Is There a Role for Unstimulated Thyroglobulin Velocity in Predicting Recurrence in Papillary Thyroid Carcinoma Patients with Detectable Thyroglobulin after Radioiodine Ablation?

Hilda Wong MBBS 1 Kai P. Wong MBBS 0 Thomas Yau MBBS 1 Vikki Tang BS 1 Roland Leung MBBS 1 Joanne Chiu MBBS 1 Brian Hung-Hin Lang MS 0 B. H.-H. Lang MS e-mail: 0 Department of Surgery, Division of Endocrine Surgery, Queen Mary Hospital, The University of Hong Kong , Hong Kong SAR, China 1 Department of Medicine, Division of Hematology and Oncology, Queen Mary Hospital, The University of Hong Kong , Hong Kong SAR, China Background. In the follow-up of papillary thyroid cancer (PTC) patients treated with curative thyroidectomy and radioiodine ablation, raised thyroglobulin (Tg) predicts recurrence with reasonable sensitivity and specificity. However, a proportion of patients present with raised Tg level but no other clinical evidence of disease. Only limited data on Tg kinetics have been reported to date. Here we aim to evaluate the prognostic and predictive significance of nonstimulated serum Tg velocity (TgV). Methods. Consecutive PTC patients treated with curative thyroidectomy and radioiodine ablation between 2003 and 2010 were analyzed. Patients with at least one detectable Tg measurement ([0.2 ng/mL) were included. TgV was defined as the annualized rate of Tg change. Logistic regression analyses were performed to evaluate the role of TgV in the prediction of disease recurrence. The optimal TgV cutoff was assigned by receiver-operating characteristic curve analysis. Overall survival of patients above versus below the TgV cutoff were determined by the Kaplan-Meier method and compared. - In papillary thyroid cancer (PTC), thyroidectomy, radioiodine (131I) therapy, and thyroid hormone suppression are the mainstay of treatment, conferring excellent overall survival.1 Despite effective initial treatment, the prognosis is significantly affected by tumor recurrence, which occurs in up to 30 % of patients at 30 years.2 Improvement of current methods to detect recurrence early and accurately is therefore clinically important. Thyroglobulin (Tg) is a glycoprotein specific to differentiated thyroid tissue; after thyroidectomy and radioiodine remnant ablation, an elevated serum Tg level is a sensitive marker of residual cancer.3 Periodical measurement of Tg after initial thyroid ablative therapy is recommended in the monitoring of PTC patients.4 Nevertheless, Tg level may be affected by the various laboratory assays used.5 Interference may also occur in the presence of anti-Tg antibodies or heterophile antibodies.6,7 The sensitivity of Tg can be increased with thyroidstimulating hormone (TSH) stimulated by either thyroid hormone withdrawal or recombinant human TSH administration.8,9 On the other hand, some patients may present with elevated interference-corrected Tg levels alone, without clinical or radiological evidence of disease at physical examination, neck ultrasound, diagnostic radioiodine whole body scan (WBS), and/or computed tomography (CT) or 18F-fluorodeoxyglucosepositron emission tomography (FDG-PET). Although possibly nonspecific especially with the development of increasingly sensitive Tg assays, this condition is generally taken to represent occult malignant disease.10,11 Empirical 131I treatment is generally recommended at a Tg level of 5 ng/mL during or 10 ng/mL off thyroxine treatment.4,12 However, its clinical significance and management options are in fact controversial based on the current literature. Empirical radioiodine treatment has not been demonstrated prospectively to be associated with improved outcome, while in a retrospective study the majority of patients with positive Tg and negative WBS remained free of disease at 8 years follow-up.13 Moreover, it has been postulated that benign radioresistant ectopic thyroid or thymus tissue may instead be the source of Tg secretion.3 In these patients, monitoring the Tg trend plays a particular role, but only limited evidence on the prognostic and predictive significance of postablation Tg kinetics has been reported to date. In the present study, we aimed to evaluate the rate of change of nonstimulated serum Tg, or Tg velocity (denoted by TgV), to predict recurrence in postthyroidectomy and postablation PTC patients who have raised Tg levels. MATERIALS AND METHODS Consecutive PTC patients undergoing primary thyroidectomy with a curative intent in a tertiary referral center between 2003 and 2010 were analyzed. Owing to the adoption of different and less sensitive biochemical assays before 2003, patients who presented before this date were excluded. Patients with pathologies other than PTC, including follicular carcinoma, Hurthle cell carcinoma, medullary carcinoma, anaplastic carcinoma, and lymphoma, were also excluded. All patients underwent total thyroidectomy and neck dissection as required, with postoperative radioiodine of 3 GBq administered to ablate thyroid remnant. External-beam radiotherapy was considered in patients aged 45 or older with extrathyroidal tumor extension, according to current guidelines.4 Postablation WBS was perf (...truncated)