Are Changes in Thyroid Hormones Associated with Mortality in Non-Thyroidal Illness Syndrome?


  •   Emre Hoca

  •   Hayriye Esra Ataoğlu

  •   Süleyman Ahbab


Introduction: Non-thyroidal illness syndrome (NTIS) can be defined as afunctional impairment of the hypothalamic-pituitary-thyroid axis accompanied by signs of non-thyroidal disease with changes in thyroid stimulating hormone (TSH), free T3 (fT3) and free T4 (fT4) levels. NTIS and thyroid hormone levels in this syndrome are thought to be related with mortality. This study was performed to evaluate the relationship between hormone levels and mortality in this syndrome.

Methods: The 5-year mortality data of patients who were hospitalized in the first 6 months of 2014 and whose thyroid hormone levels could be checked twice within 5 years were evaluated. In our study conducted with 405 patients whose thyroid function tests was repeated, the follow-up period was 5 years. Biochemical parameters including thyroid function tests were sent from all patients. NTIS was defined as a condition in patients with low fT3 levels (<2.5 pg/mL) and TSH levels within the normal range (0.38-5.33 mIU / L).

Results: 128 patients died, and the number of surviving patients was 277 during the follow-up period. Positive acute phase reactants such as CRP, sedimentation, ferritin was high and albumin (negative acute phase reactant) and fT3 levels were low in patients who died. In addition, these changes in biochemical values were statistically significant. The mortality rate was increased in patients with low fT3 and high fT4 levels. In the follow-up period, changes in TSH levels were not significantly associated with mortality.

Conclusion: Both the decrease in fT3 levels and the increase in fT4 levels can be used as predictors and independent risk factors for long-term mortality risk in chronically ill and hospitalized patients with NTIS.

Keywords: Mortality, non-thyroidal illness syndrome, serum free T3, serum free T4


Lee S, Farwell AP. Euthyroid sick syndrome. Comprehensive Physiology. 2016; 6(2): 1071–80.

Depuydt PO, Kress P, Salluh IF. The ten "diseases" that are not true diseases. Intensive Care Medicine. 2016; 42: 411-414.

deVries EM, Fliers E, Boelen A. The molecular basis of the non-thyroidal illness syndrome. The Journal of Endocrinology. 2015; 225(3): 67–81.

Wajner SM, Goemann IM, Bueno AL, Larsen PR, Maia AL. IL-6 promotes nonthyroidal illness syndrome by blocking thyroxine activation while promoting thyroid hormone inactivation in human cells. The Journal of Clinical Investigation. 2011; 121(5): 1834.

Lui DTW, Lee CH, Chow WS, Lee ACH, Tam AR, Fong CHY, et al. Role of non-thyroidal illness syndrome in predicting adverse outcomes in COVID-19 patients predominantly of mild-to-moderate severity. Clin Endocrinol (Oxf). 2021; 00: 1–9.

Hershman JM. Euthyroid Sick Syndrome: Thyroid Disorders. Merck Manual Professional. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.; 2009.

Dickerman AL, Barnhill JW. Abnormal thyroid function tests in psychiatric patients: a red herring? Am J Psychiatry. 2012; 169(2): 127-33.

Taroza S, Rastenytė D, Podlipskytė A, Kazlauskas H, Mickuvienė N. Nonthyroidal Illness Syndrome in Ischaemic Stroke Patients is Associated with Increased Mortality. Exp Clin Endocrinol Diabetes. 2020; 128(12): 811-818.

Padhi R, Kabi S, Panda BN, Jagati S. Prognostic significance of nonthyroidal illness syndrome in critically ill adult patients with sepsis. Int J Crit Illn Inj Sci. 2018; 8(3): 165–172.

Economidou F, Douka E, Tzanela M, Nanas S, Kotanidou A. Thyroid function during critical illness. Hormones. 2011; 10(2): 117-24.

Plikat K, Langgartner J, Buettner R, Bollheimer LC, Woenckhaus U, Schölmerich J, et al. Frequency and outcome of patients with nonthyroidal illness syndrome in a medical intensive care unit. Metabolism: Clinical and Experimental. 2007; 56(2): 239-44.

Ataoğlu HE, Ahbab S, Serez MK, Yamak M, Kayaş D, Canbaz ET, et al. Prognostic significance of high free T4 and low free T3 levels in non-thyroidal illness syndrome. European Journal of Internal Medicine. 2018; 57: 91–95.

Gussekloo J, van Exel E, de Craen AJ, Meinders AE, Frölich M, Westendorp RG. Thyroid status, disability and cognitive function, and survival in old age. The Journal of the American Medical Association. 2004; 292(21): 2591–9.

Tognini S, Marchini F, Dardano A, Polini A, Ferdeghini M, Castiglioni M, et al. Non-thyroidal illness syndrome and short-term survival in a hospitalised older population. Age and Ageing. 2010; 39(1): 46–50.

Croce L, Gangemi D, Ancona G, Liboà F, Bendotti G, Minelli L, et al. The cytokine storm and thyroid hormone changes in COVID 19. Journal of Endocrinological Investigation. 2021; 44: 891–904.

Straub RH, Cutolo M. Glucocorticoids and chronic inflammation. Rheumatology. 2016; 55: ii6ii14.

Ceresini G, Marina M, Lauretani F, Maggio M, Bandinelli S, Geda GP, et al. Relationship between circulating concentrations of thyrotropin, free thyroxine, and free triiodothyronine and 9-year mortality in euthyroid elderly subjects. Journal of the American Geriatric Society. 2016; 64(3): 553.

Merke A, Merke J, Silbernagel G, März W. Free thyroid hormones and mortality in caucasians undergoing angiography: the Ludwigshafen risk and cardiovascular health (luric) study. Endocrine Practice. 2017; 23(3): 288-298.

Moura Neto A, Zantut-Wittmann DE. Abnormalities of Thyroid Hormone Metabolism during Systemic Illness: The Low T3 Syndrome in Different Clinical Settings. International Journal of Endocrinology. 2016: 1–9.

Borzio M, Caldara R, Borzio F, Piepoli V, Rampini P, Ferrari C. Thyroid function tests in chronic liver disease: evidence for multiple abnormalities despite clinical euthyroidism. Gut. 1983; 24(7): 631–636.

Xu G, Yan Y, Liu Y. The cardiovascular disease risks of nonthyroidal illness syndrome and inflammatory responses on patients with chronic kidney disease: from the association to clinical prognosis. Cardiovascular Therapeutics. 2014; 32(6): 257-63.


How to Cite
Hoca, E., Ataoğlu, H. E., & Ahbab, S. (2021). Are Changes in Thyroid Hormones Associated with Mortality in Non-Thyroidal Illness Syndrome?. European Journal of Clinical Medicine, 2(6), 56–59.