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Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors

Endocrine volume 61, pages 83–93 (2018)Cite this article

Abstract

Purpose

Irisin, a newly discovered adipo-myokine, is implicated in the modulation of the adipose phenotype, increasing energy expenditure and ameliorating systemic metabolism. Our aim was to investigate circulating irisin in subclinical hypothyroidism (SH) and study its associations with cardiometabolic risk factors.

Methods

In a large case–control study, serum irisin, insulin resistance and lipid parameters, classic adipokines, inflammatory and hepatic biomarkers, and cardiovascular risk factors were determined in 120 consecutive patients with SH and 120 healthy controls matched on age, gender, and date of blood draw. Sixteen patients with SH received L-T4 treatment and, after 6 months, serum irisin and other biomarkers were assessed.

Results

SH cases exhibited significantly higher circulating irisin than controls (p < 0.001). In all participants, irisin was positively associated with TSH, anti-TG, HOMA-IR, C-peptide, lipid and inflammatory biomarkers, leptin, and cardiovascular risk factors, including Framigham score and apolipoprotein B/apolipoprotein A-I. Irisin was negatively correlated with adiponectin, HDL-C, and thyroid hormones. Serum irisin was independently associated with SH, above and beyond body mass index and cardiometabolic factors (p = 0.02). TSH was an independent predictor of circulating irisin (p = 0.003). L-T4 therapy did not reverse considerably the hyperirisinemic status in treated SH patients (p = 0.09).

Conclusions

Irisin may represent an adipo-myokine counterbalancing a potential, gradual deterioration of lipid metabolism and insulin sensitivity in SH as well as reflecting a protective compensatory mechanism against oxidative muscle and thyroid cell stress. More mechanistic and prospective studies shedding light on the pathogenetic role of irisin in SH are needed to confirm and extend these data.

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Fig. 1
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Abbreviations

ALT:

Alanine aminotransferase

anti-TG:

Anti-thyroglobulin antibodies

anti-TPO:

Anti-peroxidase antibodies

ApoA-I:

Apolipoprotein A-I

ApoB:

Apolipoprotein B

AST:

Aspartate aminotransferase

BAT:

Brown adipose tissue

BMI:

Body mass index

BP:

Blood pressure

γ-GT:

Gamma glutamyltransferase

CI:

Confidence interval

CPK:

Creatine phosphokinase

CVD:

Cardiovascular disease

DBP:

Diastolic blood pressure

DM:

Diabetes mellitus

ELISA:

Enzyme-linked immunosorbent assay

FMR:

Female to male ratio

FNDC5:

Fibronectin type III domain containing protein 5

HbA1c:

Glycated hemoglobin A1

HDL-C:

High-density lipoprotein cholesterol

HOMA:

Homeostasis model assessment score of insulin resistance

HPT:

Hypothalamic-pituitary-thyroid axis

hsCRP:

High sensitive C-reactive protein

HT:

Hashimoto’s thyroiditis

L-T4:

Levothyroxine

LDL-C:

Low-density lipoprotein cholesterol

Lp(a):

Lipoprotein a

MAPK:

Mitogen-activated protein kinase

OR:

Odds ratio

PGC-1α:

Peroxisome proliferator-activated receptor-γ coactivator-1α

SBP:

Systolic blood pressure

SD:

Standard deviation

SH:

Subclinical hypothyroidism

T3:

Tri-iodothyronine

T4:

Thyroxine

TG:

Thyroglobulin

TPO:

Thyroid peroxidase

TSH:

Thyroid stimulating hormone

UCP1:

Uncoupling protein 1

US:

Ultrasonography

WAT:

White adipose tissue

WHR:

Waist-to-hip ratio

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    Authors and Affiliations

    1. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias street, 11527, Athens, Greece

      Theodora Stratigou, Maria Dalamaga, Gerasimos Socrates Christodoulatos & Athanasios G. Papavassiliou

    2. Department of Endocrinology, ‘Evangelismos’ General Hospital of Athens, 45-47 Ypsilantou street, 10676, Athens, Greece

      Theodora Stratigou

    3. Laboratory of Clinical Biochemistry, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini street, Chaidari, 12462, Athens, Greece

      Georgios Antonakos

    4. Laboratory of Microbiology, ‘Sotiria’ General Hospital, 152 Mesogeion Avenue, 11527, Athens, Greece

      Ioanna Marinou & Evaggelos Vogiatzakis

    5. Department of Internal Medicine, Attikon General University Hospital, Medical School, National and Kapodistrian University of Athens, 1 Rimini street, Chaidari, 12462, Athens, Greece

      Irene Karampela

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    Stratigou, T., Dalamaga, M., Antonakos, G. et al. Hyperirisinemia is independently associated with subclinical hypothyroidism: correlations with cardiometabolic biomarkers and risk factors. Endocrine 61, 83–93 (2018). https://doi.org/10.1007/s12020-018-1550-3

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    Keywords

    • Adipokine
    • Cardiovascular
    • Irisin
    • Myokine
    • Subclinical hypothyroidism
    • Thyroid