Identification of novel candidate predisposing genes in familial nonmedullary thyroid carcinoma implicating DNA damage repair pathways.

The genetic basis of nonsyndromic familial nonmedullary thyroid carcinoma (FNMTC) is still poorly understood, as the susceptibility genes identified so far only account for a small percentage of the genetic burden. Recently, germline mutations in DNA repair-related genes have been reported in cases with thyroid cancer. In order to clarify the genetic basis of FNMTC, 94 genes involved in hereditary cancer predisposition, including DNA repair genes, were analyzed in 48 probands from FNMTC families, through targeted next-generation sequencing (NGS). Genetic variants were selected upon bioinformatics analysis and in silico studies. Structural modeling and network analysis were also performed. In silico results of NGS data unveiled likely pathogenic germline variants in 15 families with FNMTC, in genes encoding proteins involved in DNA repair (ATM, CHEK2, ERCC2, BRCA2, ERCC4, FANCA, FANCD2, FANCF, and PALB2) and in the DICER1, FLCN, PTCH1, BUB1B, and RHBDF2 genes. Structural modeling predicted that most missense variants resulted in the disruption of networks of interactions between residues, with implications for local secondary and tertiary structure elements. Functional annotation and network analyses showed that the involved DNA repair proteins functionally interact with each other, within the same DNA repair pathway and across different pathways. MAPK activation was a common event in tumor progression. This study supports that rare germline variants in DNA repair genes may be accountable for FNMTC susceptibility, with potential future utility in patients' clinical management, and reinforces the relevance of DICER1 in disease etiology.

Gut Microbiota Changes and Its Potential Relations with Thyroid Disorders: From Composition to Therapeutic Targets.

Composed of over 1200 species of anaerobes and aerobes bacteria along with bacteriophages, viruses, and fungal species, the human gut microbiota (GM) is vital to health, including digestive equilibrium, immunologic, hormonal, and metabolic homeostasis. Micronutrients, usually refer to trace elements (copper, iodine, iron, selenium, zinc) and vitamins (A, C, D, E), interact with the GM to influence host immune metabolism. So far, microbiome studies have revealed an association between disturbances in the microbiota and various pathological disorders, such as anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, anxiety, depression, early-onset cancers, type 1 diabetes (T1D) and type 2 diabetes (T2D). As common conditions, thyroid diseases, encompassing Graves' disease (GD), Graves' orbitopathy (GO), Hashimoto's thyroiditis (HT), benign nodules, and papillary thyroid cancer (TC), have negative impacts on the health of all populations. Following recent studies, GM might play an integral role in triggering diseases of the thyroid gland. Not only do environmental triggers and genetic predisposing background lead to auto-aggressive damage, involving cellular and humoral networks of the immune system, but the intestinal microbiota interacts with distant organs by signals that may be part of the bacteria themselves or their metabolites. The review aims to describe the current knowledge about the GM in the metabolism of thyroid hormones and the pathogenesis of thyroid diseases and its involvement in the appearance of benign nodules and papillary TC. We further focused on the reciprocal interaction between GM composition and the most used treatment drugs for thyroid disorders. However, the exact etiology has not yet been known. To elucidate more precisely the mechanism for GM involvement in the development of thyroid diseases, future work is needed.

Fetal sexual dimorphism of maternal thyroid function parameters during pregnancy, a single center retrospective real-world study.

Introduction: Thyroid function during pregnancy fluctuates with gestational weeks, seasons and other factors. However, it is currently unknown whether there is a fetal sex-specific thyroid function in pregnant women. The purpose of this study was to investigate the fetal sex differences of maternal thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in pregnant women. Methods: This single-center retrospective real-world study was performed by reviewing the medical records of pregnant women who received regular antenatal health care and delivered liveborn infants in Shanghai First Maternity and Infant Hospital (Pudong branch), from Aug. 18, 2013 to Jul. 18, 2020. Quantile regression was used to evaluate the relationship between various variables and TSH and FT4 concentrations. The quantile regression also evaluated the sex impact of different gestational weeks on the median of TSH and FT4. Results: A total of 69,243 pregnant women with a mean age of 30.36 years were included. 36197 (52.28%) deliveries were boys. In the three different trimesters, the median levels (interquartile range) of TSH were 1.18 (0.66, 1.82) mIU/L and 1.39 (0.85, 2.05) mIU/L, 1.70 (1.19, 2.40) mIU/L; and the median levels (interquartile range) of FT4 were 16.63 (15.16, 18.31) pmol/L, 14.09 (12.30, 16.20) pmol/L and 13.40 (11.52, 14.71) pmol/L, respectively. The maternal TSH upper limit of reference ranges was decreased more in mothers with female fetuses during gestational weeks 7 to 12, while their FT4 upper limit of the reference ranges was increased more than those with male fetuses. After model adjustment, the median TSH level was 0.11 mIU/L lower (P <0.001), and FT4 level was 0.14 pmol/L higher (P <0.001) for mothers with female fetuses than those with male fetuses during gestational weeks 9 to 12. Discussion: We identified sexual dimorphism in maternal thyroid function parameters, especially during 9-12 weeks of pregnancy. Based on previous research, we speculated that it may be related to the higher HCG levels of mothers who were pregnant with girls during this period. However, longitudinal studies are needed to determine if fetal sex differences impact the maternal thyroid function across pregnancy.

Construction of a new tool for predicting cancer-specific survival in papillary thyroid cancer patients who have not received surgery.

Background: The prevalence of papillary thyroid cancer is gradually increasing and the trend of youthfulness is obvious. Some patients may not be able to undergo surgery, which is the mainstay of treatment, due to physical or financial reasons. Therefore, the prediction of cancer-specific survival (CSS) in patients with non-operated papillary thyroid cancer is necessary. Methods: Patients' demographic and clinical information was extracted from the Surveillance, Epidemiology, and End Results database. SPSS software was used to perform Cox regression analyses as well as propensity score matching analyses. R software was used to construct and validate the nomogram. X-tile software was used to select the best cutoff point for patient risk stratification. Results: A total of 1319 patients were included in this retrospective study. After Cox regression analysis, age, grade, T stage, M stage, radiotherapy, and chemotherapy were used to construct the nomogram. C-index, calibration curves, and receiver operating characteristic curves all verified the high predictive accuracy of the nomogram. The decision curve analysis demonstrated that patients could gain clinical benefit from this predictive model. Survival curve analysis after propensity score matching demonstrated the positive effects of radiotherapy on CSS in non-operated patients. Conclusion: Our retrospective study successfully established a nomogram that accurately predicts CSS in patients with non-operated papillary thyroid cancer and demonstrated that radiotherapy for operated patients can still help improve prognosis. These findings can help clinicians make better choices.

Oncocytic cell carcinoma of the thyroid with TERT promoter mutation presenting as asphyxia in an elderly: a case report.

Introduction: The prevalence of thyroid nodules and malignancies in the elderly is a growing concern. Thyroid nodules in this population have unique characteristics, requiring careful treatment strategies that balance risks and benefits. Oncocytic carcinoma of the thyroid (OCA) is a rare, aggressive subtype with diagnostic challenges. Methods: This case features an 84-year-old patient who presented with a neck mass and symptoms of asphyxia. Clinical evaluation, imaging studies, and biopsy were conducted to assess the nature of the thyroid lesion. Molecular testing, including genetic analysis, was performed to identify specific mutations associated with OCA and guide treatment decisions. Results: The patient was diagnosed with oncocytic carcinoma of the thyroid. The molecular testing revealed specific genetic mutations indicative of OCA, confirming the diagnosis. The presence of these mutations guided the treatment plan, emphasizing the importance of molecular diagnostics in managing thyroid malignancies, especially in the elderly. Discussion: This case illustrates the complexities of diagnosing and treating thyroid malignancies in the elderly. Biopsy and molecular testing provided diagnostic accuracy and informed treatment. Individualized approaches are essential for better outcomes, especially in aggressive subtypes, balancing the risks and benefits of intervention.

Association of vitamin A with gestational diabetes and thyroid disorders in pregnancy and their influence on maternal, fetal, and neonatal outcomes.

Gestational diabetes mellitus (GDM) and thyroid disorders during pregnancy pose significant health concerns, impacting a substantial number of mothers globally. Globally, about 14% of pregnant women develop GDM, while thyroid disorders impact approximately 2%-3%. Both conditions contribute to adverse outcomes, including gestational hypertension, excessive fetal growth, and heightened perinatal morbidity. The central focus of this literature review is to examine the relationship between vitamin A, a crucial fat-soluble micronutrient in fetal development, and the occurrence of GDM and thyroid disorders during pregnancy. The primary research question investigates the association between vitamin A, GDM, and thyroid disorders, analyzing their combined impact on maternal, fetal, and neonatal outcomes. The review underscores the potential of vitamin A to modulate the risk and outcomes of GDM and thyroid disorders during gestation, emphasizing its role in GDM development and resolution and its influence on thyroid function in pregnancy.

A Clinical Study of Thyroid Abnormalities and Autoantibodies in Patients Diagnosed With Anti-nuclear Antibody Positive Autoimmune Connective Tissue Disorders: An Observational Cross-Sectional Study.

INTRODUCTION: Autoimmune connective tissue disorders (CTDs) are characterized by inflammation of the connective tissue structures and immune system aberrations, such as autoantibody production. This study investigates the prevalence and clinical significance of thyroid abnormalities in patients with anti-nuclear antibody (ANA)-positive autoimmune CTDs. METHODS: This prospective cross-sectional observational study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth (Deemed to be University), Pune, from September 2022 to June 2024. Eighty patients diagnosed with ANA-positive CTDs were included. Comprehensive histories were collected from them and clinical examinations and routine investigations were performed. Blood samples were collected for thyroid function tests and autoantibody tests. Thyroid ultrasound investigations were also performed. Ethical approval and informed consent were obtained. RESULTS: The study revealed a significant prevalence of thyroid dysfunction among participants, with 39 (48.75%) exhibiting some form of thyroid abnormality. Subclinical hypothyroidism was the most common condition in 18 (22.50%) participants, predominantly affecting females. Thyroid autoantibodies were present in 32 (40%) participants, with thyroid peroxidase antibodies (anti-TPO Ab) being the most common seen in 17 (21.25%) participants. Systemic lupus erythematosus (SLE) was the most prevalent CTD among participants, seen in 44 (55%) participants, followed by Sjogren's syndrome (SS) seen in 19 (23.75%) participants. CONCLUSION: The study underscores the necessity of routine thyroid function screening in patients with ANA-positive CTDs to facilitate early detection and management of thyroid abnormalities, thereby preventing progression to overt hypothyroidism or hyperthyroidism. The findings highlight the significant association between thyroid dysfunction and autoimmune CTDs, advocating for a holistic approach to patient care.

Exploring the Correlation Between Papillary Thyroid Carcinoma (PTC) and the Usage of Oral Contraceptive Pills Among Affected Females.

BACKGROUND: The increasing incidence of papillary thyroid carcinoma (PTC), particularly among women, has prompted an investigation into possible associated factors. The effect of oral contraceptive pill (OCP) usage is debatable, with varying and often conflicting results. It is not confirmed whether OCPs have a protective effect against thyroid cancer or an increased risk. OBJECTIVE: The objective of this study is to investigate the prevalence of OCP usage among females diagnosed with PTC at a tertiary hospital in Saudi Arabia. METHODS: The study included females aged 18 and above diagnosed with PTC. An OCP user was defined as a female exposed to OCPs for at least one month. Data collection involved chart reviews and phone interviews, and statistical analyses were conducted using Excel and SPSS. RESULTS: Among 58 female patients diagnosed with PTC, 29.3% (n=17) reported using OCPs, and 70.7% (n=41) were non-users. The ages of OCP users ranged from 26 to 56 years, with a median age of 44 years. The duration of OCP usage varied from 1 to 72 months, with a median duration of seven months. Additionally, for the non-users of OCPs, the age range was from 21 to 85 years, with a mean age of 46.4 years. The median ages for the total sample, OCP users, and non-users were 43.5, 44, and 43 years respectively. The timing of OCP usage among users varied from 1 to 35, with a mean timing of 13. CONCLUSION: The study found about one-third 29.3% (n=17) of patients diagnosed with PTC reported using OCPs. These results contribute to the ongoing debate within epidemiological studies regarding the association between PTC and various reproductive factors, including OCP use. Further research is needed to clarify this relationship and its implications on public health.

A Critical Investigation of Sick Euthyroid Syndrome in Chronic Heart Failure Patients: Addressing the Need for Accurate Thyroid Assessment.

Background The body undergoes numerous metabolic changes during severe illness or physiological stress to protect itself by lowering metabolism and reducing overall demands. This evolutionary adaptation dates back to early human development, long before the advent of ICU facilities and advanced treatments. One such protective mechanism is Sick Euthyroid Syndrome (SES), also known as Non-thyroidal Illness Syndrome (NTIS). SES commonly occurs in critically ill patients and is frequently observed in conditions such as heart failure, chronic kidney disease, and severe sepsis. This syndrome is characterized by abnormal thyroid function tests in patients with acute or chronic systemic illnesses who do not have intrinsic thyroid disease. Typically, these patients exhibit low serum levels of triiodothyronine (T3), normal or low levels of thyroxine (T4), and normal or low thyroid-stimulating hormone (TSH) levels. SES is believed to be an adaptive response to illness, aimed at reducing the body's metabolic rate and conserving energy during severe physiological stress. This original article delves into SES's prevalence and clinical impact in these settings. Materials and methods The study aims to determine the prevalence of SES in patients with long-standing heart failure, elucidate the relationship between thyroid function and heart failure severity, and assess its impact on various hematological and clinical parameters. This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical College, Hospital and Research Centre, Pune, India, a 2011-bed hospital, over one and a half years. This study included 70 patients with chronic heart failure, aged 18 years and above, defined by a left ventricular ejection fraction of 40% or less and a Boston criteria score of 8 or more. Patients were excluded if they had a history of thyroid dysfunction, clinical sepsis, or were taking thyroid-affecting drugs.  Results The study provides important insights into the prevalence and impact of SES in long-standing heart failure patients. It found that a significant 44.29% of these patients exhibited low T3 levels, highlighting the substantial occurrence of SES in this population. Additionally, the study revealed a negative correlation between N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels, Boston score, and total T3, suggesting that as indicators of heart failure severity worsen, total T3 levels may decrease further. Another key finding is the high prevalence of anemia among heart failure patients, with a notable gender disparity: 92.11% of male patients were affected compared to 50% of female patients.  Conclusion The study concluded that SES is significantly prevalent among long-standing heart failure patients, further indicating that thyroid suppression increases with the severity of heart failure. Recognizing SES can guide tailored treatments, prompting intensive monitoring and optimized heart failure management. Additionally, the study found a high prevalence of anemia, particularly among male patients, highlighting the need for gender-specific considerations in managing heart failure. These findings underscore the importance of routine thyroid function assessments and regular monitoring of anemia in heart failure patients. Future research should focus on improving clinical outcomes through comprehensive management of both thyroid function and anemia in these patients.

Acute Pericarditis Triggered by Severe Thyrotoxicosis.

Acute pericarditis is a common inflammatory disorder with several causes including infection, malignancy, acute myocardial infarction, and autoimmune disease. Acute pericarditis can rarely present in the setting of thyrotoxicosis. A 65-year-old man with a past medical history of HIV, diastolic dysfunction, and prediabetes presented with positional chest pain, respiratory distress, and altered mentation. He was found down on the ground in a lethargic state and was last seen normally five days before the presentation. On presentation, he was tachycardic and tachypneic, requiring supplemental oxygenation with a nonrebreather mask to maintain adequate oxygen saturation. Initial electrocardiogram (EKG) demonstrated diffuse ST-elevations with early repolarization, consistent with acute pericarditis. Laboratory diagnostics revealed elevated lactic acid, leukocytosis, acute kidney injury, undetectable thyroid stimulating hormone, and elevations in T3, T4, C-reactive protein, brain natriuretic peptide, and creatinine kinase. Given the patient's complex presentation involving thyrotoxicosis and pericarditis, a multidisciplinary team discussion was pursued involving critical care, cardiology, and endocrinology. He was started on intravenous methylprednisolone (subsequently transitioned to prednisone), methimazole, and metoprolol. Colchicine was subsequently added for the management of pericarditis and prednisone was continued (given concomitant thyroid disease) with a plan for tapering them off, per cardiology and endocrinology recommendations. A transthoracic echocardiogram revealed a small pericardial effusion. Anticoagulation was not initiated given the potential risk of developing a hemorrhagic pericardial effusion. Thyroid ultrasound was nonsuggestive of Graves' disease. Thyrotoxicosis may present with a constellation of symptoms, including acute pericarditis. Timely recognition with EKG and echocardiography can aid in prompt management.

Alterations in Thyroid Hormones in Obese Patients are Associated with Body Composition Changes after Bariatric Surgery.

BACKGROUND: This study investigates how metabolic/bariatric surgery (MBS) affects thyroid hormone (TH) levels and TH resistance in obese euthyroid individuals, focusing on their correlation with changes in body composition. METHODS: We included 470 obese individuals and 118 controls for baseline assessment, and 125 obese patients receiving MBS for longitudinal study. Data on body composition and thyroid function were collected. Correlations between baseline and changes in thyroid function and body composition were assessed. RESULTS: In the obese group, thyroid stimulating hormone (TSH), free triiodothyronine (fT3) levels, and thyroid feedback quantile-based index (TFQI) were elevated and significantly decreased post-MBS, along with visceral fat area (VFA) and body fat percentages, while skeletal muscle mass (SMM) percentage increased. Preoperative partial correlation analysis adjusted for age and sex revealed that TSH positively correlated with VFA (r=0.109, P=0.019), body fat percentage (r=0.114, P=0.013), and negatively correlated with SMM percentage (r=-0.104, P=0.024). Similar correlations were observed between central TH resistance indices and body composition, but no significant correlations were found in the control group. Post-MBS, decreased TSH positively correlated with decreased VFA (r=0.251, P=0.006) and increased SMM percentage (r=0.233, P=0.011). While reductions in VFA and body fat percentage were linked to improved central thyroid hormone resistance, a decrease in peripheral TH conversion was noted. CONCLUSIONS: MBS significantly impacts thyroid function and TH resistance, with notable correlations to changes in body composition.

Evaluation of the Her-2/neu value in papillary thyroid carcinoma and its relation to histopathological prognostic findings.

INTRODUCTION: Thyroid cancer is an important endocrine malignancy worldwide, including papillary carcinoma, which is responsible for more than 90 % of thyroid malignancies. Human epidermal growth factor receptor 2 (Her-2/neu) overexpression plays a significant act in the development, progression, and invasion of various tumors through effects on the cell cycle, angiogenesis, cell movement, and apoptosis. OBJECTIVE AND METHODS: The study was conducted as a cross-sectional study, using tissue samples from 53 patients who underwent lobectomy or total thyroidectomy between 2020 and 2022. For histopathological examination and to determine the pathological features of the tumor, tumor specimens were stained for immunohistochemistry using a monoclonal antibody against Her-2/neu. RESULTS: In this study, Her-2/neu was expressed in 13.2 % of PTC patients and not expressed in normal thyroid tissue. No significant relationship was established between Her-2/neu expression and tumor histological subtype, as well as tumor size, sex, or tumor focality. Furthermore, there was no significant association between Her-2/neu expression and vascular invasion or extrathyroidal extension of the tumor. CONCLUSION: No significant Her-2/neu expression was observed in the malignant thyroid tissue. These findings raise questions about the value of Her-2/neu as a potential prognostic factor or target of a specific anticancer treatment for thyroid cancer.

Serum chemistry, thyroxine concentration, and blood cell morphology of wild, young Blackchin Guitarfish Glaucostegus cemiculus sampled on the eastern Mediterranean coastline.

OBJECTIVE: The Blackchin Guitarfish Glaucostegus cemiculus is endemic to the Mediterranean Sea and is critically endangered, but relevant routine laboratory data are unavailable. Our objectives were to determine the packed cell volume (PCV), comprehensive serum chemistry analytes, and serum total thyroxine (sTT4) concentration; compare serum albumin and serum globulin concentrations as measured by two different methods; and describe the blood cell morphology of healthy, free-ranging Blackchin Guitarfish. METHODS: Wild Blackchin Guitarfish were captured using a seine net. Blood samples for serum chemistry and hematological analyses were obtained and measured using routine laboratory methods. The fish were tagged and released. RESULT: This study included 43 Blackchin Guitarfish (17 males and 26 females) that were younger than 6 months as estimated based on total length and body weight. The median PCV (n = 23) was 22% (minimum-maximum [min-max] = 15-25%). Median sTT4 (n = 10) measured by chemiluminescence immunoassay was 7.86 nmol/L (min-max = 7.52-9.57 nmol/L). The study included a comprehensive, 25-analyte serum chemistry analysis (e.g., serum iron and unbound and total iron-binding capacity) and a morphological description of all blood cells. Serum electrophoresis (SEP; n = 13) yielded a consistent serum albumin-migrating protein fraction and four globulin fractions. Serum electrophoretograms corroborating these results are presented. CONCLUSION: In Blackchin Guitarfish, the serum albumin-migrating fraction measured by SEP combined with serum total protein concentration yields a much higher albumin concentration compared to that measured by bromocresol green spectrophotometry. The true identity of this albumin-migrating fraction remains to be identified. The analytes' calculated 2.5-97.5% interpercentile intervals should be considered as reference intervals applying to Blackchin Guitarfish of similar age but should be applied cautiously to adult fish.

Effect of the intraoperative head hypsokinesis on sore throat after thyroid surgery: a randomized controlled trial.

PURPOSE: Postoperative sore throat (POST) after thyroidectomy is a major concern.A roll is typically inserted under the shoulder to achieve head hypsokinesis and neck extension to better expose the surgical site during thyroid surgery. However, POST and impaired voice function have been attributed to neck overextension. This study aimed to explore the rational angle of head hypsokinesis that both reduced sore throat intensity and protects voice function after thyroid surgery. METHODS: A total of 210 patients who underwent thyroidectomy were enrolled and randomized into high-tilt (Group H) and low-tilt angle groups (Group L). The primary outcome was the incidence of POST 6 h after surgery. Secondary outcomes included the severity of postoperative pharyngeal pain, voice function, swallowing pain, and coughing. RESULTS: The incidence of POST 6 h after thyroidectomy was significantly lower in Group L than that in Group H. In addition, the intensity of postoperative sore throat and swallowing pain was more severe in Group H. A lower degree of head hypsokinesis in Group L prevented transient postoperative voice injury. CONCLUSIONS: A lower degree of head hypsokinesis effectively mitigated sore throat severity after thyroidectomy and improved postoperative voice function. REGISTER INFORMATION: The trial was registered in the Chinese Clinical Trial Registry on 21 June 2022 (ChiCTR2200061329). The trial is registered at https://www.chictr.org.cn/showproj.html?proj=166254 .

Diagnostic Performance of Thyroid FNA: Experience of Belarusian National Referral Thyroid Cancer Center.

BACKGROUND: A fine-needle aspiration (FNA) biopsy is a basic procedure to verify the morphology of thyroid nodules. However, significant variations in the diagnostic performance of FNA, as well as fluctuations in the rate of malignancy (ROM) in different categories of the Bethesda System for Reporting Thyroid Cytopathology, have been discovered in many studies. The development and employment of additional molecular tests in daily clinical practice require an understanding of the prevalence and structure of thyroid malignancy in each category of the Bethesda system. METHODS: Current research is a continuous retrospective cohort study of the results of the examination and treatment of 1652 patients with thyroid tumors who have undergone primary surgery in 2021 at a national referral thyroid cancer center. FNA diagnostic performance was studied by comparing cytological diagnoses with histological outcomes. The authors evaluated ROM in each Bethesda category and identified the tumors representing a diagnostic pitfall. RESULTS: The overall ROM was 72.4%. When considering ROM in each Bethesda category, it was 16.7% in Bethesda I, 10.1% in Bethesda II, 23.0% in Bethesda IV, 74.8% in Bethesda V, 99.4% in Bethesda VI. The false-positive rate was 65.0%, false negative-0.67%. Follicular and oncocytic adenomas, as well as the follicular variant of papillary thyroid cancer, were the most troublesome entities for patients' management. CONCLUSION: ROM was comparable to the values implied by the Bethesda system. Follicular tumors were the main source of high false-positive rates. This necessitates the refinement of existing tests and the development of new diagnostic tests to overcome the abovementioned problems.

Low Dose Radioactive Iodine Ablation Therapy (1.11 GBq) for Differentiated Thyroid Cancer in Western Turkey.

OBJECTIVE: Ablation therapy is employed in low-risk differentiated thyroid cancer (DTC) cases to facilitate patient monitoring by reducing thyroglobulin (Tg) levels to measurable levels below after surgery by eliminating residual thyroid tissue. However, there is still uncertainty about the minimum activity dose required for effective ablation. Opting for low-dose [131I]-NaI for ablation offers several advantages for both patients and healthcare services. Particularly in this tumor group with a high life expectancy (approximately 90-95% at 10 years), [131I]-NaI treatment should not pose a risk to the patient's post-treatment life and should not compromise their quality of life. However, there is a need for a well-defined identification of factors predicting successful ablation. METHODS: Clinical data, laboratory findings, and imaging tests of 287 patients with low-dose 1110 MBq (30 mCi) [131I]-NaI ablation therapy for DTC were retrospectively reviewed. Post-ablation imaging and laboratory findings categorized ablation success/failure. The successful ablation group was determined according to the excellent response criteria outlined in ATA criteria. Relationships between clinical, pathological findings, biochemical common variables, and treatment failure were analyzed. RESULTS: An excellent response was achieved in 77% of the entire group according to ATA criteria post-ablation. Male gender and high tg levels on the day of ablation (Tg cut-off: 10 ng/ml and 5.35 ng/ml) were associated with unsuccessful ablation. CONCLUSIONS: Our results indicate that a 1110 MBq (30 mCi) ablation dose is sufficient to achieve an excellent response in most low-risk DTC cases 6-12 months later. When selecting the dose for ablation, besides the histological markers mentioned in guidelines and age, we observed that stimulated tg values and gender may be important in predicting ablation success.

Exacerbation of Thyroid Eye Disease and Dysthyroid Optic Neuropathy During Pregnancy: A Case Report.

A 37-year-old, never-smoker, pregnant woman diagnosed with Graves' disease who had stable thyroid eye disease (TED) before pregnancy presented with aggravated proptosis and eyelid swelling at 13 weeks of pregnancy. Despite the administration of local triamcinolone and 3 cycles of corticosteroid pulse therapy from 25 to 28 weeks, the patient's visual acuity decline necessitated postpartum orbital decompression surgery. Although TSH receptor antibody (TRAb) levels decreased during the mid- to late term of pregnancy, the TED worsened. This finding suggests that factors other than anti-TSH receptor antibodies may have a significant effect on disease severity.

Endocrinological Treatment Targets for Depressive Disorder.

Depressive disorder exhibits heterogeneity in clinical presentation, progression, and treatment outcomes. While conventional antidepressants based on the monoamine hypothesis benefit many patients, a significant proportion remains unresponsive or fails to fully recover. An individualized integrative treatment approach, considering diverse pathophysiologies, holds promise for these individuals. The endocrine system, governing physiological regulation and organ homeostasis, plays a pivotal role in central nervous system functions. Dysregulations in endocrine system are major cause of depressive disorder due to other medical conditions. Subtle endocrine abnormalities, such as subclinical hypothyroidism, are associated with depression. Conversely, depressive disorder correlates with endocrine-related biomarkers. Fluctuations in sex hormone levels related to female reproduction, elevate depression risk in susceptible subjects. Consequently, extensive research has explored treatment strategies involving the endocrine system. Treatment guidelines recommend tri-iodothyronine augmentation for resistant depression, while allopregnanolone analogs have gained approval for postpartum depression, with ongoing investigations for broader depressive disorders. This book chapter will introduce the relationship between the endocrine system and depressive disorders, presenting clinical findings on neuroendocrinological treatments for depression.

New insights into the mechanisms of the extracellular matrix and its therapeutic potential in anaplastic thyroid carcinoma.

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer, and it has a poor prognosis and high probability of metastatic recurrence. The long-term survival of cancer cells depends on their ability to settle in a favorable environment. Cancer cells interact with other cells in the tumor microenvironment to shape the "soil" and make it suitable for cell growth by forming an extremely complex tumor ecosystem. The extracellular matrix (ECM) is an essential component of the tumor ecosystem, and its biological and mechanical changes strongly affect tumor invasion, metastasis, immune escape and drug resistance. Compared to normal tissues, biological processes, such as collagen synthesis and ECM signaling, are significantly activated in ATC tissues. However, how ATC triggers changes in the properties of the ECM and its interaction with the ECM remain poorly characterized. Therefore, an in-depth study of the regulatory mechanism of the abnormal activation of ECM signaling in ATC is highly important for achieving the therapeutic goal of exerting antitumor effects by destroying the "soil" in which cancer cells depend for survival. In this research, we revealed the aberrant activation state of ECM signaling in ATC progression and attempted to uncover the potential mechanism of action of ECM components in ATC, with the aim of providing new drug targets for ATC therapy.

Demonstration of in-vivo simultaneous 3D imaging with 18F-FDG and Na131I using Compton-PET system.

Simultaneous imaging of the SPECT tracer 131I and PET tracer 18F is important in the diagnosis of high- and low-grade thyroid cancers because high-grade thyroid cancers have high 18F-FDG and low 131I uptake, while low-grade thyroid cancers have high 131I and low 18F-FDG uptake. In this study, Na131I and 18F-FDG were simultaneously imaged using the Compton-PET system, in vivo. The angular resolution and sensitivity of the Compton camera with 356 keV gamma ray measured using a 133Ba point source were 12.3° and 2 × 10-5, respectively. The spatial resolution and sensitivity of PET were measured with a 22Na point source. The transaxial and axial spatial resolutions of the PET at the center of the FOV were 1.15 mm and 2.04 mm, respectively. Its sensitivity was 1.2 × 10-4. In-vivo images of the 18F and 131I isotopes were simultaneously acquired from mice. These showed that 18F-FDG was active in the heart, brown fat, and brain, while Na131I was active in the thyroid, stomach, and bladder. Artifacts were found in the Compton camera images when the activity of 131I was much lower than that of 18F. This study demonstrates the potential of simultaneous clinical imaging of 18F and 131I.