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Biomedicines
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Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases
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Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 October 2023) | Viewed by 20626

Special Issue Editor

Prof. Dr. Tommaso Aversa

E-Mail Website
Guest Editor
Department of Human Pathology of Adulthood and Childhood "Gaetano Barresi", University of Messina, Messina, Italy
Interests: thyroid diseases in childhood; growth; puberty; GH deficiency; childhood obesity; Turner syndrome; adrenal disorders in childhood
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thyroid diseases are a wide topic that includes congenital, autoimmune, and neoplastic conditions. Diagnostic pathways and therapeutic approaches of thyroid diseases are constantly evolving both in adulthood and in childhood. This process is favored by the discovery of new pathophysiological mechanisms and by advances on molecular sciences. Novel information on natural history, complications, and mechanisms of thyroid diseases allows the application of new treatment strategies, particularly in the fields of autoimmunity and cancer.

The aim of this Special Issue is to collect updated studies on new pathophysiological mechanisms and on novel therapeutic approaches for thyroid diseases. Therefore, I cordially invite authors and investigators within this field to submit original research or review articles related to this Special Issue. Preclinical and translational research studies that can suggest new diagnostics and therapeutic approaches are also welcome.

Prof. Dr. Tommaso Aversa
Guest Editor

Manuscript Submission Information

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Keywords

  • thyroid cancer
  • thyroid nodules
  • congenital hypothyroidism
  • congenital hyperthyroidism
  • thyroid autoimmunity
  • Hashimoto’s thyroiditis
  • Graves’ disease
  • thyroid rare diseases

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Published Papers (7 papers)

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Research

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10 pages, 1542 KiB  
Article
Inflammatory Profile Assessment in a Highly Selected Athyreotic Population Undergoing Controlled and Standardized Hypothyroidism
by Tommaso Piticchio, Francesco Savarino, Salvatore Volpe, Antonio Prinzi, Gabriele Costanzo, Elena Gamarra, Francesco Frasca and Pierpaolo Trimboli
Biomedicines 2024, 12(1), 239; https://doi.org/10.3390/biomedicines12010239 - 22 Jan 2024
Cited by 1 | Viewed by 1359
Abstract
Background: Hypothyroidism (hT) presents heterogeneous symptoms and findings. Evidence on this topic comes mainly from heterogeneous populations in terms of disease duration, residual thyroid function, and comorbidities. Therefore, it would be useful to assess systemic inflammation in a homogeneous hT population. The aim [...] Read more.
Background: Hypothyroidism (hT) presents heterogeneous symptoms and findings. Evidence on this topic comes mainly from heterogeneous populations in terms of disease duration, residual thyroid function, and comorbidities. Therefore, it would be useful to assess systemic inflammation in a homogeneous hT population. The aim of this study was to investigate inflammation in a population that underwent standardized controlled hT. Methods: We recruited thyroidectomized patients diagnosed with thyroid cancer who were otherwise fit and healthy, showing hypothyroidism before I131 treatment using a standard protocol of LT4 withdrawal. The blood inflammatory indexes (BIIXs) (i.e., NLR, PLR, MLR, SII, SIRI, and AISI) were calculated using the blood tests collected just before I131 administration. Patients were divided according to sex, BMI, and thyroglobulin. The relationships between the BIIXs, age, and thyroid hormones were also investigated. Results: We included 143 patients. The median age of the sample was 43 years. The BIIX median values showed significant differences based on sex, BMI, and thyroglobulin levels (p < 0.05). No significant correlations were found between the BIIXs and age, TSH, FT4, and FT3. Conclusions: This study shows the BIIX median values of a population which underwent standardized hT. It suggests a role for some BIIXs in the evaluation of hypothyroidism in obese people and as hypothetical prognostic markers for thyroid cancer. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
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10 pages, 285 KiB  
Article
Severity of Fatigue and Its Relationship with TSH before and after Levothyroxine Replacement Therapy in Patients with Primary Hypothyroidism
by María Guadalupe Ruíz-Pacheco, Irma Hernández, Guadalupe Hernández-Estrella, Lourdes Basurto, Guadalupe Vargas-Ortega, Baldomero González-Virla, Mario Molina-Ayala, Alex Francisco Hernández-Martínez, Rosamaría Luengas-Mondragón, Angel Alejandro Hernández-Allende, Victoria Mendoza-Zubieta and Lourdes Balcázar-Hernández
Biomedicines 2023, 11(3), 811; https://doi.org/10.3390/biomedicines11030811 - 7 Mar 2023
Cited by 4 | Viewed by 2160
Abstract
Background: Fatigue is a common symptom in hypothyroidism; however, the effect of levothyroxine on fatigue has been little studied. The aim of this study was to evaluate the effect of levothyroxine on fatigue in Latino patients with primary hypothyroidism, as well as the [...] Read more.
Background: Fatigue is a common symptom in hypothyroidism; however, the effect of levothyroxine on fatigue has been little studied. The aim of this study was to evaluate the effect of levothyroxine on fatigue in Latino patients with primary hypothyroidism, as well as the association of TSH and free T4 (FT4) with the severity and persistence of fatigue. Methods: A prospective study was performed in 92 patients with primary hypothyroidism. Fatigue severity scale (FSS) scores and clinical and biochemical characteristics before and at 6 months of levothyroxine were evaluated. Results: After 6 months of levothyroxine, a reduction in FSS (53 (47–57) vs. 36 (16–38); p = 0.001) and fatigue frequency (45.7% vs. 26.1%; p = 0.008) was evident. Both before and after 6 months of levothyroxine, there was a positive correlation of the FSS score with TSH and a negative correlation with FT4. Persistent fatigue was associated with a pretreatment FSS score (r = 0.75; p = 0.001) and diabetes (r = 0.40; p = 0.001). An FSS > 34 (RR 3.9 (95% CI 1.43–10.73; p = 0.008)), an FSS > 36 (RR 3.23 (95% CI 1.21–8.6; p = 0.019)), and diabetes (RR 5.7 (95% CI 1.25–9.6; p = 0.024)) before treatment were risk factors for persistent fatigue. Conclusions: Levothyroxine improved fatigue in most patients. Diabetes and an FSS score >34 or >36 before treatment were risk factors for persistent fatigue. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
17 pages, 14853 KiB  
Article
Optimization of Thyroid Volume Determination by Stitched 3D-Ultrasound Data Sets in Patients with Structural Thyroid Disease
by Philipp Seifert, Sophie-Luise Ullrich, Christian Kühnel, Falk Gühne, Robert Drescher, Thomas Winkens and Martin Freesmeyer
Biomedicines 2023, 11(2), 381; https://doi.org/10.3390/biomedicines11020381 - 27 Jan 2023
Cited by 4 | Viewed by 1869
Abstract
Ultrasound (US) is the most important imaging method for the assessment of structural disorders of the thyroid. A precise volume determination is relevant for therapy planning and outcome monitoring. However, the accuracy of 2D-US is limited, especially in cases of organ enlargements and [...] Read more.
Ultrasound (US) is the most important imaging method for the assessment of structural disorders of the thyroid. A precise volume determination is relevant for therapy planning and outcome monitoring. However, the accuracy of 2D-US is limited, especially in cases of organ enlargements and deformations. Software-based “stitching” of separately acquired 3D-US data revealed precise volume determination in thyroid phantoms. The purpose of this study is to investigate the feasibility and accuracy of 3D-US stitching in patients with structural thyroid disease. A total of 31 patients from the clinical routine were involved, receiving conventional 2D-US (conUS), sensor-navigated 3D-US (3DsnUS), mechanically-swept 3D-US (3DmsUS), and I-124-PET/CT as reference standard. Regarding 3DsnUS and 3DmsUS, separately acquired 3D-US images (per thyroid lobe) were merged to one comprehensive data set. Subsequently, anatomical correctness of the stitching process was analysed via secondary image fusion with the I-124-PET images. Volumetric determinations were conducted by the ellipsoid model (EM) on conUS and CT, and manually drawn segmental contouring (MC) on 3DsnUS, 3DmsUS, CT, and I-124-PET/CT. Mean volume of the thyroid glands was 44.1 ± 25.8 mL (I-124-PET-MC = reference). Highly significant correlations (all p < 0.0001) were observed for conUS-EM (r = 0.892), 3DsnUS-MC (r = 0.988), 3DmsUS-MC (r = 0.978), CT-EM (0.956), and CT-MC (0.986), respectively. The mean volume differences (standard deviations, limits of agreement) in comparison with the reference were −10.50 mL (±11.56 mL, −33.62 to 12.24), −3.74 mL (±3.74 mL, −11.39 to 3.78), and 0.62 mL (±4.79 mL, −8.78 to 10.01) for conUS-EM, 3DsnUS-MC, and 3DmsUS-MC, respectively. Stitched 3D-US data sets of the thyroid enable accurate volumetric determination even in enlarged and deformed organs. The main limitation of high time expenditure may be overcome by artificial intelligence approaches. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
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11 pages, 641 KiB  
Article
Assessment of Preoperative TSH Serum Level and Thyroid Cancer Occurrence in Patients with AUS/FLUS Thyroid Nodule Diagnosis
by Krzysztof Kaliszewski, Dorota Diakowska, Marta Rzeszutko, Łukasz Nowak, Beata Wojtczak, Krzysztof Sutkowski, Maksymilian Ludwig, Bartłomiej Ludwig, Agnieszka Mikuła, Maria Greniuk, Urszula Tokarczyk and Jerzy Rudnicki
Biomedicines 2022, 10(8), 1916; https://doi.org/10.3390/biomedicines10081916 - 8 Aug 2022
Cited by 9 | Viewed by 2534
Abstract
Thyroid-stimulating hormone (TSH) is a growth factor associated with the initiation and progression of well-differentiated thyroid cancer (WDTC). Atypia of undetermined significance and follicular lesion of undetermined significance (AUS/FLUS) are the most uncertain cytological diagnoses of thyroid nodules. The aim of the study [...] Read more.
Thyroid-stimulating hormone (TSH) is a growth factor associated with the initiation and progression of well-differentiated thyroid cancer (WDTC). Atypia of undetermined significance and follicular lesion of undetermined significance (AUS/FLUS) are the most uncertain cytological diagnoses of thyroid nodules. The aim of the study was to determine the association of histopathological diagnosis with preoperative serum TSH levels in patients with AUS/FLUS thyroid nodule diagnosis. Among 5028 individuals with thyroid nodules, 342 (6.8%) with AUS/FLUS diagnoses were analyzed. The frequency of all histopathology diagnoses was assessed for associations with preoperative serum TSH levels. The median TSH concentration was significantly higher in patients with AUS/FLUS diagnosis and histopathology of WDTC than in patients with the same cytology result and histopathology of a benign tumor (p < 0.0001). The diagnostic potential of serum TSH level was determined to evaluate risk of malignancy in patients with thyroid nodules classified into the Bethesda III category. ROC analysis showed the TSH concentration at a cutoff point of 2.5 mIU/L to be an acceptable prognostic factor for WDTC. For this optimal cutoff point, the AUC was 0.877, the sensitivity was 0.830, and the specificity was 0.902. Preoperative serum TSH levels in patients with AUS/FLUS thyroid tumor diagnosis should be taken into consideration in the decision-making process and clinical management. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
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Review

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16 pages, 6344 KiB  
Review
Graves’ Eye Disease: Clinical and Radiological Diagnosis
by Kasen R. Hutchings, Seth J. Fritzhand, Bita Esmaeli, Kirthi Koka, Jiawei Zhao, Salmaan Ahmed and James Matthew Debnam
Biomedicines 2023, 11(2), 312; https://doi.org/10.3390/biomedicines11020312 - 22 Jan 2023
Cited by 5 | Viewed by 3697
Abstract
Graves’ disease is an autoimmune disorder in which hyperthyroidism results in various systematic symptoms, with about 30% of patients presenting with Graves’ eye disease (GED). The majority of patients with GED develop mild symptoms, including eyelid retraction, exposure of the globe, superior rectus–levator [...] Read more.
Graves’ disease is an autoimmune disorder in which hyperthyroidism results in various systematic symptoms, with about 30% of patients presenting with Graves’ eye disease (GED). The majority of patients with GED develop mild symptoms, including eyelid retraction, exposure of the globe, superior rectus–levator muscle complex inflammation, and fat expansion, leading to exophthalmos. More severe cases can result in extraocular muscle enlargement, restricted ocular movement, eyelid and conjunctival edema, and compression of the optic nerve leading to compressive optic neuropathy (CON). GED severity can be classified using the Clinical Activity Score, European Group on Graves’ Orbitopathy scale, NO SPECS Classification system, and VISA system. CT and MRI aid in the diagnosis of GED through the demonstration of orbital pathology. Several recent studies have shown that MRI findings correlate with disease severity and can be used to evaluate CON. Mild cases of GED can be self-limiting, and patients often recover spontaneously within 2–5 years. When medical treatment is required, immunomodulators or radiotherapy can be used to limit immunologic damage. Surgery may be needed to improve patient comfort, preserve the orbit, and prevent vision loss from optic nerve compression or breakdown of the cornea. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
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20 pages, 1052 KiB  
Review
Role of Extracellular Vesicles in Thyroid Physiology and Diseases: Implications for Diagnosis and Treatment
by Ophélie Delcorte, Jonathan Degosserie and Christophe E. Pierreux
Biomedicines 2022, 10(10), 2585; https://doi.org/10.3390/biomedicines10102585 - 15 Oct 2022
Cited by 5 | Viewed by 5577
Abstract
Extracellular vesicles are spherical subcellular structures delimited by a lipid bilayer and released by most cells in the human body. They are loaded with a myriad of molecules (i.e., nucleic acids and proteins) depending on their cell of origin and provide the ability [...] Read more.
Extracellular vesicles are spherical subcellular structures delimited by a lipid bilayer and released by most cells in the human body. They are loaded with a myriad of molecules (i.e., nucleic acids and proteins) depending on their cell of origin and provide the ability to transmit a message to surrounding or distant target cells. In several organs, including the thyroid, abundant recent literature reports that extracellular vesicles are responsible for intercellular communication in physiological and pathological processes, and that their utilization as a potential biomarker of pathological states (i.e., cancer, autoimmune diseases) or as therapeutic delivery vehicles promise clinical options. In this review, we present the current knowledge and understanding regarding the role of extracellular vesicles in developing thyroid diseases and diagnosis. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
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Other

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16 pages, 1484 KiB  
Systematic Review
Effect of Hyperthyroidism Treatments on Heart Rate Variability: A Systematic Review and Meta-Analysis
by Valentin Brusseau, Igor Tauveron, Reza Bagheri, Ukadike Chris Ugbolue, Valentin Magnon, Jean-Baptiste Bouillon-Minois, Valentin Navel and Frederic Dutheil
Biomedicines 2022, 10(8), 1982; https://doi.org/10.3390/biomedicines10081982 - 16 Aug 2022
Cited by 3 | Viewed by 2432
Abstract
The reversibility of HRV abnormalities in hyperthyroidism remains contradictory. The design of this study involves conducting a systematic review and meta-analysis on the effect of antithyroid treatments on HRV in hyperthyroidism. PubMed, Cochrane, Embase, and Google Scholar were searched until 4 April 2022. [...] Read more.
The reversibility of HRV abnormalities in hyperthyroidism remains contradictory. The design of this study involves conducting a systematic review and meta-analysis on the effect of antithyroid treatments on HRV in hyperthyroidism. PubMed, Cochrane, Embase, and Google Scholar were searched until 4 April 2022. Multiple reviewers selected articles reporting HRV parameters in treated and untreated hyperthyroidism. Independent data extraction by multiple observers was stratified by degree of hyperthyroidism for each HRV parameter: RR intervals, SDNN (standard deviation of RR intervals), RMSSD (square root of the mean difference of successive RR intervals), pNN50 (percentage of RR intervals with >50 ms of variation), total power (TP), LFnu (low-frequency normalized unit) and HFnu (high-frequency), VLF (very low-frequency), and LF/HF ratio. We included 11 studies for a total of 471 treated hyperthyroid patients, 495 untreated hyperthyroid patients, and 781 healthy controls. After treatment, there was an increase in RR, SDNN, RMSSD, pNN50, TP, HFnu, and VLF and a decrease in LFnu and LF/HF ratio (p < 0.01). Overt hyperthyroidism showed similar results, in contrast to subclinical hyperthyroidism. Compared with controls, some HRV parameter abnormalities persist in treated hyperthyroid patients (p < 0.05) with lower SDNN, LFnu, and higher HFnu, without significant difference in other parameters. We showed a partial reversibility of HRV abnormalities following treatment of overt hyperthyroidism. The improvement in HRV may translate the clinical cardiovascular benefits of treatments in hyperthyroidism and may help to follow the evolution of the cardiovascular morbidity. Full article
(This article belongs to the Special Issue Mechanisms and Novel Therapeutic Approaches for Thyroid Diseases)
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