adrenals – American ME and CFS Society

A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue

Abstract:

Fibromyalgia Syndrome (FMS) and Chronic Fatigue Syndrome (CFS) are complex medical conditions with similar symptoms such as anxiety, fatigue, depression, headaches, muscle aches and joint pain. The etiology of both these syndromes is unknown. The objective of this study is to characterize FMS, both in the presence and in the absence of CFS, by analyzing variations in cortisol secretion patterns, timings, amplitudes, and the number of the underlying pulses as well as infusion and clearance rates.

The comparison is performed against matched healthy control subjects. We estimate the hormonal secretory events by deconvolving cortisol data using a two-step coordinate descent approach. The first step implements a sparse recovery approach to infer the amplitudes and the timings of the cortisol secretion events from limited cortisol hormone data. The main advantage of this method is estimating the cortisol secretory events using a system theoretic approach. The second step is to estimate the physiological system parameters (i.e. infusion and clearance rates). This approach has been verified on healthy individuals previously.

Our results show that the clearance rate of cortisol by the liver is relatively lower in patients as compared to the matched healthy individuals. This suggests that there is a relatively higher accumulation of serum cortisol in patients when compared to matched healthy subjects.

Source: Pednekar DD, Amin MR, Azgomi HF, Aschbacher K, Crofford LJ, Faghih RT. A System Theoretic Investigation of Cortisol Dysregulation in Fibromyalgia Patients with Chronic Fatigue. Conf Proc IEEE Eng Med Biol Soc. 2019 Jul;2019:6896-6901. doi: 10.1109/EMBC.2019.8857427. https://www.ncbi.nlm.nih.gov/pubmed/31947425

An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome

Abstract:

Chronic fatigue syndrome (CFS) is one of the most intractable diseases and is characterized by severe central fatigue that impairs even daily activity. To date, the pathophysiological mechanisms are uncertain and no therapies exist. Therefore, a proper animal model reflecting the clinical features of CFS is urgently required.

We compared two CFS animal models most commonly used, by injection with lipopolysaccharide (LPS from Escherichia coli O111:B4) or polyinosinic: polycytidylic acid (poly I:C), along with bilateral adrenalectomy (ADX) as another possible model. Both LPS- and poly I:C-injected mice dominantly showed depressive behaviors, while ADX led to fatigue-like performances with high pain sensitivity.

In brain tissues, LPS injection notably activated microglia and the 5-hydroxytryptamine (HT)1A receptor in the prefrontal cortex and hippocampus. Poly I:C-injection also remarkably activated the 5-HT transporter and 5-HT1A receptor with a reduction in serotonin levels in the brain. ADX particularly activated astrocytes and transforming growth factor beta (TGF-β) 1 in all brain regions.

Our results revealed that LPS and poly I:C animal models approximate depressive disorder more closely than CFS. We suggest that ADX is a possible method for establishing a mouse model of CFS reflecting clinical features, especially in neuroendocrine system.

Source: Lee JS, Jeon YJ, Park SY, Son CG. An Adrenalectomy Mouse Model Reflecting Clinical Features for Chronic Fatigue Syndrome. Biomolecules. 2020 Jan 1;10(1). pii: E71. doi: 10.3390/biom10010071. https://www.mdpi.com/2218-273X/10/1/71 (Full article)

Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is characterized by fatigue lasting 6 months or longer. CFS has been associated with a disturbed (re-)activity of the autonomic nervous system. However, the sympathetic adrenomedulla (SAM) remains under-examined in CFS.

To investigate SAM reactivity, we implemented a submaximal cycle ergometry (ERGO) and a pharmacological test (Insulin Tolerance Test, ITT) in 21 CFS patients and 20 age-, sex-, and BMI-matched controls. Plasma norepinephrine and epinephrine were collected once before and twice after the tests (+10/+20, and +30 min).

Lower baseline levels and attenuated responses of epinephrine to the ERGO were found in CFS patients compared to controls, while the groups did not differ in their responses to the ITT.

To conclude, we found evidence of altered sympathetic-neural and SAM reactivity in CFS. Exercise stress revealed a subtle catecholaminergic hyporeactivity in CFS patients. It is conceivable that inadequate catecholaminergic responses to physical exertion might contribute to CFS symptoms.

Source: Strahler J, Fischer S, Nater UM, Ehlert U, Gaab J. Norepinephrine and epinephrine responses to physiological and pharmacological stimulation in chronic fatigue syndrome. Biol Psychol. 2013 Sep;94(1):160-6. doi: 10.1016/j.biopsycho.2013.06.002. Epub 2013 Jun 13. https://www.ncbi.nlm.nih.gov/pubmed/23770415

Disturbed adrenal function in adolescents with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate adrenal function in children and adolescents with chronic fatigue syndrome (CFS) compared with age-matched controls.

METHODS: Case-control study of low dose (500 ng/m2) synacthen tests (LDST) in 23 adolescents with CFS and 17 age-matched controls. Serum cortisol concentrations were measured at 5-min intervals from 10 to 45 minutes. Peak serum cortisol concentration, time to peak, rise in cortisol and area under the curve (AUC) were derived.

RESULTS: Patients with CFS had significantly lower mean cortisol levels during the LDST (p <0.001), lower peak cortisol (p <0.025), reduced cortisol AUC (p <0.005) and longer time to peak cortisol (p <0.05). Abnormalities were seen in both sexes but were more pronounced in females. Unstimulated adrenal androgen and 17-hydroxyprogesterone concentrations were normal.

CONCLUSIONS: Adolescents with CFS have subtle alterations in adrenal function suggesting a reduction in central stimulation of the adrenal glands. The more pronounced effects in females may reflect differential central effects of stress on hypothalamic-pituitary-adrenal axis regulation between the sexes.

Source: Segal TY, Hindmarsh PC, Viner RM. Disturbed adrenal function in adolescents with chronic fatigue syndrome. J Pediatr Endocrinol Metab. 2005 Mar;18(3):295-301. http://www.ncbi.nlm.nih.gov/pubmed/15813608

Assessing chronic fatigue

Comment on: The head-up tilt test with haemodynamic instability score in diagnosing chronic fatigue syndrome. [QJM. 2003]

Naschitz et al.1 studied patients with chronic fatigue syndrome (CFS) in comparison with some controls ‘exhibiting shared clinical features with CFS’, namely, patients with non-CFS chronic fatigue, fibromyalgia, generalized anxiety disorder, and neurally mediated syncope. Considering that those controls were included in the study on the basis of the clinical overlap of their disorders with CFS, it is surprising that Naschitz et al. failed to include also patients with Addison’s disease, which resembles CFS far more closely than does any other medical condition.2

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/96/6/454.long

Source: Baschetti R. Assessing chronic fatigue. QJM. 2003 Jun;96(6):454. http://qjmed.oxfordjournals.org/content/96/6/454.long (Full article)

Chronic fatigue syndrome: a form of Addison’s disease

Dear Sir, Evengård et al.’s article [1] on chronic fatigue syndrome (CFS) is disappointing, because in their review, despite its 15 pages and 165 references, there is not a single word about the staggering similarity between CFS and Addison’s disease. As someone whose CFS symptoms resolved dramatically with an old remedy for Addison’s disease [2], I understandably found that review even more disappointing.

To compensate for Evengård et al.’s failure to mention both the impressive overlap of CFS with Addison’s disease and its clinical implications, I summarize here these issues.

CFS and Addison’s disease share 36 features [3–6]. Three others, however, are to be added. In fact, reduction in adrenal gland size [7], antibodies against the adrenal gland [8] and respiratory muscle dysfunction [9], besides being present in CFS [7–9], have also been found in Addison’s disease [10–12]. In view of the 39 features that CFS shares with Addison’s disease [3–12] (see Table 1), which constitute a similarity between two distinctly named diseases that is probably unequalled in the medical literature, it seems arguable that CFS should practically be viewed as a form of Addison’s disease [13]. One could object that CFS patients, unlike Addisonian subjects, do not display hyperpigmentation or basal hypocortisolaemia. Neither abnormality, however, is a constant presenting feature of Addison’s disease [14].

You can read the rest of this comment here: http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2000.00695.x/full

Source: Baschetti R. Chronic fatigue syndrome: a form of Addison’s disease. J Intern Med. 2000 Jun;247(6):737-9. http://onlinelibrary.wiley.com/doi/10.1046/j.1365-2796.2000.00695.x/full (Full article)

Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study

Abstract:

No inclusive or satisfactory biomedical explanation for chronic fatigue syndrome (CFS) has as yet been forwarded. Recent research suggests that a dysregulated hypothalamic-pituitary-adrenal axis (HPA) may be contributory, and in particular that there may be diminished forward drive and adrenal under-stimulation.

In this preliminary study we wished to examine a cohort of CFS patients in whom evidence for such hypofunctioning was found. Our aim was to establish whether these patients had altered adrenal gland size.

Patients were recruited from a fatigue clinic. Those who fulfilled the Centre for Disease Control and Prevention (CDC) criteria underwent a 1 microgram adrenocorticotropin (ACTH) stimulation test, a test of adrenal gland functioning.

Eight subjects (five females, three males) with a subnormal response to this test underwent a computer tomography (CT) adrenal gland assessment. Measurements were compared with those from a group of 55 healthy subjects.

The right and left adrenal gland bodies were reduced by over 50% in the CFS subjects indicative of significant adrenal atrophy in a group of CFS patients with abnormal endocrine parameters.

This is the first study to use imaging methods to measure adrenal gland size in CFS. It is a limitation of this study that a selected CFS sample was employed. A future larger study would optimally employ an unselected cohort of CFS patients. This study has implications not only for the elucidation of CFS pathophysiology, but also for possible therapeutic strategies.

Source: Scott LV, Teh J, Reznek R, Martin A, Sohaib A, Dinan TG. Small adrenal glands in chronic fatigue syndrome: a preliminary computer tomography study. Psychoneuroendocrinology. 1999 Oct;24(7):759-68. http://www.ncbi.nlm.nih.gov/pubmed/10451910

Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health

Abstract:

BACKGROUND: Hyperactivity and hypoactivity of the HPA have been forwarded as of pathophysiological relevance in major depressive disorder and chronic fatigue syndrome (CFS), respectively.

METHODS: This study examines cortisol levels in the two disorders, and also assesses levels of the adrenal androgens, dehydroepiandrosterone (DHEA) and its sulphate derivative (DHEA-S), and 17-alpha-hydroxyprogesterone; 15 subjects with CFS diagnosed according to CDC criteria, 15 subjects with DSM III-R major depression and 11 healthy subjects were compared.

RESULTS: DHEA and DHEA-S levels were significantly lower in the CFS compared to the healthy group; DHEA-S levels, but not DHEA, were lower in the depressives; cortisol and 17-alpha-hydroxyprogesterone did not differ between the three groups.

CONCLUSIONS: A potential role for DHEA, both therapeutically and as a diagnostic tool, in CFS, is suggested.

Source: Scott LV, Salahuddin F, Cooney J, Svec F, Dinan TG. Differences in adrenal steroid profile in chronic fatigue syndrome, in depression and in health. J Affect Disord. 1999 Jul;54(1-2):129-37. http://www.ncbi.nlm.nih.gov/pubmed/10403156