Infographic: The dangers of Low T3 Syndrome

The dangers of Low T3 Syndrome

Some research articles on Low T3 Syndrome

Economidou, F., Douka, E., Tzanela, M., Nanas, S., & Kotanidou, A. (2011). Thyroid function during critical illness. Hormones (Athens, Greece), 10(2), 117–124.

  • The metabolic support of the critically ill patient is a relatively new target of active research and little is as yet known about the effects of critical illness on metabolism.
  • The nonthyroidal illness syndrome, also known as the low T3 syndrome or euthyroid sick syndrome, describes a condition characterized by abnormal thyroid function tests encountered in patients with acute or chronic systemic illnesses.
  • The laboratory parameters of this syndrome include low serum levels of triiodothyronine (T3) and high levels of reverse T3, with normal or low levels of thyroxine (T4) and normal or low levels of thyroid-stimulating hormone (TSH).
  • This condition may affect 60 to 70% of critically ill patients.
  • The changes in serum thyroid hormone levels in the critically ill patient seem to result from alterations in the peripheral metabolism of the thyroid hormones, in TSH regulation, in the binding of thyroid hormone to transport-protein and in receptor binding and intracellular uptake.
  • Medications also have a very important role in these alterations. Hormonal changes can be seen within the first hours of critical illness and, interestingly, these changes correlate with final outcome.
  • Data on the beneficial effect of thyroid hormone treatment on outcome in critically ill patients are so far controversial.
  • Thyroid function generally returns to normal as the acute illness resolves.

Ataoğlu, H. E., Ahbab, S., Serez, M. K., Yamak, M., Kayaş, D., Canbaz, E. T., … Yenigün, M. (2018). Prognostic significance of high free T4 and low free T3 levels in non-thyroidal illness syndrome. European Journal of Internal Medicine.

  • Background: Non-thyroidal illness syndrome is characterized by decreased serum free T3 (FT3) level and associates with long term mortality. Serum free T4 (FT4) may affect on mortality with FT3 in course of chronic illness. This study performed to evaluate the association between both decreased FT3 with elevated FT4 levels and mortality risk.
  • Methods: This study is a retrospective cohort analysis and consisted up 1164 (571 male, 593 female) patients with a 36 months follow up period. Patients divided into four groups according to thyroid functions.
    • Patients with euthyroidism were in Group A,
    • elevated FT3 in group B,
    • decreased FT3 in group C
    • and both decreased FT3 and elevated FT4 levels in group D.
  • The levels of thyroid hormones and all cause mortality were compared between four groups.
  • Results: Mortality rate was elevated between Groups A and B, A and C, A and D, B and C, B and D, C and D, (p < .001, p < .001, p < .001, p < .001, p < .001, p:0.019, respectively). A multivariate Cox proportional hazards model was performed to evaluate the mortality risk between groups.
  • A close relationship was observed in Group C and D patients for the mortality risk (OR:1.561, 95% CI:1.165–2.090, p:0.003 and OR:2.224, 95% CI:1.645–3.006, p:0.0001, respectively).
  • Conclusion: Both decreased FT3 and elevated FT4 levels are independent predictor for long term mortality risk in hospitalized chronic patients with non-thyroidal illness syndrome.

Ruiz-Núñez, B., Tarasse, R., Vogelaar, E. F., Dijck-Brouwer, J., A, D., & Muskiet, F. A. J. (2018). Higher Prevalence of “Low T3 Syndrome” in Patients With Chronic Fatigue Syndrome: A Case–Control Study. Frontiers in Endocrinology, 9.

  • 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.

Wang, Y., Zhou, S., Bao, J., Pan, S., & Zhang, X. (2017). Low T3 levels as a predictor marker predict the prognosis of patients with acute ischemic stroke. The International Journal of Neuroscience, 127(7), 559–566.

  • BACKGROUND: Early and accurate prediction of outcome in acute stroke is important. The aim of this prospective study was to explore the correlation between serum triiodothyronine level and prognosis in acute ischemic stroke patients.
    METHODS: A prospective observational study which included 359 consecutive patients with acute ischemic stroke from December 2014 to November 2015 was interrogated. Serum triiodothyronine (T3) concentrations were measured on admission to understand their value in predicting functional outcome within 90 d using multivariable models adjusted for confounding factors. …
    RESULTS: Triiodothyronine was significantly decreased in patients with an unfavorable functional outcome as compared to patients with a favorable functional outcome within 90 d (p = 0.01). …
    CONCLUSIONS: Low serum triiodothyronine levels can be a predictive marker of short-term outcome after ischemic stroke. A combined model (triiodothyronine, age and NIHSS score) can add significant additional predictive information to the clinical score of the NIHSS.

Liu, J., Wu, X., Lu, F., Zhao, L., Shi, L., & Xu, F. (2016). Low T3 syndrome is a strong predictor of poor outcomes in patients with community-acquired pneumonia. Scientific Reports, 6.

  • Low T3 syndrome was previously reported to be linked to poor clinical outcomes in critically ill patients. The aim of this study was to evaluate the predictive power of low T3 syndrome for clinical outcomes in patients with community-acquired pneumonia (CAP).
  • Data for 503 patients were analyzed retrospectively, and the primary end point was 30-day mortality. The intensive care unit (ICU) admission rate and 30-day mortality were 8.3% and 6.4% respectively.
  • The prevalence of low T3 syndrome differed significantly between survivors and nonsurvivors (29.1% vs 71.9%, P < 0.001), and low T3 syndrome was associated with a remarkable increased risk of 30-day mortality and ICU admission in patients with severe CAP. Multivariate logistic regression analysis produced an odds ratio of 2.96 (95% CI 1.14–7.76, P = 0.025) for 30-day mortality in CAP patients with low T3 syndrome.
  • Survival analysis revealed that the survival rate among CAP patients with low T3 syndrome was lower than that in the control group (P < 0.01).
  • Adding low T3 syndrome to the PSI and CURB-65 significantly increased the areas under the ROC curves for predicting ICU admission and 30-day mortality.
  • In conclusion, low T3 syndrome is an independent risk factor for 30-day mortality in CAP patients.

Bertoli, A., Valentini, A., Cianfarani, M. A., Gasbarra, E., Tarantino, U., & Federici, M. (2017). Low FT3: a possible marker of frailty in the elderly. Clinical Interventions in Aging, 12, 335–341.

  • INTRODUCTION: Frailty is associated with a functional decline of multiple physiological systems, of which they may be a cause or consequence. The objective of the study was to evaluate the prevalence of thyroid hormone modifications in elderly frail subjects and its relationship with frailty.
    STUDY POPULATION AND METHODS: An observational study was carried out at the University Hospital “Tor Vergata” in Rome among ambulatory and hospitalized patients. The study population consisted of 112 elderly subjects: 62 were hospitalized following hip fracture and 50 control subjects were outpatients. Participating patients received a multidimensional geriatric evaluation. The Survey of Health, Ageing and Retirement in Europe Frailty Instrument (SHARE-FI) was used to assess the degree of frailty. Thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured to evaluate thyroid status.
    RESULTS: FT3, but not FT4, was significantly correlated with Frailty score, both in patients with hip fracture and in patients from the control group. In the entire study population, FT3 under normal limits is effective in discriminating frail/prefrail subjects from nonfrail subjects.
    DISCUSSION: The reduction in serum concentrations of FT3 is a clear manifestation of stress associated with fractures. Numerous preexisting factors, such as the fracture patients’ nutritional status, sarcopenia, disability and comorbidities, which characterize the condition of frailty and influence its pathogenesis, are strongly correlated with FT3 values, suggesting the existence of latent nonthyroidal illness syndrome (NTIS).
    CONCLUSION: We conclude that measuring FT3 can be a useful laboratory parameter in clinical assessment, which can play an important role in identifying vulnerable elderly subjects and in quantifying the condition of frailty.

Further discussion

See our campaign statement rationale pages for an in-depth discussion of Low T3 Syndrome. It affects people with normal thyroid glands as well as hypothyroid patients on thyroid hormone therapy.

Learn about the biological mechanisms that can lead to T3 depletion

Learn about the effects of Low T3 on the body

Gaps in the research on Low T3

Learn more about recovery



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