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Glucocorticoid receptor mediated
negative feedback in CFS using the low dose (0.5 mg) dexamethasone
suppression test, papadopoulos.etal08.txt.
One
researcher recommends physiologic doses of cortisol to patients with CFS and
FM, holtorf07.txt, holtorf07.pdf.
Please remember that long-time side effects of cortisol are not
“safe”.
The HPA - axis in CFS
Basal circadian and pulsatile ACTH and
cortisol secretion were consistent with loss of HPA axis resiliency in both
FM and CFS, crofford.etal04.txt, crofford.etal04.pdf. Reduced ACTH over a full circadian cycle
and reduced levels during the usual morning physiological peak, digiorgio.etal05.txt,
digiorgio.etal05.pdf. A similar conclusion was
reached in this study, jerjes.etal05.txt, jerjes.etal05.pdf.
Reduced
basal HPA axis function in patients with CFS is based on lower free cortisol
and cortisone levels, not corroborated by cortisol metabolite data, jerjes.etal06.txt, jerjes.etal06.pdf.
Enhanced feedback sensitivity to prednisolone in CFS, jerjes.etal07.txt, jerjes.etal07.pdf.
Inclusion of the glucocorticoid
receptor in a hypothalamic pituitary adrenal axis model reveals bistability, gupta.etal.07.txt, gupta.etal07.txt.
Even if the HPA axis dysfunctions are secondary to other factors, they are
probably a relevant factor in symptom propagation in CFS, van.den.eede.etal07.txt,
van.den.eede.etal07.pdf
and van.den.eede.etal.07.txt,
van.den.eede.etal.07.pdf. HPA-axis
dysfunction in CFS: clinical implications, vandeneede.moorkens08.txt.
Hypothesis: Chronic ACTH
autoantibodies are a significant pathological factor in the disruption of the
hypothalamic-pituitary-adrenal axis in CFS, anorexia nervosa and major
depression, wheatland05.txt, wheatland05.pdf.
A mutation in the corticosteroid-binding globulin can cause fatigue, Torpy et al., 2001. Association
between CFS and the gene polymorphism, torpy.etal04.txt, torpy.etal04.pdf, torpy.ho07.txt, torpy.ho07.pdf.
and rajeevan.etal06.txt, rajeevan.etal06.pdf.
Urinary free
cortisol was significantly lower regardless of current or past comorbid
psychiatric illness, Cleare et al., 2001. The low
cortisol has made comparisons to Addison’s disease obvious, baschetti04.txt. A warning against relying on saliva
measurements, broderick.etal04.txt.
A Turkish study on FM and CFS suggests that, despite low
morning cortisol concentrations, the only abnormality in hormones of the HPG
axis is high LH levels in FM patients with low BDI scores, gur.etal04.txt, gur.etal04.pdf. These researchers also found low blood
cortisol in CFS patients, cevik.etal04.txt, cevik.etal04.pdf.
The diurnal
rythm of cortisol is influenced by stress and many other variables, dedert.etal04.txt. Clinical burnout is
not reflected in the cortisol awakening response, mommersteeg.etal05.txt,
mommersteeg.etal05.pdf.
If serum and
saliva cortisol levels are lower in CFS, this would suggest that metabolic
clearance of cortisol is faster in patients with CFS than in controls, jerjes.et.al06.txt, jerjes.etal.06.txt, jerjes.etal.06.pdf.
A different conclusion
was reached in this study, inder.etal05.txt, inder.etal05.pdf, and in a review which
did not include the above studies, cleare04.txt, cleare.04.txt cleare04.pdf.
Attenuated
morning salivary cortisol concentrations in a population-based study of
persons with CFS and well controls, nater.etal07.txt.
The newest research suggest an altered diurnal cortisol rhythm and IL-6
concentrations in CFS cases identified from a population-based sample, nater.etal08.txt, nater.atal08.pdf.
DHEA/cortisol
ratio after ACTH infusion showed imbalances in CFS, scott.etal00.txt. A small study from South Africa found
decreased DHEA and iron in CFS patients, vanrensburg.etal01.txt. Low DHEA in patients with inflammatory and
non-inflammatory diseases may be sympathetic nervous stimulation, kizildere.etal02.txt.
High
levels of DHEA in CFS was found, cleare.etal04.txt, cleare.etal04.pdf.
Among women with FM a strong
relationship between cortisol level and current pain symptoms was observed at
the waking time point, mclean.etal05.txt.
A review on HPA in FM, tanriverdi.etal07.pdf.
Exercise induces changes in salivary cortisol and corticosteroid
receptor-alpha mRNA expression, bonifazi.etal06.txt.
Despite low cortisol
concentrations in young women with FM, there was no abnormality in HPG axis
hormones, gur.etal.04.txt. Hypothalamic-pituitary-adrenal
stress axis function and the relationship with chronic widespread pain, mcbeth.etal05.txt.
Reported changes in the
HP-GH-IGF-1 axis are most likely hypothalamic in origin, jones.etal07.txt. Below-normal levels of urinary cortisol is also found in
FM, izquierdo.etal08.txt. Glucocorticoid sensitivity in FM:
Decreased expression of corticosteroid receptors and glucocorticoid-induced leucine
zipper, macedo.etal08.txt
A
2001-study found no difference in circadian rhythms of cortisol, melatonin
and body temperature in FM women compared to normal, Klerman et al., 2001.
However, a later study found significant differences, Guagnano et al., 2003. Also the most recent study, a measure of morning
cortisol in saliva from CFS patients, found lower values and thus
indication of disturbed diurnal variation, roberts.etal04.txt, roberts.etal04.pdf.
One study
found reduced ACTH response after infusion of the hormone vasopressin in CFS
patients, Altemus et al., 2001 ,
Altemus et al., 2001, (2). Another study found problems at the
hypothalamic level measuring ACTH and CRH, Cleare et al., 2001. Bolus infusion of CRH
[=cortitropin-releasing hormone] suggested that a second hypothalamic
hormone, somatostatin interferes with
ACTH release, Riedel et al., 2002, Riedel et al., 2002
(pdf).
Endocrine
functionality in FM disclosed abnormalities in subgroups, Geenen et al., 2002.
A German study suggested dysregulations at central level in CFS, Gaab et al., 2002
(short), Gaab et al., 2002,
Gaab et al., 2002 (pdf).
A reduction in central stimulation of the adrenal glands in CFS
adolescents, segal.etal05.txt.
ACTH Tests
ACTH-stimulation
indicated that primary adrenal insuffiency is not the cause of CFS, Gaab et al., 2003.
A later study however,
indicated a much smaller curve under the ACTH response when Insulin Tolerance
Test was used, gaab.etal04.txt, gaab.etal.04.txt,
gaab.etal04.pdf. Also a Turkish study
found clear understimulation of the HPA axis after 1 microgram ACTH, calis.etal04.txt. A thorough study including various
testing of hormones and stimulation tests did not reach an unambiguous
conclusion, cleare.etal03.pdf.
One study
found delayed response to low-dose dexamethasone
suppression and compared this enhanced negative feedback with
stress, Gaab et al., 2002. FM
patients, wingenfeld.etal07.txt.
One study
found minimal differences in corticosteroid hormones in CFS compared to
normals after exercise, Ottenweller et al.,
2001.
Pre-operative levels of corticosteroid without relevance for fatigue, rubin.etal05.txt, rubin.etal05.pdf.
Many
studies have dealt with the effects of stress on the HPA system. In FM some
effects mimic those of stress, Okifuji & Turk,
2002.
HPA, neuroendocrine factors and stress, Tsigos & Chrousos,
2002. Also
with regards to chronic pain and depression, HPA has a role, blackburn-munro04.txt, blackburn-munro04.pdf.
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