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Serum levels of fetuin-A are negatively associated with log transformation levels of thyroid-stimulating hormone in patients with hyperthyroidism or euthyroidism: An observational study at a medical center in Taiwan.
Tseng, FY, Chen, YT, Chi, YC, Chen, PL, Yang, WS
Medicine. 2018;(46):e13254
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Abstract
Fetuin-A is a protein with various biological functions. It plays a role in insulin resistance and arterial calcium deposition. Thyroid dysfunction may affect energy expenditure, glucose metabolism, and the risk of cardiovascular diseases. In the present study, we compared the serum fetuin-A concentrations in hyperthyroid patients with those in euthyroid patients.We recruited 30 newly-diagnosed hyperthyroid patients (the HY group) and treated them with anti-thyroid regimens as clinically indicated. We recruited 30 euthyroid individuals (the EU group) as controls. We compared laboratory parameters at the baseline and at 6 months. We then determined the associations between the levels of fetuin-A and free thyroxine (fT4), thyroid-stimulating hormone (TSH), or log transformation of TSH (logTSH).At the baseline, the HY patients had significantly higher serum fetuin-A levels than the EU patients (median [Q1, Q3]: 735.4 [537.9, 843.4] ng/mL vs 561.1[449.2, 670.5] ng/mL, P = .010). At 6 months, the serum fetuin-A levels of the HY patients decreased but were still higher than those of the EU patients (698.4 [627.6, 924.3] ng/mL vs 616.5 [498.2, 727.7] ng/mL, P = .002). At baseline, the serum levels of fetuin-A were negatively associated with logTSH (β = -53.79, P = .010). At 6 months, the levels of fetuin-A were positively associated with fT4 (β = 86.91, P = .039), and negatively associated with logTSH (β = -104.28, P < .001). Changes to the levels of fetuin-A within 6 months were negatively associated with changes to logTSH (β = -57.80, P = .019). The negative associations between fetuin-A levels and logTSH at baseline and at 6 months, and the changes during the 6 months remained significant after adjustment for sex and age (β = -51.72, P = .016; β = -103.11, P < .001; and β = -59.36, P = .020, respectively).The patients with hyperthyroidism had higher serum fetuin-A levels than the patients with euthyroidism. In patients with hyperthyroidism, the serum fetuin-A concentrations decreased after the anti-thyroid treatment. In the present study, serum fetuin-A concentrations were negatively associated with logTSH.
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Could short thyroid hormone withdrawal be an effective strategy for radioiodine remnant ablation in differentiated thyroid cancer patients?
Piccardo, A, Puntoni, M, Ferrarazzo, G, Foppiani, L, Bottoni, G, Altrinetti, V, Treglia, G, Naseri, M, Dib, B, Cabria, M, et al
European journal of nuclear medicine and molecular imaging. 2018;(7):1218-1223
Abstract
PURPOSE Current guidelines recommend thyroid hormone withdrawal (THW) of 3-4 weeks before radioiodine remnant ablation (RRA) of differentiated thyroid carcinoma (DTC). We aimed to evaluate (1) the reliability of a shorter THW (i.e., 14 days) to achieve adequate TSH levels (i.e., 30 mU/l), (2) the association between length of THW and response to therapy, and (3) the potential association between pre-ablation TSH levels and patients' outcome. METHODS After thyroidectomy, all patients started LT4 therapy, which was subsequently discontinued in order to perform RRA. Patients were broken down into two groups according to the length of THW: group A, 2 weeks of THW, and group B, 3-4 weeks of THW. We used clinical, biochemical, and imaging data to evaluate patients' outcome. By means of univariate and multivariate analysis, including main DTC prognostic factors, we assessed the impact of THW length and TSH levels on patients' outcome. RESULTS We evaluated 222 patients, 85 of whom were treated with RRA after a THW period of 2 weeks (group A). All other 137 patients underwent RRA after 3-4 weeks THW (group B). At the time of RRA all patients presented TSH levels ≥30 mU/l. After a median follow-up time of 3.4 years, we found 183 patients (82%) with excellent response to treatment and 39 patients (18%) showing incomplete response. Kaplan-Meier response to therapy curves showed that ablation-Tg, tumor size, and lymph node status were significantly associated with prognosis; no associations were found between THW length, TSH levels, and prognosis. Multivariate Cox model showed that only ablation-Tg was significantly associated with treatment response. CONCLUSIONS Prior to RRA, a short 2-week THW is an effective method to stimulate TSH levels. No difference in terms of incomplete response to treatment was observed between DTC patients prepared for RRA with a short THW and those with the long THW.
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BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma.
Moulana, FI, Priyani, AAH, de Silva, MVC, Dassanayake, RS
Hormones & cancer. 2018;(1):1-11
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Abstract
Oncogene-induced senescence (OIS) explains the phenomenon of cellular senescence triggered by the action of oncogenes. It is a mechanism adopted by a cell to inhibit progression of benign tumors into malignancy, occurs in premalignant lesions, and is almost never present in malignant lesions. BRAF mutations occur in about 40-45% of all papillary thyroid carcinomas (PTCs) and of which 99.7% is the BRAFV600E mutation. A unique phenotype of the BRAFV600E mutation is the upregulation of the thyroid-stimulating hormone receptor (TSHR) on thyrocyte membranes. Despite the overexpression of the receptor, BRAFV600E cells undergo cell cycle arrest leading to OIS via a negative feedback signaling mechanism. A simultaneous increase in serum thyroid-stimulating hormone (TSH) in response to hypothyroidism (common in autoimmune diseases such as Hashimoto's thyroiditis) would cause senescent tumor cells to overcome OIS and proceed towards malignancy, hence showing the importance of TSH/TSHR signaling in the development of PTCs. Increase in TSH/TSHR signaling triggers an increase in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc. Therefore, the detection of these genetic alterations as effective biomarkers for premalignant lesions of PTC is important in clinical settings and techniques such as polymerase chain reaction-mediated restriction fragment length polymorphism (PCR-RFLP) and real-time PCR can be used to detect the BRAFV600E point mutation and overexpression of TSHR, MnSOD, and DUSP6, respectively.
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The relationship between resting energy expenditure and thyroid hormones in response to short-term weight loss in severe obesity.
Marzullo, P, Minocci, A, Mele, C, Fessehatsion, R, Tagliaferri, M, Pagano, L, Scacchi, M, Aimaretti, G, Sartorio, A
PloS one. 2018;(10):e0205293
Abstract
BACKGROUND Regulating thermogenesis is a major task of thyroid hormones (THs), and involves TH-responsive energetic processes at the central and peripheral level. In severe obesity, little is known on the relationship between THs and resting energy expenditure (REE) before and after weight loss. METHODS We enrolled 100 euthyroid subjects with severe obesity who were equally distributed between genders. Each was examined before and after completion of a 4-wk inpatient multidisciplinary dieting program and subjected to measurement of thyroid function, REE, fat-free mass (FFM, kg) and percent fat mass (FM). RESULTS Baseline REE was lower than predicted in 70 obese patients, and overall associated with BMI, FFM and FM but not thyroid-related parameters. By the study end, both BMI and REE decreased (5.5% and 4.1%, p<0.001 vs. baseline) and their percent changes were significantly associated (p<0.05), while no association related percent changes of REE and FFM or FM. Individually, REE decreased in 66 and increased in 34 patients irrespective of gender, BMI and body composition. Weight loss significantly impacted TSH (-6.3%), FT3 (-3.3%) and FT4 levels (3.9%; p<0.001 for all). By the study end, a significant correlation became evident between REE and FT4 (r = 0.42, p<0.001) as well as FT3 (r = 0.24, p<0.05). In stepwise multivariable regression analysis, however, neither THs nor body composition entered the regression equation for REE response to weight loss. CONCLUSIONS In severe obesity, short-term weight loss discloses a positive relationship between REE and THs.
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Subclinical Hyperthyroidism.
Biondi, B, Cooper, DS
The New England journal of medicine. 2018;(25):2411-2419
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Statistical Evaluation of Trace Metals, TSH and T4 in Blood Serum of Thyroid Disease Patients in Comparison with Controls.
Hanif, S, Ilyas, A, Shah, MH
Biological trace element research. 2018;(1):58-70
Abstract
The present study is based on the measurement of concentrations of selected trace metals (Fe, Zn, Cu, Co, Mn, Ni, Cr, Cd and Pb) and thyroid hormones (TSH and T4) in blood serum of hypothyroid and hyperthyroid patients in comparison with healthy donors/controls in order to establish the imbalances of the trace metals in diseased subjects. The serum samples were digested in HNO3-HClO4 mixture and quantification of the metals was performed by flame atomic absorption spectrometry. Average levels of Fe, Ni, Cu, Cr, Pb and TSH were found to be significantly higher (p < 0.05) in the serum of hypothyroid patients compared with other donor categories, while mean concentrations of Mn, Cd and T4 were significantly elevated in the serum of hyperthyroid patients compared with other donor groups (p < 0.05). The correlation pattern of trace metals in the serum of patient groups revealed significantly different mutual associations compared with the controls. PCA and CA pointed out the interferences of the toxic metals with essential metals in the serum of both patient groups compared with the controls. Most of the metals exhibited noticeable disparities in their concentrations based on gender, food habits and tobacco use for all donor groups. Thus, the pathogenesis of thyroid diseases is significantly affecting the essential trace and toxic metals balance in both patients groups.
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Establishment of trimester-specific reference range for thyroid hormones during pregnancy.
Nazarpour, S, Ramezani Tehrani, F, Simbar, M, Minooee, S, Rahmati, M, Mansournia, MA, Azizi, F
Clinical biochemistry. 2018;:49-54
Abstract
OBJECTIVE Physiological gestational changes are associated with alterations in thyroid function which require different biochemical interpretation from that of non-pregnant women and necessitate established pregnancy-specific reference ranges. We aimed to identify the trimester-specific ranges of thyroid markers in a healthy population of pregnant Iranian women. METHODS In this self-sequential study, data were extracted from The Tehran Thyroid and Pregnancy Study; a total of 314 women were tested during the 1st, 2nd and 3rd trimesters for serum levels of thyrotropin (TSH), thyroxine (T4), free thyroxine index (FT4I) and thyroid peroxidase antibody (TPOAb). Trimester-specific reference intervals for TSH, T4 and FT4I and first trimester reference range for TPOAb were estimated. The normal and modulus exponential-normal models were fitted by maximum likelihood using STATA software. The 2.5th and 97.5th percentiles of thyroid parameters were determined and used as reference intervals. RESULTS Mean±SD age of participants was 26.8±5.2years. Estimated reference intervals for TSH, T4 and FT4I in the 1st, 2nd and 3rd trimesters corresponding to the 2.5th and 97.5th percentiles were 0.14-6.14, 0.43-4.64, 0.63-3.9μIU/ml; 78.01-215.19, 93.23-243.87, 89.61-211.37nmol/L; and 1.73-4.53, 1.96-5.64, 1.72-4.30, respectively. Reference interval for TPOAb in the 1st trimester was 1.40-38.02IU/mL. Median of TSH was low in the 1st trimester, and gradually increased until 2nd trimester, followed by a slight decrease onward. A decreasing trend in TSH levels was observed in higher centiles with advancing gestational age. CONCLUSION This study provides trimester-specific reference ranges for some common thyroid markers among healthy Iranian women in an iodine sufficient area, to prevent biochemical misinterpretations during pregnancy.
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TSH evaluation in hypothyroid patients assuming liquid levothyroxine at breakfast or 30 min before breakfast.
Pirola, I, Gandossi, E, Brancato, D, Marini, F, Cristiano, A, Delbarba, A, Agosti, B, Castellano, M, Cappelli, C
Journal of endocrinological investigation. 2018;(11):1301-1306
Abstract
PURPOSE To compare TSH levels of hypothyroid patients treated with liquid LT4 at breakfast or 30 min before breakfast. PATIENTS AND METHODS Subjects, aged 18-75 years old, were eligible if they presented hypothyroidism, due to Hashimoto's thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety-eight patients were recruited and enrolled in the study. Thirty-seven subjects withdrew from the trial. A total of 761 patients (mean age 46.2 ± 10.8 years) completed the study. The starting dose of LT4 was determined through clinical judgment, taking into account TSH levels, estimated residual thyroid function, age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3 evaluation to verify achievement of euthyroidism with their initial fasting state assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid function parameters were checked again. If euthyroidism was achieved, the patients were asked to take LT4 at breakfast and hormone levels were checked again after 6 months. RESULTS At the end of the study period, no significant differences in serum TSH level were observed whether LT4 was ingested at breakfast or 30 min prior in a fasting state: 2.61 ± 1.79 vs. 2.54 ± 1.86 mIU/L, respectively (p = 0.455). CONCLUSIONS This study confirms in a large set of patients that a liquid LT4 formulation can be taken directly at breakfast and potentially improve therapeutic compliance.
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Interferences With Thyroid Function Immunoassays: Clinical Implications and Detection Algorithm.
Favresse, J, Burlacu, MC, Maiter, D, Gruson, D
Endocrine reviews. 2018;(5):830-850
Abstract
Automated immunoassays used to evaluate thyroid function are vulnerable to different types of interference that can affect clinical decisions. This review provides a detailed overview of the six main types of interference known to affect measurements of thyroid stimulating hormone (TSH), free thyroxine (T4) and free triiodothyronine (T3): macro-TSH, biotin, antistreptavidin antibodies, anti-ruthenium antibodies, thyroid hormone autoantibodies, and heterophilic antibodies. Because the prevalence of some of these conditions has been reported to approach 1% and the frequency of testing for thyroid dysfunction is important, the scale of the problem might be tremendous. Potential interferences in thyroid function testing should always be suspected whenever clinical or biochemical discrepancies arise. Their identification usually relies on additional laboratory tests, including assay method comparison, dilution procedures, blocking reagents studies, and polyethylene glycol precipitation. Based on the pattern of thyroid function test alterations, to screen for the six aforementioned types of interference, we propose a detection algorithm, which should facilitate their identification in clinical practice. The review also evaluates the clinical impact of thyroid interference on immunoassays. On review of reported data from more than 150 patients, we found that ≥50% of documented thyroid interferences led to misdiagnosis and/or inappropriate management, including prescription of an unnecessary treatment (with adverse effects in some situations), inappropriate suppression or modification of an ongoing treatment, or use of unnecessary complementary tests such as an I123 thyroid scan. Strong interaction between the clinician and the laboratory is necessary to avoid such pitfalls.
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Thyrotropic hormones.
Mallya, M, Ogilvy-Stuart, AL
Best practice & research. Clinical endocrinology & metabolism. 2018;(1):17-25
Abstract
Thyroid hormones are crucial for normal cognition and neurodevelopment in children. The introduction of the screening programs for congenital hypothyroidism has decreased the incidence of untreated congenital hypothyroidism. As maternal thyroid disease is common, and may impact on thyroid gland development and function in the fetus, optimal management is crucial. This review discusses thyroid function and the impact of maternal thyroid disease on the fetus and neonate, as well as the influence of thyroid hormones, thyroid antibodies and the excretion of thyroid medication into breast milk on infant thyroid function.