Search Results (45)

Purpose: This study introduces a robust approach for establishing reference intervals (RIs) for thyroid biomarkers in the Jordanian population by incorporating symptoms-based criteria into the control group selection. This method enhances the traditional inclusion–exclusion criteria by adding a symptom layer. Five thyroid biomarkers were analyzed: thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid receptor antibodies (TRAbs), and antithyroid peroxidase antibodies (TPOAb). The study also investigated the prevalence of thyroid disorders using the established population-specific RIs. Patients and Methods: Samples from 6782 participants across different regions were collected between June 2016 and May 2017. The Kruskal–Wallis and the Mann–Whitney tests identified the best partitioning based on age–gender significant differences, and 2.5th–97.5th percentiles were used to establish the RIs. Results: The TSH, FT4, and FT3 differed significantly among males and females, while no significant differences were found among different age groups. The RIs for males were as follows: TSH, 0.50–4.18 mIU/L; FT4, 12.00–21.16 pmol/L; and FT3, 2.28–4.17 pmol/L, while the corresponding RIs for females were as follows: TSH, 0.57–4.61 mIU/L; FT4, 12.02–24.69 pmol/L; and FT3, 2.53–3.71 pmol/L. TRAbs and TPOAb RIs were 0.3–1.89 IU/L and 0.83–23.87 IU/mL, respectively. The prevalence of overt hypothyroidism was 10.63%, subclinical hypothyroidism was 3.53%, overt hyperthyroidism was 0.66%, and subclinical hyperthyroidism was 1.52%. Conclusions: This study emphasizes the role of population-specific RIs in minimizing diagnostic errors. The addition of symptom criteria improved control group identification and RI accuracy. These findings improve the diagnosis of thyroid disorders in Jordan and suggest a reproducible framework for worldwide application. 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: Subclinical hyperthyroidism grade 1 (SCH G1, TSH > 0.1 mU/L) is common in patients with thyroid unifocal autonomy (UFA) and associated with cardiovascular risks and increased mortality. While ¹³¹I radioiodine therapy (¹³¹I-RIT) effectively treats UFA, it frequently induces hypothyroidism, partly due to extra-nodular absorbed dose (AD) enhanced by residual TSH stimulation. Objective: We hypothesized that short-term LT3-induced TSH suppression at the time of RIT would promote long-term euthyroidism. Patients and Methods: A retrospective study was conducted on 95 UFA patients with SCH G1 (2001–2024). Patients underwent baseline and post-LT3 thyroid scintigraphy, and then received ¹³¹I-RIT with individualized dosimetry. Long-term bioclinical follow-up was achieved. Results: Short-term low-dose LT3 suppression caused no adverse events and significantly reduced TSH (0.45 to 0.047 mU/L). Whole-gland ¹²³I uptake decreased moderately (11.0 to 8.4%), while extra-nodular lobe uptake dropped markedly (1.77 to 0.73%) (all p < 0.0001). This focused activity on the UFA (2.5-fold increase), maintaining mean UFA AD (about 260 Gy) but reducing extra-nodular AD (61 to 37 Gy, p < 0.0001). Despite low ¹³¹I doses (mean 181 MBq), a dose–response relationship was observed: higher AD correlated with greater nodular lobe volume reduction (p < 0.033). At the 88-month follow-up, 93% of patients achieved normal thyroid function; one had persistent SCH G1, two were borderline hypothyroid, and two required LT4. Conclusions: ¹³¹I-RIT under brief LT3-induced TSH suppression induces sustained euthyroidism in SCH G1 with UFA. This simple, low-risk strategy reduces radioprotection concerns and is under evaluation to determine cardiovascular benefits. Full article

The use of highly active combined antiretroviral therapy (cART) has increased life expectancy in people living with HIV (PLWH). As a result of ongoing monitoring and surveillance in established HIV out-patient clinics, thyroid dysfunction amongst this population has become increasingly reported. In this narrative review, primary studies, case reports, and meta-analyses published on PubMed, Embase, and Cochrane were analysed. The most reported thyroid dysfunction is subclinical hypothyroidism (SCH). The prevalence of subclinical hypothyroidism was as high as 40% in PLWH with CD4 T-cell count < 350 cells/mm³, which is a level indicating a state of immunosuppression. Some less commonly reported thyroid dysfunctional conditions include overt hyperthyroidism and thyroid malignancy. Reports have linked the development of thyroid dysfunction to the use of cART, leading to immune reconstitution inflammatory syndrome (IRIS), which has also been linked to the development of Grave’s disease (GD). It is also important to check for thyroid malignancy, as PLWH are prone to having a high risk of developing non-AIDS-related or -defining cancer (NADC). Most research suggests symptom-driven monitoring. However, evidence also suggests that monitoring with cART status change, monitoring for patients with significant comorbidities, or with immune reconstitution may be useful. The screening should include Free Thyroxine (FT4), triiodothyronine (FT3), and thyroid-stimulating hormone (TSH) testing. Furthermore, vigilance for Grave’s disease and performing thyroid antibody checks are advised, especially once the reconstitution of T-cells is achieved. Full article

Background: Blood pressure is associated with overt thyroid disorders, but the role of subclinical diseases is not clear, particularly when blood pressure is assessed at the clinical office. Ambulatory blood pressure monitoring over 24 h provides additional clinical information, which correlates with many cardiovascular endpoints. The aim of our work is to examine whether thyroid function is related to systolic and diastolic blood pressure assessed by ambulatory blood pressure monitoring. Methods: We enrolled 3277 subjects from the SardiNIA project. Thyroid function and ambulatory blood pressure monitoring were assessed in all the participants. Results: TSH was associated with average 24 h and daytime DBP in males but not in females, after adjusting for confounders (respectively, Coef −0.192 p = 0.025, and Coef. −0.021, p = 0.018). We found no association between TSH and DBP or SBP during nighttime. Conclusions: Low TSH in males is positively associated with high DBP. Further studies of underlying mechanisms will need to explore our findings. Full article

Thyroid scintigraphy is a key tool for diagnosing and staging hyperthyroidism in cats, but follow-up scintigraphic studies after radioiodine treatment are limited. This multicentric study evaluated ^99mTc-pertechnetate scintigraphy findings in 234 hyperthyroid cats before and 6 months after radioiodine treatment. Based on serum T4 and TSH concentrations, 165 (70.5%) became euthyroid, 54 (23.1%) had subclinical hypothyroidism, and 15 (6.4%) developed overt hypothyroidism. On post-treatment scintigraphy, all cats showed reduced size and radionuclide uptake of “hot” thyroid nodules. Of 99 cats with unilateral nodules, 60 (61%) recovered function in the contralateral lobe. Among 135 cats with bilateral nodules, both lobes remained visible in 108 (80%). Persistent “hot” nodules with high thyroid/salivary (T/S) ratios or thyroidal pertechnetate uptake (TcTU) occurred in 26 (11%) cats, all of which were euthyroid. Conversely, 24 (10.4%) cats had minimal or absent thyroid tissue with 17 (71%) being hypothyroid, but seven (29%) were euthyroid. As a diagnostic test for iatrogenic hypothyroidism, TcTU showed the highest sensitivity (62.3), with the T/S ratio (7.3) and background-corrected T/S ratio (30.4) being much lower (p < 0.01). While follow-up scintigraphy aids in assessing thyroid tumor destruction and residual function, its diagnostic utility for differentiating euthyroidism and hypothyroidism is limited, especially for cats with mild (subclinical) hypothyroidism. Full article

Background/Objectives: Gestational trophoblastic disease (GTD) is a group of disorders including complete, partial, and invasive/metastatic hydatidiform moles, as well as gestational trophoblastic neoplasia (GTN) (choriocarcinoma; placental site trophoblastic tumor, PSTT; epithelioid trophoblastic tumor, ETT; or mixed forms). These entities are characterized by increased trophoblast proliferation, rarely complicated by hyperthyroidism. Methods: Our systematic literature review (PRISMA guidelines; PubMed, Web of Science, and Scopus databases) searched for histologically confirmed cases of GTN associated with clinical or subclinical hyperthyroidism. We described the clinical–pathologic features and the pathways of hyperthyroidism in GTD. Results: We identified just 32 choriocarcinomas and one PSTT; other non-histologically confirmed cases could have been identified, as some patients received a clinical diagnosis based on serum human chorionic gonadotropin (hCG) levels and imagining data and were treated accordingly. As regards choriocarcinomas, patients’ age range was 15–45 (mean 27) years. Metastases involved the lungs (53%), brain (25%), and liver (19%) (less frequently, the kidneys, spleen, ovaries, vagina, pelvis/abdomen, or thyroid). The time to recurrence range was 1–36 (mean 12) months. On follow-up, 10 patients (32%) were alive with disease and 6 (19%) showed no evidence of disease, while most of the women (15 cases, 48%) died of disease. The hCG level range was 10,000–3,058,000,000 (mean 128,957,613) IU/L. At least some symptoms and/or signs of hyperthyroidism were evident with variable intensity in most cases and significantly improved within 2–3 weeks after treatment. Conclusions: Increased trophoblast proliferation could stimulate thyroid function via increasing the half-life of thyroxine-binding globulin. Secondly, increased hCG demonstrates cross-reactivity with the thyroid-stimulating hormone due to similar α-subunits. Moreover, basic isoforms of hCG may facilitate thyrotropic activity. Full article

Background/Objectives: The gonadotropin-lowering effects of metformin were found to be more pronounced in the case of coexisting hyperthyroidism and absent in patients with hypovitaminosis D. Thus, the aim of the current study was to determine whether vitamin D status determines pituitary effects of metformin in individuals with thyroid hyperfunction and elevated gonadotropin levels. Methods: This prospective cohort study included three matched groups of postmenopausal women with hyperthyroidism and prediabetes: women with 25-hydroxyvitamin D levels between 50 and 75 nmol/L (uncompensated vitamin D insufficiency), women with 25-hydroxyvitamin D levels between 75 and 150 nmol/L receiving exogenous calciferol due to previously diagnosed vitamin D deficiency/insufficiency (compensated vitamin D deficiency/insufficiency), and calciferol-naïve subjects with 25-hydroxyvitamin D levels between 75 and 150 nmol/L (the control group). Over the entire study period (six months), all the women were treated with metformin. At the beginning and at the end of this study, we determined 25-hydroxyvitamin D, glucose homeostasis markers, gonadotropins, estradiol, progesterone, TSH, free thyroid hormones, prolactin, ACTH, and IGF-1. Results: Before metformin treatment, except for the 25-hydroxyvitamin D levels, there were no between-group differences in the investigated markers. In all the study groups, metformin reduced plasma glucose, HOMA1-IR, glycated hemoglobin, and FSH, but these effects were more pronounced in both groups of women with normal vitamin D status than in women with uncompensated vitamin D insufficiency. The decrease in LH concentration was observed only in patients with compensated vitamin D deficiency/insufficiency and in the control group. There were no differences between the baseline and follow-up levels of the remaining hormones. The impact of metformin on gonadotropin concentrations positively correlated with their baseline values, free thyroid hormone levels, 25-hydroxyvitamin D levels, and metformin-induced changes in HOMA1-IR. Conclusions: Our findings suggest that low vitamin D status impairs the gonadotropin-lowering effects of metformin in individuals with hyperthyroidism. Full article

Thyroid dysfunction is associated with a number of neuropsychiatric manifestations. Cognitive decline is a common feature of hypothyroidism and clinical or subclinical hyperthyroidism. In addition, there is a significant association between thyroid hormone (TH) levels and the degree of cognitive impairment in Parkinson’s disease (PD). The pathophysiology of TH-related neurodegeneration include changes in the blood–brain barrier, increased cellular stress, altered processing of β-amyloid precursor protein and the effect of TH on neuronal cell viability. The neurotoxicity of TH is partially mediated by the thyroid hormone responsive protein (THRP). This protein is 83% homologous to mouse c-Abl-interacting protein-2 (Abi2), a c-Abl-modulating protein with tumor suppressor activity. In cell cultures, increasing THRP expression either with TH treatment or exogenously through transfecting neuronal or PC 12 cells causes cell necrosis. The expression of exogenous THRP in other cells such as the colonic epithelial cell line Caco-2 and the glial cell line U251 has no effect on cell viability. The effect of THRP on cell viability is not modulated by c-Abl tyrosine kinase. The causal relationship between specific biochemical perturbations in cerebral tissue and thyroid dysfunction remains to be elucidated. Full article

Background: Hyperthyroidism, characterized by excessive thyroid hormone production, presents in diverse clinical forms, including overt and subclinical disease. Accurate and timely diagnosis is critical to prevent complications such as cardiac dysfunction, osteoporosis, and thyroid storm. Objective: To provide a comprehensive review of the clinical presentation, diagnostic methods, and management strategies for hyperthyroidism, focusing on current practices, advancements, and challenges in treatment. Methods: This review synthesizes findings from peer-reviewed literature on the diagnosis and management of hyperthyroidism. Results: Thyroid function tests (TFTs) are the cornerstone of hyperthyroidism diagnosis, with suppressed TSH levels and elevated T3 and/or T4 levels confirming overt disease. Thyroid receptor antibodies (TRAb) are critical for diagnosing autoimmune hyperthyroidism and predicting relapse risk. Iodine scintigraphy is utilized in specific cases, such as suspected toxic adenoma or multinodular goiter. Management strategies include beta-blockers for symptomatic relief, though side effects such as bradycardia and fatigue may occur. Antithyroid medications, including methimazole and propylthiouracil, inhibit hormone synthesis, with remission more likely in patients with low TRAb levels and small goiters. Definitive treatments include radioactive iodine therapy (RAI), which effectively reduces thyroid activity but often results in hypothyroidism, and thyroidectomy, a surgical option for large goiters or malignancy, with potential complications like hypocalcemia and recurrent laryngeal nerve injury. Conclusions: The management of hyperthyroidism necessitates a personalized approach integrating diagnostic precision, emerging innovations, and patient-centered care. Full article

It is documented that maternal diseases or treatments influence a newborn’s clinical status at birth. If a prenatal medical history is not available, or if signs or symptoms of a mother’s disease are revealed for the first time during pregnancy or postpartum, their effects on the newborn may be misattributed. Objective: The objective of this study is to emphasize the paramount importance of prenatal care, for both mothers and newborns, as a lack of maternal signs and symptoms during pregnancy does not exclude a potential severe neonatal condition. Materials and methods: We present a series of three cases of pregnant women who gave birth to very sick preterm newborns that required admission to the Neonatal Intensive Care Unit (NICU). The mothers were asymptomatic during pregnancy and unaware of their subclinical disease. The newborns’ complications, considered initially as consequences of prematurity or infection, subsequently revealed transient autoimmune disease in two of the cases (myasthenia gravis and hyperthyroidism) and a severe form of thrombophilia in the third case. Results: The newborns’ diagnosis preceded maternal diagnosis and contributed to the identification of the maternal pathology; adequate treatment was prescribed, with favorable short- and long-term outcomes. Conclusions: Prenatal exams and investigations throughout pregnancy are a good opportunity to detect subclinical diseases or predispositions. As newborns usually develop non-specific signs, one should have experience and pay attention to differentiating among etiologies. Our paper takes a reversed approach to the usual medical diagnosis pathway: from infant to mother instead of from mother to infant, proving that inter-specialty collaboration can work bi-directionally. Full article

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case–control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756–9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628–8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1–specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1–14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity. Full article

Myxedema is a potentially life-threatening condition typically observed in severe hypothyroidism. However, localized or diffuse myxedema is also observed in hyperthyroidism. The exact cause and mechanism of this paradoxical situation is not clear. We report here the analysis of body fluid distribution by bioelectrical impedance analysis (BIA) in 103 thyroid patients, subdivided according to their functional status. All BIA parameters measured in subclinical thyroid dysfunctions did not significantly differ from those observed in euthyroid controls. On the contrary, they were clearly altered in the two extreme, opposite conditions of thyroid dysfunctions, namely overt hyperthyroidism and severe hypothyroidism, indicating the occurrence of a typical hormetic condition. Surprisingly, differences in BIA parameters related to fluid body composition were even more evident in hyperthyroidism than in hypothyroidism. A hormetic response to thyroid hormone (TH)s was previously reported to explain the paradoxical, biphasic, time- and dose-dependent effects on other conditions. Our results indicate that myxedema, observed in both hypothyroid and hyperthyroid conditions, represents another example of a hormetic-type response to THs. BIA offers no additional valuable information in evaluating fluid body composition in subclinical thyroid dysfunctions, but it represents a valuable method to analyze and monitor body fluid composition and distribution in overt and severe thyroid dysfunctions. Full article

Background: Fc receptor-like (FCRL) genes play a role in the immune system by encoding proteins that function as receptors on the surface of immune cells. The clinical significance of FCRL gene expression in Graves’ Disease (GD) and Graves’ Orbitopathy (GO) remains unclear. We evaluated the expression of FCRL 2, 3, 4 mRNA in patients with GD and GO and its role in the development and activity of these diseases. Methods: Peripheral blood samples from patients with GD (n = 24) or GO (n = 49) hospitalized in the Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, were collected. Expressions of FCRL2, FCRL3 and FCRL4 were measured by real-time PCR. Results: FCRL3 expression was higher in patients with GD compared to GO (1.375 vs. 0.673, p = 0.004) and, specifically, active GO (1.375 vs. 0.639, p = 0.005). Regarding FCRL4, mRNA expression was higher in GD compared to Control (3.078 vs. 0.916, p = 0.003), GO (3.078 vs. 1.178, p < 0.001), active GO (3.078 vs. 1.186, p = 0.002) and inactive GO (3.078 vs. 1.171, p = 0.008). In turn, FCRL4 mRNA expression was higher in patients with hyperthyroidism (subclinical + overt) than in euthyroid patients (2.509 vs. 0.995, p = 0.001 when the whole group of individuals was considered; 2.509 vs. 1.073, p = 0.004 when GO + GD was considered). Conclusions: The increased FCRL mRNA expression in patients with GD is associated with hyperthyroidism (but not with positive TSHRAbs), and our study is the first one to confirm this relationship. Full article

Aim and Background. This study aims to explore alternative diagnostic methods to assess thyroid function in patients unable to undergo blood tests for thyroid-stimulating hormones (TSH) and thyroxine (T4), such as individuals with trypanophobia, severe medical conditions, or coagulopathy. Considering the impact of thyroid dysfunction on mitochondrial metabolism and the essential role of proper mitochondrial function in ciliary motility, we postulate that assessing nasal ciliary function could serve as a surrogate diagnostic approach for thyroid dysfunction. Methods. This cross-sectional study was performed on individuals with no history of thyroid diseases. The primary endpoint was the diagnostic value of the nasal mucociliary (NMC) test using Iranica Picris (Asteraceae) aqueous extract in differentiating hypo- or hyperthyroidism cases from euthyroid cases. Results. 232 individuals were recruited (71% females, 86% euthyroid). Receiver operating characteristic (ROC) analysis showed a good diagnostic value for the NMC test in differentiating overt hypothyroidism (area under the ROC curve [AUROC] = 0.82, p = 0.004) and its fair value in diagnosing subclinical hyperthyroidism (AUROC = 0.78, p = 0.01) from the euthyroid condition. The NMC test had a significant positive correlation with TSH (r = 0.47, p < 0.001) and a significant negative correlation with T4 (r = −0.32, p < 0.001). The NMC rate was significantly different in distinct thyroid function groups (p < 0.001). Compared with euthyroid cases, the post-hoc analysis showed that the NMC test is significantly higher in overt hypothyroidism (15.06 vs. 21.07 min, p = 0.003) and significantly lower in subclinical hyperthyroidism (15.05 vs. 10.9 min, p = 0.02). Conclusions. The Iranica Picris-based NMC test might serve as a diagnostic method to distinguish overt hypothyroidism and subclinical hyperthyroidism. Full article