Special Issue:
Challenges and Opportunities in Thyroid Cancer
Gisah Amaral de Carvalho
Federal University of Parana
Beatriz Drobrzenski
Federal University of Parana
Abstract
In recent decades, significant advancements have been made in the methodologies used for evaluating thyroid dysfunctions. These advancements include the development of radioimmunoassays, immunometric assays, and liquid chromatography coupled with mass spectrometry.
The main thyroid function tests include thyroid-stimulating hormone (TSH) and the measurement of triiodothyronine (T3) and thyroxine (T4), including their total and free fractions.
Over time, different generations of TSH tests have been developed, starting from radioimmunoassays to immunometric assays, and more recently, tests utilizing fluorophores and chemiluminescent molecules. The third-generation tests are currently the most widely used due to their high sensitivity and specificity. Thyroid-stimulating hormone is preferred as the initial test for evaluating thyroid function since it has a log-linear relationship with free T4 levels, enabling the identification of subclinical hypothyroidism and subclinical hyperthyroidism.
The reference range for normal TSH levels is typically between 0.45 and 4.5 mIU/L. However, there can be variations in TSH levels based on factors such as sex, age, and ethnicity. Specific reference values may be required for certain populations, such as the elderly, pregnancy, and neonates. In the elderly, an increase in TSH levels is expected. In the neonatal period, TSH levels are high after birth and take a few weeks to normalize. During pregnancy, various physiological changes occur, leading to alterations in thyroid hormones to meet fetal demands.
Laboratory interferences in thyroid hormone assays must be considered to ensure accurate results. Biotin interference can lead to falsely low TSH and falsely high free T3 and T4 levels. Macro-thyrotropin can cause elevated TSH levels with normal thyroid hormone levels. Heterophilic antibodies can also cause false results. Additionally, the evaluation of autoantibodies and markers used in thyroid cancer follow-up needs special attention.
Patients experiencing conditions like trauma, particularly in severe cases, may undergo changes in thyroid hormone levels, even without having a specific thyroid disease, which is called low triiodothyronine syndrome.
In conclusion, it is essential to be aware of potential laboratory interferences and consider individual variations to ensure accurate interpretation and appropriate management of patients.
Aleck Hercbergs
Oncology, The Cleveland Clinic, Cleveland OH USA
Hung-Yun Lin
Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan
Shaker A. Mousa
NanoPharmaceuticals LLC, Troy, NY USA
Matthew Leinung
Department of Medicine, Albany Medical College, Albany, NY USA
Paul J. Davis
NanoPharmaceuticals LLC, Troy, NY USA; Department of Medicine, Albany Medical College, Albany, NY USA
Abstract
The overlap of actions of nonpeptide small endocrine molecules—thyroid hormone and steroids—include two panels of actions. One set is initiated at the nuclear receptors for these hormones and a second set of actions for both hormones is initiated at the extracellular domain of plasma membrane integrin αvβ3. This brief review is concerned with integrin-based receptors on breast cancer cells. On such cells, thyroid hormone as L-thyroxine (T4) at physiological concentrations can stimulate proliferation of breast cancer cells via the thyroid hormone analogue receptor on αvβ3 and, in the absence of estrogen, via the nuclear estrogen receptor-α (ER α). Such observations emphasize the postmenopausal relevance of nuclear estrogen receptor. The deaminated T4 derivative, tetraiodothyroacetic acid (tetrac), blocks T4 actions at the integrin. An androgen receptor on the integrin mediates stimulation of breast cancer cell proliferation by dihydrotestosterone (DHT). T4 controls the activation state of the integrin, a factor that may determine the accessibility of the androgen receptor on αvβ3 to DHT and thus to DHT-driven cell proliferation. An estrogen receptor appears to be present on the integrin, but its functions have not been defined. It is not yet known whether tetrac alters function of the steroid receptors that are adjacent to the T4 binding site on αvβ3. The overlap of T4 and steroid functions in breast cancer cells may offer additional options for clinical management of this type of cancer.
Sidi Mohammed Meghelli
Associate Professor of Medical Biophysics, In vitro exploration unit, Department of Nuclear Medicine, University Hospital of Tlemcen, Faculty of Medicine Dr. B. Benzerdjeb, Tlemcen, Algeria.
Nour El Houda Khelil
Associtate Professor of Endocrinology and Metabolic Diseases, Department of Endocrinology, Diabetology and Metabolic Diseases, University Hospital of Tlemcen, Faculty of Medicine Dr. B. Benzerdjeb, Tlemcen, Algeria.
Abstract
Introduction: In clinical practice, Thyroglobulin is a tumor marker for the post-operative follow-up of differentiated thyroid cancer, provided that any thyroid residual remains are eliminated beforehand, either by simple total thyroidectomy, or most often supplemented by isotopic totalization with Iode131. The aim of this study were to compare serum Tg values measured with 02 kit manufacturers of immunoradiometric type (IRMA) and to evaluate their cost/effectiveness ratio.
Methods: We included patients followed for differentiated thyroid cancer operated and irradiated with Iodine 131 at the nuclear medicine department of Tlemcen University Hospital. Their serum Thyroglobulin was dosed in the laboratory of the department with the Tg-IRMA kit of Cisbio Bioassays taken in this study as «Gold standard» and the Tg-IRMA kit of Beckman Coulter.
Results: Ninety-nine (99) serums of patients with CDT were measured for Thyroglobulin. The correlation of the Thyroglobulin values obtained with the 02 kits is positive and significant (r= 0.98; p < 0.01). The equation of the regression line of Passing- Bablok is of type y = 0.7 x + 0 (with Y = Tg-IRMA Cisbio Bioassays and X = Tg-IRMA Beckman Coulter). The difference in the averages analyzed with the Bland-Altman diagram is = 0 (p > 0.05), indicating that there is no difference in the mean of Tg between the 02 kits. The analysis by ROC curve of the Tg-IRMA Beckman Coulter kit Thyroglobulin values at the threshold of 0.7 and 1 ng/mL finds respectively a sensitivity and a specificity of 100% and 93% with an area under the curve = 0.99.
Conclusion: There is a strong correlation between Thyroglobulin concentrations obtained with the 02 kits, so a budget reduction in the management of our patients with diffrentiated thyroid cancer is possible, in favor of the Tg-IRMA kit of Beckman Coulter with a good cost/ efficiency ratio.
Paul J. Davis, M.D.
Department of Medicine, Albany Medical College, Albany, NY USA; NanoPharmaceuticals LLC, Troy, NY USA.
Aleck Hercbergs
Department of Radiation Oncology, The Cleveland Clinic, Cleveland, OH USA.
Hung-Yun Lin
PhD Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
Matthew Leinung
Department of Medicine, Albany Medical College, Albany, NY USA; 2NanoPharmaceuticals LLC, Troy, NY USA.
Shaker A. Mousa
NanoPharmaceuticals LLC, Troy, NY USA; Vascular Vision Company, Troy, NY.
Abstract
Thyroid hormone as L-thyroxine (T4) at physiological concentrations acts at its cell surface receptor on integrin avb3 to stimulate cancer cell proliferation1. These proliferation studies have been conducted in vitro, but pharmacological reduction of T4 and substitution of nuclear receptor ligand 3,3’,5-triiodo-L-thyronine (T3) is a state of euthyroid hypothyroxinemia that has been shown clinically to arrest tumor growth in patients with cancer. T3 is inactive at physiological levels at the plasma membrane integrin receptor. A preclinical study of human basal cell carcinoma (BCC) cells has shown that the integrin thyroid hormone receptor regulates BCC radiosensitivity. While the large majority of BCCs are very manageable clinically, a small number of such tumors are aggressive. In this review of documented and proposed effects of T4 on BCC cells, we raise the possibility that BCC aggressiveness reflects T4 actions on its thyrointegrin target. The functions affected by T4 at the integrin in other human cancers include enhanced cell proliferation, anti-apoptosis, immune checkpoint regulation and metastasis, as well as state of radiosensitivity. The importance of investigating this possible pathophysiology is that euthyroid hypothyroxinemia may be tested as a treatment option.
Derick Rodriguez-Reyes
UPR School of Medicine, San Juan, Puerto Rico.
Humberto Lugo-Vicente
Section of Pediatric Surgery, Department of Surgery, UPR School of Medicine, San Juan, Puerto Rico.
Jose I. Acosta-Julbe
UPR School of Medicine, San Juan, Puerto Rico.
José Cruz-García
UPR School of Medicine, San Juan, Puerto Rico.
Abstract
This systematic review comprehensively examines the pathogenesis, diagnosis, management, and cancer risk of Hashimoto’s thyroiditis in pediatric populations. We searched the literature using PubMed, Web of Science, and critical medical journals, focusing on studies published within a specified timeframe. Inclusion criteria targeted studies on pediatric populations, while exclusion criteria filtered out irrelevant studies. Data extraction and synthesis highlighted key findings: genetic predispositions and environmental triggers such as selenium levels and gut microbiota alterations contribute to Hashimoto’s Thyroiditis pathogenesis. Diagnostic challenges arise from the often subtle and nonspecific clinical presentation, necessitating thorough clinical evaluations and diagnostic testing, including TSH, free T4, thyroid antibodies, and ultrasound. Management strategies involve levothyroxine therapy, dietary considerations, and lifestyle modifications tailored to individual patient needs. Additionally, the review discusses the controversial but significant potential association between Hashimoto’s Thyroiditis and increased thyroid cancer risk, emphasizing the need for vigilant long-term monitoring. This synthesis provides critical insights to inform clinical practice and future research directions.
