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Metabolites
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Exploring Metabolomic Signatures and the Metabolic Impact of Thyroid Dysfunction
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Exploring Metabolomic Signatures and the Metabolic Impact of Thyroid Dysfunction

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: 17 July 2026 | Viewed by 2391

Special Issue Editor

Dr. Janine Wirth

E-Mail Website
Guest Editor
School of Agriculture and Food Science, University College Dublin, Belfield, D04 V1W8 Dublin, Ireland
Interests: public health; nutritional epidemiology; metabolic health; protein intake; intervention studies; cohort studies; systematic reviews
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thyroid hormones are important regulators of metabolism and can influence energy balance, thermogenesis, lipid and glucose homeostasis, and protein metabolism. Alterations in thyroid function can significantly impact metabolic health and are associated with cardiometabolic disorders, weight dysregulation, and changes in body composition. Individual variability, possibly due to genetic factors, the gut microbiome, or unknown metabolic compensations, presents a particular challenge.

Recent metabolomic studies have identified patterns of metabolic disturbances in hypothyroidism, but interpreting which disturbances cause which symptoms is not always straightforward. Metabolomic approaches have great potential to uncover hidden or poorly understood mechanisms linking hypothyroidism to its diverse symptoms beyond conventional thyroid hormone testing. By capturing detailed metabolite profiles, metabolomics can help to uncover the tissue-specific effects of thyroid hormone deficiency, identify disrupted metabolic pathways, and monitor their alteration through treatments/interventions.

Of particular interest is the relationship between thyroid status, metabolic profiles, and other relevant comorbidities or symptoms associated with thyroid dysfunction (e.g., depression, cardiovascular disease, impaired libido, or hair loss).

The aim of this Special Issue is to investigate the interactions between thyroid physiology, dysfunction, and treatment and metabolic health using traditional biomarkers and new omics technologies. We invite the submission of original research, clinical studies, and systematic reviews addressing one or more of the following areas:

  • Metabolic and metabolomic profiling in hypothyroidism or hyperthyroidism;
  • The role of thyroid hormones in regulating specific metabolic pathways;
  • Metabolic response to thyroid treatment (pharmacological or non-pharmacological);
  • Interactions between thyroid function, diet, and nutrient metabolism;
  • Longitudinal studies on the relationship between thyroid status and metabolic risk.

We welcome your contributions to unravel the complex relationships between thyroid function and metabolism.

Dr. Janine Wirth
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • thyroid function
  • hypothyroidism
  • hyperthyroidism
  • Hashimoto
  • metabolic health
  • metabolomics
  • inflammation
  • autoimmune

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Published Papers (3 papers)

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Research

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12 pages, 938 KB  
Article
Circulating Wnt Signaling Inhibitors and Osteoprotegerin in Women with Newly Diagnosed Overt Thyroid Dysfunction
by Mariya Zhivkova Miteva, Maria Mitkova Orbetzova, Boyan Ivanov Nonchev, Delyana Miteva Davcheva and Kostadin Gigov
Metabolites 2026, 16(5), 308; https://doi.org/10.3390/metabo16050308 - 30 Apr 2026
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Abstract
Background: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to [...] Read more.
Background: Thyroid hormones influence bone metabolism, and autoimmune thyroid diseases may further impact skeletal homeostasis. Wnt signaling inhibitors, including Dickkopf-1 (DKK-1) and sclerostin (SOST), as well as osteoprotegerin (OPG), play key roles in regulating bone formation and resorption. This study aimed to evaluate circulating DKK-1, SOST, and OPG in women with newly diagnosed overt thyroid dysfunction. Methods: This cross-sectional study included 62 women with newly diagnosed, untreated overt thyroid dysfunction (35 hypothyroid and 27 hyperthyroid) and 33 age- and BMI-matched healthy controls. Serum levels of DKK-1, sclerostin, and OPG were measured using ELISA. Thyroid function and autoantibodies were assessed using automated immunoassays. Correlation analysis was performed to evaluate associations between variables. Results: Serum DKK-1 levels were significantly elevated in both hypothyroid and hyperthyroid women compared with controls (p < 0.001). Sclerostin levels showed a non-significant trend toward higher values. OPG levels were significantly increased in hyperthyroid patients and moderately elevated in hypothyroid patients. Significant positive correlations were observed between OPG and FT3 (r = 0.42, p = 0.001) and FT4 (r = 0.43, p = 0.001). In hypothyroid patients, OPG correlated positively with TgAb (r = 0.46, p = 0.007). A strong positive correlation was found between DKK-1 and SOST (p < 0.001), while DKK-1 was negatively associated with age (p < 0.05). Conclusions: Overt thyroid dysfunction is associated with significant alterations in circulating Wnt signaling inhibitors and OPG. These findings suggest a potential role of Wnt signaling and immune–bone interactions in thyroid-related changes in bone metabolism. Full article
(This article belongs to the Special Issue Exploring Metabolomic Signatures and the Metabolic Impact of Thyroid Dysfunction)
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14 pages, 1260 KB  
Article
Hepatitis C Virus Infection Induces Autoimmune Hypothyroidism with Potential Profound Metabolic Implications: A Cross-Sectional Study in a High-Prevalence Region
by Xiaoli Zhong, Waseem Abbas, Farman Ullah and Rafi Ullah
Metabolites 2026, 16(2), 104; https://doi.org/10.3390/metabo16020104 - 31 Jan 2026
Viewed by 796
Abstract
Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and [...] Read more.
Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 106 IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article
(This article belongs to the Special Issue Exploring Metabolomic Signatures and the Metabolic Impact of Thyroid Dysfunction)
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Review

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14 pages, 680 KB  
Review
The Thyroid–Metabolism Axis: Pathways of Dysregulation and the Effects of Treatment
by Martina Curcio and Royce P. Vincent
Metabolites 2026, 16(4), 267; https://doi.org/10.3390/metabo16040267 - 16 Apr 2026
Viewed by 763
Abstract
Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a [...] Read more.
Thyroid hormones regulate a complex and interconnected network of metabolic signaling. Thyroid dysfunction is, at present, defined and monitored through circulating thyroid-stimulating hormone (TSH) and free thyroid hormones. However, biochemical normalization does not entirely indicate restoration of metabolic homeostasis. This discrepancy highlights a critical limitation of the current TSH-centric paradigm, which also fails to explain the heterogeneity in cardiometabolic outcomes observed among patients with similar biochemical profiles. Metabolomics, through the analysis of tissue-specific biofluids, could aid in capturing the complex metabolic perturbations that characterize this disease. In this review, we summarize metabolomic signatures typical of thyroid dysfunction, perform a critical evaluation of limitations and variability across studies, and explore the clinical and translational implications of metabolomics in thyroid pathology. In addition, five metabolic hubs influenced by thyroid hormone activity are summarized: (i) lipid and lipoprotein remodeling; (ii) mitochondrial energetics and redox balance; (iii) amino acid metabolism and protein turnover; (iv) gut–liver–thyroid axis and (v) biological impact of subclinical thyroid diseases. Taken together, these findings challenge the sufficiency of a diagnostic model based on TSH measurement and pose metabolomics as a promising tool to refine risk stratification, uncover subclinical vulnerability and guide patient-centered management of thyroid disease. Despite its promise, clinical adoption of metabolomics is hindered by a lack of standardization and complex data interpretation. To overcome these limitations, coupling metabolomics with genomics and transcriptomics may allow its translation into practical application. Full article
(This article belongs to the Special Issue Exploring Metabolomic Signatures and the Metabolic Impact of Thyroid Dysfunction)
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