TGI Friday! Our weekly round-up of recently published research abstracts | 21 March 2014

March 21, 2014

From the Journal of Endocrinological Investigation, March 2014.

MEA Medical adviser Dr Charles Shepherd comments: “A degree of hypocortisolaemia (= lowered level of blood cortisol) is one of the most consistent research findings in ME/CFS.”

Severe fatigue in patients with adrenal insufficiency: physical, psychosocial and endocrine determinants.

Giebels V1, Repping-Wuts H, Bleijenberg G, Kroese JM, Stikkelbroeck N, Hermus A.
Nijmegen Expert Centre of Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.



Fatigue is a frequently experienced complaint in patients with adrenal insufficiency (AI) and may be influenced by cortisol levels.


The objective of this study was to determine the prevalence of severe fatigue in adrenal insufficiency (AI) patients, to assess which dimensions contribute to fatigue severity and to determine the association between salivary cortisol levels and momentary fatigue.


We performed a cross-sectional study in the outpatient department of a university hospital. Included were 27 patients with congenital adrenal hyperplasia (CAH), 26 patients with primary AI (PAI), 24 patients with secondary AI (SAI) and 31 patients with adrenal insufficiency after treatment for Cushing's syndrome (Cush-AI). Measurements included computerised questionnaires to determine fatigue severity and physical and psychosocial contributors. Patients took four saliva samples at home, in which cortisol levels were measured.


Severe fatigue was experienced by 41 % of the CAH patients, 42 % of the PAI patients, 50 % of the SAI patients and 42 % of the Cush-AI patients. Psychological distress, functional impairment, sleep disturbance, physical activity, concentration problems and social functioning contributed to the subjective experience of fatigue. Salivary cortisol levels were not correlated with momentary fatigue.


A considerable proportion of AI patients experience severe fatigue. Salivary cortisol level is not a significant predictor for momentary fatigue in AI patients.

From the Journal of Immunology Research, 11 March 2014, 5 pages. Downloads full text

Unique Cytokine Signature in the Plasma of Patients with Fibromyalgia

Jamie Sturgill(1,2). Elizabeth McGee (2,3), and Victoria Menzies (1,2).
1) School of Nursing, Virginia Commonwealth University, Richmond, VA 23298, USA
2) Institute of Women's Health, Virginia Commonwealth University, Richmond, VA 23298, USA
3) Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont, Burlington, VT 05401, USA


Fibromyalgia (FMS) is a chronic pain syndrome with a complex but poorly understood pathogenesis affecting approximately 10 million adults in the United States. The lack of a clear etiology of FMS has limited the effective diagnosis and treatment of this debilitating condition.

The objective of this secondary data analysis was to examine plasma cytokine levels in women with FMS using the Bio-Plex Human Cytokine 17-plex Assay. Post hoc analysis of plasma cytokine levels was performed to evaluate patterns that were not specified a priori.

Upon examination, patients with FMS exhibited a marked reduction in cytokines such as IL-4, IL-5, and IL-13.

The finding of this pattern of altered cytokine milieu not only supports the role of inflammation in FMS but also may lead to more definitive diagnostic tools for clinicians treating FMS. The suppression provides strong evidence of immune dysregulation in patients with FMS.

From the Journal of Neuropsychology, 24 September 2013.[Epub ahead of print]

Attention network test: Assessment of cognitive function in chronic fatigue syndrome.

Togo F(1), Lange G, Natelson BH, Quigley KS.
1) Educational Physiology Laboratory, Graduate School of Education, University of Tokyo, Japan.


Information processing difficulties are common in patients with chronic fatigue syndrome (CFS). It has been shown that the time it takes to process a complex cognitive task, rather than error rate, may be the critical variable underlying CFS patients' cognitive complaints.

The Attention Network Task (ANT) developed by Fan and colleagues may be of clinical utility to assess cognitive function in CFS, because it allows for simultaneous assessment of mental response speed, also called information processing speed, and error rate under three conditions challenging the attention system.

Comparison of data from two groups of CFS patients (those with and without comorbid major depressive disorder; n = 19 and 22, respectively) to controls (n = 29) consistently showed that error rates did not differ among groups across conditions, but speed of information processing did. Processing time was prolonged in both CFS groups and most significantly affected in response to the most complex task conditions. For simpler tasks, processing time was only prolonged in CFS participants with depression. The data suggest that the ANT may be a task that could be used clinically to assess information processing deficits in individuals with CFS.

From Biological Markers and Guided Therapy, Vol. 1, 2014, no. 1, 25-38.

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and the Potential Role of T Cells

S. L. Hardcastle(a*), E. W. Brenu(a), D.R. Staines (a,b), S. Marshall-Gradisnik(a)
a) National Centre for Neuroimmunology and Emerging Diseases, Griffith Health Institute, School of Medical Science, Griffith University, Gold Coast, QLD, Australia
b) Queensland Health, Gold Coast Public Health Unit Robina, Gold Coast, Queensland, Australia


Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) is a multifactorial disorder defined by symptom-specific criteria and characterised by severe and prolonged fatigue. CFS/ME typically affects a variety of bodily systems, including the immune system.

Patients with CFS/ME exhibit significantly reduced Natural Killer (NK) cell activity suggesting immune which may be hallmarks of changes in the adaptive immune system, potentially including T cell subsets and function. The principal purpose of T cells is to regulate immune responses and maintain immune homeostasis. These regulatory measures can often be compromised during illness and may present in a number of diseases including CFS/ME.

This review paper examines the role of T cells in CFS/ME and the potential impact of T cells on CFS/ME immune profiles with an evaluation of the current literature.

From Psychoneuroendocrinology, April 2014.

The role of hypocortisolism in chronic fatigue syndrome.

Nijhof SL(1), Rutten JM(2), Uiterwaal CS(3), Bleijenberg G(4), Kimpen JL(5), Putte EM(6).
1) Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address:
2) Department of Paediatrics, Emma Children's Hospital, Academic Medical Centre, Amsterdam, The Netherlands. Electronic address:
3) Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address:
4) Expert Centre for Chronic Fatigue, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. Electronic address:
5) Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address:
6_ Department of Paediatrics, Wilhelmina Children's Hospital, University Medical Centre Utrecht, Utrecht, The Netherlands. Electronic address:



There is accumulating evidence of hypothalamic-pituitary-adrenal (HPA) axis hypofunction in chronic fatigue syndrome (CFS). However, knowledge of this hypofunction has so
far come exclusively from research in adulthood, and its clinical significance remains unclear. The objective of the current study was to assess the role of the HPA-axis in adolescent CFS and recovery from adolescent CFS.


Before treatment, we compared the salivary cortisol awakening response of 108 diagnosed adolescent CFS patients with that of a reference group of 38 healthy peers. Salivary cortisol awakening response was measured again after 6 months of treatment in CFS patients.


Pre-treatment salivary cortisol levels were significantly lower in CFS-patients than in healthy controls. After treatment recovered patients had a significant rise in salivary cortisol output attaining normalization, whereas non-recovered patients improved slightly, but not significantly.

The hypocortisolism found in CFS-patients was significantly correlated to the amount of sleep. Logistic regression analysis showed that an increase of one standard deviation in the difference between pre- and post-treatment salivary cortisol awakening response was associated with a 93% higher odds of recovery (adjusted OR 1.93 (1.18 to 3.17), p=0.009). Pre-treatment salivary cortisol did not predict recovery.


Hypocortisolism is associated with adolescent CFS. It is not pre-treatment cortisol but its change to normalization that is associated with treatment success. We suggest that this finding may have clinical implications regarding the adaptation of future treatment strategies.

From Cell Host and Microbe, March 2014.

Endogenous retroviruses and human cancer: is there anything to the rumors?

Bhardwaj N(1), Coffin JM(2).
1) Department of Molecular Biology and Microbiology, Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA.
2) Department of Molecular Biology and Microbiology, Graduate Program in Molecular Microbiology, Sackler School of Graduate Biomedical Sciences, Tufts University, 136 Harrison Avenue, Boston, MA 02111, USA. Electronic address:


Xenotropic murine leukemia virus-related virus (XMRV) infection was incorrectly associated with prostate cancer and chronic fatigue syndrome (CFS) in recent years. In this forum, we discuss the story of XMRV and how we can apply lessons learned here to inform the debate surrounding cancers associated with human endogenous retroviruses

From Alimentary Pharmacology and Therapeutics, 18 March 2014. [Epub ahead of print].

Systematic review: faecal microbiota transplantation therapy for digestive and nondigestive disorders in adults and children.

Sha S(1), Liang J, Chen M, Xu B, Liang C, Wei N, Wu K.
1) State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi Province, China.



There has been growing interest in the use of faecal microbiota transplantation (FMT) for the treatment of gastrointestinal and nongastrointestinal diseases.


To review systematically the reported efficacy and safety of FMT in the management of gastrointestinal and non gastrointestinal disorders in adults and children.


The systematic review followed Cochrane and PRISMA recommendations. Available articles were identified using three electronic databases in addition to hand searching and contacting experts. Inclusion criteria were any reports of FMT therapy written in English.


A total of 844 patients who had undergone FMT were identified from 67 published studies. The most common indications were refractory/relapsing Clostridium difficile infection (CDI) (76.3%) and inflammatory bowel disease (IBD) (13.2%).

There has been only one placebo-controlled trial, a successful trial in 43 patients with recurrent CDI. Seven publications report FMT in paediatric patients with a total of 11 treated, 3 with chronic constipation and the remainder with recurrent CDI or ulcerative colitis (UC). 90.7% of patients with refractory/relapsing CDI were cured and 78.4% of patients with IBD were in remission after FMT. FMT therapy could also be effective in treatment of some nongastrointestinal disorders such as chronic fatigue syndrome. The only reported serious adverse event attributed to the therapy was a case of suspected peritonitis.


Although more controlled trials are needed, faecal microbiota transplantation therapy shows promise in both adults and children with gastrointestinal diseases such as CDI and IBD.

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