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PubMed2001

[Recovery test or immunoradiometric measurement of anti-thyroglobulin autoantibodies for interpretation of thyroglobulin determination in the follow-up of different thyroid carcinoma].

UNLABELLED: The determination of thyroglobulin (Tg) in the follow-up of differentiated thyroid carcinomas (DTC), is routinely used in nuclear medicine, although some problems, like a disturbed recovery-test (RT) or autoantibodies to thyroglobulin (TgAb), are well known. But it is a controversial issue in literature, whether the determination of TgAb should be performed beside or instead of the RT. OBJECTIVE: The study compares the clinical value of the determination of both TgAb and RT with sensitive assays. METHODS: 356 patients (pts) were investigated. The results were compared to the concentration of Tg in the sera of the pts. 288 pts stayed tumor-free, the remaining 68 pts showed a recurrence (local and/or metastatic) of their DTC. We measured Tg (with RT) using an immunoradiometric assay (Tg-IRMA; SELco Tg; Fa. Medipan Diagnostica GmbH) and TgAb using a direct assay (CentAK anti-Tg; also from Fa. Medipan). RESULTS: The prevalence of TgAb, and of disturbed RT respectively, in the whole population of DTC-pts was 7.6%, in the subgroup of tumor-free pts 6.6%, and in the remaining pts with tumor-recurrence 11.8%, respectively 2.0%, 1.7% and 2.9%. In a significantly higher percentage of pts with local/metastatic recurrence, both a positive TgAb (p < 0.001) and a disturbed RT (p < 0.05) were found. 7/68 pts with tumor-recurrence but Tg < 1 ng/ml showed positive TgAb, only 2/7 had a disturbed RT. In this group, no patient with Tg > 1 ng/ml demonstrated either positive TgAb or disturbed RT (p < 0.001 and p < 0.05). CONCLUSION: The determination of TgAb in the follow-up of DTC is necessary, because it supports a suspicion to tumor-recurrence in pts with negative Tg. Also the RT is of great value because of a possibly High dose hook-effect.

Adenocarcinoma, Follicular↗

PubMed2002

Importance of the detection method for thyroglobulin antibodies for the validity of thyroglobulin measurements in sera from patients with Graves disease.

BACKGROUND: The use of recovery tests has been proposed to disclose interferences from anti-thyroglobulin antibodies (TgAbs) in thyroglobulin (Tg) assays. We studied the value of a recovery test in Tg measurement by a new commercial IRMA. METHODS: Blood samples were collected from 153 patients with untreated Graves disease. Tg and TgAbs were measured by IRMA and RIA, respectively (Dynotest Tg-plus and Dynotest anti-Tgn; Brahms Diagnostica). The recoveries of added amounts of Tg were calculated for each serum. RESULTS: TgAbs were detected in 72 of the 153 patients (47%). The recovery test results for the 81 TgAb-negative sera (median, 101%; range, 80-115%) were identical to the results for the 91 controls (median, 102%; range, 80-124%). By contrast, significantly lower recovery test results were observed for the 72 TgAb-positive sera (median, 79%; range, 60-103%; Z = -8.363; P <0.0001). In the 34 of the 72 TgAb-positive sera with a normal recovery test, Tg concentrations were significantly lower (median Tg, 13.6 microg/L; range, 1.1-360 microg/L) than those measured in the TgAb-negative sera (median, 107 microg/L; range, 1.2-700 microg/L; Z = -3.797; P <0.0001). CONCLUSIONS: Tg values were decreased in TgAb-positive sera even when the results of the recovery tests were normal. This test should not be used alone to determine the validity of a serum Tg measurement in Graves disease.

Adolescent↗

PubMed1989

[Comparison of the results of radioimmunologic and hemagglutination methods in the determination of antibodies against thyroglobulin and the effect of these antibodies on thyroglobulin serum levels].

The following methods have been introduced at our institute: labeling of human thyroglobulin (H-Tg) with the radioiodine 125I by the lactoperoxidase method, radioimmunologic method for serum H-Tg determination by means of rabbit antiserum to H-Tg prepared at our institute, and radioimmunologic method for the determination of antibodies to thyroglobulin. Sera from 15 patients with different thyropathies were examined by the given methods. In the first part of the work the quality of 125I labeled H-Tg was studied. The maximum binding by antiserum was found to be substantially decreased as early as two weeks following labeling, The second part of the study presents our first experience with comparing our RIA method and the hemagglutination method for TgAb determination. The results yielded by the two methods did not differ significantly. The level of serum H-Tg is falsely affected by the competition of TgAb autoantibodies with the first rabbit antibody to H-Tg at recipitation by means of the second antibody. It is therefore important to establish the titer of autoantibodies before actual serum H-Tg determination. This approach is of importance e.g. in following up patients with malignant goiter. The introduced methods are a contribution to diagnosis and management of patients with thyropathies.

Autoantibodies↗

PubMed1986

Serum thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) in thyroid cancer.

Serum thyroglobulin antibodies (TgAb) and serum thyroglobulin (Tg) levels were measured in 28 normal controls and 32 patients with differentiated thyroid cancer. The TgAb and Tg levels were measured in the patients when they were on replacement thyroxine therapy prior to the whole body radioiodine I-131 scan (WBS), using immunoradiometric assay kits. The TgAb level in normal controls was from 0-4.8 micrograms/ml, with a mean of 0.6 microgram/ml, while the Tg level in these controls was from 0.0-48.0 ng/ml, with a mean of 4.2 ng/ml. In the patients with thyroid cancer, the TgAb levels were normal except for a few patients who had residual thyroid or tumour in the neck and had raised levels of TgAb. Their Tg levels were normal except for 7 patients who had elevated values. 2 of these 7 had no evidence of disease on X-ray, bone scan, or WBS (I-131) while the other 5 had evidence of metastases. However, 4 patients had metastatic disease with normal Tg levels, and 2 of these patients had residual thyroid in the neck and raised TgAb levels, while in the remaining 2 patients, both Tg and TgAb were low. Serum Tg is a useful tumour marker for recurrent or metastatic thyroid cancer, but the presence of residual normal thyroid would interfere with the results.

Adenocarcinoma↗

PubMed2001

Natural autoantibodies and complement promote the uptake of a self antigen, human thyroglobulin, by B cells and the proliferation of thyroglobulin-reactive CD4(+) T cells in healthy individuals.

Serum from normal individuals contains substantial amounts of natural antibodies (NA) capable of recognizing self antigens. However, the physiological implications of this autoreactivity remain unclear. We have examined the role of self-reactive NA and complement in mediating the uptake of human thyroglobulin (Tg) by human peripheral B cells in reconstituted whole blood. Significant binding of fluorescein isothiocyanate-conjugated-Tg to B cells was observed, and absorption of Tg-reactive antibodies from serum markedly reduced this uptake, as did inactivation of serum complement or blockade of complement receptor types 1 (CR1, CD35) and 2 (CR2, CD21). T cell responsiveness to Tg was examined in a preparation of peripheral blood mononuclear cells (PBMC) cultured in the presence of autologous serum. A subset of CD4(+) T cells exhibited a dose-dependent proliferative response to Tg, which was strongly inhibited by complement inactivation and by immunoabsorption of Tg-reactive antibodies. Furthermore, this T cell response was abrogated by depletion of B cells from the PBMC culture. These data imply that uptake of complement-opsonized Tg / anti-Tg complexes and subsequent presentation of Tg by B cells are prerequisites for the proliferation of Tg-reactive CD4(+) T cells, suggesting a novel role for natural autoantibodies and complement in the regulation of autoreactivity under physiological conditions.

Antigen Presentation↗

PubMed1991

Autoimmunity to human thyroglobulin. Respective epitopic specificity patterns of anti-human thyroglobulin autoantibodies in patients with Sjögren's syndrome and patients with Hashimoto's thyroiditis.

We evaluated the epitopic specificity pattern of anti-human thyroglobulin (anti-hTg) autoantibodies from patients with primary Sjögren's syndrome (SS). All of the primary SS sera tested contained both IgG and IgM anti-hTg autoantibodies recognizing at least 1 region on hTg; in 65% of the cases, 3 or more regions were recognized. A strong recognition of region II, as is seen in Hashimoto's thyroiditis, was associated with thyroid disorder in primary SS. These results emphasize the importance of region II in autoimmune thyroid disease.

Adult↗

PubMed1982

Structure-function relationship in thyroglobulin: amino acid sequence of two different thyroxine-containing peptides from porcine thyroglobulin.

From the cyanogen bromide (CNBr) treatment of porcine thyroglobulin a peptide of mol. wt. 15 000, CNBr-b1, was purified by gel filtration and ion-exchange chromatography. CNBr-b1 contained 50% of the thyroxine (T4) content of the protein. After digestion with trypsin and protease from Staphylococcus aureus V-8, thyroxine-containing peptides were purified and analyzed by microsequence analysis using the colored Edman's reagent dimethylaminoazobenzeneisothiocyanate . Two different sequences harboring T4 were identified: sequence 1, His-Asp-Asp-Asp-T4-Ala-Thr-(Glx,Gly)-Leu-Tyr-Phe-Ser-Ser-Arg, which contains 1 mol T4/mol peptide and sequence 2, Asp-(Tyr/MIT/DIT/T4)-Phe-Ile-Leu-X-Pro-Val-, which is a mixture of the same peptide at different levels of iodination and coupling. These sequences are likely to be representative of distinct hormonogenic sites, the former giving evidence of early iodinated tyrosine residues where preferential coupling into hormonal residues occurs especially at low iodine levels and the latter representing less reactive site(s) operative at higher iodine levels.

Amino Acid Sequence↗

PubMed1990

Differential levels of thyroid peroxidase and thyroglobulin messenger ribonucleic acids in congenital goiter with defective thyroglobulin synthesis.

The biosynthesis of thyroid hormones requires iodide, thyroid peroxidase (TPO), thyroglobulin (Tg) and H2O2. We have studied two sisters with congenital large goiters and hypothyroidism. Perchlorate tests were negative. Serum T3 and T4 were decreased, TSH was increased and Tg was within the lower limit of normal. Biochemical and molecular studies were performed on goiter samples obtained after surgery. Tg content in both tissues was negligible. Paper chromatography of labeled iodocompounds showed a decrease in T4, and the presence of a pronase/pancreatin-resistant iodoprotein. TPO activity was normal in the tissues. Sephacryl S-300 gel filtration demonstrated labeled iodoalbumin-like protein and the absence of a Tg peak. Salting out studies of soluble protein fraction gave an abnormal pattern. Agarose gel electrophoresis showed the presence of an iodoalbumin-like protein and the absence of Tg in the tissues. This last finding was confirmed by immunoelectrophoresis. The Tg and TPO mRNAs levels were also analyzed. Dot-blot hybridization studies with pM5 (TPO cDNA) and phTgM2 (Tg cDNA) probes showed increased and decreased signals, respectively. The increase in TPO mRNA can be explained as a compensatory mechanism vis a vis an increase in serum TSH caused by decreased serum T3 and T4 due to the impairment in Tg mRNA. The Tg mRNA of both patients was further studied with four different probes covering 5' and 3' regions (phTgM1, phTgB1, phTgB2 and phTgB3). Hybridization was observed with all four probes, thus excluding a dramatic deletion defect. Northern transfer showed a clear signal of hybridization with the phTgB1 probe in the 8-9 Kb range. We may conclude that the biochemical and molecular abnormality of these patients is characterized by a decrease of Tg mRNA and of Tg translation.

Adolescent↗

PubMed1996

The type-1 repeats of thyroglobulin regulate thyroglobulin degradation and T3, T4 release in thyrocytes.

Thyroglobulin (Tg) proteolytic steps are central phenomena in Tg processing and thyroid hormone release in thyrocytes. Based on recent literature data, we propose that the type-1 repetitive units present in the Tg sequence could act as binders and reversible inhibitors of the proteases implicated in Tg processing. The pH-dependent interactions of proteases with the repeats could permit (i) protection from degradation of low iodinated Tg to be recycled; (ii) restriction of early proteolytic attacks to N- and C-terminal hormone formation sites; (iii) increase of the half-time of acidic proteases necessary for the final, extensive degradation steps of Tg.

Animals↗

PubMed1986

Thyroglobulin-treated blood dendritic cells induce IgG anti-thyroglobulin antibody in vitro in Hashimoto's thyroiditis.

Nonadherent, low density cells of dendritic morphology from the blood of patients with Hashimoto's thyroiditis were treated with human thyroglobulin (Tg) in vitro and cultured under serum-free conditions with autologous patient B cells and irradiated T cells. The patients were selected for high serum levels of IgG antithyroglobulin antibody (anti-Tg IgG). In 2 out of 12 patients the Tg-treatment induced production of anti-Tg IgG in excess of that secreted spontaneously. The amount of antibody produced in vitro (whether increased by Tg or not) correlated with the serum levels of antibody. In 5 patients (including the 2 who responded to Tg) the ratio of supernatant IgG anti-Tg antibody to total IgG was reduced when polyclonal stimulation was done with BCGF (10%). Antibody production was absent in cultures of cells from 2 patients with Graves disease and 4 normal individuals. Thus, in some patients with Hashimoto's thyroiditis, an extrinsically added autoantigen (Tg) on blood-derived dendritic cells can induce IgG anti-Tg antibody in vitro. These data suggest that "professional" antigen-presenting cells may play a role in autoimmune thyroid disease.

Aged↗

PubMed2000

Treating the patient with differentiated thyroid cancer with thyroglobulin-positive iodine-131 diagnostic scan-negative metastases: including comments on the role of serum thyroglobulin monitoring in tumor surveillance.

Differentiated thyroid cancer (DTC) patients, especially the 10% to 15% at high risk of cancer-related death, should have long-term monitoring for detection of recurrence or metastasis. Conventional radiologic and ultrasonographic imaging is useful for localization of recurrent or persistent disease. For patients who have had ablation of residual thyroid tissue, measurement of serum thyroglobulin (Tg) levels and radioactive iodine (RAI) imaging provide highly sensitive tools for early detection. Serum Tg is reliable only in the absence of Tg autoantibodies. Sensitivity increases with TSH stimulation, either by withdrawal of thyroxine (T4) therapy, or administration of recombinant TSH (rTSH). In some patients, serum Tg levels are positive but the RAI whole body scan (WBS) is negative. In these patients, either the recurrent tumor is too small and below the sensitivity of the diagnostic scan, or there is a dissociation between Tg synthesis and the iodine-trapping mechanism. Recent literature suggests that empiric high-dose RAI therapy of Tg-positive diagnostic scan-negative patients may result in a high rate of visualization of uptake in posttherapy scans (PTS). Evidence for subsequent improvement of parameters of disease activity has also been presented. Almost all such reported cases had micrometastases that were not visualized by conventional imaging. In our experience, aggressive macrometastases with negative diagnostic WBS do not show significant uptake after therapeutic doses of RAI. The small size of micrometastases in the first group of patients and a possible defect of the iodine-trapping mechanism in the second group may explain this apparent discrepancy. Based on presently available information, a generalized recommendation for RAI therapy of Tg-positive, diagnostic scan-negative patients should await further studies. Meanwhile, in some high-risk patients, in the absence of alternative therapies, empiric RAI therapy is justified.

Biomarkers, Tumor↗

PubMed2003

Thyroglobulin autoantibody levels below the cut-off for positivity can interfere with thyroglobulin measurement.

Antithyroglobulin antibodies can interfere with the measurement of thyroglobulin yielding spuriously high or low levels depending on the method used. Interference is unrelated to the antibody concentration and can occur at very low concentrations. We report a patient in whom antithyroglobulin antibodies below the cut-off for positivity nearly led to an incorrect diagnosis of thyrotoxicosis factitia.

Adult↗

PubMed1999

In vivo expression of thyroid transcription factor-1 RNA and its relation to thyroid function and follicular heterogeneity: identification of follicular thyroglobulin as a feedback suppressor of thyroid transcription factor-1 RNA levels and thyroglobulin synthesis.

We used in situ hybridization to evaluate thyroid transcription factor-1 (TTF-1) RNA expression in individual follicles and related this to thyroglobulin (Tg) synthesis in vivo, as estimated by immunohistochemical analysis. We studied the thyroids of Wistar rats treated with thyroxine (T4) or propylthiouracil (PTU), each of which modulates TSH levels, but affects follicular function and Tg accumulation in the follicular lumen very differently. We show that TTF-1 RNA levels in vivo correlate directly with an increase in the cytoplasmic accumulation of Tg within the cells of individual follicles. Because TTF-1 increases Tg gene expression, RNA levels, and protein synthesis in thyroid cell cultures and because there is no correlation with TSH-increased Tg degradation within the follicular lumen, the increased cytoplasmic accumulation of Tg in vivo is interpreted to reflect TTF-1-increased Tg synthesis. Increases in serum TSH levels in the PTU or T4 treated animals did not always correlate with increases in this measure of increased Tg synthesis; and TSH levels did not always correlate with changes in TTF-1 RNA levels that would be expected to accompany increased Tg synthesis. As one possibility, this suggested there might be a hitherto unrecognized suppressor of TTF-1 RNA levels and TSH-induced Tg synthesis in individual follicles. The immunohistochemical data suggested that this suppressor might be follicular Tg itself. Supporting this possibility, we show that physiological concentrations of highly purified 19S follicular Tg decrease TTF-1 RNA levels in rat FRTL-5 thyroid cells and inhibit the action of TSH to increase Tg synthesis. We therefore suggest that follicular Tg is a feedback autoregulator of thyroid function that can counterregulate TSH actions on thyroid function in vivo and in thyroid cells in culture. We suggest this phenomenon contributes to follicular heterogeneity in vivo.

Animals↗

PubMed2004

Antibodies cross-reacting with thyroglobulin and thyroid peroxidase are induced by immunization of rabbits with an immunogenic thyroglobulin 20mer peptide.

Thyroglobulin (Tg) and thyroid peroxidase (TPO) are two major autoantigens in autoimmune thyroid diseases (AITD). Cross-reactive anti-Tg/TPO antibodies have been identified in patients with AITD and in mice immunized with Tg or TPO. In the present study, we investigated the production of anti-Tg/TPO antibodies in rabbits immunized with human Tg and with a highly immunogenic Tg peptide (namely TgP41, sequence 2651-2670 of human Tg), by noncompetitive and competitive ELISA. TgP41 was found previously to induce intramolecular epitope spreading. We found that Tg-immunized rabbits developed a serological immune response to TPO due to cross-reactivity with Tg, since serum TPO reactivity was inhibited by soluble Tg and affinity-purified anti-Tg antibodies cross-reacted with TPO. Moreover, TgP41-immunized rabbits responded to Tg and TPO. This serological response was attributed to anti-Tg/TPO antibodies, based on the observation that serum TPO reactivity was again inhibited by soluble Tg, and affinity-purified anti-Tg antibodies, induced by TgP41-immunization, cross-reacted with TPO. Purified anti-TgP41 antibodies did not react with TPO, suggesting that a putative common antigenic determinant is not included in the peptide sequence. We propose that intermolecular spreading of reactivity to TPO observed after administration of the Tg-peptide is a result of intramolecular epitope spreading to determinant(s) responsible for Tg/TPO cross-reactivity.

Animals↗

PubMed1983

A radioimmunoassay for murine thyroglobulin in serum: age-related increase of serum thyroglobulin levels in AKR/J mice.

Possible regulation of the synthesis of murine thyroglobulin (mTg) and a possible role for the major histocompatibility complex in this process were evaluated in 18 inbred strains of mice. A double antibody RIA was first developed to measure mTg in serum. The isolated mTG was labeled with 131I since 125I rapidly degraded the mTg molecule. The sensitivity of this mTg assay allowed detection of 15-20 ng/ml. Specificity was demonstrated by the minimal cross-reactivity with rat Tg (0.008%) and the total lack of cross-reactivity with human Tg. There was no correlation between H-2 haplotype and serum mTg levels. In five strains of mice with the H-2k haplotype, mTg levels varied from 30 +/- 2 to 48 +/- 11 ng/ml (mean +/- SD); however, only aged AKR/J mice (H-2k) exceeded this range (196 +/- 27 ng/ml). Strains with other haplotypes (a, b, d, g, q, v) demonstrated a similar range of mTg levels, but none had this age-related increase in mTg levels. The high levels of mTg were not caused by a decrease in the half-life of this protein and probably not caused by virus-induced alterations in the thyroid economy. Thyroids from the AKR/J mice, however, had larger follicles and flatter epithelia compared to thyroids from other strains. These studies suggest that AKR/J mice may represent a useful animal model for the study of goitrogenesis.

Aging↗

PubMed1987

Monoclonal antibodies to human thyroglobulin as probes for thyroglobulin structure.

A panel of monoclonal antibodies (mAbs) against human thyroglobulin (hTg) was obtained by somatic fusion of the nonsecreting myeloma cell line P3X66 Ag8/0 and spleen cells of Balb/c mice immunized with purified hTg. Antibody secreting clones were selected by solid phase enzyme immunoassay and analyzed for cross-reaction with Tg from several animal species. Twelve out of 15 mAbs cross-reacted with both rat and mouse Tg and 11 Mabs cross-reacted with bovine Tg. The cross-reaction with mouse Tg paralleled that of rat Tg, whereas discrete differences between the cross-reactivity patterns with bovine Tg were observed. Two clones secreted mAbs specific for hTg. We further characterized the mAbs and found that three mAbs recognized T4-containing determinants and one mAb reacted with both T4 and T3-containing determinants on the Tg molecule. The binding of the mAbs to hormonogenic determinants depended upon the thyroid hormone content of the molecule and the integrity of the three dimensional structure of Tg. One other mAb reacted with four peptides of CNBr-cleaved hTg, indicating the recognition of a repetitive determinant in the hTg molecule distinct from the hormonogenic regions.

Animals↗

PubMed1989

Normal-sized thyroglobulin messenger ribonucleic acid in Dutch goats with a thyroglobulin synthesis defect is translated into a 35,000 molecular weight N-terminal fragment.

The translation product of the thyroglobulin (Tg) mRNA in Dutch goats with a Tg synthesis defect has been characterized. The Tg mRNA has a normal size of 8.4 kilobases. Translation of goitrous polysomal Tg mRNA resulted, after immunoprecipitation with polyclonal rabbit antigoat Tg antibodies, in a single 35,000 mol wt (Mr) Tg fragment. To characterize the Tg antigens produced in vivo, thyroid hormone release by the goiter was suppressed by injecting T4 sc in newborn goitrous goats. Immunohistochemical studies showed the presence of Tg antigens almost solely in the colloidal lumen. Electrophoresis of the reduced thyroid proteins demonstrated the presence of two Tg fragments with Mr of 40,000 and 32,000, respectively; the latter is probably a breakdown product of the 40,000 Mr fragment. The difference in Mr between the in vivo and in vitro translation products (40,000 and 35,000 Mr, respectively) can be explained by the carbohydrate content (10% wt/wt) of the in vivo product, as was shown by periodic acid-Schiff-positive staining. Using monoclonal antibodies against the hormonogenic sites at the first and last parts of the Tg molecule, we demonstrated that only the first part of the Tg molecule is present. Both in vivo and in vitro 10% of the goitrous Tg mRNA molecule is translated, resulting in an N-terminal Tg fragment that easily aggregates to large S-S complexes in the colloidal lumen of goiter by H2O2 oxidation.

Animals↗

PubMed2006

Monitoring thyroglobulin in a sensitive immunoassay has comparable sensitivity to recombinant human tsh-stimulated thyroglobulin in follow-up of thyroid cancer patients.

CONTEXT: Most thyroglobulin (Tg) assays have a sensitivity of 0.5-1 ng/ml. A minority of patients with undetectable T4-suppressed Tg levels have a recombinant human TSH (rhTSH)-stimulated Tg above 2 ng/ml and identifiable residual disease. OBJECTIVE: The objective was to determine whether a Tg assay with improved sensitivity could eliminate the need for rhTSH stimulation when baseline Tg is below 0.1 ng/ml. DESIGN: A retrospective study of two academic endocrine practices was conducted. POPULATION: A total of 194 patients undergoing rhTSH stimulation participated in the study. RESULTS: Of the 80 patients with Tg below 0.1 ng/ml, two (2.5%) had rhTSH-stimulated Tg above 2 ng/ml. One other patient with stimulation to 0.3 ng/ml and negative 123I scan had an ultrasound-detected malignant lymph node resected. None had 131I/123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. If T4-suppressed Tg was 0.1-0.5 or 0.6-2.0 ng/ml, rhTSH Tg was above 2 ng/ml in 24.2 and 82.4%, respectively. CONCLUSIONS: Patients with differentiated thyroid carcinoma and a T4-suppressed serum Tg below 0.1 ng/ml rarely have a rhTSH-stimulated Tg above 2 ng/ml, and none of these patients had 131I or 123I imaging after rhTSH stimulation suggestive of local recurrence or distant metastasis. We recommend monitoring such patients with a T4-suppressed Tg level and periodic neck ultrasonography. An increase in T4-suppressed serum Tg to a detectable level or the appearance of abnormal lymph nodes by physical or ultrasound exam should prompt further investigation.

Adolescent↗