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19 pages, 381 KB  
Article
Prevalence, Spectrum, and Management of Thyroid Dysfunction in Children with Down Syndrome: A Retrospective Study from Southern Saudi Arabia
by Youssef Ali Alqahtani, Ayed A. Shati, Ayoub Ali Alshaikh, Ali Thamer Alshahrani, Salwa Abdullah Bin Qaed, Manar Ali Alqahtani, Omar Ayidh Alotaibi, Muteb Obaid Alharthi, Mohamed Hassan Sarhan, Abdulaziz Mohammed Alrasheed and Ramy Mohamed Ghazy
Children 2026, 13(1), 6; https://doi.org/10.3390/children13010006 - 19 Dec 2025
Abstract
Background: Down syndrome (DS) is strongly associated with a high prevalence of thyroid dysfunction. International guidelines recommend regular screening to ensure early detection and management. This study aimed to determine the prevalence, spectrum, and management outcomes of thyroid dysfunction in children with DS [...] Read more.
Background: Down syndrome (DS) is strongly associated with a high prevalence of thyroid dysfunction. International guidelines recommend regular screening to ensure early detection and management. This study aimed to determine the prevalence, spectrum, and management outcomes of thyroid dysfunction in children with DS in the Aseer region of Saudi Arabia. Methods: A retrospective cross-sectional study was conducted by reviewing the medical records of 106 children with DS from two major healthcare centers: Abha Maternity and Children Hospital and King Khalid University Medical Center. Data on demographics, clinical symptoms, thyroid function tests, autoimmune status, treatment, and follow-up patterns were collected and analyzed. Results: The prevalence of thyroid dysfunction was 52.8%. Subclinical hypothyroidism was the most common disorder (46.4%), followed by autoimmune hypothyroidism (30.4%). Patients with thyroid dysfunction had a significantly higher symptom burden, particularly in metabolic, dermatological, and gastrointestinal domains (p < 0.01). A strong family history of thyroid disease was a significant risk factor (adjusted odds ratio (aOR) = 4.57, 95% CI: 1.89–11.6, p < 0.001). While adherence to screening and follow-up was high (78.0% and 82.1%, respectively), a critical gap was identified in treatment optimization, with 74.4% of patients treated potentially requiring levothyroxine dose adjustment. Conclusions: Thyroid dysfunction is highly prevalent in the Southern Saudi children with DS, with subclinical hypothyroidism and autoimmune hypothyroidism being the most common types. Despite good screening adherence, there is a substantial need for improved treatment titration and long-term management to optimize patient outcomes in this population. Full article
(This article belongs to the Section Pediatric Endocrinology & Diabetes)
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14 pages, 835 KB  
Article
Effects of Iodine Status and Vitamin A Level on Blood Pressure, Blood Glucose, and Blood Lipid Levels in Chinese Adults: A Cross-Sectional Study
by Jingtao Zhao, Manman Chen, Yang Peng, Keyu Han, Qu Lu and Bin Dong
Nutrients 2025, 17(24), 3948; https://doi.org/10.3390/nu17243948 - 17 Dec 2025
Viewed by 148
Abstract
Background: Iodine deficiency remains a significant public health concern worldwide and may contribute to metabolic disorders beyond thyroid dysfunction. Emerging evidence suggests that nutritional factors, such as vitamin A, may influence the health effects of iodine deficiency, yet population-based evidence remains limited. This [...] Read more.
Background: Iodine deficiency remains a significant public health concern worldwide and may contribute to metabolic disorders beyond thyroid dysfunction. Emerging evidence suggests that nutritional factors, such as vitamin A, may influence the health effects of iodine deficiency, yet population-based evidence remains limited. This study aimed to investigate the associations between iodine deficiency and cardiometabolic risk factors (blood pressure, glucose, and lipids) and to explore whether these associations are different between adults with different vitamin A levels. Methods: A total of 4723 adults (1895 males and 2828 females) were included in this cross-sectional study. Participants were categorized based on iodine status and serum vitamin A levels. Demographic, anthropometric, and biochemical indicators were assessed through standardized examinations. Multivariable linear and logistic regression models were used to evaluate the associations between iodine deficiency and continuous (systolic blood pressure [SBP], diastolic blood pressure [DBP], fasting blood glucose [FBG], total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], triglycerides [TGs]) and binary outcomes (hypertension, hyperglycemia, and dyslipidemia), with stratified analyses by gender, age, and vitamin A status. Results: Iodine deficiency was significantly associated with higher SBP (β = 2.89, 95% confidence interval [CI]: 2.00–3.77), DBP (β = 1.08, 0.55–1.60), FBG (β = 0.06, 0.01–0.12) and TC (β = 0.05, 0.00–0.10). The odds of hypertension (odds ratio [OR] = 1.41, 1.23–1.63) and hyperglycemia (OR = 1.39, 1.17–1.65) were also increased. Stratified analyses indicated that these associations were more pronounced among participants with vitamin A deficiency than those with sufficient vitamin A. In this subgroup, iodine deficiency was positively associated with FBG (β = 0.14, 0.03–0.25), TC (β = 0.08, 0.00–0.15), and hyperglycemia (OR = 1.35, 1.04–1.76). Conclusions: The findings suggest that the association of iodine deficiency with adverse cardiometabolic risk factors may be stronger in individuals with concurrent vitamin A deficiency. This highlights the potential value of integrated nutritional assessments and supports the need for longitudinal studies to confirm these interactions and assess the effects of combined micronutrient supplementation. Full article
(This article belongs to the Section Micronutrients and Human Health)
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13 pages, 224 KB  
Article
Personalized Supplementation Is Associated with Reduced Inflammatory Biomarkers: A 12-Week Observational Study
by Eliza Roeth, Madeline Morris, Asher P. Reynolds, Emma M. Reynolds, Reed Hungerford, Eliza J. Livingston, Andrew W. Richardson, Benjamin T. Bikman and Paul R. Reynolds
Life 2025, 15(12), 1887; https://doi.org/10.3390/life15121887 - 10 Dec 2025
Viewed by 386
Abstract
Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring [...] Read more.
Chronic low-grade inflammation is a central contributor to the development of cardiovascular disease, metabolic dysfunction, autoimmune disorders, and cognitive decline. Blood-based biomarkers, such as C-reactive protein (CRP), ferritin, homocysteine, white blood cell (WBC) count, and anti-thyroid peroxidase (anti-TPO) antibodies enable quantification and monitoring of systemic inflammation over time. We aimed to evaluate the impact of a 12-week personalized, biomarker-guided supplementation program including micronutrients, hormone support, and peptides on inflammatory and immune-related biomarkers across age- and sex-stratified adult cohorts. Participants (n = 48; 8 per group) were stratified by sex and age (40–49, 50–59, 60–69 years) and underwent blood testing at baseline and 12 weeks. Personalized protocols were developed based on individual biomarker profiles and included targeted interventions with vitamin D, omega-3 fatty acids, B vitamins, zinc, selenium, hormone optimization, and other supportive agents. Primary outcomes were percent changes in CRP, ferritin, homocysteine, WBC count, and anti-TPO antibody levels. CRP levels decreased by 33–46% across all groups, with similarly consistent declines in homocysteine (29–37%) and WBC count (22–28%). Ferritin reductions were most notable in men, particularly in older age groups (up to 48%), while anti-TPO antibody levels declined more prominently in women (up to 22%). These changes are consistent with reduced systemic inflammation, improved methylation status, and potential modulation of autoimmune activity. This biomarker-guided, personalized supplementation protocol was associated with clinically meaningful reductions in key markers of inflammation and immune dysregulation. These findings are suggestive of potential efficacy for precision-based health optimization programs and highlight the need for larger randomized controlled trials (RCTs) to confirm causal effects. Full article
12 pages, 220 KB  
Article
Impact of Surgical Timing on Outcome in Papillary Thyroid Cancer Patients in Saudi Arabia
by Omar Zaki Alaidaroos, Saleh F. Aldhahri, Talal Banan Alanazi, Malak Satam Alanazi, Khalid H. Alqahtani, Mohammed Alessa, Naif Fnais and Faisal R. Alzahrani
J. Clin. Med. 2025, 14(24), 8662; https://doi.org/10.3390/jcm14248662 - 6 Dec 2025
Viewed by 298
Abstract
Background/Objectives: To evaluate whether the interval between diagnosis and surgery is associated with aggressive histopathological features in papillary thyroid carcinoma (PTC) among patients treated at a tertiary hospitals in Saudi Arabia. Methods: This retrospective study was conducted at King Fahad Medical City, Riyadh, [...] Read more.
Background/Objectives: To evaluate whether the interval between diagnosis and surgery is associated with aggressive histopathological features in papillary thyroid carcinoma (PTC) among patients treated at a tertiary hospitals in Saudi Arabia. Methods: This retrospective study was conducted at King Fahad Medical City, Riyadh, Saudi Arabia, from November 2009 to November 2024. A total of 350 adult patients who underwent surgical intervention for PTC were included based on predefined inclusion and exclusion criteria. Data were collected from medical records and included demographic, clinical, and histopathological characteristics. The primary outcome was the presence of aggressive histopathological features, assessed through tumor subtype, tumor size, extrathyroidal extension (ETE), lymph-node involvement, extracapsular extension (ECE), multifocality, goitrous tumor, thyroiditis, perineural invasion, lymphovascular invasion, and margin status. Surgical timing was categorized into two groups: less than six months and six months or more from diagnosis. Results: Most patients were female (76.6%), with a mean age of 40.7 years, and 78.3% were classified as overweight or obese. The analysis showed no statistically significant differences in histopathological outcomes between the two surgical timing groups. A significant association was found between positive lymph-node involvement and surgery performed within the first six months of diagnosis (p = 0.004). Conclusions: This study showed that surgical timing does not significantly affect histopathological outcomes in papillary thyroid carcinoma, particularly in patients without aggressive disease features. The association between early surgery and positive lymph-node involvement may reflect the prioritization of patients with preoperative lymph-node disease for earlier surgical intervention, highlighting the importance of individualized treatment planning. Further research is needed to explore the long-term impact of surgical timing and potential subgroup differences. Full article
(This article belongs to the Section General Surgery)
25 pages, 1740 KB  
Article
Analysis of Determinants of Dietary Iodine Intake of Adolescents from Northern Regions of Poland: Coastal Areas and Lake Districts
by Katarzyna Lachowicz and Małgorzata Stachoń
Nutrients 2025, 17(24), 3813; https://doi.org/10.3390/nu17243813 - 5 Dec 2025
Viewed by 378
Abstract
Background/Objectives: Iodine plays a central role in thyroid hormone synthesis and neurodevelopment. Its deficiency and excessive intake have been identified as risk factors for thyroid diseases and their consequences. The objective of the study was to analyze dietary iodine intake (dIi) and the [...] Read more.
Background/Objectives: Iodine plays a central role in thyroid hormone synthesis and neurodevelopment. Its deficiency and excessive intake have been identified as risk factors for thyroid diseases and their consequences. The objective of the study was to analyze dietary iodine intake (dIi) and the factors that determine its intake among post-primary school students from northern Poland, specifically those from coastal areas and lake districts. Methods: The study was conducted on a sub-national sample of 3102 adolescents (1751 females and 1351 males) aged 14–20 years, recruited from schools located in the Northern (N) and North-Western (N-W) macroregions of Poland. Dietary iodine intake was assessed using the Iodine Dietary Intake Evaluation-Food Frequency Questionnaire. Based on the data obtained, the adequacy of the intake of this micronutrient was assessed. Statistical analysis was performed using the Shapiro-Wilk, U Mann-Whitney, and Kruskal-Wallis tests and Spearman’s correlation analysis. Results: The median dIi was 66.83 µg daily, including 53 µg from natural sources. This value was below the recommended dietary allowance of 150 µg and below the estimated average requirement of 95 µg of iodine in 85% and 68% of the study participants, respectively. Milk and dairy products provided the highest iodine intake (26.4%). Iodine-enriched salt (16.2%) also significantly impacted iodine intake. However, 60% of respondents did not use iodized salt. The median iodine levels from natural sources were found to be low (dairy products: 15.02 µg, fish and fish products: 2.38 µg, and eggs: 2.10 µg). Dietary iodine intake was significantly lower in adolescents from the N than N-W macroregion of Poland (median: 65.63 vs. µg daily, 74.2 p < 0.001). However, dIi did not depend on sex (p = 0.10), age (p = 0.80), school location (p = 0.80), body mass index classification (p = 0.76), or iodine supplementation (p = 0.90). Conclusions: The study results indicate that insufficient iodine intake among adolescents in northern Poland can be attributed to a limited intake of iodine from natural food sources. A pressing need exists to closely monitor iodine intake and status among Polish adolescents and to implement nutritional education, focusing on the role of iodine, potential risks associated with iodine deficiency, and dietary sources of iodine. Full article
(This article belongs to the Special Issue Selenium and Iodine in Human Health and Disease)
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16 pages, 425 KB  
Article
Medical and Social Characteristics of Patients with Endometrial Hyperplasia in a Large City in Kazakhstan: A Retrospective Comparative Study
by Bayan Imashkyzy Imasheva, Maksut Adilkhanovich Kamaliev, Vyacheslav Notanovich Lokshin, Marina Viktorovna Kiseleva and Mariya Vladimirovna Laktionova
Healthcare 2025, 13(23), 3174; https://doi.org/10.3390/healthcare13233174 - 4 Dec 2025
Viewed by 300
Abstract
Background/Objectives: Endometrial hyperplasia (EH) is a pathology of the uterus, which is a pathological overgrowth of the endometrial glands associated with the risk of progression to endometrial cancer (EC). The purpose of this study was to conduct a retrospective comparative analysis of [...] Read more.
Background/Objectives: Endometrial hyperplasia (EH) is a pathology of the uterus, which is a pathological overgrowth of the endometrial glands associated with the risk of progression to endometrial cancer (EC). The purpose of this study was to conduct a retrospective comparative analysis of the medical and social characteristics of women with endometrial hyperplasia (EH) across two time periods (2016–2017 and 2023–2024) in Almaty, the largest city in Kazakhstan. Methods: A retrospective comparative analysis included 376 women (188 per period) with histologically confirmed EH treated in public and private healthcare facilities. Data were extracted from electronic medical systems (Damumed, Avicenna). Group differences were evaluated using the χ2 test, Fisher’s exact test, and Mann–Whitney U test. Odds ratios (OR) with 95% confidence intervals (CI) were calculated; significance was set at p < 0.05. Results: The proportion of postmenopausal women increased from 22.3% to 37.8% (OR: 2.11, 95% CI: 1.34–3.32, p < 0.001), and self-referrals to private clinics rose from 17.6% to 37.2% (OR: 2.79, 95% CI 1.73–4.49, p < 0.001). Women with higher education became more prevalent (from 26.1% to 43.6%, OR: 2.19, 95% CI: 1.42–3.39, p < 0.001), along with an increase in endocrine and metabolic disorders such as thyroid disease (from 4.8% to 12.2%, OR: 2.77, 95% CI: 1.25–6.16) and overweight status (from 51.6% to 65.4%, OR: 1.78, 95% CI: 1.17–2.69, p = 0.020). Asymptomatic cases were more frequently detected (from 18.6% to 28.2%, OR: 1.72, CI: 1.06–2.79, p = 0.028), and diagnostic approaches shifted from blind curettage (78.2% vs. 47.3%, OR: 0.25, CI: 0.16–0.39, p < 0.001) toward hysteroscopy with biopsy (from 21.3% to 53.7%, OR: 4.30, CI: 2.73–6.75, p < 0.001). Conclusions: Over seven years, the clinical and socio-demographic composition of women with EH in Almaty has changed toward older, more educated, and metabolically burdened populations, with broader access to minimally invasive diagnostic methods. The findings describe observable structural changes and risk group patterns, emphasizing the importance of prospective, registry-based, and molecularly oriented studies to refine clinical strategies for prevention and early detection. Full article
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13 pages, 849 KB  
Article
Body Composition and Eating Habits in Newly Diagnosed Graves’ Disease Patients Compared with Euthyroid Controls
by Laura Croce, Cristina Pallavicini, Vittorio Gabba, Marsida Teliti, Alessandro Cipolla, Benedetta Gallotti, Pietro Costa, Benedetta Cazzulani, Flavia Magri and Mario Rotondi
Nutrients 2025, 17(23), 3750; https://doi.org/10.3390/nu17233750 - 28 Nov 2025
Viewed by 382
Abstract
Objectives: Graves’ disease (GD) is the most common cause of hyperthyroidism and is associated with marked changes in body weight and body composition. Although weight loss is frequently reported, the extent and clinical relevance of body composition alterations, as well as their [...] Read more.
Objectives: Graves’ disease (GD) is the most common cause of hyperthyroidism and is associated with marked changes in body weight and body composition. Although weight loss is frequently reported, the extent and clinical relevance of body composition alterations, as well as their relationship with thyroid function, remain unclear. This study aimed to evaluate body composition and eating habits in patients with newly diagnosed hyperthyroid GD according to pre-morbid weight variation, and to compare these findings with those of matched euthyroid controls. Methods: Forty-four consecutive GD patients were enrolled and stratified based on the presence or absence of pre-morbid weight loss. Anthropometric measurements, thyroid function tests, thyroid volume, dietary habits (PREDIMED score, macronutrient intake and total daily caloric intake) and body composition assessed by bioelectrical impedance analysis (BIA) were collected. Standardized phase angle (SPA) and body cell mass index (BCMI) were calculated as nutritional indices. Body composition parameters and dietary adherence were compared with those of 44 age-, sex- and BMI-matched euthyroid controls. Results: Most GD patients (70.3%) reported weight loss before diagnosis; however, the magnitude of weight change did not correlate with the biochemical severity of thyrotoxicosis. Patients without weight loss showed higher fat mass percentage and higher caloric intake than those who lost weight. SPA was significantly associated with FT3, FT4 and TRAb levels, independently of age, sex, BMI and fat mass. Compared with controls, GD patients exhibited lower phase angle and SPA, higher extracellular water percentage and reduced BCMI, whereas fat mass and adherence to the Mediterranean diet were similar. Conclusions: Hyperthyroid GD patients display increased extracellular water and reduced body cell mass. SPA is inversely associated with GD severity and represents a valuable clinical tool for assessing nutritional status in thyrotoxic patients. Pre-morbid weight changes are not proportional to disease severity and may instead reflect increased caloric intake. Full article
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14 pages, 510 KB  
Article
Linking Thyroid Function, Morphology, Autoimmunity, Body Mass Index, and Reproductive Aging to Women’s Sexual Health: Evidence from a Population Study in Kaunas
by Dalia Daukšienė, Raimonda Klimaitė, Aistė Kondrotienė, Radvilė Matukaitienė, Jonas Čeponis, Agnė Rimkutė, Laura Dudonytė, Rasa Steponavičiūtė, Dalia Lukšienė, Vaiva Lesauskaitė, Džilda Veličkienė, Rasa Verkauskienė and Birutė Žilaitienė
J. Clin. Med. 2025, 14(23), 8441; https://doi.org/10.3390/jcm14238441 - 28 Nov 2025
Viewed by 283
Abstract
Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women [...] Read more.
Background/Objectives: While it is known that Hashimoto’s thyroiditis (HT), goiter, thyroid nodules, and thyroid dysfunction may affect women’s reproductive health through hormonal and metabolic mechanisms, data are limited regarding the specific impacts on female sexual function. This study evaluated sexual function in women with thyroid disorders and examined its associations with thyroid function, age, menopausal status, and body mass index (BMI). Methods: A population-based survey was conducted in Kaunas, Lithuania, within the WHO MONICA framework. A random sample of 1569 women aged 25–69 years was included in the final analysis after applying the exclusion criteria. Anthropometric measurements were taken using standardized procedures, and the BMI was calculated. Sexual function was assessed using the 19-item Female Sexual Function Index (FSFI). Thyroid structure was evaluated by a team of trained physicians using ultrasound, while thyroid function was assessed via serum analysis (ELISA-based assays for TSH, fT4, and anti-TPO antibodies). Results: Of the 1569 women analyzed, 64.1% had sexual dysfunction (SD) (FSFI ≤ 26.55). Age and BMI showed significant negative correlations with all FSFI domains, with the strongest associations for arousal, lubrication, and total FSFI score (p < 0.01). SD was more prevalent among postmenopausal (43.6%) women than in premenopausal women (22.6%, p < 0.001) and increased with a higher BMI (p < 0.001). HT was found in 28.3% of participants. Compared with the reference group, women with HT were older, had higher BMI, higher TSH levels, and more hypothyroidism (p < 0.001). SD was more common in the HT group (71.7% vs. 64.2%, p < 0.001), with significantly lower lubrication and higher pain scores. In the multivariate analysis, only goiter remained an independent predictor of SD (p = 0.04). Conclusions: In conclusion, women with HT were older; had a higher BMI; and more frequently experienced SD, particularly reduced lubrication and increased pain, compared with the reference group. Although several thyroid conditions were associated with sexual dysfunction, only goiter remained an independent predictor after adjusting for age and BMI. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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13 pages, 1705 KB  
Article
Clinical Chemistry Reference Intervals for Health Assessment in Wild Adult Harbour Seals
by Ailsa J. Hall, Debbie J. F. Russell, Paul M. Thompson, Ryan Milne, Simon E. Moss, Holly C. Armstrong and Joanna L. Kershaw
Animals 2025, 15(23), 3429; https://doi.org/10.3390/ani15233429 - 27 Nov 2025
Viewed by 458
Abstract
Reference intervals for clinical chemistry blood parameters are valuable for both individual diagnostics for animals in managed or veterinary care, and for evaluating wild population health. However, for marine mammals obtaining sufficient data from suitable groups or populations is logistically difficult. Here, we [...] Read more.
Reference intervals for clinical chemistry blood parameters are valuable for both individual diagnostics for animals in managed or veterinary care, and for evaluating wild population health. However, for marine mammals obtaining sufficient data from suitable groups or populations is logistically difficult. Here, we have assembled a large dataset of clinical chemistry results from free-living adult UK harbour seals (Phoca vitulina), analysed in the same commercial laboratory. We applied an open-source algorithm (available as the R package refineR, R version 4.5.2, refineR version 2.0.0) to produce robust reference intervals from these Real-World Data. This novel approach resulted in the generation of 95% reference intervals with 90% confidence bounds for 18 key chemistry parameters indicative of a range of physiological processes including, inflammation, nutritional status, kidney function and liver function. Reference intervals were also generated for triiodothyronine, the active thyroid hormone important in the regulation of metabolism. These intervals will provide critical baseline data for the assessment of harbour seal health as, to our knowledge, this is the largest dataset on which clinical chemistry reference intervals from wild-caught adult harbour seals have been based. Full article
(This article belongs to the Section Aquatic Animals)
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10 pages, 2472 KB  
Case Report
Elevated Alpha-Fetoprotein in Hypothyroidism
by Viola Ceconi, Valentina Kiren, Flora Maria Murru, Andrea Bon, Danica Dragovic, Lorenzo Zandonà, Alice Fachin, Gianluca Tamaro and Gianluca Tornese
LabMed 2025, 2(4), 24; https://doi.org/10.3390/labmed2040024 - 25 Nov 2025
Viewed by 253
Abstract
Alpha-fetoprotein (AFP) is a biomarker commonly used in the diagnosis of various malignancies but may also be elevated in non-neoplastic conditions, including hypothyroidism. We report the case of a 3-year-old girl with Down syndrome (DS) and newly diagnosed hypothyroidism, who presented with a [...] Read more.
Alpha-fetoprotein (AFP) is a biomarker commonly used in the diagnosis of various malignancies but may also be elevated in non-neoplastic conditions, including hypothyroidism. We report the case of a 3-year-old girl with Down syndrome (DS) and newly diagnosed hypothyroidism, who presented with a hypoechoic oval lesion adjacent to the thymic parenchyma on ultrasound and markedly elevated AFP levels (169.2 ng/mL). Further investigations, including MRI, excluded the presence of germ cell tumors. Following initiation of levothyroxine therapy, AFP levels normalized in parallel with thyroid function. No evidence of malignancy was detected despite the initial suspicion. This case underscores the association between elevated AFP and hypothyroidism, highlighting the importance of evaluating thyroid status in patients with increased AFP to avoid unnecessary oncological investigations. In particular, elevated AFP in the context of hypothyroidism and DS warrants careful thyroid assessment and follow-up to prevent redundant diagnostic procedures and reduce patient and family anxiety. Thyroid function testing should be considered before extensive oncological evaluation in children with elevated AFP. Full article
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21 pages, 2597 KB  
Article
Accurate RET Fusion Detection in Solid Tumors Using RNA Sequencing Coverage Imbalance Analysis
by Ivan Gaziev, Anna Khristichenko, Daniil Luppov, Maria Suntsova, Ekaterina Bondarenko, Maria Reinberg, Alina Matrosova, Nadezhda Khilal, Maksim Sorokin, Marina Sekacheva, Elena Poddubskaya, Anton Buzdin and Galina Zakharova
Int. J. Mol. Sci. 2025, 26(23), 11300; https://doi.org/10.3390/ijms262311300 - 22 Nov 2025
Viewed by 405
Abstract
Accurate detection of oncogenic gene fusions is becoming increasingly important given the availability of highly effective targeted therapies. However, their identification in clinical practice remains challenging due to the rarity of individual events, diversity of partner genes, and variability of breakpoint locations. Conventional [...] Read more.
Accurate detection of oncogenic gene fusions is becoming increasingly important given the availability of highly effective targeted therapies. However, their identification in clinical practice remains challenging due to the rarity of individual events, diversity of partner genes, and variability of breakpoint locations. Conventional approaches such as immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) lack multiplexing capacity and demonstrate variable sensitivity and specificity, while direct identification of fusion transcripts in whole-transcriptome sequencing (RNA-seq) profiles provides broader applicability but limited sensitivity, as fusion junctions are frequently supported by a minimal number of reads or even no reads at all. In this study, a novel approach was employed to accurately detect clinically actionable RET (REarranged during Transfection) fusions. This approach entailed the measurement of the imbalance in RNA-seq read coverage of potential fusion oncogenes at their 3′ and 5′ exons. A total of 1327 experimental solid tumor RNA-seq profiles were screened, including 154 non-small cell lung cancer and 221 thyroid cancer samples. The RET status was validated in 78 selected cases by targeted NGS and Sanger sequencing. An analysis of the coverage imbalance was conducted, which enabled the accurate discrimination between true and false positive RET fusions. This approach outperformed other methods and yielded 100% sensitivity and specificity with optimized thresholds. The findings were validated using an independent cohort of 79 thyroid cancer cases, confirming the reliability of the results. Among the 18 RET fusion-positive samples, one was identified as an extremely rare case (RUFY3::RET), and two were determined to be novel fusions (FN1::RET, PPP1R21::RET). The findings of this study demonstrate that exon coverage imbalance analysis serves as a robust complement to computational RNA-seq analysis pipelines for the detection of clinically relevant RET fusions. Full article
(This article belongs to the Special Issue Molecular Diagnostics and Genomics of Tumors, 2nd Edition)
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15 pages, 396 KB  
Article
Dual Disease Burden: Growing Older with Congenital Heart Disease and Hereditary Metabolic and Connective Tissue Disorders—Data from the PATHFINDER-CHD Registry on Heart Failure
by Ann-Sophie Kaemmerer-Suleiman, Frank Harig, Annika Freiberger, Oliver Dewald, Stephan Achenbach, Aysenur Akyol, Helena Dreher, Anna Engel, Peter Ewert, Sebastian Freilinger, Jürgen Hörer, Christopher Hohmann, Stefan Holdenrieder, Robert David Pittrow, Harald Kaemmerer, Renate Kaulitz, Frank Klawonn, Christian Meierhofer, Steffen Montenbruck, Nicole Nagdyman, Rhoia Neidenbach, Elsa Ury, Leonard Bernhard Pittrow, Benjamin Alexander Pittrow, Fabian von Scheidt, Nicole Wolfrum, Michael Huntgeburth, Pelagija Zlatic, Mathieu N. Suleiman and Fritz Mellertadd Show full author list remove Hide full author list
Geriatrics 2025, 10(6), 152; https://doi.org/10.3390/geriatrics10060152 - 20 Nov 2025
Viewed by 426
Abstract
Background: Advances in diagnosis and treatment have led to a growing population of adults with congenital heart disease (ACHD). Despite increasing life expectancy, their clinical needs—especially in older age—remain poorly defined. Cardiac and non-cardiac comorbidities are prevalent, and emerging evidence suggests accelerated biological [...] Read more.
Background: Advances in diagnosis and treatment have led to a growing population of adults with congenital heart disease (ACHD). Despite increasing life expectancy, their clinical needs—especially in older age—remain poorly defined. Cardiac and non-cardiac comorbidities are prevalent, and emerging evidence suggests accelerated biological aging compared to the general population. However, data on older patients and geriatric patients with CHD are limited. Objectives: This study aimed to characterize patients with CHD aged ≥50 years, focusing on functional status, comorbidities, sex-specific differences, and therapeutic patterns. Methods: The PATHFINDER-CHD Registry is a prospective, observational, multicenter registry enrolling patients with CHD with manifest heart failure (HF), HF history, or high HF risk. Data include anatomy, prior treatments, comorbidities, and medication use. Results: Among 1935 patients, 297 were ≥50 years old. Most had acyanotic CHD (62%); Tetralogy of Fallot (21%) was the most frequent diagnosis. A morphologic right systemic ventricle was present in 12%, and 5% had univentricular hearts. HF was manifest in 21%; 44% were classified as ACC/AHA stage B, 51% as stage C, yet 77% were in Perloff class I/II. Common cardiovascular comorbidities included aortopathy (55%), hypertension (37%), and arrhythmia (33%). Non-cardiac comorbidities included thyroid dysfunction (25%), renal impairment (18%), and neurological disease (13%). Sex-specific differences were observed. Despite HF burden, SGLT2 inhibitors and ARNIs were used in only 17% and 8.4%, respectively. Conclusions: Older patients with CHD represent a clinically complex cohort with high comorbidity burden. The findings support the concept of accelerated aging and emphasize the need for tailored interdisciplinary care strategies. Full article
(This article belongs to the Section Cardiogeriatrics)
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16 pages, 1859 KB  
Article
Autoimmune Thyroid Disease and Female Fertility: Does Anti-TPO Accelerate Ovarian Aging?
by Sefa Arlıer and Sadık Kükrer
J. Clin. Med. 2025, 14(22), 8024; https://doi.org/10.3390/jcm14228024 - 12 Nov 2025
Viewed by 843
Abstract
Background/Objectives: Thyroid autoimmunity, particularly anti-thyroid peroxidase antibodies (anti-TPO), has been implicated in reduced fertility and diminished ovarian reserve. However, the stratified effects of anti-TPO across age groups, body mass index (BMI) categories, and polycystic ovary syndrome (PCOS) status remain unclear. This study [...] Read more.
Background/Objectives: Thyroid autoimmunity, particularly anti-thyroid peroxidase antibodies (anti-TPO), has been implicated in reduced fertility and diminished ovarian reserve. However, the stratified effects of anti-TPO across age groups, body mass index (BMI) categories, and polycystic ovary syndrome (PCOS) status remain unclear. This study aims to investigate the association between anti-TPO positivity and ovarian reserve markers—antral follicle count (AFC), anti-Müllerian hormone (AMH), and follicle-stimulating hormone (FSH)—in euthyroid infertile women. Methods: This retrospective study included 1460 infertile women aged 18–45 years, evaluated between 2022 and 2025. Participants were categorized based on anti-TPO levels (≥9 vs. <9 IU/mL) using Beckman Coulter-DXI 800 analyzer, which uses chemiluminescent immunoassays to measure results. BMI (<30 vs. ≥30 kg/m2), and PCOS status. Age was categorized into five strata (18–25, 25–30, 30–35, 35–40, and 40–55 years), and <35 vs. ≥35 years. Linear regression models were used to assess the impact of anti-TPO on AMH and AFC within each subgroup. Additional logistic regression was performed to evaluate the odds of diminished ovarian reserve (DOR: AMH < 1 ng/mL or AFC < 5) after adjusting for age, BMI, and TSH. Results: Anti-TPO positivity (17.6% prevalence) was significantly associated with reduced AMH (1.47 ± 1.52 vs. 3.33 ± 3.03 ng/mL, p < 0.0001), reduced AFC (8.18 ± 5.06 vs. 15.88 ± 8.18, p < 0.0001), and elevated FSH (9.40 ± 6.21 vs. 8.06 ± 4.79 mIU/mL, p = 0.001). These associations remained significant in non-obese and PCOS-negative subgroups. Regression models revealed stronger associations in younger women (<35 years) and showed significant Anti-TPO × Age and Anti-TPO × BMI interactions. Logistic regression confirmed Anti-TPO ≥ 9 IU/mL as a strong predictor of diminished ovarian reserve (AMH < 1 ng/mL: OR = 3.13; AFC < 5: OR = 6.48). ROC analysis indicated modest predictive ability (AUC: 0.665–0.694), and path modeling confirmed direct effects of Anti-TPO on AMH and AFC independent of TSH or BMI. Conclusions: Elevated Anti-TPO levels are independently associated with diminished ovarian reserve in euthyroid women, particularly in younger, non-obese, and PCOS-negative individuals. Anti-TPO may serve as a useful biomarker in fertility risk assessment and personalized reproductive counseling, even in the absence of overt thyroid dysfunction. Full article
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17 pages, 5039 KB  
Article
Dose–Response Relationship Between BRAF V600E Abundance and Cervical Lymph Node Metastasis in Papillary Thyroid Cancer
by Yisikandaer Yalikun, Yuxin Shen, Anyun Mao, Qianlei Zhou, Jinchen Wei, Yue Zhu and Miaoyun Long
Cancers 2025, 17(21), 3562; https://doi.org/10.3390/cancers17213562 - 3 Nov 2025
Viewed by 551
Abstract
Objectives: Papillary thyroid carcinoma (PTC) frequently presents with cervical lymph node metastasis (CLNM), yet preoperative tools often encode BRAF V600E as a binary variable, potentially overlooking information contained in mutation abundance. We sought to quantify the dose–response relationship between BRAF V600E abundance [...] Read more.
Objectives: Papillary thyroid carcinoma (PTC) frequently presents with cervical lymph node metastasis (CLNM), yet preoperative tools often encode BRAF V600E as a binary variable, potentially overlooking information contained in mutation abundance. We sought to quantify the dose–response relationship between BRAF V600E abundance and CLNM and to develop an interpretable model for preoperative risk stratification. Methods: We performed a single-center retrospective study of consecutive PTC patients who underwent preoperative BRAF V600E testing and surgery from 2019 to 2023. Patients were randomly split 70/30 into training and test sets. Candidate predictors included clinical and ultrasound features and BRAF V600E abundance. We used multivariable logistic regression and restricted cubic splines (RCS) to assess nonlinearity and compared six machine-learning algorithms (LR, KNN, SVM, XGB, LightGBM, and NN). Model performance was evaluated by F1, AUC, calibration, and decision-curve analyses; SHAP aided interpretation. Ethics approval: SYSKY-2024-169-01. Results: The cohort included 667 patients; CLNM occurred in 391 (58.6%). CLNM cases had higher BRAF abundance (median 23% vs. 17%) and characteristic clinical/sonographic differences. RCS revealed a nonlinear association between abundance and CLNM, with a steep risk rise of up to ~20.7% followed by a plateau. Among six algorithms, XGBoost showed the best validation performance (AUC 0.752; F1 0.73). SHAP indicated that maximum tumor diameter, BRAF abundance, age, and microcalcifications contributed most to predictions. Conclusions: Modeling BRAF V600E as a quantitative abundance—rather than a binary status—improves preoperative CLNM risk assessment in PTC. An interpretable XGBoost model integrating abundance with routine features demonstrates acceptable discrimination and potential clinical utility for individualized surgical planning and counseling. Full article
(This article belongs to the Special Issue Thyroid Cancer: Diagnosis, Prognosis and Treatment (2nd Edition))
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25 pages, 6001 KB  
Article
Dietary Supplementation with Chenodeoxycholic Acid or Ursodeoxycholic Acid Modulates Growth, Thyroid Status, and Hepatopancreatic–Intestinal Health in Juvenile Little Yellow Croaker Larimichthys polyactis
by Rui Wu, Limin Yan, Yao Li, Ting Ye, Yu Zhang, Wei Zhan, Chenglong Wu, Bao Lou and Xiao Liang
Antioxidants 2025, 14(11), 1325; https://doi.org/10.3390/antiox14111325 - 3 Nov 2025
Cited by 1 | Viewed by 728
Abstract
Commercial feeds formulated for Larimichthys crocea are commonly used in intensive farming of Larimichthys polyactis; however, their nutritional composition is suboptimal for the latter. The study evaluated the effects of dietary chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) supplementation on mitigating nutritional [...] Read more.
Commercial feeds formulated for Larimichthys crocea are commonly used in intensive farming of Larimichthys polyactis; however, their nutritional composition is suboptimal for the latter. The study evaluated the effects of dietary chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA) supplementation on mitigating nutritional mismatch-induced growth retardation and hepatopancreatic–intestinal metabolic disorders in L. polyactis. Fish were fed seven feeds: a commercial feed (control) and feeds supplemented with 300, 600, and 1200 mg/kg of CDCA or UDCA. Results showed that both bile acids (BAs) supplementation improved growth, altered thyroid hormone metabolism, with significant changes in hepatopancreatic–intestinal types of deiodination. Both BAs increased hepatopancreatic energy metabolism and cholic acid synthesis, while inducing hepatopancreatic oxidative damage. Notably, 300 mg/kg CDCA and 600 mg/kg UDCA significantly reduced hepatopancreatic vacuolation and lipid accumulation, which was associated with enhanced protease and lipase activities (p < 0.05). Dietary both BAs supplementation enhanced intestinal antioxidant capacity, but contributed to the inflammation, with 300 mg/kg UDCA improving intestinal mucosal morphology (p < 0.05). These findings suggest that supplementation with dietary 300 mg/kg CDCA, 300 and 600 mg/kg UDCA could alleviate growth restriction and liver–intestinal structural damage caused by nutritional mismatch, reduce hepatic fat accumulation, and enhance intestinal antioxidant capacity of L. polyactis. Full article
(This article belongs to the Special Issue Natural Antioxidants and Aquatic Animal Health—2nd Edition)
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