salivary cortisol – American ME and CFS Society

A Case Report of Chronic Epipharyngitis With Chronic Fatigue Treated With Epipharyngeal Abrasive Therapy (EAT)

Abstract:

A case of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) with chronic epipharyngitis was treated with epipharyngeal abrasive therapy (EAT). The symptoms of ME/CFS improved along with the improvement of chronic epipharyngitis. The patient was followed up with endocrine and autonomic function tests.

Endocrine function tests included salivary cortisol and salivary α-amylase activity. Salivary α-amylase activity was stimulated by EAT. EAT improved the diurnal variability of salivary cortisol secretion. Autonomic function tests included heart rate variability analysis by orthostatic stress test. EAT normalized parasympathetic and sympathetic reflexes over time and regulated autonomic balance.

Based on the improvement of symptoms and test results, EAT was considered effective for ME/CFS. A literature review was conducted on the mechanism of the therapeutic effect of EAT on ME/CFS.

Source: Hirobumi I. A Case Report of Chronic Epipharyngitis With Chronic Fatigue Treated With Epipharyngeal Abrasive Therapy (EAT). Cureus. 2024 Feb 23;16(2):e54742. doi: 10.7759/cureus.54742. PMID: 38405656; PMCID: PMC10884883. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10884883/ (Full text)

Links between Serotonin Levels and Stress: Cortisol, Candida A./Mycetes, Omega 3/6 Ratio and Dysbiosis (Skatole/Indoxyl Sulfate) Role in Chronic Fatigue Syndrome (CFS) and Depression

Abstract:

Intestinal microbiota attracts daily attention of a growing number of study which have attempted to link gut dysbiosIs with a variety of disease states: irritable bowel syndrome (IBS), inflamed bowel disease (IBD), Crohn’s disease (CD), leaky gut syndrome (LGS), food intolerance, diabetes, metabolic syndrome, cancer, etc.

In our study we analyzed how intestinal dysbiosis may be related to chronic fatigue syndrome (CFS) and depression through the exchange of information through the gut-brain axis (GBA).

We studied 33 subjects, 13 males and 20 females, who reported CFS or/and depression: we investigated their salivary cortisol levels, blood serotonin, omega 3/6 ratio, intestinal dysbiosis (calculated on the urinary levels of indoxyl sulfate and skatole), and we looked for the presence of Candida a. or mycetes in the stool; the data accumulated with this research show a correlation between the presence of Candida a./miceti, indoxyl sulfate urine values beyond the physiological and low serotonin levels.

In addition, data analysis showed that the EPA/DHA values also show pro-inflammatory levels in case of dysbiosis and low serotonina levels. The relationship, however, with cortisol levels requires further research although this study showed a statistically significant positive correlation between these values, measured at specific times, and serotonin levels.

Aims: We investigated the relationship between stress (evaluated through the measurement of salivary cortisol levels) and gastrointestinal efficiency measured as a function of intestinal fermentative and putrefactive dysbiosis, evaluating the levels of urinary indoxyl sulfate in the first case (a possible correlation with the presence of Candida spp or Mycetes in the subjects feces was investigated), urinary skatole levels in the second one, in patients with chronic fatigue syndrome (SFC) and depression.

In these patients we also have studied omega 3/6 ratio, and finally we have analized the impact that the alteration of these parameters can have on the serotonin levels.

This research attemps to highlight the contact points, in some cases not so obvious, among these topics, contact points that, although they give us interesting indications, show the need to be further deepened by analyzing a larger amount of data.

Source: Orlandoni, D.; Di Fede, G.; Mantovani, M.; Nava, C.R.; Tomasi, M.; Fusi, P. Links between Serotonin Levels and Stress: Cortisol, Candida A./Mycetes, Omega 3/6 Ratio and Dysbiosis (Skatole/Indoxyl Sulfate) Role in Chronic Fatigue Syndrome (CFS) and Depression. Preprints 2023, 2023090253. https://doi.org/10.20944/preprints202309.0253.v1 https://www.preprints.org/manuscript/202309.0253/v1 (Full text available as PDF file)

Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome

Abstract:

Hypocortisolism has been found in CFS patients in blood, urine, and saliva. It is unclear if hypocortisolism can also be demonstrated using long-term cortisol measurements, such as cortisol in hair. In addition, the interaction between the HPA axis and the immune system, both expected to play an important role in CFS, is unclear. The objective of the current study was to compare hair and salivary cortisol concentrations in a cohort of female CFS patients to those in healthy controls, and to test the effect of an interleukin-1 receptor antagonist (anakinra) on the HPA axis.

Salivary cortisol concentrations of 107 CFS patients were compared to 59 healthy controls, with CFS patients showing a decreased cortisol awakening response (4.2 nmol/L ± 5.4 vs 6.1 nmol/L ± 6.3, p = 0.036). Total cortisol output during the day did not differ significantly in saliva, but there was a trend to lower hair cortisol in a subset of 46 patients compared to 46 controls (3.8 pg/mg ± 2.1 vs 4.3 pg/mg ± 1.8, p = 0.062). After four weeks of treatment with either daily anakinra (100 mg/day) or placebo, there was a slight decrease of hair cortisol concentrations in the anakinra group compared to an increase in the placebo group (p = 0.022). This study confirms the altered dynamics of the HPA axis in a group of CFS patients, and for the first time shows that this might also be present for long-term cortisol measures.

Source: Roerink ME, Roerink SHPP, Skoluda N, van der Schaaf ME, Hermus ARMM, van der Meer JWM, Knoop H, Nater UM. Hair and salivary cortisol in a cohort of women with chronic fatigue syndrome. Horm Behav. 2018 May 25. pii: S0018-506X(17)30569-X. doi: 10.1016/j.yhbeh.2018.05.016. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/29807037

Cortisol output in adolescents with chronic fatigue syndrome: pilot study on the comparison with healthy adolescents and change after cognitive behavioural guided self-help treatment

Abstract:

OBJECTIVE: This study examined cortisol in adolescents with chronic fatigue syndrome (CFS) compared to healthy adolescents and changes in cortisol after cognitive behavioural guided self-help treatment. Exploratory analyses investigated the association between cortisol output and psychological variables.

METHODS: Salivary cortisol was measured upon awakening, at 15, 30, 45 and 60 min afterwards and at 12 noon, 4:00 p.m. and 8:00 p.m., in adolescents with CFS and healthy controls (HC). Groups were matched for age, gender, menarche status, menstrual cycle and awakening time. Twenty-four adolescents with CFS provided saliva samples six months after treatment. The main outcome measure was total salivary output over the day, calculated by area under the curve (AUC). The salivary awakening response was also assessed.

RESULTS: Cortisol output over the day was significantly lower in the CFS group (n=46) than in healthy controls (n=33). Within the CFS group, lower daily cortisol output was associated with higher self-reported perfectionist striving and prosocial behaviour. There were no significant group differences in the awakening response (n=47 CFS versus n=34 HC). After treatment, adolescents with CFS (n=21) showed a significant increase in daily cortisol output, up to normal levels.

CONCLUSION: The reduced daily cortisol output in adolescents with CFS is in line with adult findings. Associations between reduced cortisol output and two psychological variables-perfectionism and prosocial behaviour-are consistent with cognitive behavioural models of chronic fatigue syndrome. The mild hypocortisolism is reversible; cortisol output had returned to healthy adolescent levels by six months after cognitive behavioural guided self-help treatment.

Source: Rimes KA, Papadopoulos AS, Cleare AJ, Chalder T. Cortisol output in adolescents with chronic fatigue syndrome: pilot study on the comparison with healthy adolescents and change after cognitive behavioural guided self-help treatment. J Psychosom Res. 2014 Nov;77(5):409-14. doi: 10.1016/j.jpsychores.2014.08.018. Epub 2014 Sep 8.https://www.ncbi.nlm.nih.gov/pubmed/25260861

Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome?

Abstract:

BACKGROUND: There is evidence that patients with chronic fatigue syndrome (CFS) have mild hypocortisolism. The clinical significance of this is unclear. We aimed to determine whether hypocortisolism exerted any effect on the response of CFS to cognitive behavioural therapy (CBT).

METHOD: We measured 24-h urinary free cortisol (UFC) in 84 patients with Centers for Disease Control and Prevention (CDC)-defined CFS (of whom 64 were free from psychotropic medication) who then received CBT in a specialist, tertiary out-patient clinic as part of their usual clinical care. We also measured salivary cortisol output from 0800 to 2000 h in a subsample of 56 psychotropic medication-free patients.

RESULTS: Overall, 39% of patients responded to CBT after 6 months of treatment. Lower 24-h UFC output was associated with a poorer response to CBT but only in psychotropic medication-free patients. A flattened diurnal profile of salivary cortisol was also associated with a poor response to CBT.

CONCLUSIONS: Low cortisol is of clinical relevance in CFS, as it is associated with a poorer response to CBT. Hypocortisolism could be one of several maintaining factors that interact in the persistence of CFS.

Source: Roberts AD, Charler ML, Papadopoulos A, Wessely S, Chalder T, Cleare AJ. Does hypocortisolism predict a poor response to cognitive behavioural therapy in chronic fatigue syndrome? Psychol Med. 2010 Mar;40(3):515-22. doi: 10.1017/S0033291709990390. Epub 2009 Jul 17. https://www.ncbi.nlm.nih.gov/pubmed/19607750

Evidence for T-helper 2 shift and association with illness parameters in chronic fatigue syndrome (CFS)

Abstract:

Few immunological markers have been consistently reported in CFS. However, a shift to a T-helper 2 (Th2) type immune response has been hypothesized for individuals with CFS. The current study investigated whether individuals with CFS who exhibited a stronger shift towards a Th2 type of immune response would also exhibit more severe symptoms, poorer neurocognitive functioning, and poorer physical and psychosocial functioning.

The current investigation measured the percentage of Th1-like and Th2-like memory cells using cell surface flow cytometry in 114 individuals with CFS. The associations between the ratio of Th1 and Th2 memory cells and various illness parameters measures were then examined, including symptom severity, psychiatric functioning, neurocognitive functioning, salivary cortisol levels, and chronic pain status.

Results indicated that individuals who exhibited a more extreme shift towards a Th2 immune response also exhibited poorer sleep and high levels of basal salivary cortisol. The implications of these findings are discussed.

Source: Torres-Harding S, Sorenson M, Jason LA, Maher K, Fletcher MA. Evidence for T-helper 2 shift and association with illness parameters in chronic fatigue syndrome (CFS). Bull IACFS ME. 2008 Fall;16(3):19-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3018761/ (Full article)

Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine diurnal salivary cortisol rhythms and plasma IL-6 concentrations in persons with chronic fatigue syndrome (CFS), persons not fulfilling a diagnosis of CFS (we term them cases with insufficient symptoms or fatigue, ISF) and nonfatigued controls (NF). Previous studies of CFS patients have implicated the hypothalamic-pituitary-adrenal axis and the immune system in the pathophysiology of CFS, although results have been equivocal.

METHODS: Twenty-eight people with CFS, 35 persons with ISF, and 39 NF identified from the general population of Wichita, Kansas, were admitted to a research ward for 2 days. Saliva was collected immediately on awakening (6:30 AM), at 08:00 AM, 12 noon, 4:00 PM, 8:00 PM and at bedtime (10:00 PM) and plasma was obtained at 7:30 AM. Salivary cortisol concentrations were assessed using radioimmunoassay, and plasma IL-6 was measured using sandwich enzyme-linked immunosorbent assay.

RESULTS: People with CFS demonstrated lower salivary cortisol concentrations in the morning and higher salivary cortisol concentrations in the evening compared with both ISF and NF groups indicating a flattening of the diurnal cortisol profile. Mean plasma IL-6 concentrations were highest in CFS compared with the other groups, although these differences were no longer significant after controlling for BMI. Attenuated decline of salivary cortisol concentrations across the day and IL-6 concentration were associated with fatigue symptoms in CFS.

CONCLUSIONS: These results suggest an altered diurnal cortisol rhythm and IL-6 concentrations in CFS cases identified from a population-based sample.

Source: Nater UM, Youngblood LS, Jones JF, Unger ER, Miller AH, Reeves WC, Heim C. Alterations in diurnal salivary cortisol rhythm in a population-based sample of cases with chronic fatigue syndrome. Psychosom Med. 2008 Apr;70(3):298-305. doi: 10.1097/PSY.0b013e3181651025. Epub 2008 Mar 31. https://www.ncbi.nlm.nih.gov/pubmed/18378875

The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome

Abstract:

Hypocortisolism has been reported in chronic fatigue syndrome (CFS), with the significance of this finding to disease etiology unclear. This study examined cortisol levels and their relationships with symptoms in a group of 108 individuals with CFS. CFS symptoms examined included fatigue, pain, sleep difficulties, neurocognitive functioning, and psychiatric status. Alterations in cortisol levels were examined by calculation of mean daily cortisol, while temporal variation in cortisol function was examined by means of a regression slope. Additionally, deviation from expected cortisol diurnal pattern was determined via clinical judgment. Results indicated that fatigue and pain were associated with salivary cortisol levels. In particular, variance from the expected pattern of cortisol was associated with increased levels of fatigue. The implications of these findings are discussed.

Source: Torres-Harding S, Sorenson M, Jason L, Maher K, Fletcher MA, Reynolds N, Brown M. The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome. J Appl Biobehav Res. 2008 Jan 1;13:157-180. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/ (Full article)

Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls

Abstract:

CONTEXT: A substantial body of research on the pathophysiology of chronic fatigue syndrome (CFS) has focused on hypothalamic-pituitary-adrenal axis dysregulation. The cortisol awakening response has received particular attention as a marker of hypothalamic-pituitary-adrenal axis dysregulation.

OBJECTIVE: The objective of the current study was to evaluate morning salivary cortisol profiles in persons with CFS and well controls identified from the general population.

DESIGN AND SETTING: We conducted a case-control study at an outpatient research clinic.

CASES AND OTHER PARTICIPANTS: We screened a sample of 19,381 residents of Georgia and identified those with CFS and a matched sample of well controls. Seventy-five medication-free CFS cases and 110 medication-free well controls provided complete sets of saliva samples.

MAIN OUTCOME MEASURES: We assessed free cortisol concentrations in saliva collected on a regular workday immediately upon awakening and 30 and 60 min after awakening.

RESULTS: There was a significant interaction effect, indicating different profiles of cortisol concentrations over time between groups, with the CFS group showing an attenuated morning cortisol profile. Notably, we observed a sex difference in this effect. Women with CFS exhibited significantly attenuated morning cortisol profiles compared with well women. In contrast, cortisol profiles were similar in men with CFS and male controls.

CONCLUSIONS: CFS was associated with an attenuated morning cortisol response, but the effect was limited to women. Our results suggest that a sex difference in hypocortisolism may contribute to increased risk of CFS in women.

Source: Nater UM, Maloney E, Boneva RS, Gurbaxani BM, Lin JM, Jones JF, Reeves WC, Heim C. Attenuated morning salivary cortisol concentrations in a population-based study of persons with chronic fatigue syndrome and well controls. J Clin Endocrinol Metab. 2008 Mar;93(3):703-9. Epub 2007 Dec 26. https://www.ncbi.nlm.nih.gov/pubmed/18160468

Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome

Abstract:

BACKGROUND: The aim of the present study was to obtain a naturalistic measure of diurnal hypothalamic-pituitary-adrenal (HPA) axis output in CFS patients unaffected by medication or comorbid psychiatric disorder likely to influence the axis.

METHOD: Cortisol and cortisone levels were measured in saliva samples collected from 0600 h to 2100 h at 3-h intervals in CFS patients and healthy controls.

RESULTS: Mean cortisol and cortisone concentrations were significantly lower in patients than controls across the whole day, as were levels at each individual time point except 2100 h. Cosinor analysis showed a significant diurnal rhythm of cortisol and cortisone that was not phase-shifted in CFS compared to controls. However, there was a lower rhythm-adjusted mean and a lower amplitude in CFS patients. The cortisol/cortisone ratio showed no diurnal rhythm and did not differ between CFS subjects and controls.

LIMITATIONS: The sample size was relatively small, and drawn from specialist referral patients who had been ill for some time; generalisation of these results to other populations is therefore unwarranted.

CONCLUSION: The main findings of this study are to provide further evidence for reduced basal HPA axis function in at least some patients with CFS and to show for the first time that salivary cortisone is also reduced in CFS and has a diurnal rhythm similar to that of cortisol. We have also demonstrated that the cortisol/cortisone ratio remains unchanged in CFS, suggesting that increased conversion of cortisol to cortisone cannot account for the observed lowering of salivary cortisol.

Source: Jerjes WK, Cleare AJ, Wessely S, Wood PJ, Taylor NF. Diurnal patterns of salivary cortisol and cortisone output in chronic fatigue syndrome. J Affect Disord. 2005 Aug;87(2-3):299-304. http://www.ncbi.nlm.nih.gov/pubmed/15922454