Chronic fatigue syndrome possibly explained by lower levels of key thyroid hormones

Press Release: New research demonstrates a link between chronic fatigue syndrome (CFS) symptoms and lower thyroid hormone levels. Published in Frontiers in Endocrinology, the study indicates that CFS, a condition with unknown causes, can be explained by lower thyroid hormones — but may be distinct from thyroidal disease. This finding can be seen as a first step to finding treatment for a debilitating illness for which there is no recognized treatment.

Chronic fatigue syndrome is a common disease marked by lengthy spells of weakness, fatigue and depression. Its diagnosis is predominantly based on symptoms and on ruling out any underlying medical condition, rather than on laboratory tests and physical examination.

Interestingly, several symptoms resemble those of hypothyroidism — a condition where the thyroid gland does not produce enough thyroid hormone. In hypothyroidism, the body tries to encourage thyroid hormone activity by releasing more thyroid-stimulating hormone — however, this does not happen in patients with chronic fatigue syndrome.

This contrast in thyroid-stimulating activity led the study’s authors to hypothesize that chronic fatigue syndrome is caused by low activity of thyroid hormones in the absence of thyroidal disease.

Led by Dr. Begoña Ruiz-Núñez at the University Medical Center Groningen, The Netherlands, the researchers compared thyroid function and markers of inflammation between 98 CFS patients and 99 healthy controls. Remarkably, the CFS patients had lower serum levels of certain key thyroid hormones such as triiodothyronine (T3) and thyroxine (T4), but normal levels of thyroid-stimulating hormone.

Additional analyses indicated that CFS patients had a lower urinary iodine status and low-grade inflammation, which possibly mirrored the symptoms of patients with hypothyroidism. These CFS patients, however, had relatively higher levels of another thyroid hormone called “reverse T3” or rT3. This appeared to be due to a shift in hormone production, where the body preferred to convert T4 to rT3 instead of producing T3. The low T3 levels found in CFS patients coupled with this switchover to rT3 could mean that T3 levels are severely reduced in tissue.

“One of the key elements of our study is that our observations persisted in the face of two sensitivity analyses to check the strength of the association between CFS and thyroid parameters and low-grade inflammation,” says Dr. Ruiz-Núñez. “This strengthens our test results considerably.”

The researchers believe inclusion of patient information, such as duration of illness, would enable a correlation with their biochemical profiles. Further, even though the study demonstrates a link between chronic fatigue syndrome symptoms and low levels of key thyroid hormones, a definitive cause for CFS remains unknown.

If the study findings are confirmed by additional research, it may pave the way for a treatment for chronic fatigue syndrome.

Source: Eurekalert

Higher prevalence of ‘low T3 syndrome’ in patients with chronic fatigue syndrome: A case-control study

Abstract:

Chronic fatigue syndrome (CFS) is a heterogeneous disease with unknown cause(s). CFS symptoms resemble a hypothyroid state, possibly secondary to chronic (low-grade) (metabolic) inflammation. We studied 98 CFS patients (21-69 years, 21 males) and 99 age- and sex-matched controls (19-65 years, 23 males). We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation.

Most remarkably, CFS patients exhibited similar TSH, but lower FT3 (difference of medians 0.1%), TT4 (11.9%), TT3 (12.5%), %TT3 (4.7%), SPINA-GD (14.4%), SPINA-GT (14.9%), 24-hour urinary iodine (27.6%) and higher %rT3 (13.3%). FT3 below the reference range, consistent with the ‘low T3 syndrome’, was found in 16/98 CFS patients vs. 7/99 controls (OR 2.56; 95% CI=1.00 – 6.54). Most observations persisted in two sensitivity analyses with more stringent cut-off values for BMI, hsCRP and WBC.

We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C). FT3, TT3, TT4 and rT3 correlated positively with hsCRP in CFS patients and all subjects. TT3 and TT4 were positively related to hsCRP in controls. Low circulating T3 and the apparent shift from T3 to rT3 may reflect more severely depressed tissue T3 levels.

The present findings might be in line with recent metabolomic studies pointing at a hypometabolic state. They resemble a mild form of ‘non thyroidal illness syndrome’ and ‘low T3 syndrome’ experienced by a subgroup of hypothyroid patients receiving T4 monotherapy. Our study needs confirmation and extension by others. If confirmed, trials with e.g. T3 and iodide supplements might be indicated.

Source: Begoña Ruiz-Núñez, Rabab Tarasse, Emar Vogelaar, Janneke Dijck-Brouwerand Frits Muskiet. Higher prevalence of ‘low T3 syndrome’ in patients with chronic fatigue syndrome: A case-control study. Front. Endocrinol. | doi: 10.3389/fendo.2018.00097 https://www.frontiersin.org/articles/10.3389/fendo.2018.00097/abstract

Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a common and disabling disorder, and a major threat against adolescent health. The pathophysiology is unknown, but alteration of neuroendocrine control systems might be a central element, resulting in attenuation of the hypothalamus-pituitary-adrenalin (HPA) axis and enhancement of the sympathetic/adrenal medulla (SAM) system. This study explored differences in neuroendocrine control mechanisms between adolescent CFS patients and healthy controls, and whether characteristics of the control mechanisms are associated with important clinical variables within the CFS group.

METHODS: CFS patients 12-18 years of age were recruited nation-wide to a single referral center as part of the NorCAPITAL project. A broad case definition of CFS was applied. A comparable group of healthy controls were recruited from local schools. A total of nine hormones were assayed and subjected to network analyses using the ARACNE algorithm. Symptoms were charted by a questionnaire, and daily physical activity was recorded by an accelerometer.

RESULTS: A total of 120 CFS patients and 68 healthy controls were included. CFS patients had significantly higher levels of plasma norepinephrine, plasma epinephrine and plasma FT4, and significantly lower levels of urine cortisol/creatinine ratio. Subgrouping according to other case definitions as well as adjusting for confounding factors did not alter the results. Multivariate linear regression models as well as network analyses revealed different interrelations between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls. Also, single hormone degree centrality was associated with clinical markers within the CFS group.

CONCLUSION: This study reveals different interrelation between hormones of the HPA axis, the SAM system, and the thyroid system in CFS patients and healthy controls, and an association between hormone control characteristics and important clinical variables in the CFS group. These results add to the growing insight of CFS disease mechanisms.

Trial registration Clinical Trials NCT010404

 

Source: Wyller VB, Vitelli V, Sulheim D, Fagermoen E, Winger A, Godang K, Bollerslev J. Altered neuroendocrine control and association to clinical symptoms in adolescent chronic fatigue syndrome: a cross-sectional study. J Transl Med. 2016 May 5;14(1):121. doi: 10.1186/s12967-016-0873-1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858924/ (Full article)

 

Giving thyroid hormones to clinically hypothyroid but biochemically euthyroid patients. Long-term treatment is being used

Editor—During the past six months I have become aware of an increasing number of patients with normal results of thyroid function tests who are being treated with a daily dose of up to 100 ìg thyroxine—mainly as a result of publicity being given in the lay media to a hypothesis put forward by Gordon R B Skinner and colleagues.2 These biochemically euthyroid patients invariably have several symptoms that are compatible with a clinical diagnosis of hypothyroidism, but many of them also have agreed diagnostic criteria for the chronic fatigue syndrome, a condition that does involve dysfunction of the hypothalamic-pituitary axis but not hypothyroidism.

You can read the full article here: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127520/pdf/9345188.pdf

 

Source: Shepherd C. Giving thyroid hormones to clinically hypothyroid but biochemically euthyroid patients. Long-term treatment is being used. BMJ. 1997 Sep 27;315(7111):814. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2127520/pdf/9345188.pdf