Thyroid Disease: Updates from Diagnosis to Treatment

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Endocrinology & Metabolism".

Deadline for manuscript submissions: 28 June 2025 | Viewed by 8185

Special Issue Editors


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Guest Editor
1. Nuclear Medicine and Thyroid Diseases, University Hospital of Zurich, Zurich, Switzerland
2. Nuclear Medicine and Thyroid Diseases, Gruppo Ospedaliero Moncucco, Lugano, Switzerland
Interests: clinical thyroidology; laboratory medicine; ultrasonography; molecular imaging; PET/CT; thyroid cancer; thyroid diseases; molecular endocrinology
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia
Interests: thyroid diseases; nuclear medicine; molecular imaging; theranostics; endocrine tumors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Thyroid disorders are frequently encountered in clinical daily life, and their diagnosis and therapy may involve different specialists using different methods. Laboratory tests and imaging procedures are integral to the diagnosis and management of thyroid disease. An appropriate integration of laboratory, imaging and (cyto)pathology data is pivotal for refining the diagnosis and selecting patients for different available therapies. In addition, radioiodine (i.e., I-131) therapy was the first application of the theranostic approach in clinical practice and is widely used in patients with differentiated thyroid cancer, hyperthyroidism and non-toxic compressive goiter since the 1940s. Accordingly, thyroid diseases represent an ideal platform to develop and evaluate integrated diagnostic and theranostic strategies. The present issue aims to provide relevant information on different diagnostic methods actionable in thyroid patients and their rationale integration (i.e., integrated diagnostics). Furthermore, surgical, pharmacologic and theragnostic applications for patients with either benign or malignant thyroid diseases will also be illustrated. We invite specialists in clinical thyroidology, endocrine surgery, imaging and theranostics, laboratory and (cyto)pathology to share their experience and contribute with original research and reviews to our present issue.

Prof. Dr. Luca Giovanella
Dr. Petra Petranović Ovčariček
Guest Editors

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Keywords

  • autoimmune thyroid diseases
  • thyroiditis
  • thyroid cancers
  • PET/CT
  • hyperthyroidism

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Published Papers (8 papers)

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Research

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11 pages, 3093 KiB  
Article
Evaluation of Changes in Clinicopathological Features and Prognosis in Patients with Thyroid Cancer
by Özlem Doğan, Melin Aydan Ahmed, Ömer Burak Ekinci, Anıl Yıldız and Izzet Dogan
J. Clin. Med. 2025, 14(5), 1482; https://doi.org/10.3390/jcm14051482 - 23 Feb 2025
Viewed by 594
Abstract
Background: In this study, we evaluated the changes in clinicopathological features and prognosis in patients with thyroid cancer in the last two decades using the Surveillance, Epidemiology, and End Results Database (SEER) data. Methods: Data from the SEER-12 registry (1992–2021) were analyzed, focusing [...] Read more.
Background: In this study, we evaluated the changes in clinicopathological features and prognosis in patients with thyroid cancer in the last two decades using the Surveillance, Epidemiology, and End Results Database (SEER) data. Methods: Data from the SEER-12 registry (1992–2021) were analyzed, focusing on patients diagnosed with malignant thyroid cancer between 2001 and 2020. The study population was divided into Cohort 1 (2001–2010) and Cohort 2 (2011–2020). Cohorts 1 and 2 were compared regarding clinicopathological features and prognosis. Results: The study included 94,892 patients diagnosed with thyroid cancer between 2001 and 2020, with 39,265 patients in Cohort 1 and 55,627 in Cohort 2. Compared to Cohort 1, in Cohort 2 showed a statistically significant increase in the proportion of patients aged 60+ (+4.2%), male patients (+2.1%), and cases of papillary cancer (+5.3%) and regional disease (+3.7%) (all p < 0.001). Although Cohort 2 demonstrated an 8% improvement in survival compared to Cohort 1, this result was not statistically significant (p = 0.057). Prognostic factors were identified, such as disease stage at diagnosis, age, gender, and origin. Among pathological subtypes, the patients with papillary + FV had the best prognosis (HR: 0.78), compared to patients in the other group, mainly comprising anaplastic tumors and sarcomas, which had the worst prognosis (HR: 9.61). Conclusions: In this large-scale study of thyroid cancer patients, we found significant differences between the two cohorts. In Cohort 2, the proportion of patients aged ≥60 years, male, and with papillary thyroid cancer was increased. We found that age, sex, origin, histopathological subtype, and stage at diagnosis were prognostic factors in patients with thyroid cancer. Also, we observed a trend toward improved survival in Cohort 2. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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13 pages, 13069 KiB  
Article
Does Radioactive Iodine Treatment Affect Thyroid Size and Tracheal Diameter?
by Kadriye Yazici Demir, Zulkuf Kaya, Ramazan Dayanan, Tolga Mercantepe and Filiz Mercantepe
J. Clin. Med. 2025, 14(1), 115; https://doi.org/10.3390/jcm14010115 - 28 Dec 2024
Viewed by 658
Abstract
Background/Objectives: There exist three principal treatment modalities employed in the management of hyperthyroidism attributable to excessive hormone secretion by the thyroid gland: antithyroid pharmacotherapy, surgical intervention, and radioactive iodine (RAI) therapy. Surgical intervention is typically indicated for markedly enlarged thyroid glands that exert [...] Read more.
Background/Objectives: There exist three principal treatment modalities employed in the management of hyperthyroidism attributable to excessive hormone secretion by the thyroid gland: antithyroid pharmacotherapy, surgical intervention, and radioactive iodine (RAI) therapy. Surgical intervention is typically indicated for markedly enlarged thyroid glands that exert pressure on the trachea. The objective of this investigation was to ascertain the influence of RAI on thyroid volume and tracheal diameter. Methods: This study included 20 patients, six females and 14 males, who received 20 mCi radioactive iodine treatment for toxic nodular goiter at a tertiary university hospital between March 2019 and February 2020. Pre-treatment and six-month post-treatment neck MRI scans were conducted on the cohort. Thyroid and tracheal volumes were quantified using the Cavalieri method based on MRI sections, and comparisons were conducted pre-and post-treatment. Statistical analysis of the comparative values was performed using the dependent samples t-test. Results: A statistically significant reduction in thyroid volume was observed among the 20 patients, averaging a decrease of 36.06% following RAI treatment compared to baseline measurements (p < 0.001). Additionally, an average increase of 12.76% in tracheal volume was noted post-treatment in comparison to initial measurements, which was also statistically significant (p < 0.05). None of the patients exhibited respiratory distress in the immediate postoperative period. Conclusions: The findings indicate that RAI therapy leads to a reduction in thyroid size, accompanied by an increase in tracheal diameters subsequent to treatment. Given the potential complications and risks associated with surgical intervention, it may be prudent to consider large thyroids for RAI therapy as an alternative to surgery. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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15 pages, 897 KiB  
Article
Oldie but Goldie: The Fundamental Role of Radioiodine in the Management of Thyroid Cancer
by Alfredo Campennì, Massimiliano Siracusa and Rosaria Maddalena Ruggeri
J. Clin. Med. 2024, 13(21), 6400; https://doi.org/10.3390/jcm13216400 - 25 Oct 2024
Viewed by 1188
Abstract
Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients’ selection) [...] Read more.
Background/Objectives: The management of differentiated thyroid cancer (DTC) patients has undergone a major paradigm shift in past years, especially regarding the role of a careful postoperative disease assessment both in deciding for or against the use of iodine-131 therapy (i.e., patients’ selection) and in selecting the correct goal of the treatment: ablative, adjuvant or therapeutic. Furthermore, diagnostic and risk-oriented uses of iodine isotopes (i.e., 123/124/131I) should always be considered during both postoperative assessment and follow-up of DTC patients to improve early staging and response assessment to initial treatments, respectively. The present review summarizes current (and real-life-related) evidence and the emerging perspectives on the therapeutic, diagnostic, and theragnostic use of radioiodine isotopes. Methods: A review of the pertinent literature was performed in PubMed, Web of Science, and Scopus without language restrictions or time limits and using one or more fitting search criteria and terms. Results: According to the literature evidence and real-life clinical practice, a risk-oriented postoperative iodine-131 therapy remains pivotal for most DTC patients and improves early disease staging through post-therapy functional imaging (i.e., theragnostic aim). Accordingly, the goal of iodine-131 therapy, the optimal strategy (empiric vs. dosimetric approach), the appropriate stimulation method [i.e., levothyroxine (L-T4) withdrawal vs. recombinant human thyrotropin (rhTSH) administration] and, finally, the suggested radioiodine activity to deliver for iodine-131 therapy (RIT) should be personalized, especially in metastatic DTC patients. Conclusions: The evidence related to the diagnostic and theragnostic use of iodine isotopes leads to a significant improvement in the postoperative risk stratification and staging of DTC patients in addition to a more accurate assessment of the response to initial treatments. In conclusion, radioiodine is really an oldie but goldie radiotracer. It has both a current fundamental role and a future perspective for the more careful management of DTC patients. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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Review

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9 pages, 207 KiB  
Review
Radioiodine Therapy of Graves’ Disease in Women with Childbearing Potential and the Pre-Conceptional Counseling About Antithyroid Drugs
by Markus Dietlein, Matthias Schmidt, Alexander Drzezga and Carsten Kobe
J. Clin. Med. 2025, 14(5), 1667; https://doi.org/10.3390/jcm14051667 - 28 Feb 2025
Viewed by 432
Abstract
Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or [...] Read more.
Graves’ disease and hyperthyroidism in women with childbearing potential are a challenge in pre-conceptional counseling. The non-surgical alternatives are radioiodine therapy or antithyroid drugs. Here, we focus on the TSH receptor antibody (TRAb) level—without or after radioiodine therapy—and the probability of fetal or neonatal hyperthyroidism. This immunological effect should be weighed against the risk of congenital malformation taking propylthiouracil during pregnancy. For up to 2 years after radioiodine therapy for Graves’ disease, TRAb levels may remain above the pre-therapeutic level. The time of conception after radioiodine therapy and a high TRAb level are associated with the likelihood of neonatal hyperthyroidism: 8.8% probability if conception occurred 6–12 months after radioiodine therapy, with a 5.5% probability for 12–18 months, and 3.6% probability for 18–24 months. The TRAb value above 10 U/L in the third trimester is the main risk factor for neonatal hyperthyroidism. If a woman does not wish to postpone her family planning, the pre-conceptional counseling has to describe the risk of propylthiouracil, thiamazole, or of an uncontrolled hyperthyroidism. According to some national cohort studies (Danish, Swedish, Korean), the risk for fetal malformations (ear, urinary tract) under propylthiouracil is increased by 1.1–1.6%, in addition to the spontaneous risk for unexposed pregnant women. For thiamazole, the additional risk for fetal malformation was about 2–3%, depending on the dose of thiamazole. Propylthiouracil has posed a lower risk for congenital malformation than an uncontrolled hyperthyroidism. To minimize the risk for the newborn, women with Graves’ disease and hyperthyroidism should offer a definitive therapy strategy (e.g., radioiodine therapy) long before planning a pregnancy. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
33 pages, 716 KiB  
Review
Circulating Biomarkers of Thyroid Cancer: An Appraisal
by Marta Codrich, Alessia Biasotto and Federica D’Aurizio
J. Clin. Med. 2025, 14(5), 1582; https://doi.org/10.3390/jcm14051582 - 26 Feb 2025
Viewed by 668
Abstract
Thyroid cancer is the most prevalent endocrine cancer. The prognosis depends on the type and stage at diagnosis. Thyroid cancer treatments involve surgery, possibly followed by additional therapeutic options such as hormone therapy, radiation therapy, targeted therapy and chemotherapy. Besides the well-known thyroid [...] Read more.
Thyroid cancer is the most prevalent endocrine cancer. The prognosis depends on the type and stage at diagnosis. Thyroid cancer treatments involve surgery, possibly followed by additional therapeutic options such as hormone therapy, radiation therapy, targeted therapy and chemotherapy. Besides the well-known thyroid tumor biomarkers, new circulating biomarkers are now emerging. Advances in genomic, transcriptomic and proteomic technologies have allowed the development of novel tumor biomarkers. This review explores the current literature data to critically analyze the benefits and limitations of routinely measured circulating biomarkers for the diagnosis and monitoring of thyroid cancer. The review also sheds light on new circulating biomarkers, focusing on the challenges of their use in the clinical management of thyroid cancer, underlining the need for the identification of a new generation of circulating biomarkers. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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32 pages, 1569 KiB  
Review
Autoimmune Thyroid Disease and Pregnancy: The Interaction Between Genetics, Epigenetics and Environmental Factors
by Tatjana Bogović Crnčić, Božena Ćurko-Cofek, Lara Batičić, Neva Girotto, Maja Ilić Tomaš, Antea Kršek, Ines Krištofić, Tea Štimac, Ivona Perić, Vlatka Sotošek and Sanja Klobučar
J. Clin. Med. 2025, 14(1), 190; https://doi.org/10.3390/jcm14010190 - 31 Dec 2024
Cited by 1 | Viewed by 1599
Abstract
Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly [...] Read more.
Autoimmune thyroid disease (AITD) is the leading cause of thyroid dysfunction globally, characterized primarily by two distinct clinical manifestations: Hashimoto’s thyroiditis (HT) and Graves’ disease (GD). The prevalence of AITD is approximately twice as high in women compared to men, with a particularly pronounced risk during the reproductive years. Pregnancy exerts profound effects on thyroid physiology and immune regulation due to hormonal fluctuations and immune adaptations aimed at fostering maternal–fetal tolerance, potentially triggering or exacerbating AITD. The impact of AITD on pregnancy outcomes is multifaceted. Both HT and GD have been associated with adverse obstetric and neonatal outcomes, including miscarriage, preterm delivery, preeclampsia and fetal growth restriction. Inadequately managed AITD can also affect fetal neurodevelopment due to disrupted maternal thyroid hormone availability during critical periods of brain maturation. This review explores the complex interplay between the genetic, epigenetic and environmental factors that drive AITD during pregnancy, highlighting their roles in disease development and impacts on pregnancy outcomes. Gaining a deeper understanding of these mechanisms is crucial for improving diagnostic tools, treatment options and preventive measures to enhance the health and well-being of both the mother and the newborn. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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16 pages, 6230 KiB  
Review
Redifferentiation Therapies in Thyroid Oncology: Molecular and Clinical Aspects
by Petra Petranović Ovčariček, Murat Tuncel, Atena Aghaee, Alfredo Campennì and Luca Giovanella
J. Clin. Med. 2024, 13(23), 7021; https://doi.org/10.3390/jcm13237021 - 21 Nov 2024
Viewed by 1713
Abstract
Since the 1940s, 131-I radioiodine therapy (RIT) has been the primary treatment for metastatic differentiated thyroid cancer (DTC). Approximately half of these patients respond favorably to RIT, achieving partial or complete remission or maintaining long-term stable disease, while the other half develop radioiodine-refractory [...] Read more.
Since the 1940s, 131-I radioiodine therapy (RIT) has been the primary treatment for metastatic differentiated thyroid cancer (DTC). Approximately half of these patients respond favorably to RIT, achieving partial or complete remission or maintaining long-term stable disease, while the other half develop radioiodine-refractory DTC (RAI-R DTC). The main genomic alteration involved in radioiodine resistance is the activated mitogen-activated protein kinase (MAPK) pathway, which results in the loss of sodium iodide symporters (NIS). Therefore, RAI-R DTC requires alternative treatment options such as tyrosine kinase inhibitors. Over the past decade, several studies have investigated pharmacological induction or enhancement of NIS expression through “redifferentiation” therapies, mainly targeting the MAPK pathway. These novel approaches can restore radioiodine sensitivity in previously refractory patients and, therefore, potentially reestablish the efficacy of RIT. This review discusses various redifferentiation strategies, including their molecular mechanisms and clinical implications. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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Other

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7 pages, 193 KiB  
Case Report
Resistance to Thyroid Hormone in a Boy with a Severe, Complex, Congenital Heart Defect (CHD) Requiring Multiple Cardiac Surgeries—Whether and How to Prepare Child for the Surgery
by Anna Fedorczak, Beata Kruk, Anna Mazurek-Kula, Łukasz Kępczyński and Renata Stawerska
J. Clin. Med. 2025, 14(4), 1209; https://doi.org/10.3390/jcm14041209 - 12 Feb 2025
Viewed by 536
Abstract
Background: Resistance to thyroid hormones (RTH) is a rare, genetically determined disease characterised by reduced tissue sensitivity to thyroid hormones (THs). It is caused by mutations in genes encoding the receptors for thyroid hormones, α (THRα) or β (THRβ), the distribution of [...] Read more.
Background: Resistance to thyroid hormones (RTH) is a rare, genetically determined disease characterised by reduced tissue sensitivity to thyroid hormones (THs). It is caused by mutations in genes encoding the receptors for thyroid hormones, α (THRα) or β (THRβ), the distribution of which varies between tissues. Therefore, patients present with elevated TH levels with unsuppressed TSH levels, and symptoms of both hypothyroidism and hyperthyroidism may be present. Methods: Hence, we report the case of a boy with a complex, cyanotic, congenital heart defect who was also diagnosed with TH resistance syndrome. Results: Because of the clinical features of hyperthyroidism in preparation for cardiac surgery, thiamazole was administered, resulting in the normalisation of TH effects on the α-receptor for HTs. Due to the effectiveness of the proposed treatment, it was further introduced before the further stages of cardiac surgeries. Conclusions: The management of RTH is a constant challenge for clinicians and must be individualised. Full article
(This article belongs to the Special Issue Thyroid Disease: Updates from Diagnosis to Treatment)
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