Undetectable Serum Thyroglobulin Research Articles

Bone metastasis from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP); a case report

BackgroundThe term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was recently proposed as a non-malignant thyroid lesion with indolent behavior that does not require post-operative radio-iodine treatment. We are reporting a case of NIFTP with bone metastasis that is the second case reported so far.Case presentationWe describe a 38-year-old woman who presented with an indeterminate thyroid nodule and underwent total thyroidectomy with the finding of NIFTP on careful pathologic examination. However, her initial follow-up evaluation revealed a serum thyroglobulin level of > 300 ng/ml and a diagnostic whole body 131I scan demonstrated a focus of increased uptake in the left hemipelvis, confirmed on CT scan to be a lytic lesion in the left iliac bone. She was treated with 7.4GBq (200 mCi) of 131I and her follow-up 1 year later revealed an undetectable serum thyroglobulin and a negative whole body 131I scan with no visible uptake in the iliac bone indicating an excellent response.ConclusionThis case presentation reminds us to be alert to the rare occurrence of distant metastasis in NIFTP and the need for a case by case analysis and continuing post-operative follow-up for detection of residual or recurrent disease.

SAT-511 Alpha Gal Allergy in a Hypothyroid Patient

Background: The IgE-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal), a carbohydrate expressed on nonprimate mammalian proteins, has gained more clinical significance as it can present with serious, potentially fatal anaphylaxis or angioedema. In general, recognizing a specific allergy is the first step in prescribing avoidance; but with delayed symptoms, uncertain prevalence, and unclear diagnostic approach, alpha-gal allergies are difficult to recognize and prevent. To further complicate the clinical picture, some patients can tolerate small portions of nonprimate mammalian meat or tolerate one kind of meat over another. We hereby present a case that highlights the lack of guidance and resources currently available to treat a patient with alpha-gal allergy and hypothyroidism. Case Presentation: A 45-year-old woman with a history of an alpha-gal allergy and follicular thyroid neoplasm status post right hemithyroidectomy presented with postoperative hypothyroidism. After the surgery, she had undetectable serum thyroglobulin levels; her thyroid stimulating hormone (TSH) levels were ranging 5–6 µIU/mL (not on thyroid replacement). The goal was to prescribe thyroid replacement to initiate cancer suppressive strategy. The American Thyroid Association (ATA) recommends a TSH of 0.5-to-2 mcIU/mL in low risk patients postoperatively. The standard treatment of choice for correcting hypothyroidism is synthetic thyroxine (T4, levothyroxine). Commercially available levothyroxine, liothyronine, combo, and desiccated thyroid formulations - whether brand name, generic, tablet, soft gel capsule, or liquid - all contain meat byproducts and can be a concern for anaphylaxis or angioedema if one has an alpha gal allergy. Because of the possible reactions with all common formulations of thyroid hormone replacement in this patient, choosing a safe option was complicated and involved a multidisciplinary team, including allergy and immunology consultation. Daily parenteral synthetic thyroid hormone therapy was considered; however, it is not practical and was not feasible for the patient. She was eventually prescribed pure Levothyroxine, with a plant-based filler and vegetarian capsule. She tolerated this pure levothyroxine well without any adverse reactions, and the TSH goal was achieved. Conclusion: This case emphasizes the importance of recognizing various risk factors and common drugs associated with the alpha-gal allergy. Further research and pharmaceutical attention to this allergy is needed.

Thyroglobulin washout from cervical lymph node fine needle aspiration biopsies in patients with differentiated thyroid cancer: an analysis of different expressions to use in post-total thyroidectomy follow-up

IntroductionAlthough frequently used as an adjunct to cytology in patients with differentiated thyroid cancers, interpretation of thyroglobulin washout remains unclear. We aim to compare the utility of different analytic tools to develop recommendations for use in post-total thyroidectomy follow-up. MethodsThis is an institutional review board-approved retrospective study of patients who underwent lymph node fine needle aspiration biopsy with thyroglobulin washout between 2012 and 2018, during the post-total thyroidectomy follow-up of differentiated thyroid cancer. The utilities of thyroglobulin washout concentration, thyroglobulin washout/serum thyroglobulin ratio, and absolute thyroglobulin content were compared. ResultsSixty-four patients underwent 79 fine needle aspirations with thyroglobulin washout of cervical lymph nodes. Fifty-two lymph nodes were found to be metastatic and 27 benign. One patient had a pathologically confirmed lymph node metastasis despite a thyroglobulin washout of 0. The optimal cutoffs of thyroglobulin washout, thyroglobulin washout/serum thyroglobulin ratio, and absolute thyroglobulin content to predict metastatic involvement were 2.5 ng/ml (94% sensitive, 100% specific), 0.1 (100% sensitive and specific), and 12.5 (94% sensitive, 100% specific), respectively. The second measure lacked utility in patients with undetectable serum thyroglobulin. ConclusionThe use of thyroglobulin washout concentration or thyroglobulin washout/serum thyroglobulin ratio has drawbacks based on variations in technique and clinical scenario. Absolute thyroglobulin content is an alternative that may be a more objective expression of thyroglobulin washout.

Increased Numbers of Circulating Tumor Cells in Thyroid Cancer Patients.

Circulating tumor cells (CTCs) have been shown to be a valuable prognostic marker for different solid cancers. Within the present study we quantified CTCs in thyroid cancer (TC) patients. Special focus was given to disease-free PTC patients with undetectable serum thyroglobulin (Tg) levels. Altogether, 67 TC patients (33 papillary, 20 follicular, 14 medullary) were included in the study. CTC numbers, which were normalized to 3.3×105 peripheral blood mononuclear cells, were correlated with clinical outcome. TC patients had significantly higher CTC numbers compared to controls. The number of CTCs correlated to the initial tumor stage. Importantly, in comparison to controls, differentiated TC patients with serum Tg levels<0.3 ng/ml (no evidence of tumor recurrence) revealed a significantly higher amount of CTCs, also associated to their former tumor stage. Regarding the tumor-free papillary TC (PTC) patients the number of CTCs additionally correlated to the time point of radioiodine (RI) therapy: PTC patients with RI therapies>8 years before CTC measurement had significantly higher CTC numbers compared to those with RI therapy<8 years ago. We found a clear correlation between the number of CTCs and the tumor stage. Importantly, PTC patients who are in remission may still have increased numbers of CTCs. Follow-up analyses in these patients will reveal whether these data will have a clinical impact.

18F-FDG PET/CT and ultrasonogrpahy in differentiated thyroid carcinoma patients with elevated serum levels of antithyroglobulin antibody, negative Tg and whole body 131I scan.

In the follow-up of patients with differentiated thyroid cancer (DTC), several patients had elevated serum levels of antithyroglobulin antibody (TgAb), undetectable serum thyroglobulin (Tg), and negative radioiodine whole body scan (131I-WBS). We describe the use of neck ultrasonography (US) and fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging in these patients to investigate this clinically challenging problem and propose treating. A total of 49 DTC patients with elevated serum levels of TgAb (>115IU/mL), undetectable Tg and negative 131I-WBS were divided into two groups (positive and negative) according to the neck US findings. Differences in the rate of recurrence between the two groups were investigated. The diagnostic value of 18F-FDG PET/CT in these patients was evaluated. Among the 49 patients, the rate of recurrence of patients with positive neck US was 50%, which was significantly higher than that of patients with negative neck US (17.24%; P=0.014). The sensitivity, specificity, and positive predictive values of 18F-FDG PET/CT imaging in diagnosing the clinical status of these patients were 93.33%, 70.59% and 58.33%, respectively. After the 18F-FDG PET/CT scan, clinical management was changed in 14 patients. Nine patients were operated and five underwent 131I ablation therapy. In the 49 DTC patients with elevated serum levels of TgAb but negative findings in serum Tg and in 131I-WBS, neck US and 18F-FDG PET/CT imaging supported the clinical diagnosis and suggested subsequent treatment.

Clinical Impact of Detectable Antithyroglobulin Antibodies Below the Reference Limit (Borderline) in Patients with Papillary Thyroid Carcinoma with Undetectable Serum Thyroglobulin and Normal Neck Ultrasonography After Ablation: A Prospective Study.

Interference of antithyroglobulin antibodies (TgAb) with serum thyroglobulin (Tg) can occur even at detectable TgAb concentrations below the reference limit (borderline TgAb). Thus, borderline TgAb is considered as TgAb positivity in patients with thyroid cancer. This prospective study evaluated patients with papillary thyroid carcinoma with undetectable Tg and normal neck ultrasonography (US) after total thyroidectomy and ablation with 131I, and compared tumor persistence/recurrence and long-term Tg and TgAb behavior in those with borderline versus undetectable TgAb. A total of 576 patients were evaluated, divided into two groups: group A with undetectable TgAb (n = 420), and group B with borderline TgAb (n = 156). Groups A and B were similar in terms of patient and tumor characteristics. The time of follow-up ranged from 24 to 120 months. During follow-up, 11 (2.6%) patients in group A and 5 (3.2%) in group B developed a recurrence (p = 0.77). In group A, recurrences occurred in 9/390 patients who continued to have undetectable TgAb and in 1/9 patients who progressed to borderline TgAb. In group B, recurrences were detected in 1/84 patients who progressed to have undetectable TgAb, in 1/45 who still had borderline TgAb, and in 3/12 who developed elevated TgAb. In the presence of Tg levels <0.2 ng/mL, recurrences were detected in 2/486 patients with undetectable TgAb, in 0/67 with borderline TgAb, and in 3/12 with elevated TgAb. The results of post-therapy whole-body scanning (RxWBS) of 216 patients with Tg ≤0.2 ng/mL and normal US at the time of ablation were also analyzed. In low-risk patients, none of the 40 patients with borderline TgAb and none of the 94 with undetectable TgAb exhibited ectopic uptake on RxWBS. In intermediate-risk patients, lymph node metastases were detected by RxWBS in 1/25 (4%) with borderline TgAb and in 2/57 (3.5%) with undetectable TgAb. The results suggest that among low- or intermediate-risk patients with undetectable Tg and normal US after thyroidectomy, those with borderline TgAb are at no greater risk of tumor persistence or recurrence than those with undetectable TgAb. When undetectable Tg levels persist, recurrence should be suspected in the case of a TgAb elevation above the reference limit.

Is Very High Thyroid Stimulating Hormone Level Required in Differentiated Thyroid Cancer for Ablation Success?

Objective:Remnant ablation with radioactive iodine (I-131) is a successful form of treatment that aims to destroy the remaining residual tissue and/or metastatic tissue after total thyroidectomy in differentiated thyroid cancer (DTC) patients. High level of thyroid stimulating hormone (TSH) (≥30 mIU/L) is recommended for success of ablation treatment. In this retrospective study, our aim was to investigate whether the TSH levels at the time of ablation effect the success of radioactive iodine remnant ablation.Methods:Patients who were diagnosed with DTC, treated with bilateral total/near total thyroidectomy and who were referred for I-131 remnant ablation were included in this study. Patients with undetectable TSH-stimulated serum thyroglobulin (Tg) level, normal physical examination, negative results on whole body scan with I-131, and no evidence of neck lymph node metastasis on ultrasound were defined as disease-free. The correlation between TSH level at the time of ablation and ablation success was assessed.Results:Two hundred sixty one consecutive patients were included in the present study. Mean TSH level was 19.47±6 mIU/L in the 34 patients with TSH <30 mIU/L, while mean TSH level was 73.65±27 mIU/L in the 227 patients with TSH ≥30 mIU/L during I-131 remnant ablation. Ablation was unsuccessful in only one patient with TSH <30 mIU/L who had lung metastasis. Ablation was unsuccessful in 5.1% of patients with TSH ≥30 mIU/L. The effect of TSH level was not significant on ablation success (p=0.472).Conclusion:In conclusion, we think that a high TSH serum level alone is not a factor for the success of ablation. Age, presence of metastasis, extent of residual thyroid mass should also be considered. Especially, in the presence of metastatic tissue, obtaining adequate increase in TSH level is not always possible. The success of ablation at lower levels of TSH elevations may be sufficient for patients, and long-term hypothyroidism may not be required.

Metastatic differentiated thyroid cancer with undetectable serum thyroglobulin: diagnostic, management and follow-up challenges

Metastatic differentiated thyroid cancer with undetectable serum thyroglobulin: diagnostic, management and follow-up challenges

The role of FDG-PET/CT in differentiated thyroid cancer patients with negative iodine-131 whole-body scan and elevated anti-Tg level.

In the follow-up of differentiated thyroid cancer (DTC) after a successful total-near total thyroidectomy and I-131 ablation therapy, anti-thyroglobulin antibodies (anti-Tg) may be persistently or progressively increased in the patients with an undetectable serum thyroglobulin (Tg) level. In these cases, further investigation was performed to search for recurrence/metastases. The aim of our study was clarifying the role of FDG-PET/CT in detecting recurrence/metastasis in patients with DTC with negative serum Tg and elevated anti-Tg level. A total of 40 patients (32 female, 8 male; mean age: 43.15years (22-65); mean age at diagnosis: 39.08 (16-64)) with DTC who had undetectable serum Tg and elevated anti-Tg level after a successful initial therapy were included in the study. All of the patients had serum anti-Tg of >40IU/ml and underwent FDG-PET/CT to search for recurrence/metastasis. Twenty patients (50%) had recurrence/metastasis on FDG-PET/CT while the other 20 had no pathologic findings. Of the 20 patients who had positive FDG-PET/CT, 12 had a histopathological final diagnosis of which 11 were true positive (TP) and 1 was false positive (FP). On the other hand, 16 of the 40 patients had a histopathological final diagnosis of which 11/16 had TP, 1/16 FP, 3/16 false negative (FN) and 1/16 true negative (TN) findings by PET/CT. The final diagnosis was made by clinical follow-up in the remaining 24 patients. Of these, 8 patients were PET positive, and in 1 (12.5%) of 8 patients a decrease in serum anti-Tg level, in 2 (25%) patients a saw-toothed pattern and in 5 (62.5%) a progressive increase in the serum anti-Tg level were noted during the follow-up. Of the 16 of 24 patients who were diagnosed by clinical follow-up, in 8 a (50%) decrease in serum anti-Tg level, in 6 (37.5%) a saw-toothed pattern, and in 2 (12.5%) a progressively increased anti-Tg level was seen. Of the 40 patients, 14 (35%) had a diagnosis of recurrence/metastasis finally, with PET/CT detecting 11 (78.6%) of them. The value of a persistently or progressively increased serum anti-Tg level in the follow-up of DTC in the prediction of recurrence/metastasis is controversial. However, it is reported that FDG-PET can be useful in the detection of recurrence/metastasis. We conclude from the available data that PET/CT can be effectively used in the detection of recurrence/metastasis in the follow-up of patients with DTC and negative serum Tg and a persistently/progressively increased anti-Tg level. Besides, one half of the patients were FDG negative, meaning that further studies are needed to assess the prognostic-clinical value of PET negativity.

Outcomes of Total Thyroidectomy with Therapeutic Central and Lateral Neck Dissection with a Single Dose of Radioiodine in the Treatment of Regionally Advanced Papillary Thyroid Cancer and Effects on Serum Thyroglobulin

Achieving an undetectable serum thyroglobulin (Tg) level (<1.0 ng/mL) after surgical and radioiodine treatment for papillary thyroid cancer (PTC) is associated with low recurrence rates and has been termed biochemical remission. This study aimed to determine the effectiveness of total thyroidectomy with therapeutic central and lateral neck dissection for regionally advanced (T1-4bN1bM0) PTC with regard to posttreatment Tg levels. This is a single-institution retrospective cohort study of patients with regionally advanced PTC initially treated with total thyroidectomy and therapeutic levels 2-7 neck dissection from 2002 to 2012. Pathologic findings, complications, serum Tg levels, and outcomes were analyzed. Sixty-one patients were initially treated with total thyroidectomy and therapeutic central and lateral neck dissection for PTC involving the lateral cervical nodes (N1b). The median number of lymph nodes excised and positive was 27 (range 5-112) and 9 (range 1-67), respectively. Extranodal extension occurred in 48 %. Radioiodine was administered after surgery with a median total dose of 150 mCi (range 30-244 mCi). Recurrent or persistent cervical disease occurred in 8 (13 %) and 3 (5 %) patients, respectively, and required additional radioiodine treatment in 2 and reoperative neck dissection in 10. Three patients developed new distant metastasis, and 1 died during the median follow-up of 20 months (range 1-109 months). Undetectable unstimulated Tg (<1.0 ng/mL) without clinically detectable recurrence was experienced in 68 % of patients with initial treatment. Biochemical remission can be experienced in most patients presenting with regionally advanced PTC with total thyroidectomy and compartment based therapeutic neck dissection followed by a single dose of radioiodine.

Follow-up of Patients with Low-risk Papillary Thyroid Carcinoma and Undetectable Basal Serum Thyroglobulin After Ablation Measured with a Sensitive Assay: A Prospective Study

The importance of thyroglobulin (Tg) stimulation after ablation in patients with papillary thyroid carcinoma (PTC) and undetectable basal Tg measured with sensitive assays has been questioned. However, there is a need for prospective studies that evaluate the evolution of these patients when stimulated Tg is omitted and this was the objective of the present investigation. One hundred twenty-two consecutive patients with PTC with the following characteristics were evaluated: submitted to total thyroidectomy and remnant ablation; low risk for recurrence; undetectable basal Tg (functional sensitivity of 0.1 ng/ml) 6 months after initial therapy; anti-Tg antibodies (TgAb) negative, and neck ultrasound (US) showing no abnormalities. These patients were not submitted to Tg stimulation. After follow-up for 24-78 months, only one patient (0.8%) presented apparent disease (lymph node metastases). TgAb were detected at low titers and without progression in 1 patient (0.8%). Tg became detectable and continued to be detectable in 3 patients (2.4%), but at concentrations ≤0.3 ng/ml in the absence of further increases, with stimulated Tg < 1.4 ng/ml. A total of 117 patients (96%) coursed with no apparent disease throughout follow-up and had undetectable Tg at the end of the study. Of these, 111 showed undetectable Tg in all measurements and 6 showed detectable Tg in some of them, although Tg later returned spontaneously to an undetectable range. After ablation, the risk of recurrence is very low in patients with low-risk PTC who show undetectable basal Tg measured with a sensitive assay, negative TgAb and negative US.

Lung nodule detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid cancer, negative 131I whole body scan, and undetectable serum-stimulated thyroglobulin levels: two case reports

IntroductionWhen a pulmonary nodular lesion is detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography in a patient with post-surgical papillary thyroid carcinoma with undetectable serum-stimulated thyroglobulin levels and negative 131I whole body scan, diagnosis and management of the nodule may be confusing.Case presentationWe describe two post-surgical patients with papillary thyroid carcinoma who showed pulmonary nodular lesions detected by F-18 fluorodeoxyglucose positron emission tomography-computed tomography. In both cases serum-stimulated thyroglobulin levels were undetectable and nodular lesions were not detected by 131I whole body scan. In the first case, a 64-year-old Asian woman showed one focal increased fluorodeoxyglucose uptake lesion in the right lower lobe of one of her lungs. Based on the histologic study, the pulmonary nodular lesion was diagnosed as a solitary pulmonary metastasis from papillary thyroid carcinoma. In the second case, a 59-year-old Asian woman showed a new pulmonary nodule in the right lower lobe. The computed tomography scan of her chest revealed a 9mm nodule in the anterior basal segment and another tiny nodule in the posterior basal segment of the right lower lobe. Six months later, both nodules had increased in size and miliary disseminated nodules were also seen in both lungs. Based on their histology, the pulmonary nodular lesions were considered to be primary lung adenocarcinoma.ConclusionsThe present cases emphasize that physicians should be cautious and make efforts for an accurate diagnosis of pulmonary nodules detected on F-18 fluorodeoxyglucose positron emission tomography-computed tomography in patients with papillary thyroid carcinoma with no evidence of metastasis such as negative 131I whole body scan and undetectable stimulated serum thyroglobulin levels.

Undetectable Sensitive Serum Thyroglobulin (&amp;lt;0.1 ng/ml) in 163 Patients with Follicular Cell-Derived Thyroid Cancer: Results of rhTSH Stimulation and Neck Ultrasonography and Long-Term Biochemical and Clinical Follow-Up

Surveillance of patients with differentiated thyroid cancer (DTC) is achieved using serum thyroglobulin (Tg), neck ultrasonography (US), and recombinant human TSH (rhTSH)-stimulated Tg (Tg-stim). Our primary aim was to assess the utility of rhTSH Tg-stim in patients with suppressed Tg (Tg-supp) below 0.1 ng/ml using a sensitive assay. Our secondary aims were to assess the utility of US and to summarize the profile of subsequent Tg-supp measures. This is a retrospective study conducted at two sites of an academic institution. A total of 163 patients status after thyroidectomy and radioactive iodine treatment who had Tg-supp below 0.1 ng/ml and rhTSH Tg-stim within 60 d of each other were included. After rhTSH stimulation, Tg remained below 0.1 ng/ml in 94 (58%) and increased to 0.1-0.5 in 56 (34%), more than 0.5-2.0 in nine (6%), and above 2.0 ng/ml in four (2%) patients. Serial Tg-supp levels were obtained in 138 patients followed over a median of 3.6 yr. Neck US were performed on 153 patients; suspicious exams had fine-needle aspiration (FNA). All positive FNA were identified around the time of the initial rhTSH test. Six of seven recurrences were detected by US (Tg-stim >2.0 ng/ml in one, 0.8 in one and ≤ 0.5 in four). One stage IV patient had undetectable Tg-stim. In patients with DTC whose T(4)-suppressed serum Tg is below 0.1 ng/ml, long-term monitoring with annual Tg-supp and periodic neck US are adequate to detect recurrences. In our experience, rhTSH testing does not change management and is not needed in this group of patients.

Undetectable Serum Thyroglobulin Levels in Patients with Medullary Thyroid Carcinoma After Total Thyroidectomy Without Radioiodine Ablation

Recently, we reported that the thyroglobulin (Tg) doubling time (DT) was the most potent prognostic factor in patients with papillary thyroid carcinoma (PTC) who underwent total thyroidectomy. Interestingly 16.2% of the study patients had a decrease in Tg levels over time, giving negative values in Tg-DT. These patients had an excellent outcome. However, most of the patients did not receive ablation with radioactive iodine. Therefore, whether the Tg in these patients was derived from persistent disease or residual thyroid tissue could not be concluded. To resolve this question, we measured serum Tg levels in patients with medullary thyroid carcinoma (MTC) who underwent total thyroidectomy using similar surgical techniques for the treatment of PTC. Twenty-seven consecutive patients with MTC who underwent total thyroidectomy were selected. Of them, five patients with antibodies to Tg were excluded from the study. In the remaining 22 patients, serum Tg levels were measured before and after surgery. None of the patients received radioactive iodine ablation. They were prescribed levothyroxine as a replacement for the lost thyroid function. Serum Tg levels were detectable preoperatively, while postoperative serum Tg levels were lower than the detectable level, 0.5 ng/mL, in all 22 patients. The results indicate that most of the patients with detectable Tg levels and negative Tg-DT values after total thyroidectomy for PTC in our previous study had persistent disease, and that their serum Tg was not from residual thyroid tissue, suggesting that up to 50% of patients with persistent PTC have a decrease in serum Tg levels in response to thyroid-stimulating hormone-suppressive therapy.

Undetectable serum thyroglobulin levels in patients with medullary thyroid carcinoma after total thyroidectomy without radioiodine ablation

Undetectable serum thyroglobulin levels in patients with medullary thyroid carcinoma after total thyroidectomy without radioiodine ablation

Thyroglobulin Gene Mutation with Cold Nodule on Thyroid Scintigraphy

Thyroglobulin gene mutation is a rare cause of congenital hypothyroidism, but thyroglobulin gene mutations are thought to be associated with thyroid cancer development. A 21-year-old Japanese man treated with levothyroxine for congenital hypothyroidism had an enlarged thyroid gland with undetectable serum thyroglobulin despite elevated serum TSH level. The patient was diagnosed with thyroglobulin gene mutation, with compound heterozygosity for Gly304Cys missense mutation and Arg432X nonsense mutation. Ultrasonography showed a hypovascular large tumor in the left lobe that appeared as a cold nodule on thyroid scintigraphy. He underwent total thyroidectomy, but pathological study did not reveal findings of thyroid carcinoma, but rather a hyperplastic nodule with hemorrhage. Strong cytoplasmic thyroglobulin immunostaining was observed, but sodium iodide symporter immunostaining was hardly detected in the hyperplastic nodule. The clinical characteristics of patients with thyroglobulin gene mutations are diverse, and some patients are diagnosed by chance on examination of goiter in adults. The presence of thyroid tumors that appear as cold nodules on thyroid scintigraphy should consider the potential for thyroid carcinoma, if the patient has relatively low serum thyroglobulin concentration in relation to the degree of TSH without thyroglobulin autoantibody.

Tuberculose pulmonaire simulant une miliaire métastatique d’un carcinome vésiculaire de la thyroïde à la scintigraphie du corps entier à l’iode 131

Iodine 131 whole body scan and serum thyroglobulin rate constitute often useful and valuable tools in the follow-up of patients differentiated thyroid carcinoma after primary therapy. For this purpose, the detection of radioiodine uptake foci outside the thyroid bed and the physiological sites of collecting are often allotted to the presence of metastatic localizations. However, the description of false-positives can induce an expensive and inadequate diagnostic and therapeutic complement. The authors report the observation of a patient followed for a treated follicular thyroid carcinoma, at which the iodine 131 whole body control had shown an aspect of metastasic miliary contrasting with an undetectable serum thyroglobulin. The tuberculin skin test and microscopic examination of sputum was positive. The patient was put under anti-tuberculous antibiotherapy and the evolution was very favorable. The identification of false-positives to the 131 iodine whole body scan appears necessary to improve the follow-up of patients and for ousting an iterative and completely useless therapeutic doses.

Treatment and follow-up of low-risk patients with thyroid cancer

The postoperative administration of radioiodine can be avoided in low-risk patients with undetectable TSH-stimulated serum thyroglobulin and no lymph-node metastases detected at surgery. Sensitive methods for serum thyroglobulin determination can be used to avoid TSH stimulation 9-12 months after surgery in low-risk patients who have an undetectable serum thyroglobulin on levothyroxine treatment; the role of these sensitive assays in the period immediately after surgery needs to be established by further studies. Finally, a low activity of radioiodine (1.1 GBq) should be administered selectively in low-risk patients receiving levothyroxine treatment following injections of recombinant human TSH. These modifications of current protocols will improve the quality of life of patients, potentially decrease morbidity and considerably reduce the cost of treatment and follow-up.

Management of Recurrent/Persistent Papillary Thyroid Carcinoma: Efficacy of the Surgical Option

It was estimated that over 44,000 people would be diagnosed with thyroid cancer in the United States in 2010 (1). With appropriate initial treatment, the majority of those patients can expect to achieve good disease-specific outcomes. However, up to 30% of patients (2) will suffer persistent disease or recurrences, the majority of which are fortunately localized to cervical lymph nodes. Although recommendations for the initial management of well-differentiated thyroid cancer are well-formulated and have considerable evidence behind them, gathered over many decades of careful follow-up, recommendations for therapeutic options for recurrent or persistent disease have less clarity. Historically, this has been a difficult literature. There have been variations in surgical technique and shifts in the use of adjuvant radioactive iodine therapy. There have been improvements in thyroglobulin assays over time and thus, changing definitions of biochemical cure. We have shifted paradigms for disease detection modalities, performing more frequent TSH-stimulated thyroglobulin assessments since the Food and Drug Administration approval of recombinant human TSH and have dramatically increased the utilization of high-resolution neck ultrasonography. In older studies, the criteria for cure after surgery was often not rigorous, or detailed information on disease assessment postoperatively was not provided. Furthermore, direct comparison of different modalities of therapy and combinations of therapy (e.g. radioactive iodine and/or surgical resection) have been rare, and those studies, such as Coburn et al. (3), usually were not randomized and suffered from significant selection bias. The 2009 Revised American Thyroid Association Management Guidelines for Patients with Thyroid Nodules and Differentiated Thyroid Cancer recommend surgical management of locoregional disease in the absence of distant metastases with an evidence rating of B (based on fair evidence that the service or intervention can improve important health outcomes) (4). Literature subsequent to that reviewed for the 2009 Revised Guidelines, including the paper by Yim et al. (5) published in this issue of the JCEM, contribute additional information to be considered in the assessment of the efficacy of lymph node dissection for locoregional disease. Specifically, three recent studies suggest that surgical intervention for locoregional recurrence can indeed achieve biochemical remission (undetectable TSH-stimulated serum thyroglobulin).LymphnodedissectionachievesaTSH-stimulatedthyroglobulinof less than1.0ng/ml in29%ofpatients (6) and less than 2.0 ng/ml in 41–46% of patients in one to three lymph node dissections (6, 7). Clayman et al. (8) reported obtaining an undetectable thyroglobulin ( 3 ng/ml) in 71% of informative cases. The paper by Yim et al. (5) describes a careful analysis of a relatively large series of 83 patients who underwent surgical intervention for recurrent/persistent papillary thyroid carcinoma. The authors report achieving a biochemical remission (undetectable TSH-stimulated thyroglobulin less than 1.0 ng/ml) in 51% of patients and less than 2.0 ng/ml in 61% of patients. Additional important findings in this study were that higher preoperative thyroglobulin levelspredicted failure toachieveabiochemical and clinical remission. However, there was only a tendency toward the number of pathological nodes to predict biochemical remission and no impact of the number of removed nodes, number of malignant nodes, extent of reoperation or adjunctive radioactive iodine on achieving

Thyroid Cancer Recurrence in Patients Clinically Free of Disease with Undetectable or Very Low Serum Thyroglobulin Values

Thyroid Cancer Recurrence in Patients Clinically Free of Disease with Undetectable or Very Low Serum Thyroglobulin Values