Background. Several minimal access approaches to the thyroid gland have been widely applied; nevertheless, such approaches are still challenging when dealing with large-sized thyroid nodules or goiters. We hereby evaluated the outcomes and highlighted the merits of endoscopic axillo-breast hemithyroidectomy (EABH) for large-sized unilateral goiters. Methods. Patients underwent EABH for unilateral large thyroid nodules ≥6 cm in its greatest dimension or unilateral large goiter (≥60 ml sonographic volume) whatever the size of its contained nodules were identified from a prospectively maintained database. Their demographic data, clinicopathological profiles, and surgical and esthetic outcomes are reported and analyzed. Results. Over a 2-year period, 33 patients matched the selection criteria. Their mean age was 34.75 ± 11.39 years. There were 30 women and 3 men. The majority of nodules were radiologically TIRADS3 and cytologically Bethesda 3. The mean sonographic dominant nodule greatest dimension was 5.29 ± 1.48 cm (range: 3–9.5 cm). The mean sonographic volume of the pathological lobe was 101.86 ± 54.45 ml (range: 60.11–236.88 ml). All cases were completed endoscopically with no conversion to open. The mean operative time was 110.76 ± 18.75 minutes. No significant postoperative complications were reported except for one case with temporary vocal cord paresis. Most (87.9%) of the patients were extremely satisfied with the procedure. Conclusion. EABH with our suggested key steps could be considered an effective valid approach for unilateral large goiters in trained hands and in patients desirous for cosmesis.
Background. Despite adequate hormone substitution in Hashimoto disease, some patients may have persistent symptoms with a possible autoimmune pathophysiology. A recent randomized trial (RCT) using patient-reported outcome measures as the primary endpoint showed benefit in total thyroidectomy, but at a cost of high complication rates. Objective. To verify results from the RCT in an observational study including a wider range of patients and explore means of predicting who may benefit from such surgery. Design. A total of 154 patients with Hashimoto disease, euthyroid with or without thyroid hormone substitution, and persistent Hashimoto-related symptoms were subjected to total thyroidectomy and followed for 18 months after surgery. The primary outcome was the General Health (GH) dimensional score in the Short Form-36 Health Survey (SF-36). Results. Eighteen months after surgery, a clinically significant improvement in GH was seen, similar to the findings in the previous RCT. Anti-TPO antibody titers were markedly reduced after surgery, but preoperative titers or other preoperative parameters could not predict the outcome of surgery. Three (1.9%) of 154 patients experienced permanent unilateral recurrent nerve palsy and six (3.9%) experienced hypoparathyroidism after surgery. Conclusions. Thyroidectomy had a beneficial symptom-reducing effect in euthyroid patients with Hashimoto disease and persistent symptoms. The pathophysiology of residual symptoms remains unclear, and surgical complication rates are high. If thyroidectomy is considered as a treatment option, it should be performed in dedicated centers with experienced endocrine surgeons and as part of further studies on persistent symptoms. This trial is registered with NCT-02319538.
Introduction. Hashimoto thyroiditis is the most common cause of chronic inflammation of the thyroid gland. Ultrasound is the modality for detection, while fine needle aspiration is the gold standard method for diagnosis. Serologic markers, such as antithyroidal peroxidase antibody (TPO) and antithyroglobulin antibody (TG), are usually elevated. Aim. The main objective is to appraise the incidence of neoplasms on a background of Hashimoto thyroiditis. Our second objective is to recognize the different sonographic appearances of Hashimoto thyroiditis, to focus on its nodular and focal patterns, and to measure the sensitivity of the ACR TIRAD system (2017) when interpreted on patients with Hashimoto thyroiditis. Methods. A single-center retrospective cross-sectional study. We studied 137 cases diagnosed cytologically as Hashimoto thyroiditis from January 2013–December 2019. The data collected were analyzed using SPSS (26th edition), and ultrasounds were reviewed by a single board-certified radiologist. The ACR thyroid imaging and Data System 2017 (ACR TI-RADs 2017) and the Bethesda System for reporting thyroid cytology 2017 (BSRTC 2017) were used for reporting ultrasound and cytology, respectively. Results. The mean age was 44.66 years and the female : male was 9 : 1. Serologically, anti-Tg was high in 22 cases (38%), while anti-TPO was positive in all of the 60 cases studied. Histologically, 11 cases were diagnosed with papillary thyroid carcinoma (8%) and a single case with follicular adenoma (0.7%). Ultrasonographically, 50% of the cases showed diffuse pattern, in which 13% of them showed micronodules. 32.2% were macronodular, and 17.7% were a focal nodular pattern. 45 nodules were interpreted with the ACR TIRAD system (2017), in which 22.2% were TR2, 26.6% were TR3, 17.7% were TR4, and 33.3% were TR5. Conclusion. Hashimoto thyroiditis is a risk factor for developing thyroid neoplasms, which necessitate a proper assessment of the cytological material studied and a correlation with the clinical and radiological features. Recognizing the different types of Hashimoto thyroiditis and its variable appearances is significantly important in performing and interpreting thyroid ultrasound imaging. Microcalcification is the most sensitive parameter to discriminate between PTC and nodular type of Hashimoto thyroiditis. The TIRAD system (2017) is a useful tool for risk stratification; however, it might create unnecessary FNA studies in the setting of Hashimoto thyroiditis because of its variable appearances on ultrasound. A modified TIRAD system for patients with Hashimoto thyroiditis is important to alleviate this confusion. Finally, anti-TPO is a sensitive marker for detecting Hashimoto thyroiditis, which could be used for future referencing of newly diagnosed cases.
Background. In this study, we evaluate the rate of CLNM and related factors in patients with cN0 PTC undergoing transoral endoscopic thyroidectomy vestibular approach (TOETVA), a feasible and safe procedure that is widely approved for early stage PTC patients. Method. A cross-sectional study was performed on 346 patients who underwent TOETVA due to thyroid cancer in the Department of Oncology and Palliative Care, Hanoi Medical University Hospital, from January 2020 to December 2021. The clinical, surgical, and pathological characteristics were recorded. Results. The mean age was 36.1 ± 9.1 (13–67) years. Females accounted for 96%. Total thyroidectomy was applied in 55 cases (15.9%), and conservative thyroidectomy accounted for 291 (84.4%). The median number of harvested lymph nodes in ipsilateral and bilateral CND groups is 5 (IQR: 3–7) and 7 (IQR: 3–10). The median number of metastasized lymph nodes in these two groups is 2 (IQR: 1–3) and 3 (IQR: 2–6), respectively. The rate of CLNM was 39.9%. Thyroiditis increased the number of harvested lymph nodes: 8.3 ± 0.7 (1–24) nodes, p=0.002. Tumor size on ultrasound, young age (<29 years old), and stage of tumor increased the possibility of CLNM, p<0.05. Univariate and multivariate logistic regression revealed that young age (<29 years old) and gross tumor invasion were independent risk factors of high number of CLNM with p<0.05. Conclusion. In summary, CLNM rate in patients with cN0 PTC accounted for 39.9%. With the facilities of pCND by TOETVA, a procedure that is widely approved for early PTC and has excellent cosmetics and oncological results, pCND should be considered in patients with risk factors like young age or large tumor. High volume of CLNM is associated with young age and gross tumor extension, and total thyroidectomy should be indicated in these patient groups.
Background. Studies in several ethnic groups reported high incidence of elevated levels of immunoglobulin E (IgE) in patients with autoimmune thyroid diseases (ATD), especially in patients with Graves' disease. Objective. To study association between serum levels of IgE and thyroid stimulating hormone receptor antibodies (TRAb) in Albanian patients with ATD. Material and Methods. Study was performed in 40 patients with Graves' disease, 15 patients with Hashimoto's thyroiditis, and 14 subjects in the control group. The IgE levels were measured by immunoradiometric assay, whereas the TRAb levels were measured by radioreceptor assay. Results. In all groups of subjects the IgE levels were within reference values (<200 kIU/L). Significant difference in mean concentration of IgE was found between two groups of Graves' disease patients, and those with normal and elevated TRAb levels (22.57 versus 45.03, P < 0.05). Positive correlation was found between TRAb and IgE only in Graves' disease patients (r = 0.43, P = 0.006). Conclusion. In Albanian patients with ATD there is no elevation of IgE levels. This could be the result of low prevalence of allergic diseases in Albanian population determined by genetic and environmental factors.
Background:It has been widely assumed that TOETVA has demonstrated a new technique and a promising approach as it is both minimally invasive and optimally cosmetic. The objective of this study was to assess the surgical outcome, aesthetic satisfaction, and postoperative quality of life of TOETVA in comparison with open thyroid surgery. Patients and Methods. The study was designed as a prospective study, in which 121 patients from a single center in Vietnam underwent thyroid surgery, and the study was divided into two groups: 60 patients in the TOETVA group and 61 patients in the open surgery group. The patients have been followed up including surgical outcomes, cosmetic satisfaction, and quality of life. These criteria were assessed at 4 weeks, 8 weeks, and 12 weeks after the surgery using SF-36 and thyroid surgery-specific questionnaire. Results:Patients in the TOETVA group are significantly younger than patients in the open surgery group (35.8 + 10.3 vs 46.9 + 11.5, p < 0.001). The mean operating time was longer in the TOETVA group (102.9 ± 26.1 mins) than that in the open surgery group (66.8 ± 23.8 mins) with p = 0.0001. Cosmetic outcomes and overall satisfaction were significantly greater in the TOETVA group p = 0.0001. The SF-36 QOL scores of the patients in the TOETVA group were generally higher than the open surgery group. Conclusions:TOETVA has been widely used with a low complication rate, cosmetic appeal, and surgical efficacy. Postoperative quality of life, cosmetic outcomes, and overall satisfaction were significantly superior to the open surgery group.
Background. Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion. Methods. We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2–4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0–4.0); (3) TSH in the low normal range (0.2–1.0); (4) TSH below the normal range (0.01–0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan. Results. PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho −0.47; p=0.0001) and FT4 (rho 0.27; p=0.018). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (−0.37 and −0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss. Conclusion. PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone.
Introduction. Renal function and thyroid metabolism are tightly related. However, evidence about subclinical hypothyroidism prevalence in patients with chronic kidney disease and its related factors is scarce. Objectives. Our aim is to analyze subclinical hypothyroidism prevalence and its related factors in patients with advanced chronic kidney disease. Materials and methods. Nondialysis-dependent patients with chronic kidney disease at stages 3 to 5 were included. Other inclusion criteria were age above 18 years and clinical stability. Patients with diagnosed thyroid illnesses were excluded. Subclinical hypothyroidism was defined as thyroid stimulating hormone (TSH) > 5.3 mU/L, with free thyroxine 4 (FT4) between 0.54 and 1.24 ng/dl. Filiation data, comorbidities, and routine blood and urine test results were registered. Results. A total of 299 patients were included. Of them, 184 (61.5%) were men. The mean age was 71 ± 13 years old. The mean glomerular filtration rate (CKD-EPI) was 22 ± 9 ml/min/1.73 m2. According to chronic kidney disease stages, global distribution of patients was as follows: Stage 3, 67 patients (22.4%); Stage 4, 155 patients (51.8%); and Stage 5, 77 patients (25.8%). We found subclinical hypothyroidism in 54 (18.1%) patients. According to chronic kidney disease stages, distribution of affected patients was as follows: Stage 3, 9 patients (13%); Stage 4, 25 patients (16.1%); and Stage 5, 20 patients (26%). Differences among stages were statistically significant. By univariate analysis, factors related with subclinical hypothyroidism were as follows: age RR 1.048 (95% CI 1.019–1.078; p=0.001), hypertension RR 2.705 (95% CI 1.026–7.130; p=0.04), glomerular filtration rate RR 0.962 (95% CI 0.929–0.996; p=0.03), and proteinuria higher than 1 gram/day RR 2.387 (95% CI 1.303–4.374; p=0.005). By multivariate analysis adjusted by age, hypertension, glomerular filtration rate, proteinuria, diabetes, and cardiovascular disease history, only age RR 1.016 (95% CI 1.009–1.028; p=0.04) and glomerular filtration rate RR 0.963 (95% CI 0.930–0.997; p=0.03) preserved their independent association with subclinical hypothyroidism. Conclusions. Subclinical hypothyroidism prevalence in patients with chronic kidney disease is high and increases with renal disease severity. Factors independently related to subclinical hypothyroidism are age and glomerular filtration rate.
Objective. Worldwide, 21 countries have insufficient iodine in their diets. Persistent iodine deficiency may result in hypothyroidism. The aim of this study is to determine whether iodine measurements can be used to determine the prevalence of iodine deficiency in patients with (subclinical) hypothyroidism compared to a control group. Design. A prospective cohort pilot study was performed at the Internal Medicine Outpatient Clinic of Isala, a large teaching hospital in Zwolle, the Netherlands. Patients. This study consisted of two groups of 24 adult patients each: a group of consecutive patients presenting with overt or subclinical hypothyroidism and a control group of euthyroid patients with type 1 diabetes mellitus. Measurements. All patients collected 24-hour urine. Iodine status was determined using urinary iodine concentration (UIC), urinary iodine excretion (UIE), and iodine creatinine ratio (I : Cr). Iodine deficiency was defined as an iodine concentration <100 µg/L for UIC, iodine level <125 µg for UIE, and <0.13 µmol/mmol for I : Cr. Results. According to UIE and UIC measurements, 54.2% of hypothyroid patients were iodine-deficient compared to 41.7–45.8% in the control group. According to the I : Cr measurement 91.7% of hypothyroid patients were iodine-deficient compared to 87.5% in the control group. No significant difference was seen between the two groups. No correlation was found between thyroid-stimulating hormone (TSH) level and iodine deficiency. Conclusions. Iodine deficiency is prevalent in both hypothyroid patients and euthyroid patients. Because there is no significant difference between the groups, a single 24-hour urine or spot urine sample to determine UIC, UIE, and I : Cr, seems not suitable to determine iodine status in an individual participant.
Background. Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5–10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms. Methods. Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods. Results. Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups. Conclusion. We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018.
Introduction. Subclinical hypothyroidism during pregnancy can be associated with numerous adverse outcomes. The purpose of this study was to compare short-term adverse pregnancy outcomes in treated versus nontreated patients who fall within the numerical range of thyroid-stimulating hormone (TSH) between the Iranian and American reference ranges. Materials and Methods. Eighty pregnant women with a known level of antithyroid peroxidase (anti-TPO) and TSH levels of 2.5–3.9 mIu/L in the first trimester and 3–4.1 mIu/L in the second and third trimesters were enrolled in the study and randomly assigned into two groups including 41 patients in the intervention group and 39 in the control group. The intervention group was treated with levothyroxine at least 50 μg/day and the control group received no treatment. The data were analyzed by SPSS software version 23. Results. The only significant findings were a correlation between pregnancy loss frequency (p − 0.011) and/or increased TSH level in the follow-up period (p = 0.008) with anti-TPO antibody positivity. Forty-four percent of mothers with positive anti-TPO Ab needed treatment initiation with levothyroxine, based on Iranian guidelines, due to increased TSH level during the follow-up period. Conclusion. Untreated pregnant women with subclinical hypothyroidism, who were placed in the intermediate range of TSH, recommended by Iranian and American guidelines, did not show any significant difference in short-term adverse pregnancy outcomes compared to the treated patients. Positive anti-TPO Ab may play a role in the development of short-term complications in mothers with subclinical hypothyroidism or it may increase the likelihood of an increase in TSH level during pregnancy.
INTRODUCTION:Thyroid cancer is the third most common cancer that occurs in children and adolescents. Papillary thyroid carcinoma (PTC) is the most common type of thyroid malignancy. Although the mortality rate of thyroid malignancy in children is usually low, the disease recurrence is higher in children with more severe clinical presentation than in adults. This study aimed to determine the demographic and clinicopathological characteristics and outcome of pediatric and adolescent patients with thyroid malignancy in Indonesia.METHODS:The retrospective study included all patients diagnosed with thyroid carcinoma aged <20 years, from January 1, 2015, to December 31, 2019. Twenty-nine subjects fulfilled the inclusion and exclusion criteria. We retrieved baseline characteristics, pathology features, TSH and fT4 status, radioactive iodine therapy data, and patients' outcomes. Then, data were analyzed using the chi-square or Fisher's exact method.RESULTS:We identified 29 eligible subjects, including 3 boys and 26 girls. The most common type of thyroid carcinoma was PTC (96.5%), and follicular type (31%) was the predominant variant of PTC. Lymph node involvement occurred in 24% of patients, while distant metastasis occurred in 17.2% of patients with PTC. Twenty-four (82.7%) patients had stage 1 disease. Disease recurrence was recorded in 31% of patients during the study period with a median follow-up time of 24 months.CONCLUSION:PTC is the most frequent type of thyroid carcinoma among children and adolescents. This malignancy has a low mortality rate, but the recurrence rate remains high among younger patients than adults even during a short-term follow-up analysis. Distant metastasis and lymph node involvement are commonly found in this age group.
Introduction. This meta-analysis was conducted to estimate the prevalence of hypothyroidism among pregnant women in India. Methods. We searched PubMed, Web of Science, Scopus, Google Scholar, and Shodhganga (Indian thesis repository) for observational studies, providing prevalence of hypothyroidism among pregnant women in India. Systematic study selection and data extraction procedures were followed. Quality assessment of each study was done using JBI critical appraisal checklist. The random effects model was used for pooling the effect sizes. Publication bias was assessed using the funnel plot and rank correlation test. I2 statistics was used to measure heterogeneity across the studies. Heterogeneity in the pooled estimates was further explored with subgroup analyses and meta-regression analysis. Results. Sixty-one studies were found eligible and included in this review. The pooled estimate of the prevalence of hypothyroidism in pregnant women was 11.07% (95% CI: 8.79–13.84, I2 = 99%). Pooled prevalence estimates of subclinical and overt hypothyroidism are 9.51% (95% CI: 7.48–12.04, I2 = 98%) and 2.74% (95% CI: 2.08–3.58, I2 = 94%). Conclusion. We documented 11.07% pooled prevalence of hypothyroidism in pregnant women in India.
Thyroid hormone (TH) perturbation is a common medical problem. Because of substantial public health impact, prior researchers have studied hyper- and hypothyroidism in animal models. Although most prior research focused on in utero and/or developmental effects, changes in circulating TH levels are commonly seen in elderly individuals: approximately 20% of persons older than 80 years have clinically impactful hypothyroidism and up to 5% have clinical hyperthyroidism, with women being more often affected than men. TH disease model methodology in mice have varied but usually focus on a single sex, and the impact(s) of TH perturbation on the adult brain are not well understood. We administered thyroxine to middle-aged (13 to 14 months) male and female mice to model hyperthyroidism and TH-lowering drugs propylthiouracil (PTU) and methimazole, to induce hypothyroidism. These pharmacological agents are used commonly in adult humans. Circulating TH-level changes were observed when thyroxine was dosed at 20 µg/mL in drinking water for two weeks. By contrast, PTU and methimazole did not elicit a consistent reproducible effect until two months of treatment. No substantial changes in TH levels were detected in brain tissues of treated animals; however, pronounced changes in gene expression, specifically for TH-processing transcripts, were observed following the treatment with thyroxine. Our study indicated a robust compensatory mechanism by which the brain tissue/cells minimize the TH fluctuation in CNS by altering gene expression. Neurobehavioral changes were related to the TH perturbation and suggested potential associations between cognitive status and hyper- and hypothyroidism.
Micronutrients are involved in various vital cellular metabolic processes including thyroid hormone metabolism. This study aimed to investigate the correlation between serum levels of micronutrients and their effects on thyroid parameters. The correlation of serum levels of micronutrients and thyroid markers was studied in a group of 387 healthy individuals tested for thyroid markers (T4, T3, FT4, FT3, TSH, anti-TPO, RT3, and anti-Tg) and their micronutrient profile at Vibrant America Clinical Laboratory. The subjects were rationalized into three groups (deficient, normal, or excess levels of micronutrients), and the levels of their thyroid markers were compared. According to our results, deficiency of vitamin B2, B12, B9 and Vit-D25[OH] (p < 0.05) significantly affected thyroid functioning. Other elemental micronutrients such as calcium, copper, choline, iron, and zinc (p < 0.05) have a significant correlation with serum levels of free T3. Amino acids asparagine (r = 0.1765, p < 0.001) and serine (r = 0.1186, p < 0.05) were found to have a strong positive correlation with TSH. Valine, leucine, and arginine (p < 0.05) also exhibited a significant positive correlation with serum levels of T4 and FT4. No other significant correlations were observed with other micronutrients. Our study suggests strong evidence for the association of the levels of micronutrients with thyroid markers with a special note on the effect of serum levels of certain amino acids.
[This retracts the article DOI: 10.1155/2014/649502.].
Background. The aim of this study was to identify germline mutation of the RET (rearranged during transfection) gene in patients with medullary thyroid carcinoma (MTC) and their first-degree relatives to find presymptomatic carriers for possible prophylactic thyroidectomy. Methods/Patients. We examined all six hot spot exons (exons 10, 11, 13, and 14–16) of the RET gene by PCR and bidirectional Sanger sequencing in 45 Iranian patients with MTC (either sporadic or familial form) from 7 unrelated kindred and 38 apparently sporadic cases. First-degree relatives of RET positive cases were also genotyped for index mutation. Moreover, presymptomatic carriers were referred to the endocrinologist for further clinical management and prophylactic thyroidectomy if needed. Results. Overall, the genetic status of all of the participants was determined by RET mutation screening, including 61 affected individuals, 22 presymptomatic carriers, and 29 genetically healthy subjects. In 37.5% (17 of 45) of the MTC referral index patients, 8 distinct RET germline mutations were found, including p.C634R (35.3%), p.M918T (17.6%), p.C634Y (11.8%), p.C634F (5.9%), p.C611Y (5.9%), p.C618R (5.9%), p.C630R (5.9%), p.L790F (5.9%), and one uncertain variant p.V648I (5.9%). Also, we found a novel variant p.H648R in one of our apparently sporadic patients. Conclusion. RET mutation detection is a promising/golden screening test and provides an accurate presymptomatic diagnostic test for at-risk carriers (the siblings and offspring of the patients) to consider prophylactic thyroidectomy. Thus, according to the ATA recommendations, the screening of the RET proto-oncogene is indicated for patients with MTC.
Graves’s disease and thyroiditis induce hyperthyroidism, the causes of which remain unclear, although they are involved with genetic and environmental factors. We aimed to evaluate polygenetic variants for hyperthyroidism risk and their interaction with metabolic parameters and nutritional intakes in an urban hospital-based cohort. A genome-wide association study (GWAS) of participants with (cases; n = 842) and without (controls, n = 38,799) hyperthyroidism was used to identify and select genetic variants. In clinical and lifestyle interaction with PRS, 312 participants cured of hyperthyroidism were excluded. Single nucleotide polymorphisms (SNPs) associated with gene-gene interactions were selected by hyperthyroidism generalized multifactor dimensionality reduction. Polygenic risk scores (PRSs) were generated by summing the numbers of selected SNP risk alleles. The best gene-gene interaction model included tumor-necrosis factor (TNF)_rs1800610, mucin 22 (MUC22)_rs1304322089, tribbles pseudokinase 2 (TRIB2)_rs1881145, cytotoxic T-lymphocyte-associated antigen 4 (CTLA4)_rs231775, lipoma-preferred partner (LPP)_rs6780858, and human leukocyte antigen (HLA)-J_ rs767861647. The PRS of the best model was positively associated with hyperthyroidism risk by 1.939-fold (1.317–2.854) after adjusting for covariates. PRSs interacted with age, metabolic syndrome, and dietary inflammatory index (DII), while hyperthyroidism risk interacted with energy, calcium, seaweed, milk, and coffee intake (P<0.05). The PRS impact on hyperthyroidism risk was observed in younger (<55 years) participants and adults without metabolic syndrome. PRSs were positively associated with hyperthyroidism risk in participants with low dietary intakes of energy (OR = 2.74), calcium (OR = 2.84), seaweed (OR = 3.43), milk (OR = 2.91), coffee (OR = 2.44), and DII (OR = 3.45). In conclusion, adults with high PRS involved in inflammation and immunity had a high hyperthyroidism risk exacerbated under low intakes of energy, calcium, seaweed, milk, or coffee. These results can be applied to personalized nutrition in a clinical setting.
Purpose We hypothesized that innate immune response pathways might be involved in thyroid carcinogenesis. To investigate this hypothesis, we aimed at analyzing the expression of several receptors and molecules in the innate immune system in papillary thyroid carcinoma (PTC) and anaplastic thyroid carcinoma (ATC) tissues. Methods Of the surgically resected specimens, 11 ATC tissues, 25 PTC tissues, and 8 nodular hyperplasia (NH) tissues were selected and examined for the expression of toll-like receptor (TLR) 2, TLR3, TLR4, TLR5, TLR7, TLR9, the myeloid differentiation primary response gene 88 (MyD88), and toll-interleukin-1 receptor domain-containing adaptor inducing INF-β (TRIF) by immunohistochemistry (IHC). Results Several TLRs were expressed in each tissue. TLR3 was strongly expressed in all tissues. In contrast, TLR4 was not detected in any tissues. While TLR5 was moderately expressed in NH but significantly reduced in PTC and ATC, TLR9 was absent in NH tissue but moderately expressed in both PTC and ATC. On MyD88 expression, no significant difference was found between PTC and ATC. TRIF was significantly upregulated in PTC and ATC compared to NH. Surprisingly, PTC and ATC tissues exhibited similar expression patterns of TLRs, MyD88, and TRIF. Conclusion These data suggest the involvement of the innate immune system in both PTC and ATC. Specifically, TLR3-mediated TRIF activation was confirmed in PTC and ATC. This provides new insight into thyroid carcinogenesis.
