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Steven-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) is a rare immunologic hypersensitivity reaction to stimuli that presents as widespread eruption with mucocutaneous detachment and involvement of other organs. Multiple causes have been noted in literature, including numerous medications. In this report, we present a 52-year-old woman who arrived at the emergency department with a complaint of rash, malaise, and pruritus. She subsequently developed diffuse cutaneous and mucosal detachment. Work-up supported a diagnosis of SJS/TEN secondary to her thyroid replacement therapy, derived from desiccated pig thyroid glands. The patient's natural thyroid medication was discontinued and she responded well to appropriate treatment. This case is unique in that thyroid replacement therapy is not a commonly reported trigger of SJS/TEN. Providers should be aware of the potential for natural thyroid and other animal-derived natural medications to cause adverse reactions such as SJS/TEN.

Objectives Few cytologically indeterminate thyroid fine-needle aspirations (FNAs) harbor BRAF V600E. Here, we assess interobserver agreement for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) category III (atypia of undetermined significance [AUS]) FNAs harboring BRAF V600E and contrast their features with those harboring non- BRAF V600E alterations, with attention to cytopathology experience. Methods Seven reviewers evaluated 5 AUS thyroid FNAs harboring BRAF V600E. To blind reviewers, cases were intermixed with 19 FNAs falling within other TBSRTC categories and in which genetic alterations other than BRAF V600E had been identified (24 FNAs total). Interobserver agreement against both "index" and most popular ("mode") diagnoses was calculated. Four additional BRAF V600E cases were independently reviewed. Results Reviewers included 3 trainees and 3 American Board of Pathology (board)–certified cytopathologists. Board-certified cytopathologists, whose experience ranged from 2 to more than 15 subspecialty practice years, had known AUS rates. BRAF V600E was identified in 5 of 260 (2%) AUS FNAs. Interobserver agreement was higher among cytopathologists with more experience. Mode diagnosis differed from index diagnosis in 6 of 11 cases harboring RAS-like alterations; mode diagnosis was AUS in 4 of 5 BRAF V600E FNAs. Conclusions Atypia of undetermined significance of thyroid FNAs harboring BRAF V600E is uncommon yet relatively reproducible, particularly among pathologists with experience. It is advisable to sequence BRAF across V600 in such cases. [ABSTRACT FROM AUTHOR]

Background: Teprotumumab, a novel IGF-1R antibody, has been shown to significantly reduce the signs of acute and chronic Thyroid Eye Disease (TED). Light sensitivity is a reported symptom in patients with TED. There is a lack of a prospective study that has explored the effects on light sensitivity in a large cohort of patients with acute and chronic TED following treatment with teprotumumab. Methods: Consecutive patients who were diagnosed with TED and reported light sensitivity at baseline were considered for study eligibility. All patients had measurements of Visual Light Sensitivity Questionnaire-8 (VLSQ-8), proptosis, clinical activity score (CAS), and MRD1 (distance between the upper eyelid margin and corneal reflex, mm) and MRD2 (distance between the lower eyelid margin and corneal reflex, mm) before and after treatment. Results: Ninety patients (41 acute, 49 chronic) met the inclusion criteria. The mean (SD) age was 47.3 (14.3). Eighty-six (95.6%) patients completed all 8 infusions. There was a significant reduction in the total score and across all categories of the VLSQ-8 (p < 0.01 for all). Seventy-two (80%) patients had a clinically significant improvement (≥2 reduction) in at least one category. There was no significant difference in the total VLSQ-8 score between the acute and chronic group (p = 0.8). Conclusion: Teprotumumab improves light sensitivity in patients with acute and chronic TED. The results of this study highlight that the improvements in light sensitivity following treatment are not directly related to the mechanical changes in TED, suggesting another underlying mechanism is potentially involved. [ABSTRACT FROM AUTHOR]

Levothyroxine (LT4), being "narrow therapeutic index" drug, may lead to significant fluctuations in thyroid stimulating hormone (TSH) levels. Such fluctuations can result in clinically noteworthy disruptions in thyroid function and give rise to adverse clinical consequences. Consequently, regulatory standards for LT4 potency have been tightened, with the most stringent specifications requiring maintenance of potency within the range of 95–105% of the labeled dose throughout the entire shelf-life of the product. The LT4 new formulation with tightened specification adheres to these rigorous standards, demonstrating established bioequivalence to its older formulation while upholding an equivalent standard of safety and efficacy. Furthermore, the novel formulation exhibits enhanced stability and an extended shelf-life. Of paramount significance is its capacity to provide patients with accurate and consistent dosing, thereby effectively catering to their medical requirements. The primary objective of the Asia-Pacific advisory board meeting (held in June 2022 with endocrinologists, experts from India, Indonesia, Philippines, Thailand, Malaysia and Singapore) was to establish the importance of appropriate communication to HCPs, patients and other stakeholders regarding the LT4 new formulation. The aim of this brief review is to highlight the importance of communication with healthcare professionals that should focus on providing accurate information on the LT4 new formulation, emphasizing efficacy, safety, and bioequivalence with clear guidance and ensure that patients and clinicians are fully informed about any changes to medications such as LT4 to reduce the risk of unrelated adverse events being incorrectly attributed to the newer formulation. [ABSTRACT FROM AUTHOR]

BACKGROUND: The widespread use of sodium propionate as a preservative in food may affect public health. We aimed to assess the effects of sodium propionate on circadian rhythms and pancreatic development in zebrafish and the possible underlying mechanisms. RESULTS: In this experiment, we analyzed the relationship between circadian rhythms and pancreatic development and then revealed the role of the thyroid endocrine system in zebrafish. The results showed that sodium propionate interfered with the rhythmic behavior of zebrafish, and altered the expression of important rhythmic genes. Experimental data revealed that pancreatic morphology and developmental genes were altered after sodium propionate exposure. Additionally, thyroid hormone levels and key gene expression associated with the hypothalamic–pituitary–thyroid axis were significantly altered. Melatonin at a concentration of 1 μmol L−1, with a mild effect on zebrafish, observably alleviated sodium propionate‐induced disturbances in circadian rhythms and pancreatic development, as well as regulating the thyroid system. CONCLUSION: Melatonin, while modulating the thyroid system, significantly alleviates sodium propionate‐induced circadian rhythm disturbances and pancreatic developmental disorders. We further revealed the deleterious effects of sodium propionate as well as the potential therapeutic effects of melatonin on circadian rhythm, pancreatic development and the thyroid system. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

A neck lump is a common presenting sign in both the paediatric and adult population and may represent a broad range of benign or malignant diagnoses. The appropriate initial assessment, investigation and management is key to delivering appropriate treatments and to avoid missing potentially serious diagnoses. There is a range of imaging modalities available to the treating clinician and huge variability in the appropriate surgical or non-surgical management of disease. In this article we discuss the approach to the assessment of patients with a neck lump, including the history and examinations which should take place. We discuss the imaging modalities which are most appropriate for each condition and the range of management options available. Both common and rarer diagnoses are discussed through the course of the review. [ABSTRACT FROM AUTHOR]

Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3, EXO1, UBE2T, UBE2C, FOXM1, CENPA, DLL3, CCNA2, SOX2, KIF23, and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1, DLL3, and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival (p = 0.041) and overall survival (p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC. [ABSTRACT FROM AUTHOR]

Background/Aim: Thyroid diseases are prevalent endocrine disorders that significantly affect overall health. Although the impact of pre-existing thyroid dysfunction on total knee replacement (TKR) outcomes has been studied, the potential for TKR to increase the risk of developing thyroid disorders remains unexplored. Patients and Methods: We examined electronic medical records from a large U.S. research network in the TriNetX research network. The study focused on patients with osteoarthritis, comparing those who had total knee replacement surgery (TKR) between 2005 and 2018 to a non-TKR group who did not have the surgery. Propensity score matching was employed to control for critical confounders. The hazard ratios (HRs) for the risk of thyroid diseases in TKR patients versus non-TKR controls were assessed. Results: Postmatching, the TKR cohort demonstrated a significantly higher risk of developing thyroid diseases compared to the non-TKR cohort (unadjusted HR=1.218, 95%CI=1.169-1.269). This elevated risk persisted after adjusting for confounders (adjusted HR=1.126, 95%CI=1.061-1.196). Stratification analysis indicated that female TKR patients and those aged ≥65 years were at higher risk of developing thyroid diseases than their respective control groups. Conclusion: This study suggests a potential link between TKR and an increased risk of thyroid diseases, particularly among older adults and females. Potential mechanisms include inflammatory processes, surgical stress, autoimmune responses, and pharmacological effects. Healthcare providers should be vigilant in monitoring and managing thyroid dysfunction in TKR patients. Further research is necessary to elucidate the underlying mechanisms and develop preventive strategies. [ABSTRACT FROM AUTHOR]

Thyroid issues are common among women in their reproductive years, and women with thyroid dysfunction often encounter challenges with fertility. Arsenic is known for its toxic effects on the thyroid and ovaries, investigated independently. However, there is no known study directly or indirectly addressing the association between arsenic, thyroid function, and ovarian reserve. This study aims to investigate the effect of arsenic on thyroid function and its possible implications on ovarian follicular reserve. Female Balb/c mice were given sodium arsenite (0.2 ppm, 2 ppm, and 20 ppm) via drinking water for 30 days. Findings showed that arsenic decreased thyroid hormone levels (fT3 and fT4) while increasing TSH levels, which might have led to elevated levels of FSH and LH. Furthermore, arsenic treatment not only decreased thyroid follicle sizes but also altered the ovarian follicular count. The finding demonstrates that arsenic significantly reduced the expression of LAMP1, a lysosomal marker protein. This reduction leads to increased lysosomal permeability in the thyroid, resulting in a significant release of cathepsin B. These changes led to hypothyroidism, which might indirectly affect the ovaries. Also, the elevated levels of growth differentiation factor-8 in arsenic-treated ovaries indicate impaired folliculogenesis and ovulation. Furthermore, arsenic significantly increased the expressions of pAkt and pFoxo3a, implying that arsenic accelerated the activation of the primordial follicular pools. In conclusion, arsenic disrupts lysosomal stabilization, potentially leading to a decline in circulating fT3 and fT4 levels. This disturbance could, in turn, affect the estrous cycle and may alter the pattern of follicular development. [ABSTRACT FROM AUTHOR]

Objective: Patient preferences regarding thyroid nodules are poorly understood. Our objective is to (1) employ a discrete choice experiment (DCE) to explore risk tradeoffs in thyroid nodule management, and (2) segment respondents into preference phenotypes. Study Design: DCE. Setting: Thyroid surgery clinic, online survey. Methods: A DCE including 5 attributes (cancer risk, voice concerns, incision/scar, medication requirement, follow‐up frequency) was refined with qualitative patient and physician input. A final DCE including 8 choice tasks, demographics, history, and risk tolerance was administered to participants with and without thyroid disease. Analysis was performed with multinomial logit modeling and latent class analysis (LCA) for preference phenotyping. Results: A total of 1026 respondents were included; 480 had thyroid disease. Risk aversion was associated with increasing age (P <.001), female gender (P <.001), and limited education (P =.038), but not previous thyroid disease. Cancer risk most significantly impacted decision‐making. Of the total possible utility change from thyroid nodule decision‐making, 47.8% was attributable to variations in cancer risk; 20.0% from medication management; 14.9% from voice changes; 12.7% from incision/scar; and 4.6% from follow‐up concerns. LCA demonstrated 3 classes with distinct preference phenotypes: the largest group (64.2%) made decisions primarily based on cancer risk; another group (18.2%) chose based on aversion to medication; the smallest group (17.7%) factored in medication and cancer risk evenly. Conclusion: Cancer risk and the need to take medication after thyroid surgery factor into patient decision‐making most heavily when treating thyroid nodules. Distinct preference phenotypes were demonstrated, reinforcing the need for individual preference assessment before the treatment of thyroid disorders. [ABSTRACT FROM AUTHOR]

Cancer is a condition that affects the psychological integrity of patients, due to the stigma that persists in relation to the disease. The aim of this study was to evaluate the presence of symptoms of anxiety, depression and the quality of life in patients undergoing total thyroidectomy for differentiated thyroid cancer and compare with patients undergoing total thyroidectomy for benign nodular disease. Cross-sectional study, conducted at the Irmandade da Santa Casa de Misericórdia in São Paulo, Brazil. A total of 64 patients submitted to total thyroidectomy were evaluated. Group A was composed of 29 patients with differentiated thyroid cancer and Group B was composed of 32 patients with benign nodular disease. Sociodemographic data were collected, Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) were used to identify symptoms of anxiety and depression. Quality of life was analyzed using Quality of Life Instrument (WHOQOL – BREF). The mean age was 49 ± 12 years, and 82.8% were female. Patients with differentiated thyroid cancer had higher levels of anxiety (BAI: 17.3 ± 11.4 vs. 10.3 ± 8.6) and depression (BDI: 12.6 ± 6.4 vs. 5.9 ± 7,2) compared to patients with benign nodular disease. The WHOQOL-BREF showed lower scores in the differentiated thyroid cancer group in relation to the benign nodular disease group for all domains evaluated: physical, psychological, social relationships, environment, self-assessment of quality of life, and general quality of life. Patients undergoing total thyroidectomy for differentiated thyroid cancer have more symptoms of anxiety and depression and a poorer quality of life when compared with patients undergoing total thyroidectomy due to benign nodular disease. [ABSTRACT FROM AUTHOR]

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis. SETTLE is a biphasic lobulated tumor composed of spindle shaped cells along with glandular formations seen on histopathological examination. Despite its typical morphology it is commonly misdiagnosed on histopathology due to its rarity and overlapping morphology with other close mimics such as a carcinoma, synovial sarcoma and thymoma. Herein we report such a case occurring in a middle aged female presenting with a neck mass. She had an initial diagnosis of metastatic poorly differentiated squamous cell carcinoma possibly with an orophayngeal primary in view of co expression of CK, p40 and p16 on immunohistochemistry. The patient underwent surgical resection with modified neck dissection. On review at our hospital it was diagnosed as SETTLE and she remains disease free after a follow-up period of 1 year. Diligent histopathological examination espoused with a judicious panel of IHC markers in conjunction with clinicoradiological findings forms the mainstay of diagnosis. Diffuse and strong p16 immunoexpression has not been documented or evaluated in literature so far, and needs to be explored for its diagnostic utility in this rare entity. [ABSTRACT FROM AUTHOR]

Perturbation of thyroid hormone (T4) synthesis is known to cause numerous developmental, metabolic, and cognitive disorders in humans. Due to species differences in sensitivity to chemical exposures, there is a need for human-based in vitro approaches that recapitulate thyroid cellular architecture and T4 production when screening. To address these limitations, primary human thyrocytes, isolated from healthy adult donor tissues and cryopreserved at passage one (p’1) were characterized for cellular composition, 3D follicular architecture, and thyroglobulin (TG)/T4 expression and inhibition by prototype thyroid disrupting chemicals (TDC). Flow analysis of the post-thaw cell suspension showed >80% EpCAM-positive cells with 10%–50% CD90-positive cells. When seeded onto 96-well Matrigel® -coated plates and treated with bovine thyroid stimulating hormone (TSH), thyrocytes formed 3D microtissues during the initial 4–5 days of culture. The microtissues exhibited a stable morphology and size over a 14-day culture period. TG and T4 production were highest in microtissues when the proportion of CD90-positive cells, seeding density and thyroid stimulating hormone concentrations were between 10%–30%, 6K–12K cells per well, and 0.03–1 mIU/mL, respectively. At maximal TG and T4 production levels, average microtissue diameters ranged between 50 and 200 µm. The T4 IC50 values for two prototype TPO inhibitors, 6-propyl-2-thiouracil and methimazole, were ~0.7 µM and ~0.5 µM, respectively, in microtissue cultures treated between days 9 and 14. Overall, p’1 cryopreserved primary human thyrocytes in 3D microtissue culture represent a promising new model system to prioritize potential TDC acting directly on the thyroid as part of a weight-of-evidence hazard characterization. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid nodules are extremely common being detected by ultrasonography in up to 67% of the population, with current surgical tenet maintaining that lobectomy is required for large symptomatic benign nodules or autonomously functionally nodules resulting in a risk of hypothyroidism or recurrent laryngeal nerve injury even in high volume centres. The introduction of radiofrequency ablation (RFA) has allowed thermal ablation of both benign and autonomously functioning thyroid nodules with minimal morbidity. The moving shot technique is the most well-established technique in performing RFA of thyroid nodules, and has proven to be safe, efficacious, accurate and successful amongst experienced clinicians. The purpose of this article to propose the use of a novel guide when performing RFA of thyroid nodules in clinical practice utilizing the moving shot technique. Methods: The technique proposed of RFA involves the use of a 10MHz linear ultrasound probe attached to an 18G guide which provides robust in line visualisation of a 7cm or 10cm radiofrequency probe tip (STARmed, Seoul, Korea) utilizing the trans isthmic moving shot technique. A geometric analysis of the guide has been illustrated diagrammatically. Results: The use of an 18G radiofrequency probe guide (CIVCO Infiniti Plus™ Needle Guide) maintains in line visualisation of the radiofrequency probe over a cross-sectional area up to 28cm2, facilitating efficient and complete ablation of conceptual subunits during RFA of thyroid nodules. Discussion: Radiofrequency ablation of thyroid nodules can be performed safely and effectively using the novel radiofrequency probe guide proposed which we believe potentially improves both accuracy and overall efficiency, along with operator confidence in maintaining visualisation of the probe tip, and hence we believe provides a valuable addition to the armamentarium of clinicians wishing to embark on performing RFA of thyroid nodules. [ABSTRACT FROM AUTHOR]

Background: Thyroid is superficially located gland, makes it easily approachable for examination. FNAC (Fine Needle Aspiration Cytology) is cost effective and OPD (Out Patient Department) based technique. Histopathological examination is gold standard. Aim: To compare the cytological and histopathological results of thyroid lesion in tertiary care center. Settings and Design: It is a cross-sectional analytical study conducted at department of pathology and ENT (otorhinolaryngology) at MGM medical college and hospital, Aurangabad. Methods and Material: 83 cases were included over a period of 1 year and 9 months. Patients presenting with thyroid lesions were included in the study while previously diagnosed cases were excluded from the study. FNAC was done on the patients and slides were reported according to Bethesda system of reporting thyroid cytopathology. Post-surgery specimen of the same patient received in the department of pathology, routine paraffin sectioned and hematoxylin and eosin stained (H & E stained) slides were reported. FNAC results were compared with histopathology results. Statistical analysis: The collected data entered in Microsoft excel and analyzed using SPSS version 24.0. Mean and SD(Standard deviation) will be calculated for quantitative variables and proportions will be calculated for categorical variables. Also, data represented in form of visual impression like bar-diagram, pie diagram etc. Results: Sensitivity of the FNAC for diagnosing malignant lesion was 50%. Specificity, PPV (Positive Predictive Value) and NPV (Negative Predictive Value) was 97%, 67% and 95% respectively. Conclusion: This study suggests preoperative diagnosis of FNAC is useful to plan the further management of the patient. [ABSTRACT FROM AUTHOR]

Introduction: Filariasis, a parasitic infection caused by several types of nematode worms, is a matter of great concern for public health in India, The disease is caused by microfilaria, which are released into the peripheral blood circulation with periodicity during the night. However, identifying microfilaria in routine peripheral blood smears, Fine Needle Aspiration (FNAC) smears, and body fluids is challenging due to their scarce nature. Our study aimed to underscore the significance of having a heightened suspicion of filarial infection in patients with swelling, particularly those from endemic regions. Furthermore, the study emphasised the importance of using FNAC as an economical and effective diagnostic tool for detecting microfilaria. Materials and Methods: This retrospective study was conducted in the Pathology Department of ESIC Medical College and Hospital Gulbarga over a period of ten years (2013-2023). A 22-23 gauze needle made aspiration smears were stained by Papanicolaou and May-Grünwald Giemsa stain. Results: In this study, 24 cases showed the presence of microfilaria, a type of parasitic worm, despite the lack of clinical suspicion. Of these cases, eight involved breast lumps, eight involved thyroid swelling, and eight involved lymph nodes. In fifteen of these cases, fragments of adult worms were also reported, indicating a potentially more severe infection. These findings suggest the need for more diligent screening and testing to detect and treat parasitic infections before they can cause further harm. Conclusion: Filariasis is a rare disease that requires thorough screening of FNA smears, particularly in asymptomatic patients from endemic regions, to avoid missing incidental findings. Moreover, the study emphasises the cost-effectiveness and efficacy of FNAC in diagnosing microfilaria. [ABSTRACT FROM AUTHOR]

Objective The aim of the study is to map the shared genetic component and relationships between thyroid and reproductive health traits to improve the understanding of the interplay between those domains. Design A large-scale genetic analysis of thyroid traits (hyper- and hypothyroidism, and thyroid-stimulating hormone levels) was conducted in up to 743 088 individuals of European ancestry from various cohorts. Methods We evaluated genetic associations using genome-wide association study (GWAS) meta-analysis, GWAS Catalog lookup, gene prioritization, mouse phenotype lookup, and genetic correlation analysis. Results GWAS meta-analysis results for thyroid phenotypes showed that 50 lead variants out of 253 (including 5/52 of the novel hits) were linked to reproductive health in previous literature. Genetic correlation analyses revealed significant correlations between hypothyroidism and reproductive phenotypes. The results showed that 31.9% of thyroid-associated genes also had an impact on reproductive phenotypes, with the most affected functions being related to genitourinary tract issues. Conclusions The study discovers novel genetic loci linked to thyroid phenotypes and highlights the shared genetic determinants between thyroid function and reproductive health, providing evidence for the genetic pleiotropy and shared biological mechanisms between these traits in both sexes. [ABSTRACT FROM AUTHOR]

Objective: Embryonic interferon-tau (IFNT) and progesterone affect expression of interferon-stimulated genes (ISGs), progesterone receptor (PGR) and progesterone-induced blocking factor (PIBF) in the ovine thyroid. Methods: Thyroids of ewes were sampled at day 16 of nonpregnancy, days 13, 16, and 25 of pregnancy, and real-time quantitative polymerase chain reaction assay, western blot and immunohistochemistry were used to detect expression of ISGs, PGR, and PIBF. Results: Free ISG15 protein was undetected, but ISG15 conjugated proteins upregulated at day 16 of pregnancy, and expression levels of ISG15 conjugated proteins, PGR isoform (70 kDa), PIBF, interferon-gamma-inducible protein 10 and myxovirusresistance protein 1 peaked, but expression level of signal transducer and activator of transcription 1 was the lowest at day 16 of pregnancy. In addition, the expression levels of PGR isoform (70 kDa) and signal transducer and activator of transcription 1 (STAT1) decreased, but levels of PGR isoform (43 kDa), 2',5'-oligoadenylate synthetase, IP-10 and MX1 increased at day 25 of pregnancy comparing with day 16 of the estrous cycle. Conclusion: Early pregnancy affects expression of ISGs, PGR, and PIBF in maternal thyroid through IFNT and progesterone, which may regulate thyroid autoimmunity and thyroid hormone secretion in ewes. [ABSTRACT FROM AUTHOR]

In this report, we describe the gross, histopathology, and immunohistochemical findings of a thyroblastoma that arose in the right lobe of the thyroid gland in a 2‐month‐old rhesus macaque (Macaca mulatta). [ABSTRACT FROM AUTHOR]

Background: The incidence of thyroid cancer in the United States has risen dramatically since the 1970s, driven by an increase in the diagnosis of small tumors. There is a paucity of published New Mexico (NM) specific data regarding thyroid cancer. We hypothesized that due to New Mexico's unique geographic and cultural makeup, the incidence of thyroid cancer and tumor size at diagnosis in this state would differ from that demonstrated on a national level. Methods: The New Mexico Tumor Registry (NMTR) was queried to include all NM residents diagnosed with thyroid cancer between 1992 and 2019. For 2010 to 2019, age-adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate and tumor size by race/ethnicity and residence (metropolitan vs non-metropolitan) were assessed with rate ratios between groups. For 1992 to 2019, temporal trends in age-adjusted incidence rates for major race/ethnic groups in NM [Non-Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software. Results: Our study included 3,161 patients for the time period 2010 to 2019, including NHW (1518), Hispanic (1425), and AI (218) cases. The overall incidence rates for NM AIs were lower than those for Hispanics and NHWs because of a decreased incidence of very small tumors (<1.1 cm). The incidence rates for large tumors (>5.1 cm) was equivalent among groups. In the early 2000s, Hispanics also had lower rates of small tumors when compared to NHWs but this trend disappeared over time. Conclusion: AIs in New Mexico have been left out of the nationwide increase in incidental diagnosis of small thyroid tumors. This same pattern was noted for Hispanics in the early 2000s but changed over time to mirror incidence rates for NHWs. These data are illustrative of the health care disparities that exist among New Mexico's population and how these disparities have changed over time. [ABSTRACT FROM AUTHOR]

Background: The National Institutes of Health (NIH) is the major funding agency for biomedical research in the United States. To initiate a scholarly dialog about research and career development in the thyroid field, here we reviewed recent trends in NIH funding for this area. We used the Research Portfolio Online Reporting Tool database to estimate the level of NIH extramural support during 2013–2022 (number of active grants/year and $amount/year weighed by the total number of active grants/year and $amount/year), provided by the NIH to the thyroid field. We determined that in 2013, the NIH supported ∼140 grants/year, totaling almost $50 million/year, the majority in the form of R01 grants. Within the thyroid field, support was evenly split between thyroid cancer and thyroid hormone metabolism and action subareas. In the subsequent years (2014–2022), the total number of active grants peaked at 150/year ($55 million) in 2014 but progressively decreased to about 100 active grants/year ($30 million) in 2022. This trend occurred while the NIH budget increased from $29 to $46 billion/year. Globally, the number of thyroid-related publications increased by ∼70% during the study period, and the fractional contribution of several countries remained relatively stable, except for China which increased by ∼600%. Remarkably, the fraction of thyroid-related publications in the United States sponsored by the NIH decreased from 5.5% to 3.1% of the global number. Conclusion: These results constitute a very concerning scenario for research and education in the thyroid field. We appeal to the NIH, the professional societies in endocrinology and thyroidology, and all other relevant stakeholders such as thyroid-related professionals and thyroid patients to engage in further discussions to identify the root causes of this trend and implement an action plan to stabilize and eventually reverse this situation. [ABSTRACT FROM AUTHOR]

Background: Serum thyroid-stimulating hormone (TSH) measurement is the diagnostic cornerstone for primary thyroid dysfunction. There is high inter-individual but limited intra-individual variation in TSH concentrations, largely due to genetic factors. The currently used wide population-based reference intervals may lead to inappropriate management decisions. Methods: A polygenic score (PGS) including 59 genetic variants was used to calculate genetically determined TSH reference ranges in a thyroid disease-free cohort (n = 6,834). Its effect on reclassification of diagnoses was investigated when compared to using population-based reference ranges. Next, results were validated in a second independent population-based thyroid disease-free cohort (n = 3,800). Potential clinical implications were assessed in a third independent population-based cohort including individuals without thyroid disease (n = 26,321) as well as individuals on levothyroxine (LT4) treatment (n = 1,132). Results: PGS was a much stronger predictor of individual TSH concentrations than FT4 (total variance in TSH concentrations explained 9.2–11.1% vs. 2.4–2.7%, respectively) or any other nongenetic factor (total variance in TSH concentrations explained 0.2–1.8%). Genetically determined TSH reference ranges differed significantly between PGS quartiles in all cohorts, while the differences in FT4 concentrations were absent or only minor. Up to 24.7–30.1% of individuals, previously classified as having subclinical hypo- and hyperthyroidism when using population-based TSH reference ranges, were reclassified as euthyroid when genetically determined TSH reference ranges were applied. Individuals in the higher PGS quartiles had a higher probability of being prescribed LT4 treatment compared to individuals from the lower PGS quartiles (3.3% in Q1 vs. 5.2% in Q4, Pfor trend =1.7 × 10−8). Conclusions: Individual genetic profiles have the potential to personalize TSH reference ranges, with large effects on reclassification of diagnosis and LT4 prescriptions. As the currently used PGS can only predict approximately 10% of inter-individual variation in TSH concentrations, it should be further improved when more genetic variants determining TSH concentrations are identified in future studies. [ABSTRACT FROM AUTHOR]

Cribriform morular thyroid carcinoma has been added under tumors of uncertain histogenesis. Its peculiar clinical, histomorphological pattern, and immunohistochemical profile have been proved different from papillary thyroid carcinoma. A 59-year-old female patient had a lesion in the left lobe of the thyroid. Fine needle aspiration cytology was reported as medullary thyroid carcinoma. The total thyroidectomy specimen showed a predominantly solid tumor of size 9.5 cm in the left lobe. Microscopy showed a mixed growth pattern with the dominant cribriform and solid morular area. Nuclear features of papillary carcinoma were not seen. Squamoid morules had nuclear clearing. Marked stromal hyalinization and calcification were noted. Extrathyroidal extension, lymphovascular invasion, and lymph node metastasis were not identified. Immunohistochemically the tumor cells were diffuse and strong nuclear positive for β-catenin, TTF1, PAX8, estrogen receptor, focal, and weak positivity for CD5. Synaptophysin, calcitonin, thyroglobulin, and CDX2 were negative. We report this rare cribriform morular thyroid carcinoma case with its associated uncommon histological and immunohistochemical features. [ABSTRACT FROM AUTHOR]

Disruption of the thyroid hormone (TH) system is connected with diverse adverse health outcomes in wildlife and humans. It is crucial to develop and validate suitable in vitro assays capable of measuring the disruption of the thyroid hormone (TH) system. These assays are also essential to comply with the 3R principles, aiming to replace the ex vivo tests often utilised in the chemical assessment. We compared the two commonly used assays applicable for high throughput screening [Luminol and Amplex UltraRed (AUR)] for the assessment of inhibition of thyroid peroxidase (TPO, a crucial enzyme in TH synthesis) using several cell lines and 21 compounds from different use categories. As the investigated cell lines derived from human and rat thyroid showed low or undetectable TPO expression, we developed a series of novel cell lines overexpressing human TPO protein. The HEK-TPOA7 model was prioritised for further research based on the high and stable TPO gene and protein expression. Notably, the Luminol assay detected significant peroxidase activity and signal inhibition even in Nthy-ori 3-1 and HEK293T cell lines without TPO expression, revealing its lack of specificity. Conversely, the AUR assay was specific to TPO activity. Nevertheless, despite the different specificity, both assays identified similar peroxidation inhibitors. Over half of the tested chemicals with diverse structures and from different use groups caused TPO inhibition, including some widespread environmental contaminants suggesting a potential impact of environmental chemicals on TH synthesis. Furthermore, in silico SeqAPASS analysis confirmed the high similarity of human TPO across mammals and other vertebrate classes, suggesting the applicability of HEK-TPOA7 model findings to other vertebrates. [ABSTRACT FROM AUTHOR]

The Canadian Association of Radiologists (CAR) Head and Neck Expert Panel consists of radiologists, a laryngologist and laryngeal surgeon, a patient advisor, and an epidemiologist/guideline methodologist. After developing a list of 11 clinical/diagnostic scenarios, a systematic rapid scoping review was undertaken to identify systematically produced referral guidelines that provide recommendations for one or more of these clinical/diagnostic scenarios. Recommendations from 17 guidelines and contextualization criteria in the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) for guidelines framework were used to develop 26 recommendation statements across the 11 scenarios. This guideline presents the methods of development and the referral recommendations for sinus disease, tinnitus, thyroid and parathyroid disease, neck mass of unknown origin, acute sialadenitis, chronic salivary conditions, and temporomandibular joint dysfunction. [ABSTRACT FROM AUTHOR]

Therapy with thyroid hormones normally is restricted to substitution therapy of patients with primary or secondary hypothyroidism. Typically, thyroid hormones are given orally. There are few indications for intravenous use of thyroid hormones. Indications for parenteral application are insufficient resorption of oral medications due to alterations of the gastrointestinal tract, partial or total loss of consciousness, sedation in the intensive care unit or shock. In almost all cases, levothyroxine is the therapy of choice including congenital hypothyroidism. In preterm infants with an altered thyroid hormone status, studies with thyroid hormones including intravenous liothyronine showed a normalisation of T3 levels and in some cases an amelioration of parameters of ventilation. A benefit for mortality or later morbidity could not be seen. Effects on neurological improvements later in life are under discussion. Decreased thyroid hormone levels are often found after cardiac surgery in infants and adults. Intravenous therapy with thyroid hormones improves the cardiac index, but in all other parameters investigated, no substantial effect on morbidity and mortality could be demonstrated. Oral liothyronine therapy in these situations was equivalent to an intravenous route of application. In myxoedema coma, intravenous levothyroxine is given for 3 to 10 days until the patient can take oral medication and normal resorption in the gastrointestinal tract is achieved by restoring at least peripheral euthyroidism. Intravenous levothyroxine is the standard in treating patients with myxoedema coma. A protective effect on the heart of i.v. levothyroxine in brain-dead organ donors may be possible. [ABSTRACT FROM AUTHOR]

Background: Gestational outcomes are known to be negatively correlated with hypothyroidism. This study was designed to compare the maternal factors affecting gestational outcomes in women with and without hypothyroidism. Methods: This retrospective analysis was carried out in a tertiary hospital in Karachi, Pakistan, between 2008 and 2016. A standardized form was used to collect information on the age of the mother, gestational duration at the prenatal appointment, gestational diabetes mellitus (GDM), hypertension, and past records of miscarriages in hypothyroid and healthy pregnant women. Gestational outcomes were recorded as live birth or pregnancy loss. Statistical analysis was performed to examine overt versus sub-clinical hypothyroidism and among those diagnosed before versus during gestation. Results: A collective of 708 women were enlisted in the hypothyroid pregnant group and 759 were recruited in healthy controls. Pregnancy loss was 9.9% (n = 70) in hypothyroid women, whereas it was 14.3% (n = 108) in the control group. The age of the mother, gestational duration at the prenatal appointment, and past records of miscarriages were discovered to be related to a higher chance of pregnancy loss in a multivariable analysis, but GDM (OR 0.04, CI 0.06-0.32, P = 0.002) and hypothyroidism (OR 0.62, CI 0.43-0.89, P = 0.01) exhibited a protective effect. Conclusion: This study found the age of the mother, gestational duration at a prenatal appointment, and past records of miscarriages to be associated with negative outcomes in hypothyroidism. These factors remained significant in overt as well as subclinical hypothyroid women. [ABSTRACT FROM AUTHOR]

The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had =50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1. [ABSTRACT FROM AUTHOR]

Hepatic glycogen storage diseases constitute a group of disorders due to defects in the enzymes and transporters involved in glycogen breakdown and synthesis in the liver. Although hypoglycemia and hepatomegaly are the primary manifestations of (most of) hepatic GSDs, involvement of the endocrine system has been reported at multiple levels in individuals with hepatic GSDs. While some endocrine abnormalities (e.g., hypothalamic‑pituitary axis dysfunction in GSD I) can be direct consequence of the genetic defect itself, others (e.g., osteopenia in GSD Ib, insulin-resistance in GSD I and GSD III) may be triggered by the (dietary/medical) treatment. Being aware of the endocrine abnormalities occurring in hepatic GSDs is essential (1) to provide optimized medical care to this group of individuals and (2) to drive research aiming at understanding the disease pathophysiology. In this review, a thorough description of the endocrine manifestations in individuals with hepatic GSDs is presented, including pathophysiological and clinical implications. [ABSTRACT FROM AUTHOR]

Background: Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se. Methods: We conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999–2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011–2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity. Results: In the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2–1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3–2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1–5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6–1.2)). Conclusions: In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia. [ABSTRACT FROM AUTHOR]

Background: Differentiated high‐grade thyroid carcinoma (DHGTC) is recently recognized by the World Health Organization (WHO) as a subgroup of thyroid carcinomas with high‐grade features while retaining the architectural and/or cytologic features of well‐differentiated follicular–cell‐derived tumors. The cytomorphology of DHGTC is not well documented despite potential implications for patient triage and management. Methods: The pathology archives of six institutions were searched for cases diagnosed on resection as "high‐grade thyroid carcinoma" using WHO criteria. The fine‐needle aspiration (FNA) cohort represents a 10‐year period (2013–2023); all were reviewed to confirm DHGTC classification. The corresponding FNAs were assessed for 32 cytomorphologic features. Results: Forty cases of DHGTC with prior FNA were identified. The mean patient age was 64.2 years. The average lesion size was 4.9 cm, and the majority demonstrated a TI‐RADS score of 4 or 5 (95.2%). Three main high‐grade subsets of DHGTC based on corresponding histology included papillary thyroid carcinoma (65%), follicular carcinoma (22.5%), and oncocytic carcinoma (12.5%). Over 97% of FNA cases were classified as Bethesda category IV or above. Approximately 25% of DHGTC showed cytologic features that included marked cytologic atypia, increased anisonucleosis, large oval nuclei, mitotic activity, or necrosis (p <.05); 68% of DHGTC cases were associated with high‐risk molecular alterations. TERT mutations occurred in 41%, of which 89% of these were associated with a second mutation, usually RAS or BRAF p.V600E. Conclusions: Cytology has a low sensitivity for DHGTC, although a subset of DHGTCs have cytologic features raising the possibility of a high‐grade thyroid carcinoma. Other findings include high‐risk molecular changes and clinicopathologic features such as older patient age and larger lesion size. A subset of thyroid FNAs of differentiated high‐grade thyroid carcinomas show marked nuclear atypia, mitotic activity, or necrosis together with high‐risk molecular alterations. [ABSTRACT FROM AUTHOR]

Background: The atypia of undetermined significance (AUS) category is heterogeneous, leading to variations in its use. To prevent excessive usage, the AUS rate should be ≤10%. Although this recommendation aims to maintain diagnostic quality, it lacks supporting data. The AUS:Malignant (AUS:M) ratio has been proposed as a metric tool to evaluate AUS use. Furthermore, integrating ThyroSeq v3 (TSV3) positive call rate (PCR) and the molecular‐derived risk of malignancy (MDROM) have been put forward as performance improvement tools. The authors reviewed their AUS:M ratios, TSV3 PCR, MDROM, and ROM. Methods: Thyroid aspirates evaluated in the laboratory (from August 2022 to September 2023) by seven cytopathologists (CPs) were identified. AUS:M ratio, MDROM, ROM, and TSV3 PCR results for the laboratory and each CP were recorded and analyzed. Results: A total of 2248 aspirates were identified (462 AUS and 80 malignant). The AUS:M ratio for the laboratory was 5.8 (CPs range, 2.8 to 7.3). The TSV3 PCR for the laboratory was 23% (CPs range, 11% to 41%). The MDROM for the laboratory was 19% (CPs range, 9% to 31%), whereas the ROM was 36% (CPs range, 29% to 50%). Linear regression analysis of AUS:M ratio versus TSV3 PCR and MDROM demonstrated a moderate positive correlation but a weak negative correlation to the ROM. Deviations from established targets were attributed to multiple factors. Conclusion: The findings of this study underscore the importance of using a combination of metrics to evaluate diagnostic practices. By dissecting the practice patterns of each CP, the authors can measure different aspects of their performance and provide individualized feedback. Quality metric tools in thyroid cytology can offer valuable feedback to individual cytopathologists and laboratories, contributing to improving diagnostic practices. [ABSTRACT FROM AUTHOR]

A modified amphibian metamorphosis assay was performed in which Nieuwkoop and Faber (NF) stage 47 Xenopus laevis larvae were exposed to different concentrations of either perchlorate (ClO4−) or nitrate (NO3−) for 32 days. Larvae were exposed to 0.0 (control), 5, 25, 125, 625, and 3125 μg/L ClO4−, or 0 (control), 23, 71, 217, 660, and 2000 mg/L NO3−. The primary endpoints were survival, hind limb length (HLL), forelimb emergence and development, developmental stage (including time to NF stage 62 [MT62]), thyroid histopathology, wet weight, and snout‐vent length (SVL). Developmental delay as evidenced by altered stage distribution and increased MT62, a higher degree of thyroid follicular cell hypertrophy, and an increase in the prevalence of follicular cell hyperplasia was observed at concentrations ≥125 μg/L ClO4−. The no observed effect concentration (NOEC) for developmental endpoints was 25.0 μg/L ClO4− and the NOEC for growth endpoints was 3125 μg/L ClO4−. Exposure to nitrate did not adversely affect MT62, but a decreasing trend in stage distribution and median developmental stage at ≥217 mg/L NO3− was observed. No histopathologic effects associated with nitrate exposure were observed. An increasing trend in SVL‐normalized HLL was observed at 2000 mg/L NO3−. Nitrate did not alter larval growth. The NOEC for developmental endpoints was 71 mg/L NO3−, and 2000 mg/L NO3− for growth endpoints. The present study provided additional evidence that the effects and potency of nitrate and perchlorate on metamorphosis and growth in X. laevis are considerably different. A modified amphibian metamorphosis assay was performed with perchlorate (ClO4−) or nitrate (NO3−) for 32 days. The no observed effect concentration (NOEC) for developmental endpoints was 25 μg/L ClO4− and NOEC for growth endpoints was 3125 μg/L ClO4−. The NOEC for developmental endpoints was 71 mg/L, and 2000 mg/L NO3− for growth endpoints. The present study demonstrated that the effects and potency of nitrate and perchlorate on metamorphosis and growth in X. laevis are considerably different. [ABSTRACT FROM AUTHOR]

Objective: Radioiodine (I-131) therapy for hyperthyroidism is a well-established and safe treatment option. This study aimed to investigate the relationship between the computed tomography (CT) value and the function and volume of the thyroid gland by identifying the factors that induce changes in the CT value of patients with hyperthyroidism. Methods: This retrospective study evaluated 38 patients with Graves' disease and 10 patients with Plummer disease. To obtain the mean CT value and volume of the thyroid gland, the entire thyroid gland was set as the region of interest. A test dose of 3.7 MBq I-131 was administered before initiating I-131 therapy, and the radioiodine uptake (RIU) rate was assessed after 3, 24, 96, and 168 h. An approximate curve was plotted based on the RIU values obtained, and the effective half-life (EHL) was calculated. The correlation between the mean CT value and the volume of the thyroid gland, 24-h RIU, EHL, and the free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and TSH receptor antibody (TRAb) levels was evaluated. Results: The CT value exhibited a significant positive correlation with EHL in patients with Graves' disease (r = 0.62, p < 0.0001) as well as patients with Plummer disease (r = 0.74, p < 0.05). However, it did not display any correlation with the remaining parameters. Conclusion: The CT value is significantly correlated with EHL, suggesting that it reflects thyroid function and is mainly related to the factors associated with iodine discharge. [ABSTRACT FROM AUTHOR]

Thyroid function is closely linked to nutrition through the diet–gut–thyroid axis. This narrative review highlights the influence of nutritional components and micronutrients on thyroid development and function, as well as on the gut microbiota. Micronutrients such as iodine, selenium, iron, zinc, copper, magnesium, vitamin A, and vitamin B12 influence thyroid hormone synthesis and regulation throughout life. Dietary changes can alter the gut microbiota, leading not just to dysbiosis and micronutrient deficiency but also to changes in thyroid function through immunological regulation, nutrient absorption, and epigenetic changes. Nutritional imbalance can lead to thyroid dysfunction and/or disorders, such as hypothyroidism and hyperthyroidism, and possibly contribute to autoimmune thyroid diseases and thyroid cancer, yet controversial issues. Understanding these relationships is important to rationalize a balanced diet rich in essential micronutrients for maintaining thyroid health and preventing thyroid-related diseases. The synthetic comprehensive overview of current knowledge shows the importance of micronutrients and gut microbiota for thyroid function and uncovers potential gaps that require further investigation. [ABSTRACT FROM AUTHOR]

The association of thyroid function with essential and non-essential amino acids is understudied, despite their common metabolic roles. Thus, our aim was to evaluate the association of thyroid function with the levels of branched-chain amino acids (BCAAs—leucine, isoleucine, and valine) and of alanine in the general population. We utilized data from the São Paulo research center of ELSA-Brasil, a longitudinal population-based cohort study. Thyroid parameters included thyroid stimulating hormone (TSH), free T4 and free T3 levels, and the FT4:FT3 ratio. BCAAs and alanine were analyzed on a fully automated NMR platform. The current analysis included euthyroid participants and participants with subclinical hyperthyroidism and hypothyroidism. We used Pearson's coefficient to quantify the correlation between thyroid-related parameters and amino acids. Linear regression models were performed to analyze whether thyroid parameters were associated with BCAAs and alanine levels. We included 4098 participants (51.3 ± 9.0 years old, 51.5% women) in this study. In the most adjusted model, higher levels of TSH were associated with higher levels of alanine, FT4 levels were inversely associated with isoleucine levels, FT3 levels were statistically significant and positively associated with valine and leucine, and the T3:T4 ratio was positively associated with all amino acids. We observed that subclinical hypothyroidism was positively associated with isoleucine and alanine levels in all models, even after full adjustment. Our findings highlight the association of subclinical hypothyroidism and thyroid-related parameters (including TSH, free T4, free T3, and FT4:FT3 ratio) with BCAAs and alanine. Further studies are needed to explore the mechanisms underlying this association. These insights contribute to our understanding of the influence of thyroid-related parameters on BCAA and alanine metabolism. [ABSTRACT FROM AUTHOR]

Background: Primary squamous cell carcinoma (SCC) of the thyroid and anaplastic thyroid carcinoma (ATC) show significant clinical and histologic overlap. Their biological behaviors are so similar that the fifthWHO updates SCC as a morphologic pattern of ATC rather than a separate entity. However, molecular genomic evidence that determines them as the same histologic type is limited. We aimed to explore whether they belong to the same classification from a molecular-typing perspective. Methods: A cohort enrolled 15 SCCs and 15 ATCs was collected. Whole exome sequencing (WES) and RNA-sequencing were performed to analyze molecular genetic and gene-expression profiles. Results: Significantly differential-mutant genes were BRAF, DPCR1, PCYOX1L, BRSK2, NRG1, PRR14L, TET1, VAMP4 suggesting differences in mutation level, as well as differences in highfrequency mutated genes, and SCC had a much lower tumor mutation burden than ATC. Mutational co-occurrence and mutual exclusion were less frequent in SCC than in ATC. 2047 differentialexpress genes were screened, indicating differences in gene expression were extremely strong. In principal component analysis, ATC and SCC could be notably clustered together, respectively, meanwhile they could be explicitly distinguished. Unsupervised clustering analysis validated they can indeed be clearly separated from each other which demonstrated that they may be two distinctive entities. Conclusions: It is controversial yet SCC is classified as a morphologic pattern of ATC. We revealed that SCC exhibited molecular genetic characteristics distinct from ATC. Although the fifth WHO categorizes them together, this study may provide strong molecular genetic evidence for the next edition of WHO classification that may allow for the separation of thyroid SCC from ATC. [ABSTRACT FROM AUTHOR]

Objectives: A risk-adjusted analysis was completed using data from the National Surgical Quality Improvement Program (NSQIP) to compare the rates of recurrent laryngeal nerve injury in thyroid surgery using traditional versus alternative sources of cautery (defined as Harmonic Scalpel© and LigaSure©). Methods: A retrospective cohort study was completed using the NSQIP database on adult patients who underwent total thyroidectomy, subtotal thyroidectomy, or completion thyroidectomy between 2016 and 2018. The primary outcome measure was recurrent laryngeal nerve injury. The exposure variable was use of conventional or alternative sources of cautery. Multivariable linear and logistic regression analyses were performed to control for potentially confounding variables. Results: A total of 13,961 cases were analyzed; 9450 used alternative sources of cautery compared to 4511 where traditional cautery was used. There was no significant difference in rates of postoperative recurrent laryngeal nerve injury between the 2 sources of cautery compared. Conclusions: Risk of recurrent laryngeal nerve injury should not be a factor when choosing method of cautery for thyroid surgery. Therefore, other factors like cost-effectiveness can be considered. [ABSTRACT FROM AUTHOR]

Primary thyroid squamous cell carcinoma is extremely rare. We report a case of primary thyroid squamous cell carcinoma diagnosed using 18F-FDG PET/CT. The patient presented with left axillary lymphadenopathy as the initial symptom. Fine-needle aspiration of the axillary lymph nodes indicated metastatic squamous cell carcinoma. To identify the primary tumor, the patient underwent an 18F-FDG PET/CT scan, which revealed a mass in the thyroid and multiple enlarged lymph nodes with abnormal FDG uptake. Pathological examination of the axillary lymph nodes and thyroid biopsy confirmed the diagnosis of primary thyroid squamous cell carcinoma with lymph node metastasis. [ABSTRACT FROM AUTHOR]

Introduction Materials and Methods Results Conclusion There are conflicting results on whether the presence of oncocytes modifies the risk of neoplasm (RON) or malignancy (ROM) for thyroid fine‐needle aspirates (FNAs): Atypia of undetermined significance AUS and Follicular Neoplasm, FN, or Oncocytic Neoplasm, ON. To our knowledge, the effect of non‐invasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) has not yet been studied. We compared RON and ROM between follicular type AUS (AUS‐FT) and oncocytic type AUS (AUS‐OT) and between FN and ON.We retrospectively analysed all thyroid FNAs with the diagnostic category of AUS‐other or Neoplasm (2005–2015). AUS‐FT had predominance of microfollicles and AUS‐OT had predominance of oncocytes. Histology follow‐up was then reviewed and RON, ROM was then calculated and compared (significant at p < 0.05). We repeated the search for 2018 to evaluate for NIFTP effect.Pre‐NIFTP, 859/5063 cases (17%) were AUS‐FT, AUS‐OT, FN, and ON. Histology follow‐up was available for 297 cases (35%). RON was 83/183 (45%) for AUS‐FT, 35/76 (46%) for AUS‐OT, 15/25 (60%) for FN and 11/13 (85%) for ON. Post‐NIFTP, RON was 11/31 (35%) for AUS‐FT, 5/8 (63%) for AUS‐OT, 1/2 (50%) for FN and 4/5 (80%) for ON. For both periods, RON, ROM of AUS‐FT was not significantly different than AUS‐OT, and no significant differences were observed comparing FN and ON.The predominance of oncocytes does not modify the implied RON, ROM for categories of AUS or FN\ON, even after the adoption of NIFTP. [ABSTRACT FROM AUTHOR]

Considering the spectrum of benefits of breast milk feeding, determining the essential components of an infant's only food-mother's milk-seems justified, especially in the case of those whose deficiency (e.g., iodine) may result in developmental disorders. The main aim of this study was the determination of the total iodine content of breast milk (including colostrum and mature milk). A secondary objective was to assess the influence of factors such as the type of delivery, hypothyroidism, gestational diabetes or the stage of lactation on this parameter. The study materials were colostrum and milk after 1 (n = 14), 2 and 3 months (n = 8) of lactation with a range of iodine concentrations (µg/L): 195–1648 and 170–842, 174–650 and 273–751, respectively. Iodine was determined using the inductively coupled plasma mass spectrometry (ICP-MS). Multivariate statistical analysis revealed, e.g., that delivery by caesarean section or dose of L-thyroxine taken by women to normalise thyroid hormones, had a significant effect on iodine concentrations in breast milk. Further research aimed at assessing the quality of breast milk should also include determining the factors influencing it. [ABSTRACT FROM AUTHOR]

Background: Patients referred for cardiac surgery usually also have other comorbidities. These include thyroid disease, which is relatively common in patients with heart problems. Objective: The aim of the study was to evaluate the feasibility of combined cardiac surgery and thyroidectomy. Material and methods: Six patients (age range: 54-74 years) qualified for elective, simultaneous surgeries on the heart and the thyroid were included in the study. In preparation for thyroidectomy, three patients were diagnosed with diseases requiring cardiac surgery. Two patients, initially referred for coronary artery bypass surgery in one case, and surgery for recurrent fluid in the pericardial sac with concomitant mitral and tricuspid valve regurgitation and atrial fibrillation in the other, were diagnosed in large hyperactive goitre. The last patient with a history of oncology (lung tumour), admitted to the Department of Cardiology due to a heart attack, had a CT scan of the chest, which revealed retrosternal goitre narrowing the lumen of the trachea to 9 mm. All patients underwent combined heart and thyroid operation and were discharged home 8-27 days after surgery. Conclusions: Although preoperative qualification requires a very cautious and individual approach, simultaneous surgeries in patients requiring thyroid and heart interventions are expedient and should be promoted. [ABSTRACT FROM AUTHOR]