Similar hypothyroid and sepsis circulating mRNA expression could be useful as a biomarker in onthyroidal illness syndrome: a pilot study

Arch Endocrinol Metab. 2023 May 25;67(5):e000625. doi: 10.20945/2359-3997000000625.


Objective: Based on hypothetical hypothyroidism and nonthyroidal illness syndrome (NTIS) gene expression similarities, we decided to compare the patterns of expression of both as models of NTIS. The concordant profile between them may enlighten new biomarkers for NTIS challenging scenarios.

Materials and methods: We used Ion Proton System next-generation sequencing to build the hypothyroidism transcriptome. We selected two databanks in GEO2 platform datasets to find the differentially expressed genes (DEGs) in adults and children with sepsis. The ROC curve was constructed to calculate the area under the curve (AUC). The AUC, chi-square, sensitivity, specificity, accuracy, kappa and likelihood were calculated. We performed Cox regression and Kaplan-Meier analyses for the survival analysis.

Results: Concerning hypothyroidism DEGs, 70.42% were shared with sepsis survivors and 61.94% with sepsis nonsurvivors. Some of them were mitochondrial gene types (mitGenes), and 95 and 88 were related to sepsis survivors and nonsurvivors, respectively. BLOC1S1, ROMO1, SLIRP and TIMM8B mitGenes showed the capability to distinguish sepsis survivors and nonsurvivors.

Conclusion: We matched our hypothyroidism DEGs with those in adults and children with sepsis. Additionally, we observed different patterns of hypothyroid-related genes among sepsis survivors and nonsurvivors. Finally, we demonstrated that ROMO1, SLIRP and TIMM8B could be predictive biomarkers in children´s sepsis.

Keywords: Nonthyroidal; RNA; Sepsis; Thyroid; Transcriptome; illness syndrome.

MeSH terms

  • Adult
  • Biomarkers
  • Child
  • Humans
  • Hypothyroidism* / genetics
  • Membrane Proteins
  • Mitochondrial Proteins
  • Nerve Tissue Proteins
  • Pilot Projects
  • Prognosis
  • RNA, Messenger / genetics
  • RNA-Binding Proteins
  • ROC Curve
  • Sepsis* / genetics
  • Syndrome


  • Biomarkers
  • RNA, Messenger
  • BLOC1S1 protein, human
  • Nerve Tissue Proteins
  • SLIRP protein, human
  • RNA-Binding Proteins
  • ROMO1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins

Grants and funding

this study was supported by a research grant from the São Paulo State Research Foundation (FAPESP), number 2014/04193-0 to C P C.