Remnant Ablation Research Articles

Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges.

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.

Radiation exposure to comforters and carers during paediatric molecular radiotherapy.

To show whether the incidental radiation exposure received by comforters and carers of children undergoing molecular radiotherapy was kept as low as reasonably achievable and was within English national dose constraints. The radiation exposure of adult comforters and carers was routinely monitored with a whole body personal dose meter while the child was in hospital. Data were collected on iodine-131 meta-iodobenzylguanidine (131 I-mIBG), lutetium-177 DOTATATE (177 Lu-DOTATATE), and iodine-131 sodium iodide (131 I-NaI) treatments. Data were available for 50 treatments with high-administered activity double-infusion 131 I-mIBG and 12 single administrations; 15 177 Lu-DOTATATE treatments and 28 131 I-NaI administrations. The median age was 7 years (1-18). The median administered activity of: 131 I-mIBG was 16.2 GBq (6.8-59 GBq) for double infusion patients and 8.1 GBq (5.26-16.25 GBq) for single administrations; 177 Lu-DOTATATE was 7.2 GBq (2.5-7.5 GBq); and 131 I-NaI was 3 GBq for thyroid remnant ablation and 5.5 GBq for cancer therapy. The median number of comforters and carers for all administrations was 2 (range 1-9). The median exposure values for comforters and carers for high-administered activity 131 I-mIBG administrations was 302 µSv (0-5282 µSv); for single fraction 131 I-mIBG 163 µSv (3-3104 µSv); 177 Lu-DOTATATE 6 µSv (1-79 µSv); and 131 I-NaI 37 µSv (0-274 µSv). Only one of the comforters and carers exceeded the dose constraint of 5 mSv. Doses to comforters and carers were in all but one case within the dose constraint nationally recommended by the Health Protection Agency, now part of Public Health England. New evidence is presented which show that comforter and carer radiation exposure levels from paediatric molecular radiotherapy in routine clinical practice are acceptably low. Pediatr Blood Cancer 2015;62:235-239. © 2014 Wiley Periodicals, Inc.

Current controversies in the initial post-surgical radioactive iodine therapy for thyroid cancer: a narrative review.

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy and the fifth most common cancer in women. DTC therapy requires a multimodal approach, including surgery, which is beyond the scope of this paper. However, for over 50 years, the post-operative management of the DTC post-thyroidectomy patient has included radioactive iodine (RAI) ablation and/or therapy. Before 2000, a typical RAI post-operative dose recommendation was 100 mCi for remnant ablation, 150 mCi for locoregional nodal disease, and 175-200 mCi for distant metastases. Recent recommendations have been made to decrease the dose in order to limit the perceived adverse effects of RAI including salivary gland dysfunction and inducing secondary primary malignancies. A significant controversy has thus arisen regarding the use of RAI, particularly in the management of the low-risk DTC patient. This debate includes the definition of the low-risk patient, RAI dose selection, and whether or not RAI is needed in all patients. To allow the reader to form an opinion regarding post-operative RAI therapy in DTC, a literature review of the risks and benefits is presented.

The Etiology, Diagnosis and Treatment of Differentiated Thyroid Carcinoma in Children and Adolescents

Differentiated thyroid carcinoma (DTC) of epithelium origin in children and adolescents is an uncommon malignancy with an excellent prognosis. However, pediatric DTC always presents at advanced stages and with higher rates of recurrence. This review aims at the current findings of etiology, diagnosis and therapeutic approach for pediatric DTC. Radiation exposure is the only established risk of pediatric DTC, which was first discovered more than half a century ago. Research uncovers family history of thyroid carcinoma and nonthyroid malignant tumors may also be a risk factor in children DTC. Conventional diagnostic methods including palpation, ultrasonography and fine needle aspiration cytology (FNAC), may provide definitive diagnoses for many patients. For patients cannot be confirmed, molecular markers such as BRAF V600E and RAS mutations as well as RET-PTC rearrangements maybe improved diagnosis of thyroid nodules. Although recurrence is common, the outcome is favorable when appropriately treated. To minimize the risk of recurrence, total thyroidectomy, central compartment dissection, with or without lateral compartment dissection should be the surgical procedure for most pediatric DTC. Furthermore, suppression of serum thyroid stimulating hormone, radioactive iodine therapy for remnant ablation and a long-term follow-up should be done for most pediatric DTC.

Is malignant nodule topography an additional risk factor for metastatic disease in low-risk differentiated thyroid cancer?

Differentiated thyroid cancer (DTC) is the most common endocrine malignancy. In recent decades, the incidence has been increasing, largely due to increased detection of patients with low-risk or very low-risk DTC. According to European Thyroid Association and American Thyroid Association guidelines, radioiodine (RAI) thyroid remnant ablation is not indicated in very low-risk patients, while its role is still debated in low-risk patients. Accordingly, risk stratification of DTC patients is pivotal when deciding for or against RAI ablation. Presently, risk stratification is based on pTNM staging integrated with clinical parameters. The aim of our study was to evaluate the relationship between location of malignant thyroid nodules within the thyroid gland and the presence of loco-regional and/or distant metastases in patients with pT1a-pT1b DTCs. We reviewed the records of 246 patients (214 women, 32 men; female-to-male ratio 6.7:1) affected by unifocal DTC ≤ 2 cm, who had undergone RAI thyroid remnant ablation (activity ranged 555-4588 MBq) after levothyroxine withdrawal or after recombinant human TSH (rhTSH) stimulation. The majority of the patients (91.5%) were affected by papillary thyroid carcinoma. Metastases were discovered by posttreatment whole-body scintigraphy in 29 out of 246 (11.8%) patients. In patients with metastases, malignant thyroid nodules were located in the right lobe (14/123, 11.4%), left lobe (7/95, 7.4%), and isthmus (8/27, 29.6%). The prevalence of metastases was significantly higher in patients with DTC located in the isthmus, compared to other sites (χ(2) = 9.6, p = 0.002). Our data show for the first time that a location of a thyroid cancer in the isthmus is an additional risk factor for RAI avid metastatic disease in pT1a-pT1b DTC patients, regardless of the presence or absence of other risk factors.

How sensitive (second-generation) thyroglobulin measurement is changing paradigms for monitoring patients with differentiated thyroid cancer, in the absence or presence of thyroglobulin autoantibodies.

Purpose of reviewTo discuss new insights regarding how sensitive (second-generation) thyroglobulin immunometric assays (Tg2GIMAs), (functional sensitivities ≤0.10 μg/L) necessitate different approaches for postoperative thyroglobulin monitoring of patients with differentiated thyroid cancer (DTC), depending on the presence of thyroglobulin autoantibodies (TgAbs).Recent findingsReliable low-range serum thyroglobulin measurement has both enhanced clinical utility and economic advantages, provided TgAb is absent (∼75% DTC patients). Basal [nonthyroid-stimulating hormone (TSH) stimulated] Tg2GIMA measurement obviates the need for recombinant human TSH stimulation because basal Tg2GIMA below 0.20 μg/L has comparable negative predictive value (>95%) to recombinant human TSH-stimulated thyroglobulin values below the cutoff of 2 μg/L. Now that radioiodine remnant ablation is no longer considered necessary to treat low-risk DTC, the trend and doubling time of low basal thyroglobulin values arising from postsurgical thyroid remnants have recognized prognostic significance. The major limitation of Tg2GIMA testing is interference by TgAb (∼25% DTC patients), causing Tg2GIMA underestimation that can mask disease. When TgAb is present, the trend in TgAb concentrations (measured by the same method) can serve as the primary (surrogate) tumor-marker and be augmented by thyroglobulin measured by a TgAb-resistant class of method (radioimmunoassay or liquid chromatography-tandem mass spectrometry).SummaryThe growing use of Tg2GIMA measurement is changing paradigms for postoperative DTC monitoring. When TgAb is absent, it is optimal to monitor the basal Tg2GIMA trend and doubling time (using the same method) in preference to recombinant human TSH-stimulated thyroglobulin testing. When TgAb is present, interference renders Tg2GIMA testing unreliable and the trend in serum TgAb concentrations per se (same method) can serve as a (surrogate) tumor-marker.

Comparison of fine-needle aspiration cytology, ultrasound and thyroglobulin examination for the differential diagnosis of enlarged neck lymph nodes in patients with differentiated thyroid cancer after radioactive iodine remnant ablation

Objective To compare the value of fine-needle aspiration cytology (FNAC),Tg,TgAb and ultrasonography (US) for the differential diagnosis of lymph node metastasis in patients with DTC after operation and radioactive iodine remnant ablation.Methods A total of 61 DTC patients with enlarged lymph nodes detected by US or physical examination after operation and radioactive iodine remnant ablation were included.FNAC was performed on the lymph nodes under US guidance within one week and the results were compared with those of Tg,TgAb and US.Final results were confirmed by comprehensive FNAC,posttreatment whole,body scan (Rx-WBS) and clinical follow-up.x2 test and Fisher's exact test were performed.Resuits Fifty-eight DTC patients had successful FNAC results,and 40 patients were confirmed as malignant and 18 as benign after overall assessment.FNAC identified 39 malignant and 19 benign cases.The coincidence rates of FNAC with postoperative pathological diagnosis and Rx-WBS for malignant cases were 100％ (20/20) and 78.9％ (15/19),respectively.For the benign cases,the coincidence rates of FNAC with clinical follow-up and Rx-WBS were 93.3％ (14/15)and 4/4,respectively.The sensitivity,specificity and accuracy were 97.5％(39/40),100％(18/18) and 98.3％(57/58) for FNAC; 87.5％(35/40),55.6％(10/18) and 77.6％(45/58) for US; 92.5％(37/40),72.2％(13/18) and 86.2％(50/58) for Tg combined with TgAb (Tg/TgAb).The accuracy of FNAC was higher than that of US and Tg/TgAb(x2 =4.336,11.697,both P＜0.05),while US and Tg/TgAb showed no significant difference (x2 =1.450,P＞0.05).Tg/TgAb and US results were consistent in 39 cases with a diagnostic accuracy of 97.4％ (38/39) verified by FNAC,while the other 19 cases with inconsistent Tg/TgAb and US results were verified as malignant in 4 cases and benign in 15 cases.Conclusions FNAC is superior to US and Tg/TgAb in the evaluation of lymph node metastasis in DTC patients after operation and radioactive iodine remnant ablation.FNAC should be recommended particularly when Tg/TgAb and US had inconsistent results. Key words: Thyroid neoplasms; Lymph nodes; Biopsy, fine-needle; Ultrasonography; Thyroglobulin

The AEC/NRC 30 mCi rule: regulatory origins and clinical consequences for 131I remnant ablative doses.

Clinical and historical uncertainty exists surrounding the regulations of the Atomic Energy Commission/Nuclear Regulatory Commission (AEC/NRC) requiring patient hospitalization when (131)I activities exceed 30 mCi. This review investigates the sometimes disturbing regulatory and clinical origins and consequences of the use of this low, 30 mCi dose as a prescription for thyroid remnant ablation. As early as in the 1940s, activities of (131)I between 30 and 200 mCi, often fractionated, were employed. The AEC deliberated from 1947 to the early 1960s before imposing as a license condition the requirement of hospitalizing patients until they contained <30 mCi of any byproduct material. The written AEC record throughout these years contains no supportive data to suggest safety issues requiring hospitalization at this activity level of (131)I. Yet the techniques for making the necessary calculations for determining radiation safety were available at this time. Declarations on the subject by nongovernmental bodies were misinterpreted as confirming such hospitalization as a legal requirement. The 30 mCi license condition was codified into NRC regulations in 1987 and was subsequently removed in 1997. Without any data, these U.S. regulatory agencies caused significant expense, inconvenience, and fear, affecting thyroid cancer patients and their families. This 30 mCi regulatory activity limit morphed, by a fortunate coincidence, into an acceptable ablative activity before there were solid confirmatory data. Studies on this 30 mCi ablative dose indicate that this activity was never associated with radiation health and safety issues, and was never more effective than higher ablative doses but led slightly more often to the need for a second (131)I dose. Nevertheless, the available data generally support the American Thyroid Association and Society of Nuclear Medicine and Molecular Imaging Guidelines, which indicate, without a treatment activity preference, that 30-100 mCi of (131)I provide adequate ablation. Follow-up data on the rates of recurrences, deaths, and second primary malignancies within this range of doses are unavailable. This history of unjustified governmental action and blind acceptance must remind the medical/radiation safety community to require solid data before ever again adopting baseless requirements. The 30 mCi dose should have never been employed as a requirement for hospitalization.

Radioiodine therapy for thyroid cancer in the era of risk stratification and alternative targeted therapies.

Differentiated thyroid cancers are typically iodine-avid and can be effectively treated with radioiodine. In most patients, radioiodine treatment is done for ablation of residual tissue, and in these cases the focus should be on using the minimum effective dose. Adjuvant therapy can be done to reduce the risk of recurrence, but optimal patient selection and dose are unclear. Patients with advanced disease benefit most from treatment with the maximum-tolerated dose. Recent research has focused on better patient selection and reduced radioiodine doses for remnant ablation. There are emerging targeted therapeutic approaches in patients who are appropriately shown to have iodine-refractory disease, with 1 drug approved by the Food and Drug Administration. Numerous trials are ongoing to assess targeted therapeutics alone or in combination with radioiodine.

Steady-State Serum T3 Concentrations for 48 Hours Following the Oral Administration of a Single Dose of 3,5,3'-Triiodothyronine Sulfate (T3S)

Sulfate conjugation of thyroid hormones is an alternate metabolic pathway that facilitates the biliary and urinary excretion of iodothyronines and enhances their deiodination rate, leading to the generation of inactive metabolites. A desulfating pathway reverses this process, and thyromimetic effects have been observed following the parenteral administration of 3,5,3'-triiodothyronine (T3) sulfate (T3S) in rats. The present study investigated whether T3S is absorbed after oral administration in humans and if it represents a source of T3. Twenty-eight hypothyroid patients (7 men and 21 women; mean age, 44 ± 11 years) who had a thyroidectomy for thyroid carcinoma were enrolled. Replacement thyroid hormone therapy was withdrawn (42 days for thyroxine, 14 days for T3) prior to 131I remnant ablation. A single oral dose of 20, 40, 80 (4 patients/group), or 160 μg (16 patients/group) of T3S was administered 3 days before the planned administration of 131I. Blood samples for serum T3S and total T3 (TT3) concentrations were obtained at various times up to 48 hours after T3S administration. At all T3S doses, serum T3S concentrations increased, reaching a peak at 2 to 4 hours and progressively returning to basal levels within 8 to 24 hours. The T3S maximum concentration (Cmax) and area under the 0- to 48-hour concentration-time curve (AUC0-48h) were directly and significantly related to the administered dose. An increase in serum TT3 concentration was observed (significant after 1 hour), and the concentration increased further at 2 and 4 hours and then remained steady up to 48 hours after T3S administration. There was a significant direct correlation between the TT3 AUC0-48h and the administered dose of T3S. No changes in serum free thyroxine (T4) concentrations during the entire study period were observed, whereas serum thyroid-stimulating hormone levels increased slightly at 48 hours, but this was not related to the dose of T3S. No adverse events were reported. (1) T3S is absorbed following oral administration in hypothyroid humans; (2) after a single oral dose, T3S is converted to T3 in a dose-dependent manner, resulting in steady-state serum T3 concentrations for 48 hours; (3) T3S may represent a new agent in combination with T4 in the therapy of hypothyroidism, if similar conversion of T3S to T3 can be demonstrated in euthyroid patients who are already taking T4.

Pyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with differentiated thyroid cancer

ObjectivesThe aim of the study was to assess the frequency of pyramidal lobe (PL) detected in iodine-131 (I-131) scans of thyroid bed in patients after thyroidectomy for differentiated thyroid cancer (DTC) and to investigate influence of PL on endogenous thyrotropin (TSH) stimulation as well as on the effects of the radio-iodine ablation in one-year follow-up. Patients and methodsThis study was designed as a retrospective analysis of 302 radio-iodine neck scans of patients thyroidectomized due to DTC. The study population was selected from patients with PL detected in thyroid bed scintigraphy. Patients without PL were included to the control group. The study and the control groups did not differ in age, sex of patients, histological type and stage of the DTC. ResultsPyramidal lobes were found in 30.5% of all patients. Patients in the study group underwent repeat surgery more often than controls without PL. Preablative TSH level in patients with PL was statistically lower than in the control group, in contrast to free thyroid hormones, which were higher in patients with PL. Preablative and postablative TSH-stimulated thyroglobulin (Tg) and antibodies against thyroglobulin (TgAbs) were measured in both groups, and comparison did not reveal differences. Moreover, for the per-patient analysis, sites of uptake in whole body scintigraphy performed 1 year after radio-iodine remnant ablation (RRA) did not differ between the study and the control groups. ConclusionPyramidal lobe decreases endogenous TSH stimulation without impact on radio-iodine therapy outcome in patients with DTC.

The Value of Postoperative Baseline Serum Thyroglobulin in Prediction of the Outcome of Radioactive Iodine-131 Thyroid Ablation in differentiated thyroid carcinoma

Background: Thyroglobulin is commonly used to monitor patients with differentiated cancer thyroid. It has also become an excellent biological marker for tumor persistence or recurrence. Aim ofstudy: To study the relation between the level of baseline serum thyroglobulin (TG) and thyroid remnant ablation outcome using radioactive iodine-131 (RAI-131) in patients with differentiated thyroid cancer after surgical treatment.Methods: A prospective study involved 64 patients (age 20-77 years) with differentiated thyroid cancer, referred for post-surgical 131I ablation. All patients performed baseline serum TG, anti-TGAb's under TSH stimulation as well as neck ultrasonography, before receiving RAI-131ablation dose 1110 - 3700 MBq (30 -100 mCi). Follow-up was performed 6-8 months later. Successful ablation was determined by negative whole body 131I scan, negative neck ultrasonography and stimulated serum thyroglobulin level less than 2 ng/mL. Results: Successful ablation was reported in 38 out of 64 cases (59.4 %). Baseline serum thyroglobulin level was significantly predictive of ablation outcome. ROC analysis showed AUC (area under curve) of 0.66 (CI: 0.53 - 0.78; P = 0.03). A cutoff value of 4.4 ng/ml showed sensitivity of 79 % and specificity of 68% in predicting ablation outcome. Patients were divided into high (n = 32) and low (n = 32) baseline TG groups using this cut-off point. Successful ablation significantly higher in low TG group (25/32 vs. 13/32; P=0.002). There was no significant difference between the two groups regarding their clinical and pathological data. Conclusion: Baseline serum thyroglobulin is associated with ablation outcome. Serum TG> 4.4 is linked to significantly higher rates of unsuccessful ablation.

Thyroid Remnant Ablation of Differentiated Thyroid Carcinoma: a comparison of Ablation success with High and Low Doses of Radio-iodine

Objectives: To assess efficiency of low dose131Iin thyroid remnant ablation of patients with differentiated thyroid cancer after surgical treatment. Material and Methods: 88 patients with differentiated thyroid cancer, (age 20-75 years) tumor stage T1 to T3, with disease confined to the thyroid or cervical lymph nodes. All patients were treated with 131I after total thyroidectomy and pathologic lymph node resection, if present. A randomized double-armed prospective trial comparing lowdose [1110MBq (30mCi)] and high-dose [3700 MBq (100mCi)] radioiodine ablation.39 patients received low dose and 49 patients received high dose. Six months after the administration of radioiodine, measurements of TG, anti-TG antibodies together with neck ultrasound exam and 131Iwhole-body scan were performed. The success rate of ablation is determined by negative whole body 131I scan, negative neck ultrasonography and serum thyroglobulin level less than 2 ng/mL.Results: Successful ablation reported in 23 out of 39 cases (58.9 %) in the group receiving low-dose radioiodine [1110MBq] versus 37 out of 49 cases (75.5 %) in the group receiving the high dose [2960-3700 MBq] (P value= 0.098). A second follow up was performed one year after the ablative dose for the cases who had successive ablation from both groups. In the low dose group, only 12 out of 23 patients (52%) were available, all of them didn't show any disease recurrence, versus 17 cases out of 37 in the high dose group, 16/17 patients didn't had recurrence, while in one case there was a recurrent disease at the thyroid bed.Conclusion: From this ongoing data, nonsignificant higher success thyroid remnant ablation was recorded for high compared to low radioiodine doses.

Radioiodine ablation with 1,850 MBq in association with rhTSH in patients with differentiated thyroid cancer

The aim of this study was to evaluate the efficacy of post-operative radioiodine ablation with 1,850 MBq after recombinant human thyrotropin (rhTSH) administration in patients with differentiated thyroid carcinoma (DTC). We also aimed to assess the prognostic role of several patient features on the outcome of ablation. We retrospectively analyzed data from a total of 125 patients with DTC who underwent post-operative radioiodine ablation with 1,850 MBq of ¹³¹I after preparation with rhTSH. One injection of 0.9 mg rhTSH was administered on each of two consecutive days; ¹³¹I therapy was delivered 24 h after the last injection, followed by a post-therapy whole-body scan. Successful ablation was assessed 6-12 months later and defined as an rhTSH-stimulated serum thyroglobulin (Tg) level ≤1.0 ng/ml and a normal neck ultrasound. Patients were stratified according to the American Thyroid Association (ATA) Management Guidelines for Differentiated Thyroid Cancer. Successful ablation was achieved in 82.4 % of patients, with an ablation rate of 95.1 % in low-risk patients and 76.2 % in intermediate-risk patients. Analyzing the correlation between ablation outcome and patient characteristics, we found a statistically significant association between failure to ablate and class of risk based on ATA guidelines (p = 0.025) and a stimulated Tg value at ablation of above 5 ng/ml (p < 0.001). The use of 1,850 MBq post-operative radioiodine thyroid remnant ablation in association with rhTSH is effective for low- and intermediate-risk patients. Moreover, in our study, we found a statistical correlation between failure to ablate and class of risk based on ATA guidelines for DTC and a stimulated Tg value at ablation.

Clinical Aggressiveness and Long-Term Outcome in Patients with Papillary Thyroid Cancer and Circulating Anti-Thyroglobulin Autoantibodies

The association between papillary thyroid cancer (PTC) and Hashimoto's thyroiditis is widely recognized, but less is known about the possible link between circulating anti-thyroglobulin antibody (TgAb) titers and PTC aggressiveness. To shed light on this issue, we retrospectively examined a large series of PTC patients with and without positive TgAb. Data on 220 TgAb-positive PTC patients (study cohort) were retrospectively collected in 10 hospital-based referral centers. All the patients had undergone near-total thyroidectomy with or without radioiodine remnant ablation. Tumor characteristics and long-term outcomes (follow-up range: 2.5-24.8 years) were compared with those recently reported in 1020 TgAb-negative PTC patients with similar demographic characteristics. We also assessed the impact on clinical outcome of early titer disappearance in the TgAb-positive group. At baseline, the study cohort (mean age 45.9 years, range 12.5-84.1 years; 85% female) had a significantly higher prevalence of high-risk patients (6.9% vs. 3.2%, p<0.05) and extrathyroidal tumor extension (28.2% vs. 24%; p<0.0001) than TgAb-negative controls. Study cohort patients were also more likely than controls to have persistent disease at the 1-year visit (13.6% vs. 7.0%, p=0.001) or recurrence during subsequent follow-up (5.8% vs. 1.4%, p=0.0001). At the final follow-up visit, the percentage of patients with either persistent or recurrent disease in the two cohorts was significantly different (6.4% of TgAb-positive patients vs. 1.7% in the TgAb-negative group, p<0.0001). At the 1-year visit, titer normalization was observed in 85 of the 220 TgAb-positive individuals. These patients had a significantly lower rate of persistent disease than those who were still TgAb positive (8.2% vs. 17.3%. p=0.05), and no relapses were observed among patients with no evidence of disease during subsequent follow-up. PTC patients with positive serum TgAb titer during the first year after primary treatment were more likely to have persistent/recurrent disease than those who were consistently TgAb-negative. Negative titers at 1 year may be associated with more favorable outcomes.

Higher Administered Activities of Radioactive Iodine Are Associated with Less Structural Persistent Response in Older, but Not Younger, Papillary Thyroid Cancer Patients with Lateral Neck Lymph Node Metastases

While radioactive iodine (RAI) adjuvant therapy is commonly recommended for most papillary thyroid cancer patients presenting with large volume nodal involvement, it remains unclear if such therapy impacts the disease-specific recurrence rate and overall survival. In this study, we compared the risk of achieving a structural persistent response after low administered activity (100 mCi), intermediate administered activity (150 mCi), and high administered activity (>200 mCi) RAI adjuvant therapy in patients presenting with pathologic N1b disease. This was a retrospective review of 181 papillary thyroid cancer patients with N1b disease treated with total thyroidectomy, neck dissection, and RAI remnant ablation. Dose-response relationships were determined between the administered activity of (131)I and the best response to initial therapy. Out of the 181 patients, only 39% achieved no clinical evidence of disease (NED) after initial therapy. Young patients (Stage I) had a statistically nonsignificant trend toward higher rates of NED with increasing dose (34% low activity, 36% intermediate activity, 46% high activity), but there was no evidence of dose-response effect with regard to the likelihood of having a structural persistent response to initial therapy or the likelihood of having persistent biochemical evidence of disease. However, analysis of the older patients (Stage IVa) did reveal a trend toward statistically significant dose-response relationships with increasing administered activities being associated with lower rates of structural persistent response (46% low activity, 23% intermediate activity, 17% high dose). Unfortunately, the lower rate of structural persistent response only modestly increased the likelihood that patients would be NED but was instead associated with a higher proportion of patients being classified as having biochemical persistent disease at 12-18 months. It appears that administering more than 100 mCi of RAI as adjuvant therapy in N1b disease is unlikely to improve the initial response to therapy. This is especially true for the younger (Stage I) patients. It is plausible that administered activities of 150-260 mCi may be associated with an improved response to initial therapy in older patients (Stage IVa) who are probably at highest risk of having poor outcomes, but the potential benefit from RAI should be balanced against potential adverse effects in those patients.

Sentinel Lymph Node Biopsy Status Correlates With Postoperative Stimulated Thyroglobulin Levels in Low-Risk Papillary Thyroid Cancer Patients

Radioactive iodine (RAI) remnant ablation in low-risk papillary thyroid cancer (PTC) is controversial. Current patient selection guidelines recommend the use of postoperative stimulated thyroglobulin (stim-Tg), neck dissections, and sonography but fail to include sentinel lymph node biopsy (SLNB). The objective of this study was to evaluate the correlation between SLNB status and postoperative stimulated thyroglobulin as a surrogate marker of clinical outcome. Retrospective chart review of low-risk PTC patients who underwent a total thyroidectomy with SLNB at the McGill Thyroid Cancer Center. SLNBs were obtained using methylene blue dye. Biochemical measurements were acquired between 4 and 12 weeks postoperatively. Statistical analyses were performed using logistic regression models and receiver operating characterisitc (ROC) curves. A P-value <.05 was considered significant. Ninety-six patients were included in this study. The positive SLNB rate was 14.6%. The mean postoperative Tg level was 1.41 μg/L. There were no significant correlations between the SLNB and the covariates analyzed (age, gender, histology, tumor size, and thyrotropin levels). Patients with negative SLNB were significantly more likely to have a lower stim-Tg (P<.0001). When postoperative Tg was analyzed as a categorical variable, a threshold of <1 μg/L was significantly associated with a negative SLNB, with a sensitivity and specificity (determined by ROC curves) of 0.86 and 0.88, respectively. There exists a correlation between SLNB and postoperative Tg. This creates the possibility of a new approach to RAI administration among low-risk PTC patients incorporating SLNB to the current guidelines.

DIAGNOSIS OF ENDOCRINE DISEASE: Thyroglobulin measurement using highly sensitive assays in patients with differentiated thyroid cancer: a clinical position paper

Differentiated thyroid cancer (DTC) is the most common endocrine cancer and its incidence has increased in recent decades. Initial treatment usually consists of total thyroidectomy followed by ablation of thyroid remnants by iodine-131. As thyroid cells are assumed to be the only source of thyroglobulin (Tg) in the human body, circulating Tg serves as a biochemical marker of persistent or recurrent disease in DTC follow-up. Currently, standard follow-up for DTC comprises Tg measurement and neck ultrasound combined, when indicated, with an additional radioiodine scan. Measurement of Tg after stimulation by endogenous or exogenous TSH is recommended by current clinical guidelines to detect occult disease with a maximum sensitivity due to the suboptimal sensitivity of older Tg assays. However, the development of new highly sensitive 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 without the need for TSH stimulation. Use of these highly sensitive Tg assays has not yet been incorporated into clinical guidelines but they will, we believe, be used by physicians caring for patients with DTC. The aim of this clinical position paper is, therefore, to offer advice on the various aspects and implications of using these highly sensitive Tg assays in the clinical care of patients with DTC.

Thyroglobulin before radio remnant ablation during levothyroxine withdrawal can be considered an accurate parameter of remission of differentiated thyroid cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Rhabdomyolysis precipitated acute renal injury during levothyroxine withdrawal for remnant ablation in a case with papillary thyroid cancer

Rhabdomyolysis precipitated acute renal injury during levothyroxine withdrawal for remnant ablation in a case with papillary thyroid cancer