



Idiopathic diseases remain a thorn in both physicians' and patient’s sides from a diagnostic and therapeutic perspective. For instance, diagnosis of chronic fatigue syndrome (CFS)—an idiopathic disorder marked by lengthy spells of weakness, fatigue, and depression—is predominantly based on symptoms and on ruling out any underlying medical condition, rather than on laboratory tests and physical examination. Yet now, new research from investigators at the University Medical Centre Groningen, The Netherlands, demonstrates a link between CFS symptoms and lower thyroid hormone levels. Findings from the new study were published today in Frontiers in Endocrinology, in an article entitled “Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study.”

The new 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. Interestingly, the researchers found that 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 CFS.

This contrast in thyroid-stimulating activity led investigators to hypothesize that CFS is caused by low activity of thyroid hormones in the absence of thyroidal disease. 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.

“We measured parameters of thyroid function, (metabolic) inflammation, gut wall integrity and nutrients influencing thyroid function and/or inflammation,” the authors wrote. “Most remarkably, CFS patients exhibited similar thyrotropin, but lower free triiodothyronine (FT3) (difference of medians 0.1%), total thyroxine (TT4) (11.9%), total triiodothyronine (TT3) (12.5%), %TT3 (4.7%), sum activity of deiodinases (14.4%), secretory capacity of the thyroid gland (14.9%), 24-h urinary iodine (27.6%), and higher % reverse T3 (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% confidence interval = 1.00–6.54). Most observations persisted in two sensitivity analyses with more stringent cutoff values for body mass index, high-sensitive C-reactive protein (hsCRP), and white blood cells (WBC).”

Through additional analyses, the research team found 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.

“We found possible evidence of (chronic) low-grade metabolic inflammation (ferritin and HDL-C [high-denisty lipoprotein cholesterol]). FT3, TT3, TT4, and rT3 correlated positively with hsCRP in CFS patients and all subjects,” the authors penned. “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.”

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

“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,” concluded lead study investigator Begoña Ruiz-Núñez, a doctoral candidate at the University Medical Center Groningen. “This strengthens our test results considerably.”



























