Treatment of lidocaine on subacute thyroiditis via restraining inflammatory factor expression and inhibiting pyroptosis pathway.

BACKGROUND: To explore the role of lidocaine on subacute thyroiditis (SAT) and the molecular mechanism. METHODS: SAT models were constructed by infecting adenovirus to thyroid follicular epithelial cells. Cells were randomly divided into five groups: model group, low lidocaine, middle lidocaine, high lidocaine, and a control group. Thyroid secretion related factors TG and TPO, T3 and T4 were separately determined by reverse transcription-polymerase chain reaction (RT-PCR) and radioimmunoassay. Flow cytometry was used to determine thyroid follicular epithelial cell apoptosis situation. RT-PCR and Western blot analysis were used to determine the expression of inflammatory cytokines and pyroptosis related factors interleukin (IL)-1α, IL-6, THF-α, ELAVL1, NLR family pyrin domain containing 3 (NLRP3), caspase-1, and IL-1ß. RESULTS: Lidocaine decreased the relative level of TG, TPO, T3, and T4 in adenovirus-infected thyroid follicular epithelial cells. All levels of concentrations, including low, middle, and high, of lidocaine, significantly decreased the apoptosis rate of adenovirus-infected cells. Lidocaine dramatically reduced the protein expression of IL-1α, IL-6, THF-α, ELAVL1, NLRP3, caspase-1, and IL-1ß in adenovirus-infected thyroid follicular epithelial cells. CONCLUSION: Lidocaine can improve SAT through inhibiting expression of inflammatory factors and the pyroptosis pathway.

Heterozygous Mutations of the DUOXA2 and DUOX2 Genes in Dizygotic Twins with Congenital Hypothyroidism.

BACKGROUND: The mutations in the dual oxidase maturation factor 2 (DUOXA2) and dual oxidase 2 (DUOX2) genes have been identified in patients with congenital hypothyroidism (CH). This study reports a set of dizygotic twins with CH due to the mutations in the DUOX2/DUOXA2 system. METHODS: The dizygotic twins, a boy and a girl, both aged 7 years, were born to euthyroid nonconsanguineous parents; they were diagnosed with CH at neonatal screening and were enrolled in this study. The DUOXA2, DUOX2, paired box 8 (PAX8), thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) genes were considered for mutation screening. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen for the mutations in the exon fragments. Family members of the patients were also enrolled and evaluated. RESULTS: The fraternal twins each harbored a single heterozygous mutation, including c.738C>G (p.Y246X) in the boy inherited from the paternal DUOXA2 allele and c.2654G>A (p.R885Q) in the girl from the maternal DUOX2 allele. The two mutations have been previously reported. The boy showed enlarged thyroid lobes and a little calcification in the left lobe, while the girl's thyroid gland was severely underdeveloped and the girl had obvious complications due to irregular treatment. The germline mutations from this family were consistent with an autosomal recessive inheritance pattern. No mutations in the PAX8, TPO, and TSHR genes were detected in this study. CONCLUSIONS: The inactivating mutations in the DUOXA2 (p.Y246X) and DUOX2 (p.R885Q) genes were identified in a set of dizygotic twins with CH. The girl was more severe in several aspects than her brother. The similar genetic defect resulted in very different outcomes.

Two novel TSHR gene mutations (p.R528C and c.392+4del4) associated with congenital hypothyroidism.

Inactivating mutations of the thyrotropin receptor (TSHR) gene are responsible for non-goitrogenic congenital hypothyroidism (CHNG). This study aimed to investigate mutations in the TSHR gene in 20 children with CHNG. Genomic DNA was extracted from peripheral blood leukocytes and was used for mutation screening by direct sequencing. Analyses of the TSHR gene revealed two novel variants in a 2-year-old boy with thyroid hypoplasia: a missense mutation c.1582C>T (p.R528C) and a splice-site deletion c.392+4del4. Bioinformatics analysis demonstrated that both variants are capable of causing disease. Family members of the patient with two mutations and normal controls were also recruited and investigated. Germline mutations from the proband's family were consistent with an autosomal recessive inheritance pattern. These findings indicate that two novel inactivating mutations (p.R528C and c.392+4del4) in the TSHR gene can cause CHNG.

Novel genetic variants in the TPO gene cause congenital hypothyroidism.

BACKGROUND: Mutations in the dual oxidase maturation factor 2 (DUOXA2) and thyroid peroxidase (TPO) genes have been reported to cause goitrous congenital hypothyroidism (GCH). The aim of this study was to determine the genetic basis of GCH in affected children. METHODS: Thirty children with GCH were enrolled for molecular analysis of the DUOXA2 and TPO genes. All subjects underwent clinical examination and laboratory testing. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen for DUOXA2 and TPO gene mutations in the exon fragments amplified from the extracted DNA. Family members of those patients with mutations were also enrolled and evaluated. RESULTS: Analysis of the TPO gene revealed six genetic variants, including two novel heterozygous mutations, c.1970T> C (p.I657T) and c.2665G> T (p.G889X), and four mutations that have been reported previously (c.670_672del, c.2268dup, c.2266T> C and c.2647C> T). Three patients harbored the same mutation c.2268dup. The germline mutations from four unrelated families were consistent with an autosomal recessive inheritance pattern. Conversely, no mutations in the DUOXA2 gene were detected. CONCLUSION: Two novel inactivating mutations (c.1970T> C and c.2665G> T) in the TPO gene were identified. The c.2268dup mutation occurred frequently. No mutations in the DUOXA2 gene were detected in this study.

Serum levels of glucagon-like peptide (GLP)-1 and GLP-2 in patients with Hashimoto's thyroiditis.

BACKGROUND: The influence of Hashimoto's thyroiditis (HT) with subclinical hypothyroidism or euthyroid status on the alteration of glucagon-like peptide (GLP)-1 and GLP-2 levels remains uncertain. MATERIALS AND METHODS: Twenty-four untreated HT patients with subclinical hypothyroidism, 24 euthyroid HT patients, and 24 age- and gender-matched controls were enrolled in the study. The levels of GLP-1, GLP-2, glucose, glycated albumin, insulin, thyroid hormone, and thyroid autoantibodies were measured and evaluated. RESULTS: The levels of GLP-1, blood glucose, and triglyceride were higher in HT patients with subclinical hypothyroidism than in controls (all P < 0.05, respectively). However, the above variables, including GLP-2, were similar in euthyroid patients and controls. Neither GLP-1 nor GLP-2 was correlated with thyroid hormone, thyroid autoantibodies or metabolic parameters. CONCLUSION: The serum levels of GLP-1, not GLP-2, were increased in patients with subclinical hypothyroidism. Our data suggest that subclinical hypothyroidism affects circulating GLP-1 levels.

Correlation between peripheral white blood cell counts and hyperglycemic emergencies.

OBJECTIVE: To determine the correlation between differential leukocyte counts and hyperglycemic emergencies. METHODS: Fifty patients with diabetic ketoacidosis (DKA), 50 patients with diabetic ketosis (DK), 50 non-DK diabetic patients with stable glycemic control, and 50 normal controls were enrolled. Their total and differential leukocyte counts were measured and evaluated at admission and after treatment. RESULTS: The patients with DKA and DK had higher plasma glucose levels (20.84±6.73 mmol/L, 15.55±2.6 mmol/L, respectively) and more median leukocytes (13325/mm(3) and 6595/mm(3), respectively) and median neutrophils (11124 /mm(3) and 4125/mm(3), respectively) but fewer median eosinophils (28/mm(3) and 72/mm(3), respectively) compared to non-DK and control groups (all p < 0.05). Acute infection increased the elevating extent. The median leukocyte counts in DK and non-DK patients (6595/mm(3) and 6008/mm(3), respectively) were within the normal range. The counts of total leukocytes and neutrophils were significantly higher but eosinophils lower in severe DKA cases than in mild/moderate cases (p < 0.05). When the DKA and DK and infection resolved, total leukocytes and neutrophils fell, but eosinophils increased. The counts of total leukocytes, neutrophils, and monocytes were negatively correlated with arterial pH levels (r = -0.515, r = -0.510, r = -0.517, all p < 0.001, respectively) and positively correlated with plasma glucose levels (r = 0.722, r = 0.733, r = 0.632, all p < 0.05, respectively) in DKA patients. The arterial pH level was the most significant factor affecting total leukocytes in DKA (ß = 0.467, p = 0.003). The diagnosis analysis showed that higher total leukocyte and neutrophil counts and lower eosinophil counts had a significant ability to reflect the presence of hyperglycemic emergencies. CONCLUSION: More total leukocytes and neutrophils but fewer eosinophils was significantly correlated with DKA and DK. Leukocyte counts can add valuable information to reflect the presence of hyperglycemic crisis and acute infection.

Assessment of the platelet parameters and serum butyrylcholinesterase activity in type 1 diabetes patients with ketoacidosis.

The potential roles of serum butyrylcholinesterase (BChE) activity and platelet indices in type 1 diabetes (T1D) remain uncertain. We aimed to investigate the correlation among the platelet indices, serum BChE activity, and diabetic ketoacidosis (DKA). Sixty-one T1D patients, 29 patients with DKA, and 30 age- and sex-matched controls were enrolled. Mean platelet volume (MPV), platelet distribution width (PDW), and serum BChE activity were measured and evaluated at admission and after the treatment. The serum BChE activity was significantly lower in patients with DKA at admission to the hospital compared with non-DKA and control subjects; however, plasma glucose level, HbA1c level, MPV and PDW were significantly higher. Serum BChE activity, variables related to glycemic control, and platelet parameters were higher in non-DKA patients than in controls. Serum BChE activity was correlated with the serum HCO3 level (r = 0.375, p < 0.05) and plasma glucose level (r = -0.387, p < 0.05). Receiver operating characteristic curve analyses showed no difference between serum BChE activity and the platelet parameters with respect to the ability to reflect DKA. Logistic regression showed that increased PDW can act as a risk marker for the presence of DKA. Serum BChE activity and the platelet parameters returned to normal along with the plasma glucose levels when metabolic acidosis was well controlled. Serum BChE activity and the platelet parameters were significantly correlated with DKA. Measurement of PDW can provide complementary information and a risk biomarker reflecting the presence of DKA.

The ratio of red cell distribution width to mean corpuscular volume in patients with diabetic ketoacidosis.

BACKGROUND: The relationship between erythrocyte parameters and diabetic ketoacidosis (DKA) remains uncertain. This study aimed to investigate the potential role of erythrocyte indices in type 1 diabetes (T1D) patients with DKA. METHODS: This study included 48 patients with T1D, 26 patients with DKA, and 30 age- and gender-matched controls. Erythrocyte parameters were measured and evaluated at the time of admission and after treatment. RESULTS: Data were analyzed by One-Way ANOVA Tukey analysis with SPSS software. The DKA patients had higher levels of plasma glucose (28.87 +/- 9.01 mmol/L), HbA1c (13.08 +/- 3.10%), osmotic pressure (332.11 +/- 11.67 mosm/L), red cell distribution width (RDW, 41.24 +/- 3.08 fL), and the RDW to mean corpuscular volume (MCV) ratio (47.50 +/- 3.70%) compared to non-DKA cases and controls (all p < 0.05). Pearson's correlation test showed that osmolality was positively correlated with plasma glucose (r = 0.699, p < 0.001) and negatively correlated with mean corpuscular hemoglobin concentration (MCHC) (r = -0.409, p = 0.049). Receiver operating characteristic curve analyses demonstrated that the areas under the curves were 0.924 for the RDW/MCV ratio and 0.802 for RDW in the ability of reflecting DKA (z = 2.086, p = 0.0369). A logistic regression revealed that the RDW/MCV ratio can act as a robust risk marker for the presence of DKA (OR = 1.548, p = 0.0360, 95% CI: 1.029 - 2.330). The RDW returned to normal, and plasma glucose levels and metabolic acidosis were well controlled following treatment. CONCLUSIONS: The RDW and the RDW/MCV ratio were significantly correlated with DKA. The RDW/MCV ratio can act as a robust biomarker that is more sensitive than RDW in reflecting the presence of DKA.

Real-world effect of the treatment for painful subacute thyroiditis: The combined injection of lidocaine and triamcinolone using an insulin pen.

Objective: : Intrathyroidal injection using an insulin pen filled with a mixture of lidocaine and triamcinolone acetonide is a therapy for subacute thyroiditis (SAT) reported by us previously. We aimed to evaluate the clinical efficacy of ultrasound-guided intrathyroidal injection in the treatment of SAT. Subjects and methods: A total of 93 patients with SAT completed the study. All patients were evaluated via a history and clinical examination followed by thyroid function tests and ultrasonography of the thyroid. After ultrasound-guided intrathyroidal injection, the patients were followed up with respect to the injection frequency, treatment duration, and patient satisfaction. The visual numerical rating scale was used as a pain questionnaire for a given interval. Results: Thyroid pain instantly decreased to scores below 3.0 following the first injection. Sixty-three patients (67.74%) avoided relapse of thyroid pain within 3 injections, which occurred within only 3 days after the first injection. The pain in 27 patients (29.03%) disappeared completely after 4-6 injections. Only 3 patients (3.23%) were found to need more than 6 injections, with 10 cited as the maximum number of injections, the injection took only 17 days altogether. The mean treatment cycle of the intrathyroidal injection was 3.98 days. There were no other associated complications with the novel therapy except infrequent small subcutaneous hematomas, which could be prevented with skilled practice. The average patient satisfaction score was as high as 9.0. Conclusion: Intrathyroidal injection of lidocaine and triamcinolone acetonide using an insulin pen was found to be an advantageous and satisfactory treatment for SAT.

Evaluation of serum ischemia-modified albumin levels in pregnant women with and without gestational diabetes mellitus.

OBJECTIVE: To investigate serum ischemia-modified albumin (IMA) levels in gestational diabetes mellitus and the effect of treatment with continuous subcutaneous insulin infusion on the biomarker. METHODS: The gestational diabetes mellitus women in the second trimester were evaluated before and after the two kinds of treatments with continuous subcutaneous insulin infusion and medical nutrition therapy for 6 weeks. Maternal serum ischemia-modified albumin and metabolic parameters were measured at baseline and at the 6th week. RESULTS: Serum ischemia-modified albumin levels and metabolic parameters were higher in patients with gestational diabetes mellitus at baseline than in controls. Ischemia-modified albumin levels were correlated with plasma glucose (p < 0.05). Variables of glycemic control and ischemia-modified albumin levels were significantly reduced at the 6th week. The effect of insulin treatment was generally better than diet therapy. Linear regression analysis showed that fasting plasma glucose was an independent determinant for IMA levels (ß = 0.611, p = 0.035).Fetal outcome was similar except for macrosomia and Apgar score at 5 min. CONCLUSION: Serum ischemia-modified albumin levels were higher in gestational diabetes mellitus compared to normal pregnancy. Continuous subcutaneous insulin infusion consistently improved metabolic disorder control. Gestational diabetes mellitus women were associated to a higher risk of oxidative stress and pregnancy complications.

The R450H mutation and D727E polymorphism of the thyrotropin receptor gene in a Chinese child with congenital hypothyroidism.

BACKGROUND: Congenital hypothyroidism (CH) is the most prevalent congenital endocrine disorder. The molecular cause of CH in the majority of newborns is unknown. The aim of this study was to investigate the mutation of thyrotropin receptor (TSHR) gene in Chinese children with congenital hypothyroidism (CH). and the hereditary characteristic. METHODS: Eighteen Chinese children with CH were enrolled for molecular analysis of the TSHR gene and 105 normal controls were evaluated. The exons 1-9, and 10 of TSHR gene were detected by PCR-SSCP (single-stranded conformation polymorphism) and sequenced. RESULTS: A slower and a faster mobility SSCP shift showed in a 12-year old child with hypoplasic gland. Sequencing of TSHR gene revealed a homozygous mutation (CGC --> CAC, Arg450His) and a polymorphism (GAC --> GAG, Asp727Glu). The controls revealed no variants. The 12 relatives of the proband were enrolled and investigated. Six relatives, including his mother and father, were heterozygous for R450H mutation and D727E polymorphism of the TSHR gene. Thyroid hormone levels were normal except for circulating TSH (5.96-6.92 mU/L) level slightly elevated in six heterozygous family members. CONCLUSIONS: Homozygous mutation R450H of the TSHR gene led to CH. Heterozygous mutation R450H was the cause of subclinical hypothyroidism.

Suppression of long non-coding RNA TNRC6C-AS1 protects against thyroid carcinoma through DNA demethylation of STK4 via the Hippo signalling pathway.

OBJECTIVES: Thyroid carcinoma (TC) represents a malignant neoplasm affecting the thyroid. Current treatment strategies include the removal of part of the thyroid; however, this approach is associated with a significant risk of developing hypothyroidism. In order to adequately understand the expression profiles of TNRC6C-AS1 and STK4 and their potential functions in TC, an investigation into their involvement with Hippo signalling pathway and the mechanism by which they influence TC apoptosis and autophagy were conducted. METHODS: A microarray analysis was performed to screen differentially expressed lncRNAs associated with TC. TC cells were employed to evaluate the role of TNRC6C-AS1 by over-expression or silencing means. The interaction of TNRC6C-AS1 with methylation of STK4 promoter was evaluated to elucidate its ability to elicit autophagy, proliferation and apoptosis. RESULTS: TNRC6C-AS1 was up-regulated while STK4 was down-regulated, where methylation level was elevated. STK4 was verified as a target gene of TNRC6C-AS1, which was enriched by methyltransferase. Methyltransferase's binding to STK4 increased expression of its promoter. Over-expressed TNRC6C-AS1 inhibited STK4 by promoting STK4 methylation and reducing the total protein levels of MST1 and LATS1/2. The phosphorylation of YAP1 phosphorylation was decreased, which resulted in the promotion of SW579 cell proliferation and tumorigenicity. CONCLUSION: Based on our observations, we subsequently confirmed the anti-proliferative, pro-apoptotic and pro-autophagy capabilities of TNRC6C-AS1 through STK4 methylation via the Hippo signalling pathway in TC.

Real-world effect of the treatment for painful subacute thyroiditis: The combined injection of lidocaine and triamcinolone using an insulin pen

ABSTRACT Objective: Intrathyroidal injection using an insulin pen filled with a mixture of lidocaine and triamcinolone acetonide is a therapy for subacute thyroiditis (SAT) reported by us previously. We aimed to evaluate the clinical efficacy of ultrasound-guided intrathyroidal injection in the treatment of SAT. Subjects and methods: A total of 93 patients with SAT completed the study. All patients were evaluated via a history and clinical examination followed by thyroid function tests and ultrasonography of the thyroid. After ultrasound-guided intrathyroidal injection, the patients were followed up with respect to the injection frequency, treatment duration, and patient satisfaction. The visual numerical rating scale was used as a pain questionnaire for a given interval. Results: Thyroid pain instantly decreased to scores below 3.0 following the first injection. Sixty-three patients (67.74%) avoided relapse of thyroid pain within 3 injections, which occurred within only 3 days after the first injection. The pain in 27 patients (29.03%) disappeared completely after 4-6 injections. Only 3 patients (3.23%) were found to need more than 6 injections, with 10 cited as the maximum number of injections, the injection took only 17 days altogether. The mean treatment cycle of the intrathyroidal injection was 3.98 days. There were no other associated complications with the novel therapy except infrequent small subcutaneous hematomas, which could be prevented with skilled practice. The average patient satisfaction score was as high as 9.0. Conclusion: Intrathyroidal injection of lidocaine and triamcinolone acetonide using an insulin pen was found to be an advantageous and satisfactory treatment for SAT.

Improvement of therapeutic effects of mesenchymal stem cells in myocardial infarction through genetic suppression of microRNA-142.

Transplanted mesenchymal stem cells (MSCs) have been shown to contribute to myocardial repair after myocardial infarction (MI), primarily through production and secretion some growth factors and cytokines related to cell survival and regeneration. Further improvement of the therapeutic potential of MSCs appears to be an attractive strategy for MI treatment. CXC chemokine receptor (CXCR) 7 is the receptor for stromal cell-derived factor-1 (SDF-1), an important chemokine that is essential for tissue repair and angiogenesis. SDF-1/CXCR7 axis plays a critical role in the mobilization, recruitment and function of MSCs during tissue regeneration. Here, we depleted miR-142 that targets CXCR7 in MSCs cells through expression of antisense of miR-142, resulting in enhanced expression of CXCR7 in these miR-142-depleted MSCs (md-MSCs). In vitro, presence of md-MSCs reduced hypoxia-induced cardiac muscle cell apoptosis in a more pronounced manner than MSCs. In vivo, compared to transplantation of MSCs, transplantation of md-MSCs further enhanced cardiac re-vascularization and further improved cardiac functions after MI in mice. Together, our data suggest that depletion of miR-142 in MSCs may improve their therapeutic effects on MI.

Compound Heterozygous Mutations in the DUOX2/DUOXA2 Genes Cause Congenital Hypothyroidism.

The mutations in the dual oxidase 2 (DUOX2) and dual oxidase maturation factor 2 (DUOXA2) genes can cause congenital hypothyroidism (CH). This study reports the pedigree with goitrous congenital hypothyroidism (GCH) due to the coexistence of heterozygous mutations in the DUOX2 and DUOXA2 genes. The two sisters with GCH were diagnosed with CH at neonatal screening and were enrolled in this study. The DUOX2, DUOXA2, and thyroid peroxidase (TPO) genes were considered for genetic defects screening. Family members of the patients and normal controls were also enrolled and evaluated. The two girls harbored compound heterozygous mutations, including a new mutation of c.2654G>T (p.R885L) in the maternal DUOX2 allele and c.738C>G (p.Y246X) in the paternal DUOXA2 allele, that has been previously reported. The germline mutations from the families were consistent with an autosomal recessive inheritance pattern. No mutations in the TPO gene and the controls were observed.

Compound heterozygous mutations (p.T561M and c.2422delT) in the TPO gene associated with congenital hypothyroidism.

BACKGROUND: The objective of the study was to determine the genetic basis of goitrous congenital hypothyroidism (GCH) in Chinese siblings. METHODS: The proband and her younger brother with GCH were enrolled for molecular analysis of the dual oxidase 2 (DUOX2), dual oxidase maturation factor 2 (DUOXA2), and thyroid peroxidase (TPO) genes. Mutation screening was performed by Sanger sequencing the fragments amplified from genomic DNA. The detected mutations were verified among the close relatives of the patients and 105 controls. All participants underwent clinical examination and laboratory tests. RESULTS: Analysis of the TPO gene revealed two heterozygous mutations, the frameshift mutation c.2422delT in the exon14 of the TPO gene, that has been reported previously, and a novel missense mutation c.1682C>T (p.T561M) in the exon10 of the TPO gene. Nine family members of the patients were enrolled for mutation screening. The patients' parents and grandfathers harbored a single heterozygous mutation. The germline mutations from this family were consistent with an autosomal recessive inheritance pattern. No mutations in the DUOXA2 and DUOX2 genes were observed. CONCLUSIONS: The inactivating mutations (c.2422delT and p.T561M) in the TPO gene were identified in the Chinese siblings with GCH. The compound heterozygous mutations can cause GCH.

A Novel c.554+5C>T Mutation in the DUOXA2 Gene Combined with p.R885Q Mutation in the DUOX2 Gene Causing Congenital Hypothyroidism.

The coexistence of mutations in the dual oxidase maturation factor 2 (DUOXA2) and dual oxidase 2 (DUOX2) genes is rarely identified in congenital hypothyroidism (CH). This study reports a boy with CH due to a novel splice-site mutation in the DUOXA2 gene and a missense mutation in the DUOX2 gene. A four-year-old boy was diagnosed with CH at neonatal screening and was enrolled in this study. The DUOXA2, DUOX2, thyroid peroxidase (TPO), and thyrotropin receptor (TSHR) genes were considered for genetic defects screening. Genomic DNA was extracted from peripheral blood leukocytes, and Sanger sequencing was used to screen the mutations in the exon fragments. Family members of the patient and the controls were also enrolled and evaluated. The boy harbored compound heterozygous mutations including a novel splice-site mutation c.554+5C>T in the maternal DUOXA2 allele and c.2654G>A (p.R885Q) in the paternal DUOX2 allele. The germline mutations from his parents were consistent with an autosomal recessive inheritance pattern. No mutations in the TPO and TSHR genes were detected. A novel splice-site mutation c.554+5C>T in the DUOXA2 gene and a mutation p.R885Q in the DUOX2 gene were identified in a 4-year-old patient with goitrous CH.

Coexistence of resistance to thyroid hormone and ectopic thyroid: ten-year follow-up.

Resistance to thyroid hormone (RTH) coexisting with ectopic thyroid is rare. Here we report a case of RTH with ectopic thyroid. A ten-year-old girl had been misdiagnosed as congenital hypothyroidism and treated with levothyroxine since she was born. Ten-year follow-up showed that the elevated thyrotropin was never suppressed by levothyroxine and no signs indicating hyperthyroidism or hypothyroidism despite elevated FT3 and FT4 levels. Therefore the girl developed no defects in physical and cognitive development. Pituitary adenoma was excluded by magnetic resonance imaging. Ultrasonography did not find the thyroid gland in the normal place, while the thyroid scan found a large lingual thyroid gland. The octreotide inhibition test showed a reduction in thyrotropin by 41.98%. No mutation was detected in the thyroid hormone receptor (THR) ß, THRα, thyrotropin receptor (TSHR), and GNAS1 genes. To our knowledge, it is an interesting RTH case coexisting with lingual thyroid.

TPO gene mutations associated with thyroid carcinoma: Case report and literature review.

BACKGROUND: The thyroperoxidase (TPO) genetic variants in thyroid carcinoma is scarcely reported. OBJECTIVE: We report on a pedigree of thyroid papillary carcinoma and hypoechoic thyroid nodules with the TPO gene mutations. METHODS: The compound heterozygotic mutations of the TPO gene (c.2268-2269 insT and c.2090 G>A) in two patients with congenital goiters hypothyroidism were demonstrated. Fifteen family members of the proband and 105 control individuals were enrolled. The participants underwent clinical examination and molecular screening for TPO mutation. The hypoechoic thyroid nodules underwent fine needle aspiration biopsy. RESULTS: The mutation c.2268-2269 insT was detected in the four family members with normal thyroid hormone levels. The other two members harbored the c.2090 G>A mutation. The heterozygotes had degeneratively hypoechoic thyroid nodules. The control individuals showed no mutation. The maternal grandfather developed a multifocal papillary thyroid carcinoma with lymph gland and nerve invasion in the left lobe of the thyroid gland. The maternal grandfather harbored the TPO c.2268-2269 insT mutation but without BRAFV600E mutation. Malignant cells were not observed in other members by fine needle aspiration biopsy. CONCLUSION: TPO genetic variants may be associated with thyroid carcinoma and hypoechoic thyroid nodules in a few cases. Long-term follow-up in the pedigree with congenital goiter is reasonable.

Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism.

OBJECTIVE: To investigate well-controlled congenital hypothyroidism on the markers associated with early kidney injury and oxidative DNA damage. METHODS: Twenty-three children with euthyroid congenital hypothyroidism aged 3-6 years and 19 age- and gender-matched controls were enrolled. Serum levels of albumin, C-reactive protein, cysteine C, globulin, pre-albumin, and total protein were detected. Urine levels of albumin, fibrin degradation products, IgG, ß2-microglobulin, and 8-hydroxydeoxyguanosine (8-OHdG) were also measured. Clinical and biochemical characteristics were evaluated between the two groups. RESULTS: Serum levels of C-reactive protein were higher, but pre-albumin was lower in patients with congenital hyperthyroidism compared with the controls (all p<0.001). Urinary levels of IgG were higher in patients with congenital hyperthyroidism than in the controls (p=0.011). However, urinary levels of albumin excretion and 8-OHdG were similar to those in the controls. Serum pre-albumin levels were negatively correlated with urinary 8-OHdG levels (r=-0.479, p=0.016) in patients with congenital hypothyroidism. CONCLUSION: It is concluded that inflammatory and oxidative markers were slightly altered in well-controlled congenital hypothyroidism. The levels of urinary 8-OHdG and albumin excretion were not significantly different.