Follow-up Of Differentiated Thyroid Carcinoma Research Articles

Personalized treatment for differentiated thyroid cancer: current data and new perspectives.

More conservative and personalized treatment options have been developed in recent years to face the rising diagnosis of low-risk differentiated thyroid carcinoma (DTC). The present review describes the change towards a more risk-adapted management either in the treatment or in the follow-up of DTC. Particular attention is given to the innovations introduced by the latest guidelines for low-risk tumors, starting from the most appropriate extension of surgery up to the postoperative management. The emerging role of active surveillance for low-risk microcarcinoma is discussed, as well as the development of percutaneous strategies in the setting of malignant thyroid disease. The recent use of approved new systemic target therapies for advanced radioiodine refractory thyroid cancer is reported, together with the description of new compounds in trial. Finally, we provide some considerations to improve the risk evaluation in a presurgical setting, especially related to the rising role of genetics, to enable better risk-based cancer management and personalized treatment choices.

Application of ultrasensitive thyroglobulin assays in the follow-up of differentiated thyroid carcinoma

DTC is the most common endocrine carcinoma and its routine treatment consists of total thyroidectomy and 131I thyroid remnant ablation. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound as well as an additional radioiodine scan when indicated. As thyroid cells are assumed to be the only source of Tg in serum, circulating Tg serves as an excellent marker of persistent or recurrent disease in DTC follow-up. With the development of highly sensitive Tg assays, now it is possible to detect very low Tg concentrations which reflect minimal amounts of thyroid tissue without the need for TSH stimulation. This review is to introduce clinical implications of highly sensitive Tg assays. Key words: Thyroid neoplasms; Thyroglobulin; Trends

Clinical Consequences of a Change in Anti-Thyroglobulin Antibody Assays During the Follow-up of Patients with Differentiated Thyroid Cancer

Thyroglobulin (Tg) quantitation by immunometric assays is compromised by anti-thyroglobulin antibodies (TgAbs), potentially resulting in falsely low Tg concentrations. TgAb screening is recommended when measuring Tg, but current TgAb immunoassays do not detect all possible TgAbs in circulation. We assessed the impact of a change in TgAb assay on apparent disease status of patients with differentiated thyroid carcinoma (DTC). Patients seen at the Mayo Clinic, Rochester, Minnesota, for follow-up of DTC, who had been tested using 2 different TgAb assays (Beckman Access and Roche Elecsys) were identified. Electronic medical records were reviewed to evaluate any impact the change in TgAb assay had on clinical disease status assessment and follow-up. A total of 1,457 patients were tested using both assays. A change in TgAb status was found in 124 (8.5%) patients; a total of 117 patients who were TgAb-negative on the Beckman assay became TgAb-positive with the Roche assay. Additional testing was performed in 5 of these patients. Seven patients previously considered TgAb-positive were now TgAb-negative. In all 7 cases, physicians documented that they considered these patients now to be truly TgAb-negative and free of disease. Discrepancies in TgAb status are seen when using different TgAb assays. Relying on Tg and TgAb measurements to determine disease status may lead to underestimation of residual cancer. A multimodal (clinical, biochemical, and radiologic) approach to follow up on patients with DTC should be continued, pending the development of Tg quantitation methods that are highly sensitive and not affected by TgAb interference.

INNOVATION IN THE POST-SURGICAL MENAGMENT OF DIFFERENTIATED THYROID CARCINOMA

Differentiated thyroid carcinoma (DTC), either papillary or follicular, has usually a very good prognosis with an overall mortality of less than 10%. In recent decades, the clinical presentation of DTC has been changing from advanced cases requiring intense treatment and surveillance to cancer detected by fortuitous neck ultrasonography requiring less aggressive treatment and follow-up. The initial treatment for DTC is total or near-total thyroidectomy whenever the diagnosis is made before surgery. Central compartment and possible lateral neck dissections should be performed when nodal metastases are present in the respective nodal basins. Post-operatively, radioactive iodine ablation with 131I followed by thyroid stimulating hormone (TSH) suppression is indicated in certain patients to improve locoregional control and reduce recurrence. After initial treatment thyroidectomy and radioiodine ablation), the objectives of the follow-up of DTC is to maintain adequate thyroxine therapy and to detect persistent or recurrent disease through the combined use of neck ultrasound and basal and stimulated serum thyroglobulin (Tg) with or without diagnostic whole body scan (WBS). Recent advances in the radioidine therapy and follow-up of DTC are related to the use of recombinant human TSH (rhTSH) in order to stimulate Tg production and radioiodine uptake, and the ultrasensitive methods for Tg measurement during follow-up.

Recombinant human TSH acutely impairs endothelium-dependent vasodilation

We read with interest the review article by Duntas & Biondi dealing with clinical and quality of life consequences induced by short-term hypothyroidism (1). Withdrawal of levothyroxine therapy exacerbates neuropsychiatric symptoms and increases cardiovascular risk, although these effects are usually reversible restoring a condition of stable euthyroidism (1). Shortterm hypothyroidism is associated with cardiac abnormalities, increased peripheral vascular resistance, and endothelium dysfunction. In this setting, the recent use of recombinant human thyrotropin (rhTSH) in the clinical practice of thyroid carcinoma represents a valid alternative to levothyroxine withdrawal. The authors state that rhTSH administration is not accompanied by significant cardiac alterations and induces beneficial effects on the vascular system by increasing circulating nitric oxide (2). In this regard, we have recently assessed the acute effects of TSH on endothelial function in patients monitored for differentiated thyroid carcinoma (DTC) (3). Our data demonstrate that acutely raising serum TSH into the supraphysiological range leads to an acute impairment of endothelium-dependent vasodilation along with a significant increase in blood interleukin (IL)-6, tumour necrosis factor a (TNFa), and lipoperoxide levels. These observations are in keeping with the in vitro evidence of functional TSH receptors in several extra-thyroidal tissues, such as cardiomyocytes (4), aortic endothelium (5), and bone marrow cells (6), in which TSH is able to directly induce IL-6 and TNFa production (7) .T NFa is a pivotal NO-controlling cytokine and may promote the expression of inducible NO synthase, leading to increased oxidative stress (8). This mechanism may explain the increased NO metabolites previously described in patients receiving rhTSH for the follow-up of DTC (2). Therefore, while agreeing with the authors that rhTSH administration is generally safe and able to avoid most signs and symptoms of short-term hypothyroidism, we underline that rhTSH per se may acutely induce low-grade inflammation and endothelial function impairment.

Rendimiento diagnóstico de la determinación plasmática de tiroglobulina y del rastreo corporal con 131INa según el tipo de recurrencia en el carcinoma diferenciado de tiroides

There is no consensus about the best follow-up protocol in differentiated thyroid carcinoma (DTC). The aim of this study is to evaluate the usefulness and prognostic value of serum thyroglobulin (Tg) and the iodide-131 whole body scan (WBS) in DTC recurrences as a whole and according to the type of recurrence (local recurrence or distant metastases). Thirty-four patients with recurrent DTC recruited in our institution over 15 years, with a minimum 5 years of follow-up and without either distant metastases at time of diagnosis nor detectable anti-Tg antibodies were included in the study. All patients were submitted to total or near-total thyroidectomy and 131INa ablation of postsurgical thyroid remnants. The follow-up included Tg measurement and WBS performed in hypothyroid state. Serum Tg was increased in the 67.4% of the patients and the WBS was positive in the 82.3%. In the isolated local recurrences the sensitivity of WBS was higher than Tg measurement (93.7 vs 43.7%; p < 0.05), but patients with positive Tg had a worse prognostic. By contrast, in patients with distant metastases the sensitivity of Tg was higher than WBS (83.3 vs 58.3%; p = NS). In 14 patients (41.2%) the results of WBS and Tg were in disagreement. In these cases a worse prognosis was observed when Tg was positive and WBS negative. The sensitivity of Tg and WBS is different depending on the type of recurrence. Therefore, both tests complement each other and it is not recommended to omit one of them in the follow-up of DTC.