Research progress of relation between thyroid stimulating hormone and differentiated thyroid cancer / 中华核医学与分子影像杂志

Thyroid cancer is one of the most common tumors of the endocrine system, characterized by high morbidity and low mortality. Thyroid stimulating hormone (TSH) is an important factor in the development of thyroid cancer. TSH suppression therapy is widely used in clinical practice to reduce recurrence and metastasis through long-term strict monitoring and control of postoperative TSH level in patients with differentiated thyroid cancer (DTC). However, the specific mechanism of the effect played by TSH in the proliferation and progression of DTC has not been clarified. The current researches focus on classifying the relation between TSH and the onset risk, adverse clinicopathological factors and prognosis of DTC, and the applicable scope of TSH suppression therapy and targeted TSH receptor (TSHR) therapy. This article reviews the relation between TSH and DTC and the latest research progress of TSH suppression therapy and TSHR targeted therapy.

Syndrome of inappropriate secretion of thyrotropin: Differential diagnosis / 中华内分泌代谢杂志

Objective:Through comprehensive analysis of symptoms and signs, biochemistry, imaging, and dynamic tests, to explore the diagnosis and differential diagnosis of thyrotropin-secreting pituitary adenoma(TSH adenoma) and syndrome of resistance to thyroid hormone(RTH).Methods:A retrospective analysis was conducted on clinical data from 14 patients who visited the First Affiliated Hospital of Zhengzhou University from July 2016 to September 2022, exhibiting elevated levels of free thyroxine(FT4) and free triiodothyronine(FT3) in the presence of increased TSH.Results:There were 7 cases of TSH adenoma and 7 cases of RTH, with the average age of diagnosis at 40.0 years and 26.6 years, respectively. Thirteen patients showed thyrotoxicosis or occasional palpitation, some with pituitary occupancy manifestations or abnormal growth and development; One patient presented with neck thickening. Sex hormone binding globulin was elevated in 3 cases of TSH adenoma. Pituitary magnetic resonance imaging showed that all 7 cases of TSH adenoma were macroadenomas and 1 case of RTH was microadenoma. The octreotide suppression test in 13 patients was inhibited, but there was a significant difference in the inhibition rate of 24 h/2 h TSH inhibition rate of TSH adenoma and RTH, ranging from 46.6% to 83.9% and 4.6% to 28.8% respectively. Six cases of RTH had thyroid hormone receptor β mutation.Conclusion:Syndrome of inappropriate secretion of thyrotropin is a rare condition, mainly including TSH adenoma and RTH. The diagnosis and differentiation of the two conditions require comprehensive assessment incorporating family history, symptoms and signs, laboratory tests, dynamic test, and genetic test. Among these, the 24 h/2 h TSH inhibition rate of octreotide suppression test can effectively distinguish TSH adenoma from RTH.

Physicians' preferences for radioiodine treatment of differentiated thyroid cancer in Brazil: an observational study

ABSTRACT Objective The aim of this observational, cross-sectional study was to investigate physicians' preferences for radioiodine (RAI) treatment in patients with differentiated thyroid cancer (DTC) in Brazil and the factors influencing RAI indications. Materials and methods A survey was distributed to physicians potentially involved in DTC care in Brazil to understand the factors influencing RAI indications. The survey collected information on the profiles of the physicians, along with the characteristics of their workplaces and their preferences regarding RAI indications in three hypothetical clinical cases. Cases 1, 2, and 3 described the cases of patients with DTC and variations to the case that included different scenarios to assess how the respondents would change their RAI recommendations. The analysis included the RAI indications across different medical specialties. Results A total of 175 physicians answered the survey. There was considerable variability in RAI recommendations in all three cases. The training background influenced the respondents' preferences for RAI indications and their approaches to preparing patients for RAI treatment. Conclusion The findings of this study reaffirm the need for a Brazilian consensus among physicians across multiple specialties to help guide health care professionals treating patients with DTC in Brazil.

Uso adecuado de las pruebas de laboratorio para la evaluación de la función tiroidea en pediatría / Appropriate use of laboratory tests for evaluation of thyroid function in pediatrics

Las pruebas de función tiroidea (PFT) son esenciales para el diagnóstico preciso y el seguimiento eficaz de la disfunción tiroidea. Existe un incremento progresivo y estable de los pedidos de PFT, incluso se han incorporado las mismas a los exámenes de salud anuales en niños sanos. Representan más del 60% de las pruebas realizadas en el laboratorio de endocrinología, tanto en adultos como en los laboratorios especializados en pediatría. Para hacer un uso eficiente de las PFT, antes de solicitarlas debemos preguntarnos… ¿Para quién? ¿Cuándo solicitarlas? ¿Qué pruebas solicitar? ¿Cómo solicitarlas? y ¿Cómo interpretar correctamente los resultados? Un resultado anormal en las PFT no siempre implica patología tiroidea asociada. Las PFT tienen importante variabilidad intra e interindividual lo que hace más compleja su correcta interpretación. La pesquisa de enfermedad tiroidea neonatal es un importante aporte a la prevención de la deficiencia mental en la infancia, su aplicación obligatoria posibilita un diagnóstico temprano, para asegurar su éxito debe considerarse en el marco de un programa integral de detección con estrategias de confirmación, tratamiento temprano y seguimiento a corto, mediano y largo plazo. No debe hacerse un uso indiscriminado de la prueba de estímulo con TRH en el diagnóstico de la patología tiroidea. En pediatría la estrategia de tamiz de enfermedad tiroidea es conveniente realizarla mediante la medición de por lo menos TSH y T4 libre e incluir la determinación de ATPO en grupos de riesgo, a diferencia de la determinación aislada de TSH como es recomendado en adultos. (AU)

Thyroid function tests (TFTs) are essential for accurate diagnosis and effective monitoring of thyroid dysfunction. There is a progressive and steady increase in requests for TFTs, and they have even been incorporated into annual health examinations in healthy children. They represent more than 60% of the tests performed in the endocrinology laboratory, both in adults and in specialized pediatric laboratories. To efficiently use TFTs, before requesting them we should ask ourselves... For whom? When to request them? Which tests to request? How to request them? and How to correctly interpret the results? An abnormal TFT result does not always imply thyroid disease. TFTs have significant intra- and inter-individual variability, which makes their correct interpretation more complex. Screening for newborn thyroid disease is an important contribution to the prevention of intellectual disability in childhood and its mandatory use enables early diagnosis; however, to ensure the test to be successful, it should be considered within the framework of a comprehensive screening program with strategies for confirmation, early treatment, and short-, medium-, and long-term follow-up. The TRH stimulation test in the diagnosis of thyroid disease should not be used indiscriminately. In children, the screening strategy for thyroid disease should be performed by measuring at least TSH and free T4 and include the measurement of TPO-ab in risk groups, as opposed to the isolated measurement of TSH as recommended in adults. (AU)

Effects of arsenic exposure on E2 and TRH and their receptor mRNA expressions in rats / 环境与职业医学

Background Arsenic can enter the hypothalamus to induce estrogen effect and interfere with the function of the neuroendocrine system. The thyroid endocrine system (hypothalamic-pituitary-thyroid axis) is one of the main endocrine systems, and the mechanism of arsenic-induced thyroid endocrine toxicity is still unclear. Objective To investigate the effects of different arsenic exposure levels on estradiol (E2), hypothalamic thyrotropin-releasing hormone (TRH), and their receptor (ERα, ERβ, and TRHR) mRNAs in rats and the possible hypothalamic toxic pathway and mechanism. Methods Seventy Wister rats were randomly divided a control group (sterile water); low-, medium-, and high-dose arsenic exposure groups [0.8, 4.0, and 20.0 mg·kg−1 sodium arsenite (NaAsO2)]; estrogen receptor inhibitor (ICI182780) intervention + low-, medium-, and high-dose arsenic exposure groups; with 10 animals in each group, half male and half female. Rats in the arsenic exposure groups were exposed to NaAsO2 by drinking water for 19 weeks, and rats in the intervention groups were injected with 0.5 mg·kg−1 ICI182780 via tail vein at week 9, 3 times a week. The levels of E2 and TRH in serum of rats were detected by ELISA. The expression levels of estrogen receptor α (ERα), estrogen receptor β (ERβ), and TRH receptor (TRHR) mRNAs in hypothalamus of rats were detected by real-time PCR (RT-PCR). Results (1) E2 and its receptor mRNA: Compared with the control group, the serum E2 level of female rats was increased in the low-dose and the medium-dose arsenic exposure groups (P<0.05), and the serum E2 level of male rats was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), and the change of female E2 was greater than that of male rats. Compared with the control group, the relative expression levels of ERα mRNA and ERβ mRNA in female rats were increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05), so were the relative expression levels of ERα mRNA in male rats (P<0.05). (2) TRH and its receptor mRNA: Compared with the control group, the serum TRH level of female rats was increased in the high-dose arsenic group (P<0.05), the relative expression level of TRHR mRNA was increased in the low-dose, the medium-dose, and the high-dose arsenic exposure groups (P<0.05). Results (1) and results (2) suggested that females were more likely than males to have abnormal changes in E2, TRH, and related receptor genes after arsenic exposure. (3) Compared with female rats in the medium-high dose arsenic exposure group, the expressions of TRH and TRHR induced by arsenic exposure were inhibited after the intervention of ICI182780 (P<0.05), suggesting that arsenic in the hypothalamus may have toxic effects on TRH and TRHR by inducing estrogen-like effects. Conclusion Arsenic exposure can induce estrogen-like effects in the hypothalamus, interfere with thyroid function, and show dose-dependent and sex differences. E2 and TRH and their receptors may be the toxic pathway of arsenic-related estrogen-like effect.

Gut microbiota and thyroid-associated ophthalmopathy / 中南大学学报(医学版)

Thyroid-associated ophthalmopathy(TAO)is a multifactorial-mediated autoimmune orbital disease with the highest incidence of orbital disease in adults.Due to the complex clinical manifestations and prolonged course,TAO seriously affect the physical and mental health of patients.The pathogenesis of TAO has not been fully elucidated and the treatment lacks specificity.Therefore,in-depth research on the pathogenesis of TAO is to find effective treatments.In recent years,studies have suggested that there is gut microbiota disorder in TAO,and the risk factors of TAO can promote gut microbiota disorder.Disordered gut microbiota can participate in the occurrence and development of TAO via influencing T cell differentiation,mimicking autoantigens,and influencing host non-coding RNA expression.Modulating the gut microbiota also has therapeutic effects on TAO and is a promising therapeutic approach.

To explore the value of TRAb in predicting permanent hypothyroidism after 131I treatment of Graves' disease / 中国综合临床

Objective:The effect of serum thyrotropin receptor antibody (TRAb) on permanent hypothyroidism (HT) after 131I treatment in Graves disease patients and its predictive value Methods:479 Graves' disease patients who underwent 131I treatment at the Nuclear Medicine Department of North China University of Technology Affiliated Hospital from October 2013 to October 2021 were selected. Among them, 350 cases (permanent HT group) had permanent HT during follow-up, while 129 cases (non permanent HT group) did not. Collect general clinical data such as gender, age, degree of thyroid enlargement, as well as indicators such as iodine intake rate, thyroid function, and treatment dose 24 hours before treatment, from two groups of patients. Compare the general clinical data and pre treatment levels of various detection indicators between two groups of patients, analyze the risk factors for permanent HT in Graves disease patients after 131I treatment, and evaluate the predictive value of pre treatment serum TRAb levels, and evaluate the consistency between the predicted results and clinical diagnosis. The econometric data with a normal distribution is represented by xˉ± s, and two independent sample t-tests are used for comparison between the two groups; The econometric data that do not conform to the normal distribution are represented by M（ Q1， Q3）, and the Wilcoxon rank sum test is used for comparison between the two groups; The counting data is represented as an example (%), and the comparison between the two groups is conducted using the four grid χ 2 test, while the comparison of grade data is conducted using the Willcoxon rank sum test; The logistic regression model was used for multivariate analysis. Draw a subject work characteristic curve to evaluate the predictive efficacy of TRAb, and screen the predictive threshold based on the Chayoden index; Calculate sensitivity and specificity, and evaluate the consistency between the predicted results and clinical diagnosis by calculating Kappa values. Results:There were no statistically significant differences in gender, age, degree of thyroid enlargement, 24-hour iodine uptake rate, serum thyroid stimulating hormone, free triiodothyronine, free thyroxine levels, and 131I treatment dose between the permanent HT group and the non permanent HT group (all P>0.05); The pre treatment TRAb levels in the permanent HT group were higher than those in the non permanent HT group [14.51(4.95,33.58) U/L vs 3.40(1.67,16.5) U/L], with a statistically significant difference ( Z=5.87, P<0.001). The results of multivariate logistic regression analysis showed that pre treatment TRAb levels were a risk factor for permanent HT in Graves' disease patients after 131I treatment (odds ratio=1.042,95% confidence interval: 1.025-1.059, P<0.001). The area under the working characteristic curve for predicting permanent HT in Graves' disease patients after 131I treatment with pre-treatment TRAb levels is 0.674 (95% confidence interval: 0.616~0.732), and the optimal critical value is 7.025 U/L. Using TRAb>7.025 U/L before treatment as the standard for predicting postoperative permanent HT in patients, the sensitivity and specificity were 73.7% and 75.2%, respectively. The predicted results showed moderate consistency with clinical diagnosis ( Kappa=0.426). Conclusions:The pre treatment TRAb level is a risk factor for permanent HT in Graves disease patients after 131I treatment ( P<0.001), and the diagnostic efficacy of permanent HT is best when TRAb>7.025 U/L.

Factors influencing transient hypothyroxinemia in one premature twin / 中华围产医学杂志

Objective:To study the factors influencing transient hypothyroxinemia (TH) in one premature twin.Methods:This retrospective study enrolled 283 sets of preterm twins who were born at the gestational age of 26-36 weeks and admitted to the Neonatology Department of the Second Affiliated Hospital of Wenzhou Medical University from June 2009 to September 2021. The levels of thyroxine (T 4), triiodothyronine (T 3) and thyroid stimulating hormone (TSH) were detected at 11-20 d after birth. Finally, 47 sets of twins were further analyzed, in which one twin met the diagnostic criteria of TH (TH group, n=47) and the other twin with exclusion of the diagnosis (control group, n=47). Pearson correlation was used to analyze the correlation of T 4 with gestational age and birth weight. Paired t test, Wilcoxon signed-rank test or McNemar test, and conditional logistic regression were used to analyze the factors influencing TH in premature twins. Results:The gestational age and birth weight of the 47 sets of preterm twins (94 cases) were (31.4±2.3) weeks (26-36 weeks) and (1 611.9±389.3) g (800-2 510 g), respectively. There were 35 sets of dizygotic twins, 11 sets of monozygotic twins, and one set of twins with unknown zygosity. The serum T 4 level in premature infants was positively correlated with the gestational age and birth weight (the correlation coefficients were 0.209 and 0.376, respectively, both P<0.05). Univariate analysis showed that compared with the control group, the factors influencing TH in premature infants ( P<0.1) included female [29.8% (14/47) vs 14.9% (7/47), χ2=3.27 ], bronchopulmonary dysplasia [31.9% (15/47) vs 19.1% (9/47), χ2=3.13], birth weight [(1 547.9±348.0) vs (1 676.0±420.5) g, t=－3.61], white blood cell count [(10.0±3.3)×10 9/L vs (10.9±3.3)×10 9/L, t=－2.19] and vitamin D level [(42.8±12.1) vs (45.9±16.6) nmol/L, t=－1.76]. The data on vitamin D were incomplete and after excluding the factor, the logistic regression showed that female was a risk factor ( OR=18.388 95% CI: 1.317-256.743); while higher birth weight was a protective factor ( OR=0.996, 95% CI: 0.993-0.999). In order to exclude the influence of monozygotic twins on gender, 11 sets of monozygotic twins and one set with unknown zygosity were excluded from multivariate analysis. The results suggested that female was a risk factor ( OR=18.527, 95% CI: 1.209-283.820), while higher birth weight was a protective factor ( OR=0.996, 95% CI: 0.992-1.000). Conclusion:Female and birth weight are the factors influencing TH at 11-20 d after birth in one preterm twin.

Effects of thyroid-stimulating hormone suppressive therapy on programmed death ligand 1 and matrix metalloproteinase-2 expression in thyroid cancer tissue and prognosis / 中国基层医药

Objective:To investigate the effects of thyroid-stimulating hormone (TSH) suppressive therapy on the expression of programmed death ligand 1 (PD-L1) and matrix metalloproteinase 2 (MMP-2) in thyroid cancer tissue and prognosis.Methods:A total of 102 patients with thyroid cancer who underwent surgical resection in Weihai Central Hospital, Qingdao University from April 2016 to April 2018 were included in this study. They were divided into a hormone replacement group and a TSH suppressive therapy group ( n = 51/group). The hormone replacement group was given hormone replacement therapy after surgical resection, and the TSH suppressive therapy group was given TSH suppressive therapy. The expression of PD-L1 and MMP-2 in the pericancerous tissue was compared between the two groups during surgery and 3 and 6 months after surgery. Tumor recurrence and metastasis were compared between the two groups after 6 months, 1 year, and 3 years of follow-up. Results:At 3 and 6 months after surgery, the PD-L1 positive expression rate in the TSH suppressive therapy group was 9.8% (5/51) and 13.7% (7/51), respectively, and the MMP-2 positive expression rate in the TSH suppressive therapy group was 9.8% (5/51) and 13.7% (7/51), respectively, which were significantly lower than 25.5% (13/51), 31.4% (16/51), 27.5% (14/51), and 33.3% (17/51) in the hormone replacement group ( χ2 = 4.32, 5.24, 4.55, 5.45, P = 0.038, 0.022, 0.033, 0.020). At 3 years after surgery, the tumor recurrence and metastasis rate in the TSH suppressive therapy group was 5.9% (3/51), which was significantly lower than 17.6% (10/51) in the hormone replacement group ( χ2 = 4.32, P = 0.038). Conclusion:For patients with thyroid cancer undergoing surgery, TSH suppressive therapy can better inhibit the expression of PD-L1 and MMP-2 in thyroid cancer tissue, reduce the risk of long-term recurrence and metastasis, and have a better clinical application value for improving the prognosis compared with hormone replacement therapy.

Relationship between thyroid hormone level and obesity related indices in patients with type 2 diabetes mellitus / 中国基层医药

Objective:To investigate the relationship between serum thyroid hormone levels in the normal range and body weight, blood glucose, blood lipids, and other obesity-related indexes in patients with type 2 diabetes mellitus.Methods:Seventy obese patients with type 2 diabetes mellitus and ninety-two patients with type 2 diabetes mellitus with normal weight who were treated in the Nangang Branch of Heilongjiang Provincial Hospital from May 2020 to May 2021 were included in this study. Thyroid-stimulating hormone level was in the normal range (0.35-4.94 mU/L) in all participants. Serum levels of free triiodothyronine, free thyroxine, thyroid-stimulating hormone, thyroid peroxidase antibody, thyroglobulin antibody, triglyceride, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting blood glucose, glycosylated hemoglobin, fasting C peptide, fasting insulin, systolic blood pressure, diastolic blood pressure, and serum uric acid were measured in all participants.Results:Free triiodothyronine level was positively correlated with fasting blood glucose and glycosylated hemoglobin levels ( r = 0.19, P = 0.021; r = 0.21, P = 0.017). Free thyroxine level was positively correlated with serum glycosylated hemoglobin level ( r = 0.25, P = 0.009) and negatively correlated with total cholesterol ( r = -0.17, P = 0.029). Thyroid-stimulating hormone level was positively correlated with body mass index as well as total cholesterol and low-density lipoprotein cholesterol levels ( r = 0.33, P < 0.001; r = 0.33, P < 0.001; r = 0.32, P < 0.001). Conclusion:Thyroid hormones in the normal range play an important role in the regulation of body weight, blood glucose, and blood lipids in patients with type 2 diabetes mellitus. Blood glucose level increases markedly in patients with relatively high free triiodothyronine and free thyroxine levels. The risks of obesity and dyslipidemia increase in patients with relatively high serum thyroid-stimulating hormone levels

Correlation of serum 25-hydroxyvitamin D level with Thyrotropin receptor antibody and bone metabolism markers in patients with Graves' disease / 中华临床营养杂志

Objective:To investigate the serum 25-hydroxyvitamin D [25(OH)D] level in patients with Graves' disease (GD) and its correlation with thyrotropin receptor antibody (TRAb) and bone metabolism markers.Methods:A total of 124 patients with newly diagnosed or relapsed GD were selected and divided into three groups according to serum 25(OH)D level, namely vitamin D deficiency group with 25(OH)D <12 μg/L, vitamin D insufficiency group with 25(OH)D of 12 to 20 μg/L, and vitamin D sufficiency group with 25(OH)D ≥ 20 μg/L. The levels of serum 25(OH)D, TRAb, type I procollagen N-terminal pro-peptide (PINP), type I collagen cross-linked C-terminal peptide (S-CTX), parathyroid hormone (PTH), total triiodothyronine (TT 3), total thyroxine (TT 4) and thyroid-stimulating hormone (TSH) were measured in all patients, and the differences of these biochemical indices were compared across groups. Oneway analysis of variance or Kruskal-Wallis test was used for comparison between groups, and Pearson or Spearman correlation analysis was applied for correlation test. Results:The levels of serum TT 3, TT 4, PINP, and S-CTX significantly increased ( P < 0.01) and the level of phosphorus (P) decreased ( P < 0.01) with the decreased vitamin D levels. The levels of PTH and calcium (Ca) were significantly lower in the vitamin D sufficiency group compared with the vitamin D insufficiency group and vitamin D deficiency group ( P < 0.01). Correlation analysis showed that serum 25(OH)D level was negatively correlated with the levels of TT 3, TT 4, PINP, S-CTX, PTH and Ca ( P < 0.01), and positively correlated with the levels of P and TSH ( P < 0.01). Conclusions:Decreased serum 25(OH)D level is closely related with increased bone turnover, PTH, and thyroid hormone levels in patients with GD, but not related with TRAb. Thyroid hormone levels have a certain predictive value regarding vitamin D deficiency in GD patients. It is necessary to monitor the vitamin D levels in patients with GD and provide vitamin D supplementation to reduce the incidence of osteoporosis, improve the effectiveness of antithyroid treatment and reduce the recurrence of GD.

Palmitic acid inhibits the synthesis and secretion of thyroglobulin of rat thyroid follicular epithelial cell by downregulating thyrotropin receptor / 中华内分泌代谢杂志

Objective:Exploring the role of thyrotropin receptor(TSHR) in lipotoxicity-induced thyroid function damage.Methods:Rat thyroid follicular epithelial cells(RTC) were stimulated with different doses of palmitic acid(PA), and the lipid content of the cells was observed through Oil Red O staining. The expression levels of TSH receptor(TSHR), Ttf1, and SSBP1 mRNA and protein in each group were detected using RT-PCR and Western blot. The TSHR protein level in the cell culture supernatant was measured using ELISA. Membrane TSHR was assessed through immunofluorescence and compared with the control group. We used PA to stimulate the TSHR over-expression(TSHR OE) and normal RTC, as PA+ TSHR OE group and PA group respectively, then testing Tg mRNA and protein, cAMP and Tg in cell supernatants levels, then comparing with the control.Results:RTC were stained into peau d′orange in PA groups. Compared with the control group, we found TTf1, SSBP1 and TSHR mRNA as well as protein levels in PA groups were decreased(all P<0.05), TSHR of the cell membrane and supernatants were reduced(all P<0.05), characterizing dose-dependent changes partly. Moreover, we found in PA group Tg mRNA level was downregulated( P<0.05), Tg protein levels were reduced in the supernatants and cells( P<0.05), cAMP level was decreased in cells( P<0.05); in TSHR OE group, Tg mRNA level was upregulated( P<0.05), Tg protein levels in cells and supernatants were increased(all P<0.05), cAMP level was similar. Compared with the PA group, we found in PA+ TSHR OE group Tg mRNA level was upregulated( P<0.05), Tg protein levels were increased in the supernatants and cells(all P<0.05), cAMP level was elevated in cells( P<0.05). Conclusion:PA induces lipid deposition in RTC, decreased synthesis and secretion of Tg. This effect is likely achieved through the downregulation of the TSHR/cAMP signaling pathway.

Reference ranges and influencing factors of thyroid function in preterm infants at 14 d after birth / 中华围产医学杂志

Objective:To investigate the reference ranges for thyroid function and its influencing factors in preterm infants at 14 d after birth.Methods:This retrospective study involved 514 preterm infants who met the inclusion criteria in Affiliated Hospital of Inner Mongolia Medical University from January 1, 2019 to December 31, 2021. They were divided into three group according to their gestational age [early premature group (26-31 +6 weeks, n=153), middle premature group (32-33 +6 weeks, n=129) and late premature group (34-36 +6 weeks, n=232)] or birth weight (BW) [<1 500 g group ( n=129), 1 500-2 000 g group ( n=120) and ≥2 000 g group ( n=265)]. Venous blood samples were collected from the infants at 14 d after birth and their thyroid function was determined by chemiluminescence immunoassay. The reference values of free triiodothyronine (FT 3), free thyroxine (FT 4) and thyroid stimulating hormone (TSH) were calculated based on the values of 95% confidence intervals ( CI) and expressed as percentiles in the range from P2.5 to P97.5. Mann-Whitney U test or Kruskal-Wallis H test was used to compare those thyroid hormone levels between groups. Spearman correlation analysis was used to study the correlation of gestational age or birth weight with FT 3, FT 4 and TSH levels. The factors influencing the levels of thyroid hormones were analyzed by multiple linear regression. Results:The reference ranges for FT 3, FT 4 and TSH were 1.53-3.72 pg/ml, 0.81-1.91 ng/dl and 1.32-7.80 μIU/ml in the early premature infants, 1.74-4.16 pg/ml, 0.90-2.82 ng/dl and 0.63-7.64 μIU/ml in middle prematures and 2.07-4.88 pg/ml, 1.09-2.27 ng/dl and 1.14-7.06 μIU/ml in late prematures. The reference ranges for the above three indexes were 1.53-4.06 pg/ml, 0.81-1.83 ng/dl and 1.14-7.84 μIU/ml in premature infants with BW<1 500 g, 1.67-3.98 pg/ml, 0.88-2.97 ng/dl and 0.94-7.64 μIU/ml in those whose BW between 1 500 g and 2 000 g and 1.91-4.75 pg/ml, 1.09-2.31 ng/dl and 1.14-6.32 μIU/ml in those whose BW≥2 000 g. Multiple linear regression showed that the level of FT 3 was positively correlated with gestational age ( β=0.119, P<0.05) and birth weight ( β=1.950×10 －4, P<0.05); that of FT 4 was positively correlated with gestational age only ( β=0.031, P<0.05); and TSH level was negatively correlated with birth weight ( β=－4.250×10 －4, P<0.05). Conclusions:Gestational age and birth weight are the factors influencing thyroid function in preterm infants at 14 d after birth. Evaluation of thyroid function with FT 4 and TSH should based on the references ranges of different gestational age and birth weight .

Predictive factors for the diagnosis of permanent congenital hypothyroidism and its temporal changes in Sergipe, Brazil - A real-life retrospective study

ABSTRACT Objectives: Congenital hypothyroidism (CH) can be permanent (PCH) or transient (TCH). While the importance of thyroxine in myelination of the brain is undisputed, the benefits to neurodevelopmental outcomes of TCH treatment are controversial. Our objectives were to determine predictive factors for PCH and verify its prevalence changes over time. Subjects and methods: A total of 165 children were evaluated at 3 years of age to verify the diagnosis of PCH. 130 were submitted to a two-step cluster analysis, with the aim of grouping them into homogeneous clusters. The mean incidence of PCH and TCH was calculated from 2004 to 2010 and 2011 to 2015. Results: Sixty-six children were diagnosed with PCH, and 99 were diagnosed with TCH. Eighty-one percent of PCH children and all TCH children with thyroid imaging had glands in situ. Eighty children (61.5%) were in Cluster 1, 8 children (6.2%) were in Cluster 2 and 42 children (32.3%) were in Cluster 3. No children had PCH in Cluster 1, while 87.5% of children in Cluster 2 and all children in Cluster 3 had PCH. The most important predictor for PCH was the initial serum TSH, which was marginally higher in importance than the blood spot TSH, followed by the initial serum free T4. The mean incidence of PCH (odds ratio: 1.95, 95% CI 1.36 to 2.95, p < 0.0001) and TCH (odds ratio 1.33, 95%, CI 1.02 to 1.77, p = 0,038) increased over time. Conclusions: The most important PCH predictors are the initial serum TSH and the blood spot TSH. The mean incidence of both PCH and TCH in our series increased.

Valores de referencia para la tirotropina y hormonas tiroideas en embarazadas cubanas / Reference values for thyrotropin and thyroid hormones in pregnant women in Cuba

Introducción: Los parámetros de función tiroidea en las embarazadas se modifican durante el embarazo y son específicos para cada población. Objetivo: Establecer los valores de referencia para la tirotropina y las hormonas tiroideas en una población de embarazadas cubanas. Métodos: Estudio transversal, en el municipio Plaza de la Revolución de La Habana, Cuba, a 362 gestantes sin antecedentes personales o familiares de enfermedad tiroidea, con anticuerpos anti-tiroideos negativos y ausencia de lesiones en el ultrasonido tiroideo. Se analizaron edad materna, edad gestacional, raza, hábito de fumar, paridad, uso de suplementos yodados, índice de masa corporal, tirotropina, tiroxina total y libre, triyodotironina total y libre. Se establecieron los intervalos de referencia para cada parámetro mediante los percentiles 2,5 y 97,5 como límites inferior y superior, respectivamente. Resultados: Los valores de referencia en el primer, segundo y tercer trimestres fueron para la tirotropina 0,1-3,3 mUI/L, 0,6-3,4 mUI/L y 0,3-3,9 mUI/L; para la TT4 90,1-204,1 nmol/L, 92,2-189,2 nmol/L y 79,8-170,4 nmol/L; para la FT4 7,3-16,7 pmol/L, 6,3-17,3 pmol y 5,6-12,7 pmol/L; para la TT3 1,8-3,9 nmol/L, 1,8-3,9 nmol/L y 1,7-4,0 nmol/L y para la FT3 1,0-7,4 pmol/L, 0,7-6,3 pmol/L y 0,7-5,4 pmol/L, respectivamente. Conclusiones: Se determinaron por primera vez los valores de referencia para la tirotropina y las hormonas tiroideas en una población de embarazadas cubanas; estos difieren de los establecidos por los kits diagnósticos y de los recomendados por las guías internacionales previas (AU)

Introduction: Thyroid function parameters in pregnant women are modified during pregnancy and are specific for each population. Objective: To establish reference values for thyrotropin and thyroid hormones in a population of Cuban pregnant women. Methods: Cross-sectional study, in the Plaza de la Revolución municipality, of 362 pregnant women without personal or family history of thyroid disease, with negative anti-thyroid antibodies and absence of lesions in the thyroid ultrasound. Maternal age, gestational age, race, smoking, number of pregnancies, use of iodine supplements, body mass index, thyrotropin, total (TT4) and free (FT4) thyroxine, total (TT3) and free (FT3) triiodothyronine were analyzed. Reference intervals were established for each parameter using the 2.5 and 97.5 percentiles as lower and upper limits, respectively. Results: The reference values in the first, second and third trimesters were for thyrotropin 0.1-3.3 mIUI/L, 0.6-3.4 mIU/L and 0.3-3.9 mIU/L; for TT4 90.1-204.1 nmol/L, 92.2-189.2 nmol/L and 79.8-170.4 nmol/L; for FT4 7.3-16.7 pmol/L, 6.3-17.3 pmol and 5.6-12.7 pmol/L; for TT3 1.8-3.9 nmol/L, 1.8-3.9 nmol/L and 1.7-4.0 nmol/L and for FT3 1.0-7.4 pmol/L, 0.7-6.3 pmol/L and 0.7-5.4 pmol/L, respectively. Conclusions: Reference values for thyrotropin and thyroid hormones were determined for the first time in a population of Cuban pregnant women. These values differ from those established by the manufacturer of the diagnostic kits and from those recommended by previous international guidelines (AU)

Recombinant human thyroid-stimulating hormone for post-operative assessment in patients with low- to intermediate-risk differentiated thyroid cancer: results of phase Ⅰ study / 中华核医学与分子影像杂志

Objective:To evaluate the efficacy by using domestic recombinant human thyroid-stimulating hormone (rhTSH) in patients with differentiated thyroid cancer (DTC) before or after 131I therapy. Methods:From May 2019 to November 2020, a total of 24 patients with DTC (5 males, 19 females, median age 41 years) in Peking Union Medical College Hospital and Affiliated Tumor Hospital of Zhengzhou University were enrolled into the open-label, dose escalation phase Ⅰ study. All patients were divided into 4 domestic rhTSH dose groups: 0.9 mg×1 d (group A), 0.9 mg×2 d (group B), 1.8 mg×1 d (group C), 1.8 mg×2 d (group D) in succession, with 6 patients in each group. Each patient underwent rhTSH phase and thyroid hormone withdrawal (THW) phase. The end point included safety, tolerability, the quality of life (hypothyroidism symptom and sign score (Billewicz score), profile of mood states (POMS)), effectiveness (thyroid-stimulating hormone (TSH) and thyroglobulin (Tg) levels, diagnostic whole-body scan (Dx-WBS)) and pharmacokinetic characteristics (peak time, peak concentration) of rhTSH. Paired t test and Wilcoxon signed rank test were used for statistical analysis. Results:There were no dose-limiting toxicities, serious adverse events, or no grade ≥3 adverse events reported. The quality of life in rhTSH phase was significantly better than those in THW phase, including the lower Billewicz score (-53.00(-53.00, -53.00) vs -39.50(-47.00, -23.00); S=119.50, P<0.001) and the lower POMS score (91.92±12.06 vs 99.67±19.13; t=0.95, P=0.025). Serum TSH level was increased from 0.04(0.02, 0.11) mU/L (baseline) to 150.00(105.20, 173.31) mU/L 24 h after the last rhTSH administration, which was increased along with the elevation of rhTSH doses. In the THW phase, patients′ TSH levels were≥30 mU/L after 23 d (median) of THW, with the median of 73.51(57.22, 106.22) mU/L. Median Tg level of baseline was 0.10(0.10, 0.41) μg/L, which reached a peak of 0.85(0.12, 3.01) μg/L at 48 h after rhTSH administration. The peak Tg level in the THW phase was 0.88(0.15, 8.04) μg/L. The Dx-WBS consistency rate between rhTSH and THW phase was 95.8%(23/24). Conclusion:rhTSH is a safe and effective method to stimulate the serum Tg level and radioiodine uptake in patients undergoing post-operation or post- 131I assessment for DTC, as well as maintain a higher quality of life in comparison to THW phase.

Targeting TSHR and ICAM-1 for treatment of Graves′ disease in BALB/c mice / 中华核医学与分子影像杂志

Objective:To explore new methods of treating Graves′ disease (GD) by targeting thyroid stimulating hormone receptor (TSHR) and intercellular adhesion molecule-1 (ICAM-1).Methods:The small interfering RNA (siRNA) targeting TSHR and the ICAM-1 monoclonal antibody (mAb) were designed and synthesized. Thirty GD model mice were randomly divided into siRNA treatment group, ICAM-1 mAb treatment group, and untreated GD group (10 mice in each group), and 10 normal mice were taken as blank control. Serum thyroxine (T 4), thyroid stimulating hormone (TSH), TSH receptor-stimulating antibody (TSAb) and TSH-stimulation blocking antibody (TSBAb) were measured before and after treatment. At the end of the treatment, body mass and heart rate of mice in each group were measured, and thyroid uptake of 99Tc mO 4-, thyroid size and pathological changes were evaluated. Independent-sample t test, paired t test and one-way analysis of variance were used to analyze data. Results:After three treatments, the body mass of mice in siRNA group and ICAM-1 mAb group were significantly lower than that of normal mice ( F=3.50, P=0.025); the heart rates of the mice in two groups were significantly lower than that of untreated GD mice ( F=24.73, P<0.001). Heart rate of mice treated with siRNA decreased significantly, close to that of normal mice. After treatment, the serum T 4((27.58±1.94) vs (65.71±6.89) μg/L, (27.24±3.50) vs (70.84±8.46) μg/L), TSAb ((331.44±43.38) vs (457.33±45.85) mU/L, (275.16±45.80) vs (443.91±42.32) mU/L) and TSBAb ((13.94±1.11) vs (15.83±5.92) mU/L, (14.59±1.02) vs (17.05±6.16) mU/L) levels of mice in both siRNA group and ICAM-1 mAb group significantly decreased ( t values: 4.45-10.87, all P<0.05), while the serum TSH levels of mice in two groups significantly increased ((0.13±0.05) vs (0.04±0.05) mU/L, (1.46±0.34) vs (0.06±0.03) mU/L; t values: -2.22, -5.87, P values: 0.007, <0.001). The elevated TSH level and decreased TSAb level of mice treated with ICAM-1 mAb were significantly different from those treated with siRNA ( t values: 1.03, -1.63, P values: 0.002, 0.031). After treatment, the uptake of 99Tc mO 4- in part of the thyroid lobes of mice was decreased, and the enlargement degree of the corresponding lobes was reduced. The thyroid pathology of mice in the treated groups showed that the absorption vacuoles of thyroid follicles were reduced, and the phenomenon of thinner colloids was improved. No obvious damage was observed in the heart, liver and kidneys of the mice. Conclusions:Both the siRNA targeting TSHR and ICAM-1 mAb have therapeutic effects on GD model mice. The siRNA is better at controlling heart rate, and ICAM-1 mAb is better at increasing TSH and decreasing TSAb. Each of the above treatment methods is safe and effective, which can provide new ideas for GD targeted therapy.

Thyrotropin receptor antibody and bone turnover markers in the patients with newly-diagnosed Graves′ disease / 中华内分泌代谢杂志

Objective:To investigate the correlation between the level of thyrotropin receptor antibody(TRAb) and bone turnover markers(BTMs) in the patients with newly-diagnosed Graves′ disease(GD).Methods:The clinical data of GD patients who were newly-diagnosed in the First Affiliated Hospital of Zhengzhou University from October 2016 to June 2021 were collected, including free triiodothyronine(FT 3), free thyroxine(FT 4), thyroid stimulating hormone, thyroid related antibodies, N-terminal procollagen of type I collagen(PINP), N-terminal osteocalcin(N-MID), β-cross-linked C-telopeptide of type I(β-CTX), blood lipid and renal function, etc. Results:There were 618 GD patients with an average age of(43.7±13.2) years(male∶female=1∶1.99). The PINP and β-CTX level in male GD patients were significantly higher than those in female(all P<0.05). Spearman correlation analysis showed that PINP, N-MID and β-CTX were positively correlated with FT 3, FT 4, TRAb, serum calcium and serum phosphorus; and negatively correlated with body mass index and low density lipoprotein cholesterol(all P<0.05). Linear regression analysis showed that TRAb was positively correlated with lg-PINP, lg-N-MID and sqrt-β-CTX in the univariate model of total GD patients( β were 0.006, 0.005, and 0.006, respectively; all P<0.001); positive correlation remained after adjusting for thyroid function(all β=0.004, all P<0.001); and for multiple confounding factors(model 3 and 4, all P<0.05). Results of univariate and adjusted thyroid function models with GD in different genders were consistent with the total patients(all P<0.05). Conclusion:TRAb is a risk factor for accelerated bone turnover in GD patients which is independent of thyroid function.

Effect of Helicobacter pylori infection on standard dose of postoperative thyrotropin suppression therapy for differentiated thyroid cancer / 中华内分泌外科杂志

Objective:To study the effect of Helicobacter pylori (HP) infection on the standardized dose of postoperative thyrotropin suppression of differentiated thyroid carcinoma.Methods:A total of 82 patients diagnosed with differentiated thyroid carcinoma and receiving total thyroidectomy in Beijing Rehabilitation Hospital affiliated to Capital Medical University from Jan. 2019 to Jun. 2020 were enrolled in this study prospectively.19 patients with higher standardized dose of the thyrotropin suppression (>2.5 μg·kg -1·d -1) were selected as the experimental group, and 63 patients with the lower standardized dose of the thyrotropin suppression (≤2.5 μg·kg -1·d -1) were selected as the control group. The presence of HP infection was measured by C13 method, and the HP infection rate was compared between the two groups. The patients with HP infection in the experimental group received standard quadruple therapy to eradicate Helicobacter pylori. The standardized dose before and after treatment were observed and compared. Results:The HP infection rate in the experimental group (73.7%, 14/19) were significantly higher ( P<0.05) than those in the control group (31.7%, 20/63). In the experimental group, 14 patients with HP infection in the experimental group received standard quadruple therapy to eradicate HP. HP was successfully eradicated in 11 patients after the treatment (one patient quit the treatment before completion, the actual eradication rate was 84.6%) ; Eight weeks after the treatment, the dose adjustment of thyrotropin suppression reached steady-state in 13 patients completed the therapy. The average standardized dose was (2.15±0.25) μg·kg -1·d -1, significantly lower than that before treatment [ (2.89±0.21) μg·kg -1·d -1] ( P<0.05) . Conclusions:HP infection may be an important factor affecting the standardized dose of thyrotropin suppression in postoperative patients with thyroid cancer. For those patients with HP infection, eradication treatment of HP can significantly reduce the standardized dose and treatment-related complications.

Association between thyroid function in the first trimester in twin pregnancies and gestational diabetes mellitus / 中华围产医学杂志

Objective:To explore the associations between thyroid function in the first trimester in twin pregnancies and gestational diabetes mellitus (GDM) and the risk factors of twin pregnancies complicated by GDM.Methods:Retrospective analysis was performed on 745 twin pregnancies delivered after 28 weeks at the Third Affiliated Hospital of Sun Yat-sen University from January 2015 to December 2021, and they were divided into GDM group ( n=186) and the control (non-GDM) group ( n=559). Thyroid dysfunction was diagnosed based on the reference range of singleton and twin pregnancies recommended by the Guideline on diagnosis and management of thyroid diseases (2nd edition) in China and the literature, respectively. Independent sample t-test, Chi-square test, or Fisher exact test, and Mann-Whitney U test were used to compare the general clinical characteristics and thyroid function between the two groups. Spearman rank correlation analysis was performed to analyze the correlation between free thyroxine (FT 4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and fasting plasma glucose (FPG) in the first trimester as well as glucose levels in 75 g oral glucose tolerance test (OGTT). The associations between FT 4, TSH at different levels, and the detection rate of GDM, and the risk factors of GDM in twin pregnancies were analyzed using logistic regression. Results:(1) The prevalence of GDM in twin pregnancies was 25.0% (186/745). The positive rate of TPOAb was 13.6% (101/745). FPG in the first trimester was higher in the GDM group than that in the control [(4.7±0.5) vs (4.5±0.4) mmol/L, t=－5.08, P<0.001]. (2) No correlation between FT 4, TSH levels, the positive rate of TPOAb in the first trimester and FPG in the first trimester as well as OGTT results was found (all P>0.05). (3) There was no significant difference when using the thyroid function reference range for twin or singleton pregnancy in detecting hypothyroidism [0.5% (4/745) vs 0.4% (3/745)] and subclinical hypothyroidism [1.2% (9/745) vs 1.3% (10/745)] among the included subjects (both P>0.05), however, there were significant differences in the detection rates of hypothyroxinemia alone [25.0% (186/745) vs 12.9% (96/745)], hyperthyroidism [2.4% (18/745) vs 12.9% (96/745)] and subclinical hyperthyroidism [5.8% (43/745) vs 12.1% (90/745)]( χ2 were 35.43, 33.43 and 18.24, all P<0.001). There was no significant difference in the detection rate of thyroid disease between the GDM and control groups (all P>0.05). (4) FT 4 and TSH levels were grouped into quartiles ( Q1, Q2, Q3, and Q4), which showed that the detection rate of GDM was the highest [27.8% (52/187)] in women with FT 4 in Q1 and was the lowest [23.0% (43/187)] in those with FT 4 in Q2. However, the detection rate was the lowest in women with TSH in Q1 [24.1% (45/187)] and was the highest [27.4%(51/186)] in those with TSH in Q4. Taking Q1 of FT 4 and TSH as a reference, the logistic regression model showed that there were no statistically significant differences between FT 4, TSH at different levels, and GDM, even after adjusting for age, preconception-body mass index (pre-BMI), family history of diabetes, mode of conception, and chorionicity (all P>0.05). (5) Multivariate logistic regression analysis showed that maternal age ( OR=1.10, 95% CI: 1.05-1.15), pre-BMI ( OR=1.13, 95% CI: 1.07-1.21), family history of diabetes ( OR=2.73, 95% CI: 1.53-4.85), and FPG in the first trimester ( OR=2.14, 95% CI: 1.38-3.32) were independent risk factors for twin pregnancies complicated by GDM. Conclusions:Twin pregnant women with higher maternal age, pre-BMI, FPG in the first trimester and family history of diabetes were at higher risk of GDM. No significant correlation is found between maternal thyroid function in the first trimester and GDM in twin pregnancies.