Up to date with human thyroglobulin

Graaf, S. A. R. Van De; Ris‐Stalpers, Carrie; Pauws, Erwin; Mendive, Fernando; Targovnik, Héctor M.; Vijlder, J. J. M. De

doi:10.1677/joe.0.1700307

Cited by 134 publications

(97 citation statements)

References 59 publications

(39 reference statements)

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“…It is a glycoprotein comprising two 330 kDa protein chains synthesized in the thyrocyte (10). After synthesis, Tg is transported and stored in the follicular colloid of the thyrocyte (11).…”

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confidence: 99%

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Feei

Skeaff²

2014

Thyroid

130

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Background: Thyroglobulin, produced exclusively by the thyroid gland, has been proposed to be a more sensitive biomarker of iodine status than thyrotropin or the thyroid hormones triiodothyronine and thyroxine. However, evidence on the usefulness of thyroglobulin (Tg) to assess iodine status has not been extensively reviewed, particularly in pregnant women and adults. Summary: An electronic literature search was conducted using the Cochrane CENTRAL, Web of Science, PubMed, and Medline to locate relevant studies on Tg as a biomarker of iodine status. Since urinary iodine concentration (UIC) is the recommended method to assess iodine status in populations, only studies that clearly reported both Tg and UIC were included. For the purpose of this review, a median Tg <13 lg/L and a median UIC ‡100 lg/L (UIC ‡150 lg/L for pregnant women) were used to indicate adequate iodine status. We excluded studies conducted in subjects with either known thyroid disease or those with thyroglobulin antibodies. The search strategy and selection criteria yielded 34 articles of which nine were intervention studies. The majority of studies (six of eight) reported that iodine-deficient pregnant women had a median Tg ‡13 lg/L. However, large observational studies of pregnant women, including women with adequate and inadequate iodine status, as well as well-designed intervention trials that include both Tg and UIC, are needed. In adults, the results were equivocal because iodine-deficient adults were reported to have median Tg values of either <13 or ‡13 lg/L. Only studies in school-aged children showed that iodine-sufficient children typically had a median Tg <13 lg/L. Some of the inconsistent results may be partially explained by the use of different methodological assays and failure to assess assay accuracy using a certified reference material. Conclusions: These data suggest that Tg does hold promise as a biomarker of iodine deficiency. However, it is associated with limitations. A median Tg cutoff of 13 lg/L warrants further investigation, particularly in adults or pregnant women, as there is a lack of both observational and intervention studies in these groups.

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confidence: 99%

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Feei

Skeaff²

2014

Thyroid

130

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“…We consider that this compound heterozygous mutation in the thyroglobulin gene resulted in hypothyroidism for the following reasons: (1) undetectable thyroglobulin levels in the serum in the presence of goiter, (2) the asymptomatic mother was a carrier of only one mutation, (3) these single nucleotide substitutions were not found to be polymorphic in previous reports (Hishinuma et al 1999;van de Graaf et al 2001). Two novel missense mutations in the thyroglobulin gene were found in this study.…”

Section: Discussionmentioning

confidence: 59%

“…Two novel missense mutations in the thyroglobulin gene were found in this study. Residue Arg2336 is located in the acetylcholinesterase (ACHE) homology domain (van de Graaf et al 2001). Recently, the ACHE homology domain has been shown to be essential for the normal secretion of thyroglobulin (Park and Arvan 2004).…”

Section: Discussionmentioning

confidence: 99%

A novel compound heterozygous mutation in the thyroglobulin gene resulting in congenital goitrous hypothyroidism with high serum triiodothyronine levels

et al. 2006

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A novel compound heterozygous mutation in the thyroglobulin gene resulting in congenital goitrous hypothyroidism with high serum triiodothyronine levels Abstract Thyroglobulin abnormality is a rare cause of congenital hypothyroidism and only a limited number of mutations in the thyroglobulin gene have been reported. We analyzed the thyroglobulin gene in a patient with congenital goitrous hypothyroidism. This girl was identified with hyperthyrotropinemia in a neonatal mass-screening test. The patient had goiter, and her body weight gain was poor. Distal femoral epiphysis was absent on roentgenography. Her serum thyroxine level was low; however, her triiodothyronine level was high. Autoantibodies against triiodothyronine, thyroid peroxidase, and thyroglobulin were all negative. Her serum thyroglobulin level was undetectable. The thyroglobulin gene from the genomic DNA of the patient was analyzed by direct sequencing. Two novel heterozygous missense mutations, Cys1897Tyr (exon 31) and Arg2336Gln (exon 40), were found in the patient. The former mutation was derived from her mother, suggesting a compound heterozygous state. Normal triiodothyronine and low thyroxine concentrations are often observed in patients with thyroglobulin gene mutations. We considered that some patients with thyroglobulin abnormality might have high triiodothyronine levels. In cases of congenital goitrous hypothyroidism with normalto-high triiodothyronine levels and low serum thyroglobulin levels, thyroglobulin abnormality should be considered.

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“…É codificada por um gene de pelo menos 300 kb, contendo 48 exons e localizado no cromossomo 8 (16)(17)(18). O produto final é uma glicoproteína de 660 kDa, formada por 2 subunidades idênticas, unidas por ligação não-covalente.…”

Section: Dificuldades Técnicas Da Dosagem De Tireoglobulina Séricaunclassified

Amplificação de mRNA de tireoglobulina no sangue de pacientes com carcinoma diferenciado da tireóide: qual o seu verdadeiro significado?

Coelho

Carvalho

2006

Arq Bras Endocrinol Metab

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RESUMOApesar do excelente prognóstico, aproximadamente 20-40% dos pacientes com carcinoma diferenciado da tireóide (CDT) evoluem com recidiva tumoral e o prognóstico está relacionado principalmente à detecção precoce da doença. Desta forma, o acompanhamento permanente dos pacientes com exames sensíveis é fundamental. A tireoglobulina (Tg) sérica já demonstrou importância como marcador de recidiva. Entretanto, sua dosagem apresenta ainda algumas dificuldades, como a interferência com anticorpo anti-Tg, e a sensibilidade dependente do nível de TSH. A amplificação de mRNA tumor-específico extraído a partir de células neoplásicas na corrente sangüínea apresentou resultados iniciais promissores. No entanto, após quase uma década de estudo da detecção do mRNA de Tg no sangue, ainda não foi estabelecida sua real contribuição no acompanhamento dos pacientes com CDT. Após análise crítica dos estudos publicados, verifica-se a enorme diversidade de protocolos empregados e resultados conflitantes. Desta forma, até o momento, a amplificação de mRNAs tireóide-específicos não é superior à dosagem de Tg sérica existente. A possibilidade de transcrição ilegítima e splicing alternativo são fatores que podem interferir com a especificidade do método. Despite the excellent prognosis, differentiated thyroid carcinoma (DTC) may recur in 20-40%, and prognosis is particularly related to early detection of recurrent disease. Therefore, long-term follow-up with sensitive tests is need. Serum thyroglobulin (Tg) has an established role as a tumor marker of relapse. However, there are technical limitations of Tg immunoassays, in special, the interference of anti-Tg antibodies and the method sensitivity is dependent on TSH stimulation. Detection of circulating malignant cells by amplification of tumor-specific mRNA showed initial promising results. However, almost one decade of studies of Tg mRNA detection in peripheral blood, its real contribution for DTC follow-up had not yet been established. After a critical analysis of published data, it is clear that there are many protocol differences and conflicting results. Therefore, it seems that amplification of thyroidspecific mRNAs is not superior to sensitive Tg assays and illegitimate transcription and alternative splicing of Tg are factors that may influence mRNA test specificity.

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Up to date with human thyroglobulin

Cited by 134 publications

References 59 publications

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

Thyroglobulin as a Biomarker of Iodine Deficiency: A Review

A novel compound heterozygous mutation in the thyroglobulin gene resulting in congenital goitrous hypothyroidism with high serum triiodothyronine levels

Amplificação de mRNA de tireoglobulina no sangue de pacientes com carcinoma diferenciado da tireóide: qual o seu verdadeiro significado?

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