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Thyroid Disease: From Mechanism to Therapeutic Approaches
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Thyroid Disease: From Mechanism to Therapeutic Approaches

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 16757

Special Issue Editor

Dr. Beata Wojtczak

E-Mail Website
Guest Editor
Department of General, Minimally Invasive and Endocrine Surgery, Wrocław Medical University Borowska Street 213, 50-556 Wrocław, Poland
Interests: endocrinology; endocrine surgery; thyroid disorders; thyroid cancer; parathyroid disorders; intraoperative nerve monitoring (IONM); quality of life in endocrine disorders

Special Issue Information

Dear Colleagues,

Thyroid diseases along with diabetes mellitus are among the most common endocrinopathies worldwide. Thyroid cancer is still the most common malignancy of the endocrine system with the fastest growing incidence particularly in women.

Over the last two decades the epidemiology, clinical presentation, strategies for diagnosis, approaches to treatment have changed. We observe milestones in the field of molecular genetic research. This undoubtedly influences new strategies for treating thyroid disease. The treatment of most thyroid conditions has been very successful. Nevertheless, diseases such as anaplastic cancer and recurrent thyroid cancer remain a challenge and lead to the search for new therapeutic treatments. Moreover, in the last two decades we observe the progress in the surgical treatment of thyroid diseases, new technological devices have been developed and widely used to improved surgical outcome.  Minimally invasive techniques begin to play an increasingly important role in therapeutic approaches.

This special issue is a review of the latest achievements in the treatment of thyroid disorders: from mechanism to therapeutic approaches.

Dr. Beata Wojtczak
Guest Editor

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Keywords

  • pathogenesis and molecular mechanism of thyroid diseases
  • genetic disorders of the thyroid biomarkers for thyroid dysfunctions
  • diagnostic challenges
  • new thyroid’s therapies
  • immunotherapy
  • nuclear medicine
  • minimal invasive treatment

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Published Papers (8 papers)

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Research

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19 pages, 4509 KiB  
Article
Prognostic Protein Biomarker Screening for Thyroid Carcinoma Based on Cancer Proteomics Profiles
by Pu Xie, Qinglei Yin, Shu Wang and Dalong Song
Biomedicines 2024, 12(9), 2066; https://doi.org/10.3390/biomedicines12092066 - 10 Sep 2024
Cited by 1 | Viewed by 1462
Abstract
Thyroid carcinoma (THCA) ranks among the most prevalent cancers globally. Integrating advanced genomic and proteomic analyses to construct a protein-based prognostic model promises to identify effective biomarkers and explore new therapeutic avenues. In this study, proteomic data from The Cancer Proteomics Atlas (TCPA) [...] Read more.
Thyroid carcinoma (THCA) ranks among the most prevalent cancers globally. Integrating advanced genomic and proteomic analyses to construct a protein-based prognostic model promises to identify effective biomarkers and explore new therapeutic avenues. In this study, proteomic data from The Cancer Proteomics Atlas (TCPA) and clinical data from The Cancer Genome Atlas (TCGA) were utilized. Using Kaplan–Meier, Cox regression, and LASSO penalized Cox analyses, we developed a prognostic risk model comprising 13 proteins (S100A4, PAI1, IGFBP2, RICTOR, B7-H3, COLLAGENVI, PAR, SNAIL, FAK, Connexin-43, Rheb, EVI1, and P90RSK_pT359S363). The protein prognostic model was validated as an independent predictor of survival time in THCA patients, based on risk curves, survival analysis, receiver operating characteristic curves and independent prognostic analysis. Additionally, we explored the immune cell infiltration and tumor mutational burden (TMB) related to these features. Notably, our study proved a novel approach for predicting treatment responses in THCA patients, including those undergoing chemotherapy and targeted therapy. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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12 pages, 1242 KiB  
Article
Cut-off Value for Thyroglobulin Washout Concentration in the Detection of Cervical Lymph Node Metastases in Patients after Thyroidectomy Due to Differentiated Thyroid Cancer
by Paweł Mikosiński, Emilia Wołowiec-Korecka, Lech Pomorski, Agnieszka Mikosińska, Krzysztof Kaczka and Sławomir Mikosiński
Biomedicines 2023, 11(9), 2433; https://doi.org/10.3390/biomedicines11092433 - 31 Aug 2023
Cited by 1 | Viewed by 1839
Abstract
The aim of this study was to establish the cut-off value for the thyroglobulin (Tg) concentration in washout fluid from fine needle aspiration biopsy (FNA-Tg) in the detection of cervical lymph node metastases of differentiated thyroid cancer (DTC). We evaluated the validity and [...] Read more.
The aim of this study was to establish the cut-off value for the thyroglobulin (Tg) concentration in washout fluid from fine needle aspiration biopsy (FNA-Tg) in the detection of cervical lymph node metastases of differentiated thyroid cancer (DTC). We evaluated the validity and clinical utility of fine needle aspiration biopsy cytology (FNAB-C), FNA-Tg, and the combined method in detecting DTC recurrences. The study included 82 patients after the total thyroidectomy and elective and, in some cases, also selective cervical lymphadenectomy. The majority of patients also underwent subsequent 131I ablative therapy. The patients presented with 1–6 enlarged and/or ultrasonographically suspicious cervical lymph nodes. One to four aspirates of each lymph node were taken, with a total of 297 samples. An FNA-Tg of 4.34 ng/mL was established as the cut-off value for detecting cervical lymph node DTC metastases for the IRMA Brahms DYNO test, Tg-S. FNAB-C is highly specific (91–99%) but not sensitive enough (53–69%) to be used as a standalone method in the detection of cervical lymph node metastases. FNA-Tg is more sensitive (91%), but caution should be taken when selecting patients for surgery with an FNA-Tg higher than the established cut-off value but lower than the serum Tg concentration. To select patients for lymphadenectomy, we recommend using the combined method (FNAB-C and FNA-Tg) with a sensitivity of 96% and specificity of up to 97%. More than one sample should be taken with each fine needle aspiration biopsy (FNAB) to obtain a representative set of samples. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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17 pages, 818 KiB  
Article
Risk Factors for Calcium-Phosphate Disorders after Thyroid Surgery
by Monika Sępek, Dominik Marciniak, Mateusz Głód, Krzysztof Kaliszewski, Jerzy Rudnicki and Beata Wojtczak
Biomedicines 2023, 11(8), 2299; https://doi.org/10.3390/biomedicines11082299 - 18 Aug 2023
Cited by 2 | Viewed by 1912
Abstract
Introduction: Iatrogenic hypoparathyroidism following thyroidectomy is one of the most common complications significantly reducing patients’ quality of life. Objectives: This study aimed to analyze the risk factors for calcium-phosphate disorders following thyroidectomy. Patients and methods: The study group consisted of 211 patients who [...] Read more.
Introduction: Iatrogenic hypoparathyroidism following thyroidectomy is one of the most common complications significantly reducing patients’ quality of life. Objectives: This study aimed to analyze the risk factors for calcium-phosphate disorders following thyroidectomy. Patients and methods: The study group consisted of 211 patients who underwent thyroidectomy for different conditions in 2018–2020. Demographic, clinical and surgical risk factors were analyzed against hypoparathyroidism and hypocalcemia. Results: Hypoparathyroidism occurred in 15.63% of patients, and hypocalcemia occurred in 45% of those operated on. There was statistical significance between hypoparathyroidism and the extent of thyroid surgery: thyroidectomy vs. lobectomy (p = 0.02, OR = 4.5) and surgeon experience (p = 0.016, OR = 6.9). Low preoperative PTH levels were associated with a higher incidence of hypoparathyroidism (p = 0.055, OR = 0.9). There was a statistically significant correlation between the occurrence of hypocalcemia and preoperative vitamin D deficiency (p = 0.04, OR = 3.5). Low calcium levels before surgery were associated with a higher incidence of hypocalcemia (p = 0.051, OR = 0.5). Meta-analyses of selected risk factors confirmed that the most significant factor in the incidence of hypocalcemia was a decrease in PTH levels (p < 0.001). Conclusions: The extent of thyroid surgery and the experience of the surgeon are the most significant risk factors for hypoparathyroidism. Hypocalcemia is much more common than hypoparathyroidism. Among the risk factors for hypocalcemia, in addition to the decrease in parathormone levels due to iatrogenic parathyroid damage, we should mention vitamin D deficiency in the preoperative period. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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11 pages, 1568 KiB  
Article
Compensatory Increase of Serum Hepassocin Protects Hyperthyroidism-Induced Hepatic Dysfunction
by Chih-Chen Wang, Ching-Han Lin, Hsuan-Wen Chou, Chung-Teng Wang, Yu-Cheng Liang, Hung-Tsung Wu and Horng-Yih Ou
Biomedicines 2023, 11(7), 1936; https://doi.org/10.3390/biomedicines11071936 - 7 Jul 2023
Cited by 1 | Viewed by 1374
Abstract
Hepatic dysfunction is commonly observed in subjects with hyperthyroidism. Hepassocin is a hepatokine playing an important role in metabolic diseases and exhibiting a hepatic protective effect. Nevertheless, the relationship between hepassocin and hyperthyroidism was still unknown. In the present study, a total of [...] Read more.
Hepatic dysfunction is commonly observed in subjects with hyperthyroidism. Hepassocin is a hepatokine playing an important role in metabolic diseases and exhibiting a hepatic protective effect. Nevertheless, the relationship between hepassocin and hyperthyroidism was still unknown. In the present study, a total of 36 subjects with Graves’ disease were enrolled, and we found that the alanine aminotransferase (ALT) levels were significantly decreased in parallel with the decrement in serum hepassocin concentrations at 6 months after standard treatment for hyperthyroidism. In addition, HepG2 cell line was used to investigate the role of hepassocin in hyperthyroidism-induced hepatic dysfunction. Treatment of hepassocin recombinant protein in HepG2 cells dose-dependently decreased triiodothyronine (T3)-induced ALT and aspartate aminotransferase (AST) elevation. Moreover, hepassocin significantly increased the expression of phosphoenolpyruvate carboxykinase (PEPCK) in a dose-dependent manner. Deletion of hepassocin in HepG2 cells reversed the effects of T3 on PEPCK expressions. Furthermore, we found that T3 increased the expression of hepassocin through a hepatocyte nuclear factor 1α-dependent pathway. Taken together, these results indicated a compensatory increase in serum hepassocin might have a protective role in hyperthyroidism-induced hepatic dysfunction. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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Review

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13 pages, 246 KiB  
Review
When Should the Treatment of Obesity in Thyroid Disease Begin?
by Edyta Sutkowska, Michał Kisiel and Agnieszka Zubkiewicz-Kucharska
Biomedicines 2025, 13(1), 157; https://doi.org/10.3390/biomedicines13010157 - 10 Jan 2025
Viewed by 527
Abstract
Obesity often coexists with thyroid diseases, and the prevalence of these disorders has been on the rise for years. While hypothyroidism can contribute to excess fat tissue, the relationship between Body Mass Index (BMI) and thyroid function hormones is bidirectional. Research confirms that [...] Read more.
Obesity often coexists with thyroid diseases, and the prevalence of these disorders has been on the rise for years. While hypothyroidism can contribute to excess fat tissue, the relationship between Body Mass Index (BMI) and thyroid function hormones is bidirectional. Research confirms that fat tissue reduction can positively impact thyroid function. Thus, delaying the initiation of therapies beyond substitution treatment to achieve optimal weight reduction in individuals with thyroid dysfunction seems unwarranted. The authors summarize current knowledge on this topic in the article. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
16 pages, 2726 KiB  
Review
Current Knowledge on the Use of Neuromonitoring in Thyroid Surgery
by Beata Wojtczak, Karolina Sutkowska-Stępień, Mateusz Głód, Krzysztof Kaliszewski, Krzysztof Sutkowski and Marcin Barczyński
Biomedicines 2024, 12(3), 675; https://doi.org/10.3390/biomedicines12030675 - 18 Mar 2024
Cited by 7 | Viewed by 3667
Abstract
Thyroid surgery rates have tripled over the past three decades, making it one of the most frequently performed procedures within general surgery. Thyroid surgery is associated with the possibility of serious postoperative complications which have a significant impact on the patient’s quality of [...] Read more.
Thyroid surgery rates have tripled over the past three decades, making it one of the most frequently performed procedures within general surgery. Thyroid surgery is associated with the possibility of serious postoperative complications which have a significant impact on the patient’s quality of life. Recurrent laryngeal nerve (RLN) palsy and external branch of the superior laryngeal nerve (EBSLN) palsy are, next to hypoparathyroidism and postoperative bleeding, some of the most common complications. The introduction of neuromonitoring into thyroid surgery, which enabled both the confirmation of anatomical integrity and the assessment of laryngeal nerve function, was a milestone that began a new era in thyroid surgery. The International Neural Monitoring Study Group has produced a standardization of the technique of RLN and EBSLN monitoring during thyroid and parathyroid surgery, which in turn increased the prevalence of neural monitoring during thyroidectomy. The current status of IONM and the benefits of its use have been presented in this publication. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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15 pages, 531 KiB  
Review
The Influence of SARS-CoV-2 Infection on the Thyroid Gland
by Aleksandra Piekarska, Marta Góral, Marta Kozula, Aleksandra Jawiarczyk-Przybyłowska, Katarzyna Zawadzka and Marek Bolanowski
Biomedicines 2023, 11(2), 614; https://doi.org/10.3390/biomedicines11020614 - 18 Feb 2023
Cited by 6 | Viewed by 3162
Abstract
It is important to acknowledge the impact that COVID-19 has on the thyroid gland and how the thyroid gland status before and during infection affects SARS-CoV-2 severity. To this day those dependencies are not fully understood. It is known that the virus uses [...] Read more.
It is important to acknowledge the impact that COVID-19 has on the thyroid gland and how the thyroid gland status before and during infection affects SARS-CoV-2 severity. To this day those dependencies are not fully understood. It is known that the virus uses angiotensin-converting enzyme-2 as the receptor for cellular entry and it can lead to multiple organ failures due to a cytokine storm. Levels of proinflammatory molecules (such as cytokines and chemokines) which are commonly elevated during infection were significantly higher in observed SARS-CoV-2-positive patients. In terms of hypothyroidism, hyperthyroidism, and autoimmune thyroid diseases, there is no proof that those dysfunctions have a direct impact on the more severe courses of COVID-19. Regarding hyper- and hypothyroidism there was no consequential dependency between the frequency of SARS-CoV-2 infection morbidity and more severe post-infectious complications. When it comes to autoimmune thyroid diseases, more evaluation has to be performed due to the unclear relation with the level of antibodies commonly checked in those illnesses and its binding with the mentioned before virus. Nonetheless, based on analyzed works we found that COVID-19 can trigger the immune system and cause its hyperactivity, sometimes leading to the new onset of autoimmune disorders. We also noticed more acute SARS-CoV-2 courses in patients with mainly reduced free triiodothyronine serum levels, which in the future, might be used as a mortality indicating factor regarding SARS-CoV-2-positive patients. Considering subacute thyroiditis (SAT), no statistically important data proving its direct correlation with COVID-19 infection has been found. Nevertheless, taking into account the fact that SAT is triggered by respiratory tract viral infections, it might be that SARS-CoV-2 can cause it too. There are many heterogenous figures in the symptoms, annual morbidity distribution, and frequency of new cases, so this topic requires further evaluation. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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Other

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16 pages, 1068 KiB  
Case Report
Pituitary Hyperplasia Due to Longstanding Primary Hypothyroidism: A Case Report and Comprehensive Review of the Literature
by Anna Roux, Daniela Rosso, Daniela Cuboni, Mauro Maccario, Silvia Grottoli, Emanuela Arvat and Valentina Gasco
Biomedicines 2024, 12(6), 1368; https://doi.org/10.3390/biomedicines12061368 - 19 Jun 2024
Viewed by 1637
Abstract
Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic [...] Read more.
Hypothyroidism is a frequently diagnosed endocrine disorder. Common signs and symptoms include fatigue, cold intolerance, hoarseness, dry skin, constipation, a slow relaxation phase of deep tendon reflexes, and bradycardia. However, some patients may exhibit atypical signs and symptoms, which can result in diagnostic confusion. Pituitary hyperplasia resulting from longstanding primary hypothyroidism was first described by Niepce in 1851. It is usually asymptomatic, but sometimes, in addition to symptoms of overt hypothyroidism, patients may complain of headaches, hypopituitarism, visual field impairment, and hyperprolactinemia. Furthermore, on imaging, pituitary hyperplasia can be mistaken for a pituitary adenoma. Distinguishing between the two is crucial, as their management differs; the former often responds to thyroid hormone replacement therapy, while the latter might need treatment with surgery and/or radiotherapy. Here we describe a patient who developed pituitary hyperplasia in the setting of longstanding uncompensated primary hypothyroidism due to a lack of compliance with levothyroxine replacement therapy. We also review the clinical, laboratory, and radiologic findings of the case reports available in the literature up to now in order to improve the knowledge and the care of the disease. Full article
(This article belongs to the Special Issue Thyroid Disease: From Mechanism to Therapeutic Approaches)
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