Advanced glycation end products and their soluble receptor (sRAGE) in patients with Hashimoto's thyroiditis on levothyroxine substitution

Sára Csiha; István Molnár; Sándor Halmi; Dávid Hutkai; Hajnalka Lőrincz; Sándor Somodi; Mónika Katkó; Mariann Harangi; György Paragh; Endre V Nagy; Eszter Berta; Miklós Bodor

doi:10.3389/fendo.2023.1187725

Advanced glycation end products and their soluble receptor (sRAGE) in patients with Hashimoto's thyroiditis on levothyroxine substitution

Front Endocrinol (Lausanne). 2023 May 26:14:1187725. doi: 10.3389/fendo.2023.1187725. eCollection 2023.

Authors

Sára Csiha^{1

2

3}, István Molnár^{2

3

4}, Sándor Halmi^{1

3}, Dávid Hutkai^{5

6}, Hajnalka Lőrincz⁴, Sándor Somodi^{4

7}, Mónika Katkó¹, Mariann Harangi^{4

8}, György Paragh⁴, Endre V Nagy¹, Eszter Berta^{2

4}, Miklós Bodor^{1

2}

Affiliations

¹ Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
² Department of Clinical Basics, Faculty of Pharmacy, University of Debrecen, Debrecen, Hungary.
³ Doctoral School of Health Sciences, University of Debrecen, Debrecen, Hungary.
⁴ Division of Metabolism, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁵ Division of Nephrology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁶ Kálmán Laki Doctoral School, University of Debrecen, Debrecen, Hungary.
⁷ Department of Emergency Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
⁸ Institute of Health Studies, Faculty of Health Sciences, University of Debrecen, Debrecen, Hungary.

Abstract

Background: Advanced glycation end products (AGEs) are heterogenous group of irreversible chemical moieties originated from non-enzymatic glycation and oxidation of proteins, nucleic acids, and lipids. The engagement of AGEs with their chief cellular receptor (RAGE) activates a myriad of signaling pathways contributing to the progression of chronic diseases like autoimmune thyroiditis, type 2 diabetes mellitus and its complications. Soluble RAGE (sRAGE) prevents AGE-RAGE interaction in a competitive manner.

Objective: We investigated the association between serum AGE, sRAGE and thyroid function in 73 Hashimoto thyroiditis patients (HT) on levothyroxine substitution, and in 83 age, BMI and gender-matched healthy controls.

Methods: The serum AGEs levels were determined by autofluorescence on a multi-mode microplate reader, and the serum sRAGE levels by ELISA method.

Results: Mean AGE level was lower (10.71 vs 11.45 AU/µg protein; p=0.046), while mean sRAGE level was higher (923 vs 755 pg/mL; p<0.0005) in the serum of HT patients than the controls. AGE correlated with age, while sRAGE correlated negatively with BMI in both groups. We found negative correlation between AGE and fT3 levels (r=-0.32; p=0.006) and sRAGE and TSH levels (r=-0.27; p=0.022) in HT patients, while we failed to find association between AGE, sRAGE and parameters of thyroid function in the control group. Median AGE/sRAGE ratio was lower in HT patients than in controls (2.4, IQR 1.9 - 3.1 vs 3.3, IQR 2.3 - 4.1 AU/pg; p < 0.001). In HT patients, the AGE/sRAGE ratio correlated positively with BMI and correlated negatively with fT3.

Conclusion: According to our results in HT patients lower TSH and higher fT3 levels within the reference range is accompanied by a favorable AGE/RAGE balance. Further investigations are needed to confirm these results.

Keywords: Hashimoto’s thyroiditis; advanced glycation end products; hyperlipidemia; hypothyroidism; levothyroxine; obesity; sRAGE; thyroid.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus, Type 2* / drug therapy
Glycation End Products, Advanced
Hashimoto Disease* / drug therapy
Humans
Thyrotropin
Thyroxine

Substances

Thyroxine
Glycation End Products, Advanced
Thyrotropin

Grants and funding

This research was supported by the National Research, Development, and Innovation Office-NKFIH, grant number: K142273 and by the ÚNKP-21-4.2 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund.