Begoña Ruiz-Núñez, Rabab Tarasse, Emar F Vogelaar, D A Janneke Dijck-Brouwer, Frits A J Muskiet PMID: 29615976, PMCID: PMC5869352, DOI:10.3389/fendo.2018.00097, Front Endocrinol (Lausanne), 2018 Mar 20;9:97. doi: 10.3389/fendo.2018.00097. 2018.



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 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%) and 24-h urinary iodine (27.6%). The % of reverse T3 (rT3) was higher (13.3%), among the patients. 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 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.

Keywords: chronic fatigue syndrome, thyroid, “low T3 syndrome”, triiodothyronine, reverse triiodothyronine, urinary iodine, inflammation, high-sensitive C-reactive protein


This is a truly excellent paper. However it raises an important question: in view of the implied relationship of CFS and “Functional Hypothyroidism”, is any therapy available?

The answer is as follows: “Low T3 syndrome” is a synonym for Functional (Intracellular) Hypothyroidism (IH).
Those presenting with CFS, or other symptoms of IH should have “Thyroid Profile” tests, including TSH, free T4, free T3 and reverse T3.
If the FT3/rT3 ratio is less than 20, subjects, male or female of whatever age, should be treated with Triiodothyronine, using a protocol of upward titration of Triiodothyronine dose (monitored with weekly retesting of FT3 and rT3, at 3-4 hours post-dose)* to achieve a serum T3 between 5.0 and 6.1 Picomoles/Litre.

Treatment can be expected to be successful and if it is, the Intracellular Hypothyroidism will be eliminated, “low thyroid” symptoms will disappear and to all intents and purposes, the CFS will be CURED ! **

  • * Since the half-life of Triiodothyronine is just 2-3 hours, there is no need for a 6-week dose-test interval, as is done with Levothyroxine.
  • ** Weaning off Triiodothyronine can be attempted 3-6 months after confirming the curative dose. However IH is a stress-dependent condition and will recur, with relapse of CFS, if and when the patient is subjected to stress.
    In such cases, T3 therapy can be continued, with dose adjustment ad hoc, indefinitely.

Published by Dr. Gervais Harry

I am a Toronto-trained Urologist. I practiced in downtown Toronto, from 1977 to 1997, when I went to Saudi Arabia as chief of Urology at the Armed Forces (teaching) hospital in Tabuk. Returning to Toronto in Y2000, I switched to family practice. In 2007, began to prescribe Hormone Restoration Therapy and in 2012, I became a member of the American Academy of Antiaging Medicine [A4M]. I successfully wrote the A4M's written examination in December, 2013 and In May, 2016 I passed the oral examination, for accreditation as a BHRT consultant. In 2014 I began BHRT practice in Collingwood, Ontario and in January, 2017, joined the Stone Tree Naturopathic Clinic. Now I am 82 and have retired, but it seems wasteful to jettison my learning and experience: the medical establishment knows nothing of BHRT / Functonal medicine and I feel obliged to offer my knowledge in the interest of those who are willing to think outside the box. MY QUALIFICATIONS: MB, BS, (from UWI), 1964. LMCC 1969. FRCSC (Urology), 1974. ECFMG 1984. Florida license 1998 [inactive], ABAARM Certification [A4M], 2016. I am a Member of CSAMM [the Canadian Society for Aging and Metabolic Medicine], the OMA&CMA, SUSO, CUA, RCP&S/C. PRACTICE TO DATE: Consultation in Functional Medicine, including assessment of Chronic Fatigue Syndrome, Fibromyalgia, Andropause, Menopause, Teenage and Postpartum Depression/Panic Attacks, Thyroid Hormone malfunction, Infertility, Sexual Dysfunction and “the Undiagnosable”. ALL ARE WELCOME to read, comment or question!

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