Search Results (78)

Sunitinib, a tyrosine kinase inhibitor (TKI) targeting vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors (PDGFRs), is widely used in renal cell carcinoma. A broad spectrum of thyroid dysfunctions has been observed during TKI therapy, yet their mechanisms and clinical progression remain only partially explained. A longitudinal case analysis of a woman with metastatic clear-cell renal cell carcinoma treated with cyclical sunitinib therapy (4 weeks on, 2 weeks off) was performed. Thyroid function tests, clinical symptoms, and ultrasound imaging findings were evaluated over time and compared with treatment exposure and dose adjustments. Baseline thyroid function was normal. During the third cycle, thyroid-stimulating hormone (TSH) increased markedly (33.44–41.26 mIU/L), with free thyroid hormones initially remaining within reference limits. TSH fluctuations corresponded to treatment intervals before stabilising into persistent hypothyroidism requiring levothyroxine replacement. Thyroid ultrasound revealed progressive parenchymal destruction and a reduction in gland volume from 18 mL to approximately 2 mL over three years. Endocrine management enabled maintenance of biochemical euthyroidism, and systemic oncological treatment continued without interruption. Sunitinib treatment may lead to progressive destructive hypothyroidism. Routine surveillance of thyroid function is essential, and timely levothyroxine therapy facilitates continued anticancer treatment and symptom control. Full article

Thyroid hormones (THs) regulate metabolism, proliferation, and genomic stability. Clinical studies have linked levothyroxine therapy with higher Oncotype DX Recurrence Scores in breast cancer (BC), suggesting a potential effect of thyroid hormone signaling on genomic risk. Here, we investigated the impact of triiodothyronine (T3) on DNA damage and repair pathways in estrogen receptor-positive T47D breast cancer and non-tumorigenic MCF10A cells. RNA sequencing revealed significant upregulation of RAD51 and enrichment of DNA repair pathways following 24 h T3 exposure. Consistently, T3 increased γH2AX and 53BP1 nuclear foci, indicating transient activation of the DNA damage response (DDR). These effects were transient, returning to baseline after 48 h, suggesting cellular adaptation. T3 also enhanced proliferation at 10 μM but inhibited growth at higher concentrations. Our findings indicate that acute exposure to T3 induces transient genomic stress, providing a potential mechanistic basis for the observed association between thyroid hormone therapy and increased BC recurrence risk. Full article

Background: Thyroid dysfunction is a prevalent endocrine disorder with significant cardiovascular consequences, particularly through its effects on cardiac electrophysiology. Electrocardiography (ECG), as a widely available and cost-effective diagnostic tool, provides valuable insight into these alterations. This systematic review and meta-analysis aimed to evaluate the relationship between thyroid hormone imbalance and ECG parameters. Methods: A comprehensive search of PubMed, ScienceDirect, and Google Scholar identified 1099 studies, of which 121 underwent full-text analysis. Ultimately, 37 studies with complete datasets were included in the quantitative synthesis, encompassing 167,074 participants across overt hyperthyroidism, subclinical and overt hypothyroidism, and euthyroid control groups. Results: Meta-analysis revealed significant alterations in key electrophysiological markers. Overt hyperthyroidism was associated with QTc and Tp-e prolongation, consistent with increased repolarization heterogeneity and arrhythmic risk. In overt hypothyroidism, QTc and Tp-e intervals were also prolonged, accompanied by reduced heart rate variability, reflecting autonomic imbalance. Subclinical forms demonstrated more variable results, though trends toward conduction and repolarization disturbances were observed. Importantly, several studies indicated that levothyroxine therapy or surgical treatment normalized abnormal ECG findings, underscoring their reversible nature. Conclusions: These results highlight the strong association between thyroid hormone abnormalities and ECG alterations, which may serve as early markers of arrhythmic risk and sudden cardiac death. Incorporating ECG screening into thyroid disease management could improve early detection, risk stratification, and cardiovascular prevention strategies. Full article

Background/Objectives: Patients with differentiated thyroid cancer (DTC) receive thyroxine substitution targeting thyroid-stimulating hormone (TSH) levels based on their treatment response category. However, variations in prescribing and inter-assay TSH variability may result in over or undertreatment. Methods: We measured TSH in 220 consecutive DTC patients using three automated immunoassay platforms (Elecsys, Atellica, Alinity). Each patient was assigned to a response-to-therapy category (Excellent Response [ER], Indeterminate Response [IndR], Biochemical Incomplete Response [BIR], Structural Incomplete Response [SIR]) by an experienced thyroid oncologist. We defined recommended TSH targets according to the American Thyroid Association (ATA) 2015 guidelines and the response-adapted ATA 2025 framework that allows progressive relaxation of TSH suppression in patients with ER while maintaining tight suppression in those with persistent disease. Analytical agreement between assays was assessed using Passing–Bablok regression and Bland–Altman analysis. Clinical appropriateness was evaluated by classifying each measured TSH value as below, within, or above the recommended range for that patient’s response category. Results: The three immunoassays demonstrated high analytical agreement with only minor biases unlikely to affect clinical interpretation. However, significant deviations from guideline-defined TSH targets were observed. Among ER patients, 37% remained oversuppressed despite the absence of active disease. Conversely, in IndR or BIR patients, 76% had TSH levels above the recommended range, indicating undersuppression where residual disease could not be excluded. SIR patients were generally managed appropriately. The ATA 2025 framework reclassified more ER patients as appropriately managed, but undersuppression persisted in non-ER patients. Conclusions: Guidelines are not uniformly applied in thyroxine dosing for DTC patients. TSH immunoassays have achieved adequate analytical performance. The focus must now shift toward addressing clinical, educational, and systemic factors that prevent optimal levothyroxine management. Full article

Background: Autoimmune thyroid disease (AITD) is common in women of reproductive age and is characterized by thyroid-specific autoantibodies, mainly TPOAbs and TgAbs. Its impact on pregnancy outcomes is not fully understood. However, evidence suggests a potential association with adverse maternal and neonatal outcomes. Objective: To assess the association between AITD and adverse pregnancy outcomes and evaluate the effect of levothyroxine (LT4) therapy in high-risk populations. Methods: A systematic search of PubMed and Web of Science was performed per PRISMA guidelines. Randomized controlled trials (RCTs) on pregnancy outcomes in women with AITD were included. Primary outcomes were preterm delivery, miscarriage, and live birth; secondary outcomes included maternal and neonatal complications. Risk of bias was assessed using RoB 2.0, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: Eight RCTs with TPOAb-positive euthyroid or subclinical hypothyroid women were included. AITD increased preterm delivery risk (pooled OR 3.92, 95% CI 2.54–6.05). Miscarriage risk showed high heterogeneity (pooled OR 1.27, 95% CI 0.16–9.82). LT4 reduced miscarriage (pooled OR 0.52, 95% CI 0.34–0.80) and preterm delivery (pooled OR 0.37, 95% CI 0.17–0.80). Live birth rates favored LT4 but were not statistically significant. Maternal and neonatal complications were inconsistently reported. Conclusions: AITD is associated with higher preterm delivery risk. LT4 in high-risk women may reduce miscarriage and preterm birth. Further RCTs should stratify by AITD subtype, antibody titer, and thyroid function, and report perinatal outcomes systematically. Full article

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

Background/Objectives: Vitamin D deficiency is highly prevalent worldwide and is associated with multiple comorbidities and pharmacological treatments that may interfere with its metabolism. Evidence on the effect of supplementation across different drug user groups remains limited. Methods: A prospective study was conducted across community pharmacies over twelve months. Baseline socio-demographic, serum 25(OH)D concentration, quality of life (QoL), lifestyle habits, and medication use were collected. Participants received vitamin D supplementation for 12 months. Changes in vitamin D status and QoL were analyzed according to medication use. Logistic regression identified predictors of achieving adequate serum vitamin D levels (>30 ng/mL). Statistical significance was set at p < 0.05. Results: At baseline, 87.2% of 210 participants had insufficient or deficient vitamin D levels. After supplementation, mean serum vitamin D increased significantly from 21.3 ± 8.2 to 32.1 ± 12.6 ng/mL (p < 0.001), and QoL scores improved from 68.6 ± 18.7 to 77.8 ± 18.5 (p < 0.001). Dietary intake of vitamin D–rich foods and outdoor activity also increased. Supplementation improved vitamin D status among users of benzodiazepines, proton pump inhibitors, beta-blockers, statins, levothyroxine, metformin, and angiotensin-converting enzyme inhibitors, but not among corticosteroid, nonsteroidal anti-inflammatory drugs, or vitamin K antagonist. Multivariate analysis confirmed adherence as a strongest predictor of vitamin D adequacy (OR = 15.31, 95% CI = 2.90–80.75), while corticosteroid therapy, diabetes, and hypercholesterolemia were negatively associated. Conclusions: Vitamin D supplementation effectively corrected deficiency and improved QoL, but its efficacy varied according to comorbidities and medication use. Personalized supplementation strategies, emphasizing adherence and considering pharmacological profiles, may optimize outcomes. Further studies should explore mechanistic drug–nutrient interactions and long-term clinical implications. Full article

In this cross-sectional observational study, we investigated whether recreational exercise (RE) influences systemic inflammation in Hashimoto’s thyroiditis (HT) across different disease severity groups. We analyzed 403 participants from the Croatian Biobank of Patients with HT (CRO-HT), including 173 controls and 230 HT patients (euthyroid, levothyroxine [LT4]-treated, and hypothyroid). Serum levels of 92 inflammatory proteins were measured using the Olink^® Target 96 Inflammation panel, and exercise status was assessed via structured questionnaires. Linear regression revealed distinct protein associations depending on thyroid status. In controls, RE was associated with reduced MMP-10 and FGF-5, reflecting cardiovascular and muscle benefits. In euthyroid patients, RE was associated with decreased CXCL9 and TRAIL, implicating reduced type 1 inflammation and vascular risk. LT4-treated patients showed increases in IL-15RA and IL-24 with RE, suggesting improved muscle metabolism and anti-inflammatory effects. In hypothyroid patients, RE was associated with reduced CCL20 and increased HGF, while changes in TRANCE and TWEAK indicated mixed effects on bone and immune regulation. Notably, RE was associated with reduced CXCL9 and CCL20, two proteins previously linked to HT risk. Overall, RE is associated with distinct changes in inflammatory profiles across HT disease severity groups, with the most favourable responses observed in LT4-treated patients, suggesting synergy with hormone therapy. Full article

Background/Objectives: Neonatal screening programmes for thyroid function testing, based on thyroid-stimulating hormone (TSH) assessment, detect both Permanent Congenital Hypothyroidism (PCH) and Transient Congenital Hypothyroidism (TCH). Maternal iodine-deficient dietary intake may result in compensatory neonatal TSH elevation; screening for Congenital Hypothyroidism (CH) is used as an indicator of the degree of iodine deficiency and of its control. In Greece, newborn screening for CH, using TSH measurement in dried blood spots (Guthrie card), began in 1979 through the Institute of Child Health (ICH). Although the general Greek population is considered iodine-replete, most pregnant Greek people are mildly iodine deficient according to the stricter WHO criteria. The aim of this retrospective study was to record the cases of TCH and the main causative factors over a 10-year period (2010–2019) in Greece, when the country was deemed to be iodine-replete. Methods: The number of births in Greece between 2010 and 2019 was retrieved from the Hellenic Statistical Authority (ELSTAT) archives: 952,109 births were recorded. The total number of newborns assessed through the ICH was 951,342 (99%). During this period, 22,391 newborns were identified to have TSH > 7 mIU/L after the second check on the initial card. Among those, 17,992 underwent retesting with a serum sample. Out of the retested newborns, 1979 were screened positive for CH and immediately began treatment with levothyroxine. We followed up with families, paediatricians, and paediatric endocrinologists to determine whether L-thyroxine therapy had been successfully discontinued for at least two months after the child’s third birthday. Successful contact was achieved with 889 individuals. From this group, 329 children had successfully discontinued thyroxine, classified as TCH. Demographic data, including gender, gestational age, and birth weight, were collected from the archives of the ICH. Maternal data, including thyroid medication use and the presence of elevated thyroid autoantibodies during pregnancy and childbirth, were also recorded. Results: Logistic regression analysis revealed that, while controlling for all other predictor variables, the odds ratio of transient hypothyroidism was 2.078 (95% CI: 1.530 to 2.821) for prematurely born children compared to those born at term. The effects of other factors on TCH versus PCH were not significant. Conclusions: It seems that prematurity is the main factor contributing to Transient Congenital Hypothyroidism in Greece, a recently iodine-replete country. Full article

Background/Objectives: Levothyroxine (L-T4) replacement therapy is essential following total thyroidectomy. While liquid L-T4 formulations exhibit superior pharmacokinetic properties compared to tablets, their specific metabolic impact—particularly on insulin resistance—remains unclear. The aim of this study was to compare the short-term effects of liquid versus tablet L-T4 replacement therapy on insulin resistance indices in recently thyroidectomized women and to identify baseline predictors of metabolic response. Methods: A post hoc analysis included 130 women randomized to receive either liquid or tablet L-T4 after total thyroidectomy. Metabolic parameters—including the homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides-glucose (TyG) index, and triglycerides-to-HDL cholesterol (TG/HDL-C) ratio—were assessed at baseline and after two months. Results: Both L-T4 formulations significantly improved insulin resistance indices over two months. Liquid L-T4 induced a more pronounced reduction in HOMA-IR (treatment effect p = 0.022) and fasting insulin levels (treatment effect p = 0.017) compared to the tablet formulation. No significant between-group differences were observed for TyG index or TG/HDL-C ratio. Changes in insulin resistance markers were independent of body mass index variations and were predicted by baseline metabolic parameters including insulin, glucose, and lipid levels. Conclusions: L-T4 replacement therapy improves insulin resistance markers shortly after thyroidectomy, with the liquid formulation exerting a greater effect on hepatic insulin sensitivity. These findings support the individualized selection of L-T4 formulations to optimize both endocrine and metabolic outcomes post-thyroidectomy. Full article

Background/Objectives: Mitotane is a key component in the treatment of adrenocortical carcinoma (ACC), but its endocrine side effects in children remain under-characterized. Methods: We conducted a retrospective analysis of 11 pediatric patients (6 males, 5 females) diagnosed with ACC and followed between 2000 and 2025. Seven received mitotane therapy. Data included age at diagnosis, treatment duration and dosage, serum mitotane levels, and endocrine complications. Results: The mean age at diagnosis was 6.6 ± 1.45 years, with a mean follow-up of 10.05 ± 2.45 years. Patients received mitotane for an average of 2.5 ± 0.54 years, with a mean daily dose of 2805.5 ± 145.82 mg and a mean serum level of 16.1 ± 5.92 mg/mL. All mitotane-treated patients developed adrenal insufficiency, requiring supraphysiological hydrocortisone replacement. Four also required mineralocorticoid therapy. Five developed precocious puberty; two males presented with prepubertal gynecomastia; three females were managed with GnRH analogs or aromatase inhibitors followed by estrogen receptor antagonists. Four patients developed central hypothyroidism, treated with levothyroxine. A positive correlation was found between mean serum mitotane levels and the onset of precocious puberty (p = 0.04), while mitotane levels correlated negatively with the development of central hypothyroidism (p = 0.001). Conclusions: Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment. Full article

Background: Risk assessment in hyperthyroidism remains challenging. The aim of the present study is to determine the influence of hyperthyroid metabolic status on blood clotting and an increased risk of thrombosis. Methods: This prospective study included 50 patients after radical thyroidectomy and ablative radioiodine therapy because of thyroid carcinoma who were compared with 50 control subjects in a euthyroid metabolic state. Latent hyperthyroid patients with basal thyroid-stimulating hormone (TSH) ≤ 0.15 mU/L on levothyroxine hormone therapy were included. The control group was selected to match the patient group based on age and sex. The evaluation data were collected using laboratory coagulation tests and patient questionnaires. A bleeding and a thrombosis score were determined. Results: The coagulation parameters between the patient and control groups showed statistically significant differences. In particular, the patients’ group showed a significantly shortened activated partial thromboplastin time (aPTT/p = 0.009) and a significantly higher plasminogen activator inhibitor 1 (PAI-1/p < 0.001) compared to the control group. Age, sex, and medication use were not found to influence the patients’ laboratory results. Only body mass index was higher in the patient group than in the control group. Conclusions: Our results support a shift in the coagulation system in latent hyperthyroid metabolism towards increased coagulability and reduced fibrinolysis. A latent hyperthyroid metabolic state appears to be associated with an increased risk of thrombosis. Further prospective cohort studies with large patient populations are needed to verify the association between (latent) hyperthyroidism and thromboembolic events as well as to determine therapeutic anticoagulation or to adjust the indication for exogenous administration of thyroid hormone. Full article

Background: Hashimoto’s thyroiditis (HT), the most prevalent autoimmune thyroid disorder in reproductive-age women, has been linked to diminished ovarian reserve and subfertility. This study aimed to evaluate the relationship between HT and key fertility parameters, including hormonal markers and reproductive outcomes, while also exploring the potential impact of thyroid hormone replacement therapy. Methods: A retrospective observational study was conducted on 86 women undergoing fertility evaluation. Participants were divided into two groups based on anti-thyroid peroxidase antibodies (ATPO): the HT group (n = 49) and the control group (n = 37). Among women with HT, 57% were receiving levothyroxine (Euthyrox^®) at the time of assessment. Variables analyzed included serum levels of anti-Müllerian hormone (AMH), thyroid-stimulating hormone (TSH), insulin resistance index (HOMA-IR), number of oocytes retrieved, blastocysts formed, pregnancies achieved, and live births. Statistical methods included t-tests, Mann–Whitney U tests, Pearson/Spearman correlations, and linear regression models. Results: Women in the HT group had slightly lower AMH levels and oocyte counts compared to controls, though these differences did not reach statistical significance. TSH values were higher in the HT group and showed a significant negative correlation with blastocyst formation (p = 0.03). Although TSH also showed negative trends with oocyte count, pregnancies, and live births, these correlations did not reach statistical significance. A post-hoc subgroup analysis revealed that HT patients receiving levothyroxine tended to have higher numbers of oocytes retrieved and blastocysts formed compared to untreated HT patients, suggesting a possible beneficial effect of thyroid hormone replacement, although the differences were not statistically significant. Conclusions: HT is associated with subtle but clinically relevant impairments in ovarian reserve and reproductive potential. Thyroid hormone replacement may offer modest benefits and should be considered in the individualized management of fertility in women with thyroid autoimmunity. Full article

Cholestyramine, a bile acid sequestrant, has been used primarily for lipid-lowering purposes but has also shown potential in managing hyperthyroidism and thyrotoxicosis. The objective of this review is to assess the efficacy, safety, and clinical indications of cholestyramine in the treatment of hyperthyroidism, thyrotoxicosis, and associated conditions, particularly when conventional therapies fail or are contraindicated. A literature review of clinical guidelines, original research articles, and case reports was conducted, focusing on studies that explored cholestyramine’s use in the treatment of hyperthyroidism, thyrotoxicosis, and levothyroxine overdose. Cholestyramine has demonstrated effectiveness in rapidly reducing thyroid hormone levels in these conditions. Studies indicates that cholestyramine accelerates the reduction of T3 and T4 levels when used as adjunctive therapy alongside standard treatments, particularly in severe or refractory cases. Evidence from case reports also supports its utility in managing conditions such as amiodarone-induced thyrotoxicosis, thyroid storm, and preparation for thyroidectomy. However, the long-term effectiveness of cholestyramine remains uncertain, with potential challenges regarding gastrointestinal side effects and medication interactions. Further studies are needed to integrate it more widely into clinical guidelines for the management of thyroid disorders. Full article

Background/Objectives: Hashimoto thyroiditis (HT) is an autoimmune disease affecting the thyroid, often leading to hypothyroidism, even in individuals with adequate iodine intake. Despite achieving biochemical euthyroidism through levothyroxine (LT4) therapy, many patients continue to experience persistent symptoms, likely due to ongoing thyroid autoimmunity. Photobiomodulation (PBM) has shown promise in treating autoimmune conditions, but its effect on thyroid volume (TV) remains unclear. This study aimed to assess the efficacy of PBM combined with supplements in restoring thyroid function and normalising TV compared to the use of supplements alone. Methods: Ninety-eight females aged 20–50 years old were divided into two groups: Group 1 received PBM and supplements and Group 2 received supplements only. The PBM parameters were as follows: 820 nm wavelength, 200 mW power, continuous mode, 20 s per point at 8 points (32 J/cm² per point), twice weekly for three weeks. Both groups received vitamin D3 supplementation (if serum < 40 ng/dL) and 100 µg of oral selenium daily. Results: Ninety-seven participants completed the study (51 in Group 1, 46 in Group 2). Group 1 showed significantly greater improvements in TV normalisation and weight loss and reductions in BMI, waist/hip circumference, waist-to-hip ratio, TSH, anti-TPO, anti-TG, and LT4 dosage (p < 0.05). Conclusions: This study demonstrates that low-fluence PBM combined with supplements can effectively improve thyroid function, reduce TV, and enhance anthropometric and clinical outcomes in HT patients. The protocol holds potential for broader application and further validation in larger trials. Full article