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Non-thyroidal illness (euthyroid sick) syndrome: Laboratory aspects and clinical significance in critically ill patients and other diseases – A narrative review Cover

Non-thyroidal illness (euthyroid sick) syndrome: Laboratory aspects and clinical significance in critically ill patients and other diseases – A narrative review

Open Access
|Jan 2026

Figures & Tables

The relationship between NTIS, thyroid hormones and outcomes in critically ill patients

AuthorsCountrySubjectsAgeMain Findings
Wang et al.[10]Shanghai, China480 ICU patients71.71 years (mean)T3, T4, FT3, FT4, TSH levels were lower in non-survive compare to survive patients
FT3 (cut-off <3.33 pmol/L) has the largest AUC (0.762) to predict mortality (specificity = 0.78, sensitivity = 0.62)

Praven et al.[11]Hyderabad, India119 critically ill patients60.15 years (mean)NTI prevalence was lower in survive (63%) compared to non-survive (93%) patients
T3 and TSH levels were lower in non-survive compare to survive patients
T3 has the largest AUC (0.677) to predict mortality (specificity = 0.56, sensitivity = 0.83)

Sayarifard et al.[12]Tehran, Iran35 children with critical illness4 months to 15 yearsT3 levels were lower among non-survive patients in the 1st day of hospitalization while T4 levels were lower in the 3rd day

Carreras et al.[13]Spain103 PICU patientsmedian 8.51 years (higher mortality risk score group) and 5.78 years (lower mortality risk score group)FT4 (cut-off <16.60 pmol/L) has the largest AUC (0.655) to predict higher mortality risk (specificity = 0.615, sensitivity = 0.76)
Subjects with NTIS had 6.04 times higher mortality risk while those with FT4<16.60 pmol/L had 4.92 times higher mortality risk

Wang et al.[14]Wuxi, China51 ICU patients15 to 88 yearsAPACHE II score has positive correlation with rT3 (r = 0.379) and negative correlation with TSH (r =−0.256), T3 (r =−0.370), T4 (r =−0.364) (all p≤0.05)

Krug et al.[15]Leipzig, German1790 ICU patients44–77 years (interquartile range)TSH, FT3, and FT4 levels were lower in NTIS compared to non-NTIS
NTIS condition was associated with longer ICU length of stay but not associated with higher ICU mortality rate

Vidart et al.[16] 6869 adult with critical illness (meta-analysis of 25 studies) Subjects with NTIS had 2.21 times higher mortality risk compared to non-NTIS

The association between NTIS, thyroid hormones and outcomes in patients with infection and sepsis

AuthorsCountrySubjectsAgeMain Findings
Yao et al.[17]Shanghai, China1219 septic patients, 318 with DIC, 831 without DIC70 years (mean)Sepsis patients with NTIS had 3.19 times higher risk to suffer DIC. The higher the DIC score the higher NTIS prevalence

Abdelgawad et al.[18]Cairo, Egypt40 children with sepsis and septic shock6 to 120 monthsNTI prevalence was lower in sepsis (30%) compared to septic shock (65.5%) patients.
FT3 levels were higher in 5th day, rT3 levels were lower in 1st and 5th day in survive compared to non-survive patients

Sharma et al.[19]New Delhi, India40 neonates patients with sepsis, 40 control subjectsneonatesFT4 and FT3 levels were lower in septic patients, and also lower in non-survive compared to survive patients
The higher the CRP levels the lower the FT3 levels in survive-septic shock and non-survive patients

Lee et al.[20]Seoul, South Korea213 ICU patientsmean 58.9 years (euthyroid group), 69.1 years (mild NTIS), 66.9 years (moderate NTIS), 64 years (severe NTIS)Subjects with infection had higher prevalence of moderate (39.8% vs 30.7%) and severe NTIS (8% vs 0%) compared to non infection patients. Subjects with moderate to severe NTIS had 3.1 times higher mortality risk compared to normal-mild NTIS

Changes in thyroid hormone patterns in NTIS

Thyroid HormonesAcute Phase of Critical IllnessChronic Phase of Critical IllnessRecovery Phase of Critical Illness
TSHN or slightly ↓N or slightly ↓N or slightly ↑
FT4N or slightly ↑N or slightly ↑mostly N
FT3N or gradual ↓↓↓gradual ↑ to baseline
T3N or gradual ↓↓↓gradual ↑ to baseline
T4N or slightly ↓↓↓gradual ↑ to baseline
rT3N to gradual ↑↑↑gradual ↓ to baseline

The relationship between NTI, thyroid hormones and outcomes in patients with non-infectious diseases

AuthorsCountrySubjectsAgeMain Findings
Cardiovasular Disease

Adawiyah et al.[22]Kuala Lumpur, Malaysia85 ACS patients, 6-month cohort study58.3 years (mean)NTIS prevalence was 56% in ST elevation myocardial infarction, 54% in non-ST elevation myocardial infarction, and 48% in unstable angina
Peak Troponin T levels was associated with FT3 levels (r =−0.22, p = 0.049)

Dal et al.[23]Istanbul, Turkey70 acute myocardial infarction patients64.46 years (mean)Non-survive acute myocardial infarction patients had lower FT3 levels compared to survive ones

Zhang et al.[24]Shanghai, China501 acute myocardial infarction patients, cohort study (mean follow up 10±2 months)69 years (mean)Mortality rate in low FT3 subjects were higher than normal FT3 (14 vs 2.7%). FT3 level was determinant factor of mortality and MACE (HR = 0.142 and 0.748, p<0.05 respectively) during follow up

Okayama et al.[25]Tokyo, Japan270 ADHF patientsmean 65 years (normal FT3 group) and 72.3 years (low FT3 group)FT3 (cut-off <2.05 pg/mL) has the largest AUC (0.791) to predict mortality risk (specificity = 0.72, sensitivity = 0.85)

Zhao et al.[26]Gansu, China594 ADHF patients with euthyroid57 years (mean)Low FT3 level was not associated with mortality during hospitalization but associated with 1 year mortality (HR = 1.85)

Hayashi et al.[27]Japan274 ADHF patients70 years (mean)Subclinical hypothyroidism (HR = 2.31) but not low FT3, associated with cardiovascular events

Kidney Disease

Obasuyi et al.[28]Benin, Nigeria184 CKD subjects, 80 controls5 to 90 years42.4% CKD patients had NTIS (54.5% of stage 3; 51.1% of stage 4; and 37.2% of stage 5 CKD patients)

Yuasa et al.[29]Tokyo, Japan510 CKD subjects67 years (median)33.1% of CKD patients had NTIS. Urine protein, eGFR, and age were determeninat factor of NTIS

Li et al.[30]Chengdu, China384 nephrotic syndrome patients41.3 years (mean, normal thyroid subjects); 40.65 years (mean, thyroid dysfunction subjects)NTIS prevalence ranged from 31% to 66.66% among different nephrotic syndrome types. Blood creatinine, cholesterol, platelet, hemoglobin, albumine, and urine protein are determinant factors of thyroid dysfunction

Other Diseases

Yasar et al.[31]Turkiye125 COPD subjects65 years (mean)NTIS prevalence in COPD patients was 53.8%. NTIS was linked to higher APACHE II scores (29 in NTIS vs 24 in non-NTIS)

Langer et al.[32]Germany437 liver cirrhosis patients52.1 to 55.8 years (mean, among liver cirrhosis type)NTIS prevalence was 72.1% in ACLF and 39.3% in AD patients. Subjects with low FT3 had higher 3-month mortality rate

Deng et al.[33]Guangzhou, China396 diabetic ketoasidosis and ketosis patients57.5 years (mean)NTIS prevalence was 57.8% among diabetic ketoasidosis and ketosis patients. FT3 had negative association with blood hsCRP, urine albumine levels, and leukocytes count

Zhang et al.[34]Nanjing, China223 SLE patients36.7 years (mean, subjects with NTIS); 36.9 years (subjects without NTIS)Prevalence NTIS in SLE patients was 58.74%. FT3 had negative association with SLE activity (r =−0.313), creatinine (r =−0.298), blood urea nitrogen (r =−0.325), CRP (r =−0.200) and urine protein (r =−0.301) among NTIS patients
DOI: https://doi.org/10.2478/jccm-2026-0008 | Journal eISSN: 2393-1817 | Journal ISSN: 2393-1809
Language: English
Page range: 46 - 55
Submitted on: Sep 7, 2025
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Accepted on: Jan 15, 2026
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Published on: Jan 30, 2026
In partnership with: Paradigm Publishing Services
Publication frequency: 4 issues per year

© 2026 Liong Boy Kurniawan, published by University of Medicine, Pharmacy, Science and Technology of Targu Mures
This work is licensed under the Creative Commons Attribution 4.0 License.