• Journal of Life Science
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• v.13 no.3
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• pp.248-251
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• 2003

The kinetics of dimerization of a newly synthesized thyroglobulin (Tg), the precursor protein in the manufacture of thyroid hormone, was investigated in the endoplasmic reticulum of thyrocytes FRTL-5 cell line. The folded monomeric Tg was first detectable in a conformationally unstable form, from the examination of lysates of pulse labeled cultured thyrocytes by denaturing and nondenaturing gel electrophoresis by 15 min after biosynthesis. The first dimeric Tg was formed by 30 min after; the monomer declined and the dimer progressively increased, and 40 min after remarkable dimeric Tg form was found. Finally, dimerization was complete at 60 min after.

• The Korean journal of internal medicine
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• v.33 no.6
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• pp.1050-1057
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• 2018

Thyroglobulin antibody (TgAb) is a class G immunoglobulin and a conventional marker for thyroid autoimmunity. From a clinical perspective, TgAb is less useful than thyroid peroxidase antibodies for predicting thyroid dysfunction. However, TgAb is found more frequently in differentiated thyroid cancer (DTC) and can interfere with thyroglobulin (Tg) measurements, which are used to monitor the recurrence or persistence of DTC. Recent studies suggested a small but consistent role for preoperative TgAb in predicting DTC in thyroid nodules, and in reflecting adverse tumor characteristics or prognosis, including lymph node metastasis, but this is still controversial. Postoperative TgAb can serve as a biomarker for remnant thyroid tissue, so follow-up measures of TgAb are useful for predicting cancer recurrence in DTC patients. Since high serum TgAb levels may also affect the fine needle aspiration washout Tg levels from suspicious lymph nodes of DTC patients, it is important to use caution when interpreting the washout Tg levels in patients who are positive for TgAb.

• The Korean Journal of Nuclear Medicine Technology
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• v.13 no.3
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• pp.152-155
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• 2009

Purpose: The most widely accepted tool for follow up management of thyroid cancer patients is serum thyroglobulin (Tg) measurement, but its value is limited by the interference of anti-thyroglobulin antibodies (anti-Tg Ab). Recently thyroglobulin measurement in the wash out of fine-needle aspiration biopsy specimens (Tg-FNAB) is frequently used for differential diagnosis of recurrences/metastases. The aim of this study was the investigation of the diagnostic utility of Tg-FNAB compared with serum Tg. Materials and Methods: We enrolled 41 consecutive patients with thyroid cancer who were evaluated for Tg-FNAB between January 2007 and February 2008 retrospectively. We ruled out 6 patients who anti-Tg Ab positive (${\geq}$100 U/mL) in the RIA (BRAHMS anti-Tgn RIA 100Det; BRAHMS Aktiengesell schaft, Berlin, Germany). Serum Tg and Tg-FNAB were measured by immunoradiometric assay (BRAHMS Tg pluS RIA 100 Det; BRAHMS Aktienge sellschaft, Berlin, Germany). We evaluated for Tg-FNAB compared with serum Tg and corresponding cytological smear. To compare the values of the two the t-test was used. Results: Tg-FNAB values were significantly higher (median 1,060 ng/mL, range 0.2~434,000 ng/mL) than serum Tg (median 2.5 ng/mL, range 0.9~131 ng/mL) (p=0.0394). The rate of correspondence with Tg-FNAB between cytological result was 87.9% and 65.9% in the case of serum Tg. Tg-FNAB was positive in 28 (24 with positive and 4 with suspicious cytology). Of the remaining 13 patients with negative Tg-FNAB, 1 had suspicious and 12 had unsuspicious cytology. serum Tg was positive in 26 (17 with positive and 3 with suspicious and 6 with unsuspicious cytology), Of the remaining 15 patients with negative serum Tg, 8 was positive in cytological result and 1 had suspicious and 6 had unsuspicious cytology. Conclusions: Tg-FNAB measurement is more accurate with high sensitivity (87.9%) than serum Tg (65.9%). The Tg-FNAB was a useful predictor for detecting recurrences/metastases with serum Tg.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.1065-1072
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• 2005

The nascent thyroglobulin (Tg) multimer molecule, which is generated during the initial fate of Tg in ER, undergoes the rapid reductive depolymerization. In an attempt to determine the depolymerization process, various types of Tg multimers, which were generated from deoxy­cholate-treated/reduced Tg, partially unfolded Tg or partially unfolded/reduced Tg, were subjected to various GSH (reduced glutathione) reducing systems using protein disulfide isomerase (PDI), glutathione reductase (GR), glutaredoxin or thioredoxin reductase. The Tg multimers generated from deoxycholate-treated/reduced Tg were depolymerized readily by the PDI/GSH system, which is consistent with the reductase activity of PDI. The PDI/GSH-induced depolymerization of the Tg multimers, which were generated from either partially unfolded Tg or partially unfolded/reduced Tg, required the simultaneous inclusion of glutathione reductase, which is capable of reducing glutathionylated mixed disulfide (PSSG). This suggests that PSSG was generated during the Tg multimerization stage or its depolymerization stage. In particular, the thioredoxin/thioredoxin reductase system or glutaredoxin system was also effective in depolymerizing the Tg multimers generated from the unfolded Tg. Overall, under the net GSH condition, the depolymerization of Tg multimers might be mediated by PDI, which is assisted by other reductive enzymes, and the mechanism for depolymerizing the Tg multimers differs according to the type of Tg multimer containing different degrees and types of disulfide linkages.

• Archives of Pharmacal Research
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• v.25 no.4
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• pp.485-492
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• 2002

The molecular fate of thyroglobulin (Tg) is controlled by oligomerization, a means of storing Tg at high concentrations, and deoligomerization. The oligomerization of bovine Tg are intermolecular reactions that occur through oxidative processes, such as disulfide and dityrosine formation, as well as isopeptide formation; disulfide formation is primarily responsible for Tg oligomerization. Here, the protein disulfide isomerase (PDI) and/or peroxidase-induced oligomerization of unfolded thyroglobulins, which were prepared by treating bovine Tg with heat, urea or thiol/urea, was investigated using SDS-PAGE analyses. In addition, the enzymatic oligomerization was compared with non-enzymatic oligomerization. The thermally-induced oilgomerization of Tg, dependent on glutathione redox state, was affected by the ionic strength or the presence of a surfactant. Meanwhile, PDI-catalyzed oligomerization, time and pH-dependent, was the most remarkable with unfolded/reduced Tg, which was prepared from a treatment with urea/DTT, while the thermally-unfolded Tg was less sensitive. Similarly, the oligomerization of unfolded/reduced Tg was also mediated by peroxidase. However, PDI showed no remarkable effect on the peroxidase-mediated oligomerization of either the unfolded or unfolded/reduced Tg. Additionally, the reductive deoligomerization of oligomeric Tg was exerted by PDI in an excessively reducing state. Based on these results, it is proposed that PDI catalyzes the oligomerization of Tg through the disulfide linkage and its deoligomerization in the molecular fate, and this process may require a specific molecular form of Tg, optimally unfolded/reduced, in a proper redox state.

• The Korean Journal of Nuclear Medicine
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• v.39 no.4
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• pp.252-256
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• 2005

Purpose: Thyroglobulin (Tg) is a valuable and sensitive tool as a marker for diagnosis and follow-up for several thyroid disorders, especially, in the follow-up of patients with differentiated thyroid cancer (DTC). Often, clinical decisions rely entirely on the serum Tg concentration. But the Tg assay is one of the most challenging laboratory measurements to perform accurately owing to antithyroglobulin antibody (Anti-Tg). In this study, we have compared the degree of Anti-Tg effects on the measurement of Tg between availale Tg measuring kits. Materials and Methods: Measurement of Tg levels for standard Tg solution was performed with two different kits commercially available (A/B kits) using immunoradiometric assay technique either with absence or presence of three different concentrations of Anti-Tg. Measurement of Tg for patient's serum was also performed with the same kits. Patient's serum samples were prepared with mixtures of a serum containing high Tg levels and a serum containg high Anti-Tg concentrations. Results: In the measurements of standard Tg solution, presence of Anti-Tg resulted in falsely lower Tg level by both A and B kits. Degree of Tg underestimation by h kit was more prominent than B kit. The degree of underestimation by B kit was trivial therefore clinically insignificant, but statistically significant. Addition of Anti-Tg to patient serum resulted in falsely lower Tg levels with only A kit. Conclusion: Tg level could be underestimated in the presence of anti-Tg. Anti-Tg effect on Tg measurement was variable according to assay kit used. Therefore, accuracy test must be performed for individual Tg-assay kit.

• The Korean Journal of Nuclear Medicine
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• v.17 no.2
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• pp.41-47
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• 1983

To evaluate the significance of assay of serum thyroglobulin(Tg) in monitoring the course of the thyroid cancer or its response to treatment, serum thyroglobulin levels were measured in 41 patients with thyroid cancer who visited Seoul National University Hospital from August, 1981 to August, 1982. The results were as follows: 1) Serum Tg levels $1\sim3$ months after thyroidectomy was $31{\pm}23$ ng/ml$(mean{\pm}S.D.)$ in 14 patients without metastasis, $66{\pm}41$ ng/ml in 21 patients with regional metastasis and $176{\pm}59$ ng/ml in 6 patients with distant metastasis and there were significant differences among three groups(p<0.01). 2) Serum Tg levels in 13 patients with metastasis before and after $^{131}I$ treatment were $134{\pm}62ng/ml$ and $67{\pm}52ng/ml$ respectively. 3) In the follow-up measurement of serum Tg levels every 3 months for about 1 year, almost all serum Tg levels were below 60 ng/ml in 12 patients without distant metastasis and serum Tg levels were elevated above 60 ng/ml in 5 of 6 patients with distant metastasis. 4) In 6 patients with distant metastasis, serum Tg levels were elevated in 5 patients and $^{131}I$ whole body scan showed definite metastatic evidence in 3 patients and suspicious evidence in 1 patient. From above results, we concluded that serum Tg level is very useful as an indicator of recurrence or metastasis in patients with thyroid cancer after operation.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.181-185
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• 2010

Purpose: Several studies report that detection of thyroglobulin (Tg) in fine-needle aspiration (FNA) biopsy washout fluid from lymph nodes identifies recurrences or metastases of differentiated papillary thyroid cancer (DPTC) in the neck with higher sensitivity and specificity than fine-needle aspiration cytology (FNAC). We evaluate the diagnostic efficacy and usefulness of Tg measurement in FNA washout fluid (FNA-Tg) and compare with FNAC. Materials and Methods: Forty-eight FNA samples of 37 patients who undergone ultrasonography to detect cervical lymph node metastasis of DPTC, were included for this study. Lymph node metastasis was confirmed by histopathologic examination or long-term imaging follow-up. Sensitivity, specificity and accuracy of FNA-Tg and FNAC were calculated. In 34 patients, we evaluated diagnostic accuracy of FNA-Tg according to the presence or absence of Tg antibody. Results: Sensitivity, specificity and accuracy of FNAC were 75.0%, 97.2% and 91.7%, respectively, and those of FNA-Tg were 100%, 88.9% and 91.7%, respectively. The presence of Tg antibody was not relevant to the diagnostic accuracy of FNA-Tg. Conclusion: FNA-Tg is a as accurate as FNAC with higher sensitivity. FNA-Tg and FNAC are complement techniques for diagnosing lymph node metastasis of DTPC.

• Journal of Medicine and Life Science
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• v.19 no.3
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• pp.95-102
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• 2022

This retrospective study aimed to investigate whether there was a difference in the success rate of removal of residual thyroid tissue in patients with the same cutoff serum thyroglobulin (Tg) value-measured 2 weeks after thyroid hormone withdrawal (THW)-for different radioactive iodine (RAI) activities. We identified 132 patients with papillary thyroid cancer who were treated with total thyroidectomy and RAI therapy to evaluate the efficacy of three radioactivities of I-131: 1,110, 3,700, and 5,550 MBq. Serum Tg testing was performed 1 week before RAI treatment and 2 weeks after THW (pre-Tg); the cutoff pre-Tg level was below 10 ng/mL. Stimulated Tg levels were measured on the day of I-131 administration (off-Tg). After 6 months of treatment, we compared the groups for complete ablation, defined as no uptake on a diagnostic I-131 scan, stimulated Tg level of <1.0 ng/mL, and Tg antibody level of <100 ng/mL. Ninety-five patients (72.0%) achieved complete ablation, with 57.1% (8/14), 78.2% (68/87), and 61.3% (19/31) in the 1,110 MBq, 3,700 MBq, and 5,550 MBq groups, respectively. There was no significant difference in the complete ablation rates between the three groups. In the multivariate analysis, the off-Tg level was a significant predictor of complete ablation. RAI therapy with low radioactivity (1,110 MBq) seemed sufficient for ablation in patients with papillary thyroid cancer with a pre-Tg level below 10 ng/mL. The off-Tg level is a promising and useful predictor of complete ablation after initial RAI therapy.

• Archives of Pharmacal Research
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• v.27 no.12
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• pp.1275-1283
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• 2004

Fate of the nascent thyrolglobulin (Tg) molecule is characterized by multimerization. To establish the formation of Tg multimers, the partially unfolded/reduced Tg or deoxycholate-treated/ reduced Tg was subjected to protein disulfide isomerase (PDI)-mediated multimerization. Oxidized glutathione/PDI-mediated formation of multimeric Tg forms, requiring at least an equivalent molar ratio of PDI/Tg monomer, decreased with increasing concentration of reduced glutathione (GSH), suggesting the oxidizing role of PDI. Additional support was obtained when PDI alone, at a PDI/Tg molar ratio of 0.3, expressed a rapid multimerization. Independently, the exposure of partially unfolded Tg to GSH resulted in Tg multimerization, enhanced by PDI, according to thiol-disulfide exchange. Though to a lower extent, a similar result was observed with the dimerization of deoxycholate-pretreated Tg monomer. Consequently, it is implied that intermolecular disulfide linkage may be facilitated at a limited region of unfolded Tg. In an attempt to examine the multimerization site, the cysteine residue-rich fragments of the Tg were subjected to GSH-induced multimerization; a 50 kDa fragment, containing three vicinal dithiols, was multimerized, while an N-terminal domain was not. Present results suggest that the oxidase as well as isomerase function of PDI may be involved in the multimerization of partially unfolded Tg or deoxycholate-treated Tg.