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Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies

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A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Endocrinology".

Deadline for manuscript submissions: closed (1 December 2020) | Viewed by 39069

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Ass. Prof. Dr. Spyridoula Maraka

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Guest Editor

University of Arkansas for Medical Sciences, Little Rock, United States
University of Arkansas for Medical Sciences
Central Arkansas Veterans Healthcare System
Knowledge and Evaluation Research-Endo, Mayo Clinic
Interests: thyroid diseases; evidence-based endocrinology; knowledge translation; health services research

Special Issue Information

Dear Colleagues,

Thyroid hormones are critical determinants of health in adults as they affect the function of virtually every organ system. Autoregulatory mechanisms within the thyroid gland tend to maintain a constant thyroid hormone pool. In addition, the hypothalamic-pituitary feedback mechanism senses variations in the availability of free thyroid hormones, however small, and acts to correct them.

Despite these protective mechanisms, thyroid dysfunction is one of the most common diseases of the endocrine system. The American Thyroid Association reports that more than 12% of the U.S. population will develop a thyroid disorder during their lifetime, mainly hypothyroidism. Thyroid dysfunction is five to eight times more common in women, with a higher frequency in older women. Anatomic and genetic abnormalities at any level of the hypothalamic-pituitary-thyroid axis could lead to thyroid dysfunction. Moreover, a number of changes take place in thyroid function during iodine abnormalities (excess or deficiency), illness, pregnancy, aging, neuropsychiatric illness, and use of certain medications. Finally, even if an anatomic abnormality, such a thyroid nodule, does not result in thyroid dysfunction, it results in a diagnostic cascade which affects up to 50% of the population.

Given the importance of thyroid dysfunction and thyroid nodules in the field of medicine and research, the journal Medicina is launching this Special Issue. We warmly invite you and your colleagues to submit your articles, preferably reviews or original articles, regarding the pathogenesis and diagnosis of thyroid dysfunction and thyroid nodules in humans. In addition, articles providing new evidence or an up-to-date review regarding the impact of thyroid dysfunction on various health outcomes and therapeutic strategies are particularly welcome. Special focus is given on thyroid dysfunction in selected populations (e.g. elderly, pregnant women, and adults with neuropsychiatric illness) and innovative approaches to the evaluation and management of thyroid nodules.

Ass. Prof. Dr. Spyridoula Maraka
Guest Editor

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Keywords

Hypothyroidism
Hyperthyroidism
Pregnancy
Neuropsychiatric illness
Elderly
Levothyroxine
Liothyronine
Antithyroid drugs
Radioactive iodine
Thyroid nodules

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Published Papers (9 papers)

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Research

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18 pages, 6336 KiB

Open AccessArticle

Ultrasound Image Classification of Thyroid Nodules Using Machine Learning Techniques

by Vijay Vyas Vadhiraj, Andrew Simpkin, James O’Connell, Naykky Singh Ospina, Spyridoula Maraka and Derek T. O’Keeffe

Medicina 2021, 57(6), 527; https://doi.org/10.3390/medicina57060527 - 24 May 2021

Cited by 27 | Viewed by 5575

Abstract

Background and Objectives: Thyroid nodules are lumps of solid or liquid-filled tumors that form inside the thyroid gland, which can be malignant or benign. Our aim was to test whether the described features of the Thyroid Imaging Reporting and Data System (TI-RADS) could improve radiologists’ decision making when integrated into a computer system. In this study, we developed a computer-aided diagnosis system integrated into multiple-instance learning (MIL) that would focus on benign–malignant classification. Data were available from the Universidad Nacional de Colombia. Materials and Methods: There were 99 cases (33 Benign and 66 malignant). In this study, the median filter and image binarization were used for image pre-processing and segmentation. The grey level co-occurrence matrix (GLCM) was used to extract seven ultrasound image features. These data were divided into 87% training and 13% validation sets. We compared the support vector machine (SVM) and artificial neural network (ANN) classification algorithms based on their accuracy score, sensitivity, and specificity. The outcome measure was whether the thyroid nodule was benign or malignant. We also developed a graphic user interface (GUI) to display the image features that would help radiologists with decision making. Results: ANN and SVM achieved an accuracy of 75% and 96% respectively. SVM outperformed all the other models on all performance metrics, achieving higher accuracy, sensitivity, and specificity score. Conclusions: Our study suggests promising results from MIL in thyroid cancer detection. Further testing with external data is required before our classification model can be employed in practice. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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9 pages, 4239 KiB

Open AccessArticle

Postoperative Chylothorax after Modified Radical Neck Dissection for Thyroid Carcinoma: A Missable Rare Complication of Thyroid Surgery

by Junghyun Lee, In Eui Bae, Jin Yoon, Keunchul Lee, Hyeong Won Yu, Su-jin Kim, Young Jun Chai, June Young Choi and Kyu Eun Lee

Medicina 2020, 56(9), 481; https://doi.org/10.3390/medicina56090481 - 21 Sep 2020

Cited by 10 | Viewed by 4618

Abstract

Background and objectives: Currently, few studies have been conducted on postoperative chylothorax, specifically in total thyroidectomy with modified radical neck dissection (MRND) in papillary thyroid carcinoma patients. This study provides the actual incidence, etiology, and clinical features of postoperative chylothorax and reports the clinical outcomes after treatment, which were dependent upon the severity of the complications. Materials and Methods: The medical charts of 111 papillary thyroid cancer (PTC) patients who underwent total thyroidectomy with modified radical neck dissection from January 2016 to December 2018 were reviewed retrospectively. The results were compared in three groups: the no chylothorax group, the subclinical (asymptomatic) group, and the clinical (symptomatic) group. Results: Chylothorax occurred in 23 patients (20.7%, 23/111). Nineteen (82.6%, 19/23) were subclinical chylothorax cases, which implies a small amount of chyle leakage with no respiratory symptoms. Four (17.4%, 4/23) were clinical, meaning they had either respiratory symptoms, such as dyspnea, desaturation, or a large amount of chylothorax in the images. The incidence was significantly higher in patients who underwent left modified radical neck dissection, and this corresponds to the side in which chylothorax occurred. There were also statistical differences in the drainage color, peak amount, or drain removal time. Conclusions: Postoperative chylothorax is a rare complication following neck dissection. However, it can be fatal if the condition progresses. Therefore, patients who undergo total thyroidectomy with modified radical neck dissection, especially on the left side, should be monitored for respiratory symptoms, and serial chest x-ray images obtained. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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14 pages, 452 KiB

Open AccessArticle

Management of Hypothyroidism in Patients with Acute Myocardial Infarction

by Danielle Eagan, Gabriela Spencer-Bonilla, Spyridoula Maraka, Monica Aggarwal and Naykky Singh Ospina

Medicina 2020, 56(5), 214; https://doi.org/10.3390/medicina56050214 - 28 Apr 2020

Cited by 6 | Viewed by 3754

Abstract

Background and Objectives: Thyroid hormones (TH) affect cardiac function through effects on cardiac contractility and systemic vascular resistance. While TH replacement for patients with hypothyroidism might be necessary for restoration of cardiac output after an acute myocardial infarction (AMI), it could theoretically lead to excessively rapid restoration of the metabolic rate. The appropriate management of hypothyroidism in patients with AMI is unknown. We describe the practice patterns in the management of hypothyroidism in the setting of AMI as well as patients’ clinical outcomes. Material and Methods: Retrospective study of patients that were admitted to a tertiary care hospital with AMI and newly diagnosed or uncontrolled hypothyroidism (TSH ≥ 10 mIU/L) between 2011–2018. Eligible patients were identified using diagnosis codes for AMI and laboratory values, followed by medical record review. We categorized patients according to treatment status with TH and by degree of hypothyroidism. Clinical outcomes included: 30-day mortality/readmission, bleeding, stroke, arrhythmia, sudden cardiac death, and new or worsening heart failure. Summary statistics and group comparisons are presented. Results: Sixty-four patients were included, their median age was 64 years and 61% (n = 39) were women. Most of the patients (59%) had a documented history of hypothyroidism. Of these, all were restarted on levothyroxine (LT4) during the index admission when compared to patients without a history of hypothyroidism, of which 54% received LT4 treatment (p = 0.001). The median TSH in those treated with LT4 was higher (25 mIU/L) when compared to those who were not (12 mIU/L), (p = 0.007). Patients who received intravenous LT4 had higher TSH levels and other variables suggesting worse clinical presentation, but these differences were not statistically significant. No statistically significant differences were noted on clinical outcomes according to LT4 treatment status. Conclusion: A history of hypothyroidism and the degree of TSH elevation seem to guide the management of hypothyroidism in patients with AMI. The clinical effect of correcting hypothyroidism in this setting requires further evaluation. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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12 pages, 303 KiB

Open AccessArticle

Patient Experiences and Perceptions Associated with the Use of Desiccated Thyroid Extract

by Freddy J. K. Toloza, Nataly R. Espinoza Suarez, Omar El Kawkgi, Elizabeth H. Golembiewski, Oscar J. Ponce, Lixia Yao, Spyridoula Maraka, Naykky M. Singh Ospina and Juan P. Brito

Medicina 2020, 56(4), 161; https://doi.org/10.3390/medicina56040161 - 3 Apr 2020

Cited by 14 | Viewed by 5870

Abstract

Background and objectives: It is unclear why many patients with hypothyroidism prefer the use of desiccated thyroid extract (DTE) as a thyroid hormone replacement formulation over levothyroxine (LT4) treatment, as recommended by clinical practice guidelines. We analyzed patient-reported information from patient online forums to better understand patient preferences for and attitudes toward the use of DTE to treat hypothyroidism. Materials and Methods: We conducted a mixed-methods study by evaluating the content of online posts from three popular hypothyroidism forums from patients currently taking DTE (n = 673). From these posts, we extracted descriptive information on patient demographics and clinical characteristics and qualitatively analyzed posts’ content to explore patient perceptions on DTE and other therapies further. Results: Nearly half (46%) of the patients reported that a clinician initially drove their interest in trying DTE. Patients described many reasons for switching from a previous therapeutic approach to DTE, including lack of improvement in hypothyroidism-related symptoms (58%) and the development of side effects (22%). The majority of patients described DTE as moderately to majorly effective overall (81%) and more effective than the previous therapy (77%). The most frequently described benefits associated with DTE use were an improvement in symptoms (56%) and a change in overall well-being (34%). One-fifth of patients described side effects related to the use of DTE. Qualitative analysis of posts’ content supported these findings and raised additional issues around the need for individualizing therapy approaches for hypothyroidism (e.g., a sense of each patient has different needs), as well as difficulties obtaining DTE (e.g., issues with pharmacy availability). Conclusions: Lack of individualized treatment and a feeling of not been listened to were recurrent themes among DTE users. A subset of patients may prefer DTE to LT4 for many reasons, including perceived better effectiveness and improved overall well-being, despite the risks associated with DTE. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

Review

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12 pages, 976 KiB

Open AccessReview

Association of Thyroid Function with Suicidal Behavior: A Systematic Review and Meta-Analysis

by Freddy J. K. Toloza, Yuanjie Mao, Lakshmi Menon, Gemy George, Madhura Borikar, Soumya Thumma, Hooman Motahari, Patricia Erwin, Richard Owen and Spyridoula Maraka

Medicina 2021, 57(7), 714; https://doi.org/10.3390/medicina57070714 - 15 Jul 2021

Cited by 18 | Viewed by 4503

Abstract

Thyroid disease is a very common condition that influences the entire human body, including cognitive function and mental health. As a result, thyroid disease has been associated with multiple neuropsychiatric conditions. However, the relationship between thyroid dysfunction and suicide is still controversial. We conducted a systematic review and meta-analysis to describe the association of thyroid function with suicidal behavior in adults. We searched four data bases (MEDLINE, EMBASE, PsycINFO, and Scopus) from their inception to 20 July 2018. Studies that reported mean values and standard deviation (SD) of thyroid hormone levels [Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3)] in patients with suicidal behavior compared with controls were included in this meta-analysis. The abstracts and papers retrieved with our search strategies were reviewed independently and in duplicate by four reviewers for assessment of inclusion criteria and data extraction, as well as for evaluation of risk of bias. Random-effects models were used in this meta-analysis to establish the mean difference on thyroid function tests between groups. Overall, 2278 articles were identified, and 13 studies met the inclusion criteria. These studies involved 2807 participants, including 826 participants identified with suicidal behavior. We found that patients with suicide behavior had lower levels of FT3 (−0.20 pg/mL; p = 0.02) and TT4 (−0.23 µg/dL; p = 0.045) compared to controls. We found no differences in either TSH, FT4, or TT3 levels among groups. With our search strategy, we did not identify studies with a comparison of overt/subclinical thyroid disease prevalence between patients with and without suicide behavior. The studies included in this meta-analysis had a low-to-moderate risk of bias. In the available literature, the evidence regarding the association of thyroid disorders and suicidal behavior is limited. We found that patients with suicidal behavior have significantly lower mean FT3 and TT4 levels when compared to patients without suicidal behavior. The clinical implications and pathophysiologic mechanisms of these differences remain unknown and further research is needed. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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14 pages, 1697 KiB

Open AccessReview

TGF-β Physiology as a Novel Therapeutic Target Regarding Autoimmune Thyroid Diseases: Where Do We Stand and What to Expect

by Efstratios Kardalas, Spyridoula Maraka, Maria Papagianni, George Paltoglou, Charalampos Siristatidis and George Mastorakos

Medicina 2021, 57(6), 621; https://doi.org/10.3390/medicina57060621 - 14 Jun 2021

Cited by 11 | Viewed by 3135

Abstract

Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-β, scientific interest was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-β in thyroid autoimmunity. Suggested TGF-β-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmunity. For example, the application of hr-TGF-β can be used to bolster the inhibitory role of TGF-β regarding the development of thyroid diseases, whereas anti-TGF-β antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-β biosynthesis and activation pathways. In conclusion, TGF-β could evolve to a promising, novel therapeutic tool for thyroid autoimmunity. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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12 pages, 315 KiB

Open AccessReview

Hemithyroidectomy for Thyroid Cancer: A Review

by Noor Addasi, Abbey Fingeret and Whitney Goldner

Medicina 2020, 56(11), 586; https://doi.org/10.3390/medicina56110586 - 3 Nov 2020

Cited by 19 | Viewed by 5094

Abstract

Thyroid cancer incidence is on the rise; however, fortunately, the death rate is stable. Most persons with well-differentiated thyroid cancer have a low risk of recurrence at the time of diagnosis and can expect a normal life expectancy. Over the last two decades, guidelines have recommended less aggressive therapy for low-risk cancer and a more personalized approach to treatment of thyroid cancer overall. The American Thyroid Association (ATA) and National Comprehensive Cancer Network (NCCN) thyroid cancer guidelines recommend hemithyroidectomy as an acceptable surgical treatment option for low-risk thyroid cancer. Given this change in treatment paradigms, an increasing number of people are undergoing hemithyroidectomy rather than total or near-total thyroidectomy as their primary surgical treatment of thyroid cancer. The postoperative follow-up of hemithyroidectomy patients differs from those who have undergone total or near-total thyroidectomy, and the long-term monitoring with imaging and biomarkers can also be different. This article reviews indications for hemithyroidectomy, as well as postoperative considerations and management recommendations for those who have undergone hemithyroidectomy. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

Other

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9 pages, 785 KiB

Open AccessCase Report

Central TSH Dysregulation in a Patient with Familial Non-Autoimmune Autosomal Dominant Hyperthyroidism Due to a Novel Thyroid-Stimulating Hormone Receptor Disease-Causing Variant

by Jasna Suput Omladic, Maja Pajek, Urh Groselj, Katarina Trebusak Podkrajsek, Magdalena Avbelj Stefanija, Mojca Zerjav Tansek, Primoz Kotnik, Tadej Battelino and Darja Smigoc Schweiger

Medicina 2021, 57(3), 196; https://doi.org/10.3390/medicina57030196 - 25 Feb 2021

Cited by 3 | Viewed by 2598

Abstract

Background and Objectives. Familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) is a rare cause of childhood hyperthyroidism. It is caused by the thyroid-stimulating hormone receptor (TSHR) gene variants. So far, only around 40 families with FNAH have been reported. Patients with activating TSHR variants demonstrated the same classical signs and symptoms of hyperthyroidism as seen in patients with Graves’ disease. Since 2012, ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences. Case Presentation. We presented a young adult male patient with a novel heterozygous TSHR disease-causing variant p.Arg418Lys (c.1253G>A) in the exon 10, who presented with a mild but progressive FNAH, with a follow-up since infancy. Discussion. Constantly suppressed TSH, including during the euthyreosis in childhood and hypothyreosis after iodine ablation therapy, suggested central dysregulation of the TSH secretion. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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6 pages, 480 KiB

Open AccessCase Report

Hypercholesterolemia in Two Siblings with Resistance to Thyroid Hormones Due to Disease-Causing Variant in Thyroid Hormone Receptor (THRB) Gene

by Maja Pajek, Magdalena Avbelj Stefanija, Katarina Trebusak Podkrajsek, Jasna Suput Omladic, Mojca Zerjav Tansek, Tadej Battelino and Urh Groselj

Medicina 2020, 56(12), 699; https://doi.org/10.3390/medicina56120699 - 15 Dec 2020

Cited by 3 | Viewed by 2435

Abstract

Resistance to thyroid hormone beta (RTHβ) is a syndrome characterized by a reduced response of target tissues to thyroid hormones. In 85% of cases, a pathogenic mutation in the thyroid hormone receptor beta (THRB) gene is found. The clinical picture of RTHβ is very diverse; the most common findings are goiter and tachycardia, but the patients might be clinically euthyroid. The laboratory findings are almost pathognomonic with elevated free thyroxin (fT4) levels and high or normal thyrotropin (TSH) levels; free triiodothyronin (fT3) levels may also be elevated. We present three siblings with THRB mutation (heterozygous disease-variant c.727C>T, p.Arg243Trp); two of them also had hypercholesterolemia, while all three had several other clinical characteristics of RTHβ. This is the first description of the known Slovenian cases with RTHβ due to the pathogenic mutation in the THRB gene. Hypercholesterolemia might be etiologically related with RTHβ, since the severity of hormonal resistance varies among different tissues and hypercholesterolemia in patients with THRB variants might indicate the relatively hypothyroid state of the liver. We suggest that cholesterol levels are measured in all RTHβ patients. Full article

(This article belongs to the Special Issue Thyroid Disorders: Pathogenesis, Diagnosis, Impact on Health and Therapies)

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