which you age
Consider that for a moment...
1 Bengtsson A, Henriksson KG, Jorfeldt L, K~agedal B, Lennmarken
C, Lindstrom F: Primary fibromyalgia. A clinical and laboratory
study of 55 patients. Scand.J.Rheumatol. 1986, 15:340-347.
2 Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C,
Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P,
Fam AG, Farber SJ, Fiechtner JJ, Franklin CM, Gatter RA, Hamaty
D, Lessard J, Lichtbroun AS, Masi AT, McCain GA, Reynolds
WJ, Romano TJ, Russell IJ, Sheon RP: The American College
of Rheumatology 1990 criteria for the classification of fibromyalgia:
Report of the Multicenter Criteria Committee. Arth.Rheum.
3 Yunus MB, Masi AT: Juvenile primary fibromyalgia syndrome.
A clinical study of thirty-three patients and matched normal
controls. Arth.Rheum. 1985, 28:138-145.
4 Yunus MB, Holt GS, Masi AT, Aldag JC: Fibromyalgia syndrome
among the elderly. Comparison with younger patients. J.Am.Geriatr.Soc.
5 Waxman J, Zatzkis SM: Fibromyalgia and menopause. Examination
of the relationship. Postgrad.Med. 1986, 80:165-7, 170-1.
6 · Crofford LJ: Neuroendocrine abnormalities in fibromyalgia
and related disorders. Am.J.Med.Sci. 1998, 315:359-366.
A useful review of the HPA axis perturbations and hypotheses
regarding the associations with pain.
7 Neeck G: From the fibromyalgia challenge toward a new bio-psycho-social
model of rheumatic diseases. Z.Rheumatol. 1998, 57 Suppl 2:A13-A16.
8 · Weigent DA, Bradley LA, Blalock JE, Alarcon GS:
Current concepts in the pathophysiology of abnormal pain perception
in fibromyalgia. Am.J.Med.Sci. 1998, 315:405-412.
A good review of the pathophysiology of aberrant pain perception
and its relationships to neuroendocrine dysfunction.
9 Veldhuis JD, Iranmanesh A: Physiological regulation of the
human growth hormone (GH)-insulin-like growth factor type
I (IGF-I) axis: predominant impact of age, obesity, gonadal
function, and sleep. Sleep 1996, 19:S221-S224.
10 · Muller EE, Locatelli V, Cocchi D: Neuroendocrine
control of growth hormone secretion. Physiol Rev. 1999, 79:511-607.
An uptodate review of the neuro-physiology of GH secretion.
11 Hindmarsh PC, Brain CE, Robinson IC, Matthews DR, Brook
CG: The interaction of growth hormone releasing hormone and
somatostatin in the generation of a GH pulse in man. Clin.Endocrinol.(Oxf)
12 Reid GJ: Textbook of Endocrinology, edn 8. Edited by Wilson
JD, Foster MD. Philadelphia: W.B. Sanders; 1992.
13 Veldhuis JD, Iranmanesh A, Weltman A: Elements in the pathophysiology
of diminished growth hormone (GH) secretion in aging humans.
Endocrine. 1997, 7:41-48.
14 Holl RW, Hartman ML, Veldhuis JD, Taylor WM, Thorner MO:
Thirty-second sampling of plasma growth hormone in man: Correlation
with sleep stages. J.Clin.Endocrinol.Metab. 1991, 72:854-861.
15 Davidson JR, Moldofsky H, Lue FA: Growth hormone and cortisol
secretion in relation to sleep and wakefulness. J Psychiatr
Neurosci 1991, 16:96-102.
16 Florini JR, Prinz PN, Vitiello MV, Hintz RL: Somatomedin-C
levels in healthy young and old men: relationship to peak
and 24-hour integrated levels of growth hormone. J Gerontol
17 Wallymahmed ME, Foy P, Shaw D, Hutcheon R, Edwards RH,
MacFarlane IA: Quality of life, body composition and muscle
strength in adult growth hormone deficiency: the influence
of growth hormone replacement therapy for up to 3 years. Clin
Endocrinol.(Oxf.) 1997, 47:439-446.
18 Verhelst J, Abs R, Vandeweghe M, Mockel J, Legros JJ, Copinschi
G, Mahler C, Velkeniers B, Vanhaelst L, Van Aelst A, De Rijdt
D, Stevenaert A, Beckers A: Two years of replacement therapy
in adults with growth hormone deficiency. Clin Endocrinol.(Oxf.)
19 Lieberman SA, Hoffman AR: The somatopause: should growth
hormone deficiency in older people be treated? Clin Geriatr.Med.
20 Cuneo RC, Salomon F, McGauley GA, Sönksen PH: The
growth hormone deficiency syndrome in adults. Clin Endocrinol
21 Wallymahmed ME, Baker GA, Humphris G, Dewey M, MacFarlane
IA: The development, reliability and validity of a disease
specific quality of life model for adults with growth hormone
deficiency. Clin.Endocrinol.(Oxf). 1996, 44:403-411.
22 Johannsson G, Grimby G, Sunnerhagen KS, Bengtsson BA: Two
years of growth hormone (GH) treatment increase isometric
and isokinetic muscle strength in GH-deficient adults [see
comments]. J Clin Endocrinol.Metab. 1997, 82:2877-2884.
23 Rutherford OM, Beshyah SA, Schott J, Watkins Y, Johnston
DG: Contractile properties of the quadriceps muscle in growth
hormone-deficient hypopituitary adults. Clin.Sci.(Colch).
24 McGauley GA, Cuneo RC, Salomon F, Sönksen PH: Psychological
well-being before and after growth hormone treatment in adults
with growth hormone deficiency. Horm.Res. 1990, 33 Suppl 4:52-54.
25 Salomon F, Cuneo RC, Hesp R, Sonksen PH: The effects of
treatment with recombinant human growth hormone XX on body
composition and metabolism in adults with growth hormone deficiency.
N Engl J Med 1989, 321:1797-1803.
26 Florini JR: Hormonal control of muscle growth. Muscle Nerve
27 Armstrong RB, Warren GL, Warren JA: Mechanisms of exercise-induced
muscle fibre injury. Sports Med. 1991, 12:184-207.
28 Bennett RM: The contribution of muscle to the generation
of fibromyalgia symptomatology. J Musculoskeletal Pain 1996,
29 Christ ER, Carroll PV, Russell-Jones DL, Sonksen PH: The
consequences of growth hormone deficiency in adulthood, and
the effects of growth hormone replacement. Schweiz.Med.Wochenschr.
30 ·· Cuneo RC, Judd S, Wallace JD, Perry-Keene
D, Burger H, Lim-Tio S, Strauss B, Stockigt J, Topliss D,
Alford F, Hew L, Bode H, Conway A, Handelsman D, Dunn S, Boyages
S, Cheung NW, Hurley D: The Australian Multicenter Trial of
Growth Hormone (GH) Treatment in GH- Deficient Adults. J Clin
Endocrinol.Metab. 1998, 83:107-116.
An Australian multicenter, randomized, double-blind, placebo-controlled
trial of the effects of recombinant human GH treatment in166
adults patients (72 females and 91 males) with GH deficiency.
GH treatment resulted in 1) prominent increases in serum IGF-I
at the doses employed, in some cases to supraphysiological
levels; 2) modest decreases in total- and low- density lipoprotein
cholesterol, together with substantial reductions in total-body
and truncal fat mass; 3) substantial increases in lean tissue
mass; and 4) modest improvements in perceived quality of life.
31 · Giusti M, Meineri I, Malagamba D, Cuttica CM,
Fattacciu G, Menichini U, Rasore E, Giordano G: Impact of
recombinant human growth hormone treatment on psychological
profiles in hypopituitary patients with adult-onset growth
hormone deficiency. Eur.J Clin Invest. 1998, 28:13-19.
A study of the effect of growth hormone (GH) administration
on the psychological capacity and sense of well-being in 25
patients with adult-onset GH-deficiency. There were significantly
improved psychological profiles, but the quality of life was
not significantly improved over the a 6-month period of treatment.
32 Almqvist O, Thoren M, Saaf M, Eriksson O: Effects of growth
hormone substitution on mental performance in adults with
growth hormone deficiency: a pilot study. Psychoneuroendocrinology
33 Shahi M, Beshyah SA, Hackett D, Sharp P, Johnston DG, Foale
R: Cardiac function and structure in growth hormone deficiency.
Br.Heart J. 1991, 66:58-63.
34 Cuneo RC, Salomon F, Wiles CM, Hesp R, Sönksen PH:
Growth hormone treatment in growth hormone-deficient adults.
I. Effects on muscle mass and strength. J Appl.Physiol. 1991,
35 Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C,
Bellone J, Camanni F, Ghigo E: Usefulness of IGF-I assay for
the diagnosis of GH deficiency in adults. J.Endocrinol.Invest
36 · Hoeck HC, Vestergaard P, Jakobsen PE, Falhof J,
Laurberg P: Diagnosis of growth hormone (GH) deficiency in
adults with hypothalamic-pituitary disorders: comparison of
test results using pyridostigmine plus GH-releasing hormone
(GHRH), clonidine plus GHRH, and insulin-induced hypoglycemia
as GH secretagogues. J.Clin.Endocrinol.Metab 2000, 85:1467-1472.
A definitive study suggesting that a diagnosis of adult GH
deficiency be based upon an abnormally low IGF-1 level plus
one abnormal GH stimulation tests, or 2 abnormal GH stimulation
tests in patients with normal IGF-1 levels.
37 Moldofsky H, Scarisbrick P, England R, Smythe H: Musculosketal
symptoms and non-REM sleep disturbance in patients with "fibrositis
syndrome" and healthy subjects. Psychosom Med 1975, 37:341-351.
38 Bennett RM: Beyond fibromyalgia: ideas on etiology and
treatment. J.Rheumatol.Suppl. 1989, 19:185-191.
39 Bennett RM, Clark SR, Campbell SM, Burckhardt CS: Low levels
of somatomedin C in patients with the fibromyalgia syndrome.
A possible link between sleep and muscle pain. Arthritis Rheum.
40 ·· Bennett RM, Cook DM, Clark SR, Burckhardt
CS, Campbell SM: Hypothalamic-pituitary-insulin-like growth
factor-I axis dysfunction in patients with fibromyalgia. J.Rheumatol.
A study of 500 fibromyalgia patients with IGF-1 levels and
GH stimulation tests, demonstrating adult GH deficiency in
about one third of patients.
41 · Dinser R, Halama T, Hoffmann A: Stringent endocrinological
testing reveals subnormal growth hormone secretion in some
patients with fibromyalgia syndrome but rarely severe growth
hormone deficiency . J Rheumatol 2000, 27:2482-2488.
Supports finding of GH deficiency in about one third of fibromyalgia
patients, but concludes that this is seldom a clinically severe
42 · Leal-Cerro A, Povedano J, Astorga R, Gonzalez
M, Silva H, Garcia-Pesquera F, Casanueva FF, Dieguez C: The
growth hormone (GH)-releasing hormone-GH-insulin-like growth
factor-1 axis in patients with fibromyalgia syndrome. J Clin.Endocrinol.Metab
A report of 24-h spontaneous GH secretion, GH responses to
GHRH, and IGF-1 and IGF binding protein (BP)-3 levels in fibromyalgia
before and after 4 days treatment with human (h)GH. Found
a marked decrease in spontaneous GH secretion, but normal
pituitary responsiveness to exogenously administered GHRH
and an increased in IGF-1 and IGFBP-3 levels after GH treatment.
43 ·· Riedel W, Layka H, Neeck G: Secretory
pattern of GH, TSH, thyroid hormones, ACTH, cortisol, FSH,
and LH in patients with fibromyalgia syndrome following systemic
injection of the relevant hypothalamic-releasing hormones.
Z.Rheumatol. 1998, 57 Suppl 2:81-87.
An excellent review of pituitary axis perturbations in fibromyalgia
following injections with corticotropin- releasing hormone
(CRH), thyrotropin-releasing hormone, growth hormone- releasing
hormone, and luteinizing hormone-releasing hormone. Concludes
that elevated activity of hypothalamic CRH neurons in fibromyalgia
patients thus may play a key role not only in "resetting"
the various endocrine loops but also in nociceptive and psychological
44 Hallegua D.S., Wallace DJ, Silverman S, Bonert V, Mathur
R, Klinenberg JR: Prevalence of fibromyalgia in Xgrowth hormone
deficiency adults. J Musculoskeletal Pain 2001, 9:35-42.
45 ·· Bennett RM, Clark SR, Walczyk J: A randomized,
double-blind, placebo-controlled study of growth hormone in
the treatment of fibromyalgia. Am.J Med 1998, 104:227-231.
The only controlled study of supplemental GH therapy in fibromyalgia
to date. Found a benefit after about 6 months of therapy with
a relapse on discontinuing therapy.
46 Moorkens G, Wynants H, Abs R: Effect of growth hormone
treatment in patients with chronic fatigue syndrome: a preliminary
study. Growth Horm.IGF.Res. 1998, 8 Suppl B:131-133.
47 Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson
P, Hennekens CH, Pollak M: Plasma insulin-like growth factor-I
and prostate cancer risk: a prospective study. Science 1998,
48 Mantzoros CS, Tzonou A, Signorello LB, Stampfer M, Trichopoulos
D, Adami HO: Insulin-like growth factor 1 in relation to prostate
cancer and benign prostatic hyperplasia. Br.J Cancer 1997,
49 Yee D: The insulin-like growth factors and breast cancer--revisited.
Breast Cancer Res.Treat. 1998, 47:197-199.
50 Stoll BA: Breast cancer: further metabolic-endocrine risk
markers? Br.J Cancer 1997, 76:1652-1654.
51 · Sanmarti A, Lucas A, Hawkins F, Webb SM, Ulied
A: Observational study in adult hypopituitary patients with
untreated growth hormone deficiency (ODA study). Socio-economic
impact and health status. Collaborative ODA (Observational
GH Deficiency in Adults) Group. Eur.J Endocrinol. 1999, 141:481-489.
A study documenting more cardiovascular risk factors, higher
mortality, worse quality of life and higher absolute health
costs than the general population in Spain.
52 Bengtsson BA: The consequences of growth hormone deficiency
in adults. Acta Endocrinol. 1993, 128:2-5.
53 · Paiva, E.S., Deodhar, A., Jones, K.D., Bennett,
R.M., Impaired growth hormone secretion in
fibromyalgia patients: evidence for augmented hypothalamic
somatostatin tone. Arthritis
Rheum. (in Press 2002)
This study shows that GH deficiency in fibromyalgia is probably
more common than previously reported from the
measurements of IGF-1 levels. It provides evidence that perturbed
GH secretion in fibromyalgia is probably, in part,
a result of increased hypothalamic tone of somatostatin.
54 Valcavi R, Valente F, Dieguez C, Zini M, Procopio M, Portioli
I, Ghigo E: Evidence against deletion of the growth hormone
(GH)-releasable pool in human primary hypothyroidism: studies
with GH-releasing hormone, pyridostigmine, and arginine. J
Clin Endocrinol Metab 1993, 77:616-620.
55 ·· Neeck G, Crofford LJ: Neuroendocrine perturbations
in fibromyalgia and chronic fatigue syndrome Rheum.Dis.Clin.North
Am. 2000, 26:989-1002.
A comprehensive review of neuroendocrine disorders in fibromyalgia.
56 Crofford LJ, Engleberg NC, Demitrack MA: Neurohormonal
perturbations in fibromyalgia. Baillieres.Clin.Rheumatol.
57 Thorner O: The anterior pituitary. In Textbook of endocrinology,
edn 8th. Edited by Wilson JD, Foster DW. Philadelphia: W.B.
58 Devesa J, Lima L, Tresguerres JAF: Neuroendocrine control
of growth hormone secretion in humans. Trends Endocrinol Metab.
59 · Neeck G, Riedel W: Hormonal pertubations in fibromyalgia
syndrome . Ann.N.Y.Acad.Sci. 1999, 876:325-38; discussion
Postlulates a common primary disturbance in fibromyalgia which
is hypothesized to originate within higher levels of the central
nervous system. Recent studies of the entire endocrine profile
of FM patients following a simultaneous challenge of the hypophysis
with corticotropin- releasing hormone (CRH), thyrotropin-releasing
hormone, growth hormone- releasing hormone, and luteinizing
hormone-releasing hormone support the hypothesis that an elevated
activity of CRH neurons determines not only many symptoms
of FM but may also cause the deviations observed in the other
hormonal axes. Hypothalamic CRH neurons thus may play a key
role not only in "resetting" the various endocrine
loops but possibly also nociceptive and psychological mechanisms
60 Katakami H, Arimura A, Frohman LA: Involvement of hypothalamic
somatostatin in the suppression of growth hormone secretion
by central corticotropin-releasing factor in conscious male
rats. Neuroendocrinology 1985, 41:390-393.
61 Rivier C, Vale W: Involvement of corticotropin-releasing
factor and somatostatin in stress-induced inhibition of growth
hormone secretion in the rat. Endocrinology 1985, 117:2478-2482.
62 Hauger R.L. DFM: Regulation of the stress response by corticotropin-releasing
factor receptors. In Neuroendocrinology in physiology and
medicine. Edited by Conn PMFME. Totowa N.J.: Humana Press,
63 Bonaz B, Rivest S: Effect of a chronic stress on CRF neuronal
activity and expression of its type 1 receptor in the rat
brain. Am.J.Physiol 1998, 275:R1438-R1449.
64 Heim C, Ehlert U, Hanker JP, Hellhammer DH: Abuse-related
posttraumatic stress disorder and alterations of the hypothalamic-pituitary-adrenal
axis in women with chronic pelvic pain. Psychosom.Med. 1998,
65 Demitrack MA, Dale JK, Straus SE, Laue L, Listwak SJ, Kruesi
MJP, Chrousos GP, Gold PW: Evidence for impaired activation
of the hypothalamic-pituitary-adrenal axis in patients with
chronic fatigue syndrome. J Clin Endocrinol Metab 1991, 73:1224-1234.
66 Heim C, Ehlert U, Hanker JP, Hellhammer DH: Psychological
and endocrine correlates of chronic pelvic pain associated
with adhesions. J.Psychosom.Obstet.Gynaecol. 1999, 20:11-20.
67 Wittert GA, Livesey JH, Espiner EA, Donald RA: Adaptation
of the hypothalamopituitary adrenal axis to chronic exercise
stress in humans. Med.Sci.Sports Exerc. 1996, 28:1015-1019.
68 · Clauw DJ, Chrousos GP: Chronic pain and fatigue
syndromes: overlapping clinical and neuroendocrine features
and potential pathogenic mechanisms. Neuroimmunomodulation.
Hypothesizes that fibromyalgia and chronic fatigue syndrome
may be a result of genetic and environmental factors that
interact to cause the development of named syndromes. Various
components of the central nervous system are envisaged to
be involved, including the hypothalamic pituitary axes, pain-processing
pathways, and autonomic nervous system.
69 Dessein PH, Shipton EA, Stanwix AE, Joffe BI: Neuroendocrine
deficiency-mediated development and persistence of pain in
fibromyalgia: a promising paradigm? . Pain 2000, 86:213-215.
70 Neeck G, Riedel W: Thyroid function in patients with fibromyalgia
syndrome. J Rheumatol. 1992, 19:1120-1122.
71 Winfield JB: Pain in fibromyalgia. Rheum.Dis.Clin.North
Am. 1999, 25:55-79.
72 Dorn LD, Chrousos GP: The neurobiology of stress: understanding
regulation of affect during female biological transitions.
Semin.Reprod.Endocrinol. 1997, 15:19-35.
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