Prediction of Disease Status by Recombinant Human TSH-Stimulated Serum Tg in the Postsurgical Follow-Up of Differentiated Thyroid Carcinoma

Pacini, Furio; Molinaro, Eleonora; Lippi, Francesco; Castagna, Maria Grazia; Agate, Laura; Ceccarelli, Claudia; Taddei, Donatella; Elisei, Rossella; Capezzone, Marco; Pinchera, Aldo

doi:10.1210/jcem.86.12.8065

Cited by 147 publications

(98 citation statements)

References 18 publications

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“…A hindrance for the preeminent position of Tg measurement thus far consisted of the need, recommended in all guidelines, for TSH stimulation in order to achieve optimal sensitivity. A 'negative' TSH-stimulated Tg measurement in combination with a negative clinical examination, negative neck US and, when indicated, negative additional imaging procedures, predicts a very low risk of recurrence in both low-and high-risk patients [56,57]. Once these findings have been established, routine DTC follow-up should therefore consist of periodic clinical examination combined with neck ultrasound and Tg measurement on LT4 medication [2,3].…”

Section: Clinical Impact Of New Highly Sensitive Tg Assaysmentioning

confidence: 99%

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

Giovanella

Feldt‐Rasmussen

Verburg

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. The initial treatment consists of total thyroidectomy followed by ablation of thyroid remnants by radioiodine in most cases. As thyroid cells are the only source of thyroglobulin (Tg), circulating Tg serves as a biochemical marker of persistent or recurrent disease in the follow-up of DTC. Due to the suboptimal clinical detection rate of older Tg assays endogenous or exogenous thyrotropin (TSH) stimulations are recommended for unmasking occult disease. However, the development of new Tg assays with improved analytical sensitivity and precision at low concentrations now allows detection of very low Tg concentrations, reflecting minimal amounts of thyroid tissue, even without the need for TSH stimulation. Even if the use of these assays still has not found its way in current clinical guidelines, such assays are now increasingly used in clinical practice. As serum Tg measurement is a technically challenging assay and criteria to define a 'highly sensitive' assay may be different, a good knowledge of the technical difficulties and interpretation criteria is of paramount importance for both clinical thyroidologists, laboratory physicians and scientists involved in the care of DTC patients.

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Section: Clinical Impact Of New Highly Sensitive Tg Assaysmentioning

confidence: 99%

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

Giovanella

Feldt‐Rasmussen

Verburg

et al. 2015

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Even minor increases from undetectable baseline serum Tg may be associated with recurrent or metastatic disease. 34 Survival rates of 86-100% are reported in young patients with thyroid carcinomas. 8,9,19 At last followup, all patients were alive but 11 still had residual disease (Table 5).…”

Section: Patientsmentioning

confidence: 99%

Thyroid carcinoma in children and adolescents. Presentation, clinical course, and outcome of therapy in 23 children and adolescents in Northern Greece

Pazaitou‐Panayiotou¹,

Kaprara²,

Boudina³

et al. 2005

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OBJECTIVE: To define clinical presentation, surgical complications, follow-up characteristics, and survival of 23 children and adolescents with thyroid carcinoma. DESIGN: Retrospective analysis of data of 23 children and adolescents with thyroid carcinoma cared for in the Theagenion Cancer Hospital, Thessaloniki. RESULTS: At the time of diagnosis cervical lymph node metastases were present in 18 (78.2%), mediastinal in 2 (8.69%), and pulmonary in 3 patients (13%). Total thyroidectomy was performed in 21 patients, with lymph node dissection in 18 and subtotal thyroidectomy in 2. No significant post-operative complications were observed. Histological examination revealed differentiated thyroid carcinoma (DTC). Tumor was multifocal in 11 (47.8%) and bilateral in 7 subjects (63.6%). Thyroid capsule invasion, vascular invasion, soft tissue involvement, and parathyroid gland invasion was observed in 12 out of 23 patients (52.1%). All patients received thyroxine suppressive therapy and 21 of them additional therapy with radioactive iodine ( 131 I). During follow-up (5.5 years), 6 out of the 23 patients presented new metastases in the cervical and mediastinal lymph nodes, lungs, and bones. At last follow-up, 11 patients (47.8%) had residual disease but all were alive. CONCLUSIONS: Thyroid carcinoma in children and adolescents can be quite aggressive. When a young patient presents thyroid nodule or multinodular goiter or palpable lymph nodes, the existence of thyroid carcinoma must be seriously considered.

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“…By using a cut-off value of Ͼ2 g/l, the sensitivity of this test in the detection of tumor relapse decreased to 84.6%, although the specificity improved (93.6%). Based on these results, 20,[27][28][29][30] we suggest that patients with any detectable serum TG level after rhTSH should undergo further investigation, in particular those with serum TG of Ͼ2 g/l, which should require prompt evaluation to localize the source of TG production. Stimulated serum TG should not be used as the only follow-up test in all patients operated for DTC.…”

Section: Discussionmentioning

confidence: 79%

Evaluation of circulating thyroid‐specific transcripts as markers of thyroid cancer relapse

Barzon¹,

Boscaro²,

Pacenti³

et al. 2004

Intl Journal of Cancer

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Circulating thyroid-specific transcripts have been suggested as potential molecular markers of residual or recurrent thyroid cancer. We assessed the accuracy of real-time RT-PCR-based detection of a panel of thyroid-specific markers, including TG, TPO, TSHR, NIS and PDS, in comparison with serum TG measurements in a series of 55 patients operated for differentiated thyroid cancer (DTC). Serum TG levels were higher in patients with residual thyroid tissue or metastatic cancer than in disease-free patients during thyroid hormone suppressive therapy (THST) and after stimulation with rhTSH (P < 0.05). Recombinant hTSH increased serum TG values in patients with tumor relapse (P < 0.05), but not in disease-free patients. This assay showed high specificity and good sensitivity in detecting tumor relapse (accuracy under THST ‫؍‬ 81.4%; after rhTSH stimulation ‫؍‬ 90.9%). TPO and TSHR mRNA, either under THST or after rhTSH, showed a significant correlation with disease status for molecular assays. Qualitative analysis of baseline and stimulated TG, NIS and PDS mRNA showed high sensitivity but low specificity in the prediction of thyroid cancer recurrence or metastases (accuracy under THST ‫؍‬ 51%, 43% and 54%, respectively), whereas TPO and TSHR mRNA assays had higher specificity but low sensitivity, with accuracy under THST of 67% and 61%, respectively, that improved when these tests were combined. Differentiated thyroid carcinoma (DTC), which comprises papillary and follicular thyroid cancer, is the most common thyroid malignancy and accounts for 1% of all human cancers. Its incidence is increasing in many countries, likely due to exposure of the population to thyroid radiation. Differentiated thyroid carcinoma generally has an excellent prognosis after treatment with total or near-total thyroidectomy followed by 131-iodine ( 131 I) ablation. However, about 20 -40% of patients with DTC may develop recurrences or metastases even after successful initial therapy. A lifelong follow-up is therefore recommended for early discovery of residual or recurrent disease.Management protocols include periodic radioiodine whole body scanning (WBS) and measurements of serum thyroglobulin (TG) protein by immunoassay. 1 Thyroid hormone withdrawal or, more recently, administration of recombinant human thyroid-stimulating hormone (rhTSH) is required to produce the TSH stimulation needed to achieve maximal accuracy for these diagnostic tests. In comparison with thyroid hormone withdrawal, stimulation with rhTSH avoids side-effects associated with hypothyroidism. Serum TG measurement shows some advantages over WBS in the follow-up of DTC, having a higher sensitivity and no false positive results after TSH stimulation, 2,3 besides avoidance of exposure to radiation, lower costs and wide availability. A major disadvantage of this test, however, is the presence of interfering anti-TG antibodies in 10 -20% of patients.In the search of a more accurate test for diagnosis of residual or recurrent DTC, the possibility to detect transcripts from cir...

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Prediction of Disease Status by Recombinant Human TSH-Stimulated Serum Tg in the Postsurgical Follow-Up of Differentiated Thyroid Carcinoma

Cited by 147 publications

References 18 publications

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges

Thyroid carcinoma in children and adolescents. Presentation, clinical course, and outcome of therapy in 23 children and adolescents in Northern Greece

Evaluation of circulating thyroid‐specific transcripts as markers of thyroid cancer relapse

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