Group on Scientific Research into ME: Neuroendocrinology of CFS/ME Dr Anthony Cleare Reader, Kings College London, Institute of Psychiatry
Slide 2
Background Series of studies from our research group into the neuroendocrinology of CFS/ME, beginning in 1994 Focussing on the role of cortisol, the end product of the hypothalamo-pituitary-adrenal axis Original theory came from the known effects of low cortisol in other illnesses, including fatigue
Slide 3
NEGATIVE FEEDBACK METABOLIC EFFECTS
Slide 4
Questions addressed Is cortisol low? Is there abnormal control of cortisol? Is cortisol related to symptoms? When does cortisol change in the natural history of CFS? What are the causes of altered cortisol?
Slide 5
1. Is there low cortisol output in CFS?
Slide 6
24 h Urinary Free Cortisol Output Cleare et al, Am J Psych, 2001
Slide 7
Salivary Cortisol in CFS Jerjes et al, 2005
Slide 8
Summary of literature Basal Studies Urine – 4/6 low cortisol Serial blood samples – 3/6 low cortisol Serial saliva samples – 2/5 low cortisol About 50% studies support low cortisol Cleare, Endo Rev, 2003
Slide 9
2. Is there an abnormal control of cortisol release?
Slide 10
HPA axis in CFS Cleare et al, J Clin Endocrinol Metab, 2001 CRH Test - cortisol response Roberts et al, Br J Psychiatry, 2004 Salivary cortisol response to awakening
Slide 11
Summary of Literature Challenge Studies (ACTH and/or cortisol response to a variety of challenges) Overall - 11/16 blunted, none enhanced Cleare, Endo Rev, 2003
Slide 12
3. Is low cortisol is related to the symptom of fatigue in CFS? Randomised, double blind, placebo- controlled trial of a low dose cortisol replacement strategy (hydrocortisone 5- 10mg) to raise levels of cortisol
Slide 13
Hydrocortisone therapy in CFS Effect on fatigue Cleare et al, Lancet, 1999
Slide 14
4. When do patients develop low cortisol levels in the evolution of the illness?
Slide 15
Prospective Cohort Studies Prospective model of a fatigue syndrome using high risk cohorts – post-viral (EBV infection) and postoperative naturalistic salivary cortisol profiles. Cohort followed up after EBV infection No relation of low cortisol to fatigue (acute, 3 and 6 months) Cohort assessed pre and post major surgery No relation of low cortisol to fatigue (acutely, 3 weeks and 6 months) Low cortisol not a risk factor pre-operatively Candy et al, Psychol Med, 2003; Rubin et al, Psychosom Med, 2004
Slide 16
Phase of Illness Conclusions Acute/sub acute fatigue – No link to cortisol Early chronic fatigue (6 months) – No link to cortisol Late chronic fatigue – Low cortisol Cortisol does not appear to be a primary cause of fatigue in these cohorts But – studies are of CF, and too small to exclude a different pattern in tightly defined CFS
Slide 17
5. What causes changes in cortisol levels and regulation? Are they a primary feature of the illness or secondary to some of the consequences of being ill with CFS? If some HPA axis disturbance is secondary to effects of the illness – e.g. physical inactivity, sleep disturbance, stress levels etc. – then therapy targeting these (e.g. CBT) should reverse the HPA axis changes
Slide 18
CBT in CFS: Endocrine Effects All significant at P
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Group on Scientific Research into ME: Neuroendocrinology of CFS/ME Dr Anthony Cleare Reader, Kings College London, Institute of Psychiatry.
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Transcript
Slide 1
Group on Scientific Research into ME: Neuroendocrinology of CFS/ME Dr Anthony Cleare Reader, Kings College London, Institute of Psychiatry
Slide 2
Background Series of studies from our research group into the neuroendocrinology of CFS/ME, beginning in 1994 Focussing on the role of cortisol, the end product of the hypothalamo-pituitary-adrenal axis Original theory came from the known effects of low cortisol in other illnesses, including fatigue
Slide 3
NEGATIVE FEEDBACK METABOLIC EFFECTS
Slide 4
Questions addressed Is cortisol low? Is there abnormal control of cortisol? Is cortisol related to symptoms? When does cortisol change in the natural history of CFS? What are the causes of altered cortisol?
Slide 5
1. Is there low cortisol output in CFS?
Slide 6
24 h Urinary Free Cortisol Output Cleare et al, Am J Psych, 2001
Slide 7
Salivary Cortisol in CFS Jerjes et al, 2005
Slide 8
Summary of literature Basal Studies Urine – 4/6 low cortisol Serial blood samples – 3/6 low cortisol Serial saliva samples – 2/5 low cortisol About 50% studies support low cortisol Cleare, Endo Rev, 2003
Slide 9
2. Is there an abnormal control of cortisol release?
Slide 10
HPA axis in CFS Cleare et al, J Clin Endocrinol Metab, 2001 CRH Test - cortisol response Roberts et al, Br J Psychiatry, 2004 Salivary cortisol response to awakening
Slide 11
Summary of Literature Challenge Studies (ACTH and/or cortisol response to a variety of challenges) Overall - 11/16 blunted, none enhanced Cleare, Endo Rev, 2003
Slide 12
3. Is low cortisol is related to the symptom of fatigue in CFS? Randomised, double blind, placebo- controlled trial of a low dose cortisol replacement strategy (hydrocortisone 5- 10mg) to raise levels of cortisol
Slide 13
Hydrocortisone therapy in CFS Effect on fatigue Cleare et al, Lancet, 1999
Slide 14
4. When do patients develop low cortisol levels in the evolution of the illness?
Slide 15
Prospective Cohort Studies Prospective model of a fatigue syndrome using high risk cohorts – post-viral (EBV infection) and postoperative naturalistic salivary cortisol profiles. Cohort followed up after EBV infection No relation of low cortisol to fatigue (acute, 3 and 6 months) Cohort assessed pre and post major surgery No relation of low cortisol to fatigue (acutely, 3 weeks and 6 months) Low cortisol not a risk factor pre-operatively Candy et al, Psychol Med, 2003; Rubin et al, Psychosom Med, 2004
Slide 16
Phase of Illness Conclusions Acute/sub acute fatigue – No link to cortisol Early chronic fatigue (6 months) – No link to cortisol Late chronic fatigue – Low cortisol Cortisol does not appear to be a primary cause of fatigue in these cohorts But – studies are of CF, and too small to exclude a different pattern in tightly defined CFS
Slide 17
5. What causes changes in cortisol levels and regulation? Are they a primary feature of the illness or secondary to some of the consequences of being ill with CFS? If some HPA axis disturbance is secondary to effects of the illness – e.g. physical inactivity, sleep disturbance, stress levels etc. – then therapy targeting these (e.g. CBT) should reverse the HPA axis changes
Slide 18
CBT in CFS: Endocrine Effects All significant at P