Negative Tg Research Articles

9188 Hashitoxicosis To Graves': A Case Of Fluctuating Thyroid Autoimmunity Induced By The Covid Vaccine

Abstract Disclosure: K. Lamar: None. N. Meda: None. J. Straughan: None. D. John: None. S.K. Suryanarayanan: None. Introduction: Thyroid antibodies are essential for identifying autoimmune thyroid disease. In Graves' disease thyroid stimulating immunoglobulin (TSI) is crucial to diagnosing, guiding treatment, and determining prognosis for ophthalmopathy; thyroid peroxidase (TPO) antibody is likewise crucial in the diagnosis of Hashimoto’s Thyroiditis. Conversion between these two diseases is extremely rare. Case: The patient is a 60-year-old female with a medical history of hypertension, asthma, T2NxM0 low grade gastrointestinal stromal tumor (GIST), and hyperaldosteronism who was referred to the endocrine clinic for “thyroid disorders'' with symptoms including weight gain and palpitations. Her labs showed thyroid stimulating hormone (TSH) <0.01mIU/L, free Triiodothyronine (fT3) 6.5ng/mL, free Thyroxine (fT4) 1.6ng/dL, TPO antibodies 46IU/mL, negative TSI antibodies 102%, and a negative Thyroglobulin antibody (Tg Ab) <1IU/mL. A slightly enlarged thyroid was noted on ultrasound. Radioactive iodine uptake (RAI) was normal with 15% uptake at 6 hours and 25% at 24 hours. These findings led to the diagnosis of Hashimoto thyrotoxicosis. She started methimazole 10mg and atenolol 50mg. One year later, she received the Pfizer mRNA COVID-19 vaccine and had her GIST tumor resected. She then began switching between hyper-, hypo-, and euthyroid states with multiple titrations of her Methimazole dose. Repeat testing demonstrated a positive TPO 41 IU/mL, negative Tg Ab <1, positive TSI 294%, and positive RAI with 47% uptake at 6 hours and 61% at 24 hours, consistent with Graves’ disease. It was found that even minor titration by 2.5mg in her Methimazole led to profound changes in her thyroid laboratory values and symptoms. She underwent total thyroidectomy and was started on levothyroxine with significant improvement. Discussion: This patient initially presented with antibodies as well as low uptake on the radio-iodine scan indicating her state of hyperthyroidism was due to Hashitoxicosis, but then later these tests were repeated and were more indicative of Grave’s disease. This was possibly due to immune challenges in the patient, assay inter-variability of thyroid autoantibodies, or an effect of the patient receiving the COVID vaccine. The phenomenon of TSI antibodies converting from negative to positive has not been well documented previously. The goal of this case was to report an interesting conversion of Grave’s disease identifying antibodies and the importance of evaluating underlying immune challenges which could play a role in altering clinical disease. Presentation: 6/1/2024

Sufficiency of a Single Negative Thyroglobulin Standard for Judging the Success of Ablation in Low- and Intermediate-risk Differentiated Thyroid Cancer: A Retrospective Study.

We investigated how reduced successful ablation criteria may be used to evaluate radioiodine remnant ablation in patients with low- and intermediate-differentiated thyroid carcinoma (DTC). Overall, 254 low- and intermediate-risk patients with DTC were categorized into three groups (positive, weak, positive, and negative) on the basis of a visual study of thyroid imaging performed before postoperative iodine treatment. Semi-quantitative analysis parameters were incorporated into the positive Tc-99m pertechnetate scanning to further examine the clinical use of thyroid imaging. We investigated the value of successful judgment criteria and the influencing factors of radioiodine ablation. At the same time, the predictive value of thyroglobulin (Tg) for radioiodine treatment and the overall clinical efficacy were assessed. A total of 250 (98.43%) patients were identified as having functional thyroid tissue residue on the Rx-whole-body scan, and 137 (53.94%) patients had positive Tc-99m pertechnetate scans using semi-quantitative analysis. The single Tg standard could not substitute the double standard (χ2c=22.042, p<0.001) for patients with residual thyroid weight by a semiquantitative analysis. However, the semi-quantitative analysis revealed no association between 99mTcO4-thyroid scan and ablation treatment using semi-quantitative analysis; only preablation sTg levels were related with success in the multivariate logistic regression analysis, with a cut-off value of 2.88 ng/mL. The pre-ablation stimulated Tg level was also the primary factor of satisfactory response following follow-up with an optimal cut-off of 6.506 ng/mL. Even in low- and intermediate-risk patients with DTC, a single negative Tg standard also requires receiving some restrictions in the evaluation of ablation success and is inadequate. Conventional 99mTcO4 thyroid imaging combined with a quantitative analysis program can improve the clinical practice of single negative Tg standard.

Thermomechanical transitions of meat-analog based fried foods batter coating

This study aimed to characterize the thermomechanical transitions of meat-analog (MA) based coated fried foods. Wheat and rice flour-based batters were used to coat the MA and fried at 180 °C in canola oil for 2, 4 and 6 min. Glass-transition-temperature (Tg) of the coatings were assessed by differential scanning calorimetry, directly after frying or after post-fry holding. Mechanical texture analyzer and X-ray microtomography were employed to assess textural attributes and internal microstructure, respectively. Batter-formulation substantially impacted the Tg of fried foods coating i.e., crust. Tg of fried foods crust were ranged between −20 °C to −24 °C. Tg was positively correlated with frying time and internal microporosity (%), whereas negatively correlated with moisture content. Internal microstructure greatly influenced the textural attributes (hardness, brittleness, crispiness). Post-fry textural stability considerably impacted by Tg. Negative Tg value explains post-fry textural changes (hard-to-soft, brittle-to-ductile, crispy-to-soggy) of MA-based coated products at room-temperature (25 °C) and under IR-heating (65 °C).

THU653 Subacute Thyroiditis Following Covid19 Infection

Abstract Disclosure: E. Fanous: None. J.G. Karam: None. Background: Subacute thyroiditis is a self-limiting inflammatory condition of the thyroid gland which usually occurs as a post-viral reaction, leading to the destruction of thyroid follicular cells due to infiltration of lymphocytes. During the first outbreak of COVID-19 virus, subacute thyroiditis had been reported as a complication that may occur in patients without any previous thyroid disorder [1]. Clinical Case: A 62-year-old female patient presented with few weeks history of generalized weakness, fatigue, chills, malaise, low appetite, and unintentional weight loss of around 10lbs. She stated that she feels "internal tremors" and palpitations with heart rate increasing from baseline 60 bpm to 90bpm. She had one episode of near syncope at work prompting her presentation. She reports no change in bowel movements, no heat intolerance, no fever or night sweat, no shortness of breath, no visual changes or eyes problems. Five weeks prior to presentation, the patient was diagnosed with COVID-19 infection by PCR, with a mild disease pattern that consisted of upper respiratory symptoms lasting for few days, however she continued to feel fatigue and low appetite since then, attributing her symptoms to long-term sequelae of Coivd-19. Her past medical history is remarkable for obesity, hypercholesterolemia, and two prior Covid 19 infections: in 2020, treated with monoclonal antibodies, and early 2022. The physical exam was significant for slightly tender thyroid and heart rate of 94 bpm. Thyroid function tests were consistent with hyperthyroidism; TSH&amp;lt;0.01mIU/ml, FT4=2.55ng/dl (0.58-1.64), T4=19.6 mcg/dl (4.4-9.5), T3=1.45ng/ml (0.72-1.35), with negative TSI, TPO AB, and TG AB. ESR was 44mm/hr, RAI uptake and scan showed very low uptake which is indicative for subacute thyroiditis. The patient was given supportive therapy. She developed mild and transient hypothyroidism at 6 weeks follow-up with TSH of 8.59 IU/ml and FT4=0.62 ng/dl (0.89-1.76) before her thyroid tests return to normal at 9 weeks with complete resolution of her symptoms. Conclusion: Prolonged diverse symptoms following Covid19 infection are often attributed to long term Covid symptoms. Health Care providers should be aware of the possibility of subacute thyroiditis following Covid 19 infection and should obtain thyroid function tests in patients who present with malaise, decreased appetite, weight loss and palpitations in the weeks following Covid 19 infection. Reference:1. Mattar SAM, Koh SJQ, Rama Chandran S, Cherng BPZ. Subacute thyroiditis associated with COVID-19. BMJ Case Rep. doi: 10.1136/bcr-2020-237336 Presentation: Thursday, June 15, 2023

Abstract #1404395: Metastatic Choriocarcinoma: A Rare Cause of Thyrotoxicosis

Although Graves’ disease continues to be considered the most frequent cause of clinical hyperthyroidism in pregnancy, the disproportionately high production of human chorionic gonadotropin (HCG) as occurs in gestational trophoblastic disease (TSG), is another possible cause that should be considered when evaluating thyrotoxicosis in pregnancy. A 19-year-old female with unremarkable past medical history who was admitted for nausea, vomiting and abdominal pain for 2 weeks. Her last period was 4 weeks prior to her presentation and patient denied any vaginal bleeding. Her period had been irregular since her last miscarriage a year earlier. She denied being sick recently, and her last flulike illness was 4 months ago. Denied using any medication at home including herbal medication or OCPs. Review of systems was significant for fatigue, heat intolerance, palpitation, tremor, loss of appetite and unintentional weight loss over the last week. She denied diarrhea or anxiety. On presentation, Patient was hypotensive 90s/40s mmHg and tachycardic 140s bmp. EKG showed sinus tachycardia. Initial work-up was significant for HB 6.2, WBC 11.6 and B-hCG 9678 IU/ml. Liver enzymes were elevated. Transvaginal ultrasound showed empty uterus. Pan CT showed hemoperitonium and liver, lung and kidney lesions concerning for metastatic choriocarcinoma which was confirmed with positive liver biopsy. Work-up also showed suppressed TSH 0.01uIU/ml, high free T4 2.54ng/dl, and high free T3 5.1ng/dl, absent TSI, normal Tg level with negative Tg antibodies. There was no baseline TSH to compare. BHCG with dilution was 5,430,055IU/ml. Thyroid ultrasound was normal. Patient was diagnosed with metastatic choriocarcinoma and treated with 3 cycles of cisplatin/etoposide chemotherapy. Patient did not receive any antithyroid medication due to elevated liver enzymes and mild symptoms. B-HBG following the treatment was 3mIU/ml, TSH was 1.5 uIU/ml and FT4 was 1.1ng/dl. Hyperthyroidism has been reported in many patients with GTD. The beta subunit of β-hCG is structurally similar to TSH, allowing it to bind to the TSH receptor on thyroid follicular cells. It has been reported that β-hCG levels of greater than 200,000 m[IU]/ml sustained for several weeks are required to induce clinical hyperthyroidism. It is estimated that for every 10,000 m[lU]/ml increase in serum hCG, TSH decreases by 0.1 mlU/ml and free T4 increases by 0.1 ng/dL. No clear risk factors for hyperthyroidism in GTD were identified. Presentations can range from subclinical hyperthyroidism to thyrotoxicosis and thyroid storm. This case was challenging because the initial B-HCG was not high enough to cause thyrotoxicosis but delusional B-HCG confirmed our suspicion. While hyperthyroidism can be definitively managed with surgical evacuation of the uterus in GTD, hyperthyroidism secondary to metastatic choriocarcinoma could be successfully treated with chemotherapy with or without antithyroid medication. The increase in TSH usually parallel the reduction in BHCG.

The prognostic value of post thyroidectomy Tc-99m pertechnetate thyroid scan in patients with differentiated thyroid cancer.

To evaluate the prognostic value of postoperative Tc-99m pertechnetate scanning in patients with differentiated thyroid cancer (DTC). Patients with pathologically proven low or intermediate-risk DTC were enrolled in this study. Postoperative Tc-99m pertechnetate scintigraphy was performed 20 min after IV of 185 MBq of Tc-99m pertechnetate Positive thyroid residual uptake was characterized as higher Tc-99m pertechnetate uptake at the thyroid bed than the surrounding background's activity. A negative residual was considered if there was no definite abnormal radioactivity at the thyroid bed. Follow-up by thyroglobulin, thyroglobulin antibodies (Tg Abs), neck ultrasound (US) and diagnostic I-131 WBS (Dx WBS) were considered the reference standard. Successful ablation outcome was considered if there was free Dx WBS, stimulated serum thyroglobulin < 1 ng/ml with negative Tg Abs, and free US. Two hundred and two patients, mean age; of 38.8 years were retrospectively recruited in this study. Positive residual uptake at the thyroid scan was detected in 131 patients wherea the remaining 71 patients had no detectable uptake. According to the reference standard we encountered 114 and 88 cases with successful ablation and unsuccessful ablation respectively, Tc-99m pertechnetate scanning successfully detected 63 true positive and 46 true negative cases giving 72% sensitivity, 40% specificity, 48% positive predictive value and 56% negative predictive value. In low- and intermediate-risk DTC patients; despite the relatively high sensitivity of postoperative Tc-99m pertechnetate thyroid scan, it has low specificity and low negative predictive value so it cannot be used to predict the ablation outcome.

ODP493 Malignant Struma Ovarii with Papillary Thyroid Carcinoma and concomitant High Risk Thyroid Nodule

Abstract Introduction Struma ovarii is a rare teratoma consisting of &amp;gt;50% thyroid tissue. Malignant transformation very seldomly occurs; most pathology shows papillary thyroid carcinoma. The risk and prevalence of concurrent thyroid gland neoplasm is unclear. Thyroid cancer surveillance post-oophorectomy in these patients may be pertinent but has not yet been established. Case Report A nulliparous 54 year-old woman with one year of menopause without HRT had pelvic and back pain. Imaging detected bilateral ovarian teratomas. Pathology from laparoscopic bilateral salpingo-oophorectomy revealed a 10.7×9.9×10.9cm noninvasive struma ovarii with focal papillary thyroid carcinoma of the left ovary and a benign teratoma of the right ovary. Importantly, the patient had a known thyroid nodule. Two years prior, a FNA of the 1.4cm hypoechoic, hypervascular nodule in the left lower pole yielded benign (Bethesda 2) cytology. After struma ovarii resection, thyroid ultrasound showed highly suspicious TIRAD5. She denied symptoms of hyper- or hypothyroidism and had a normal TSH. She consequently underwent two FNA biopsies, both of which were non-diagnostic. The patient deferred further attempts. History of an initial benign biopsy and stability of the nodule size provide some reassurance. With the patient's reluctance for surgery, serial thyroglobulin (Tg) and ultrasounds will be followed. Post-operative Tg was normal with negative Tg antibody. If Tg becomes markedly elevated, a thyroidectomy will be indicated. Discussion Given the TIRAD5 nodule, this patient's risk of thyroid malignancy is 60-70%. This is compounded with her setting of malignant struma ovarii, which may imply genetic predisposition for thyroid carcinogenesis. Since cytology could not be obtained on the two recent biopsies, definitive pathology by diagnostic lobectomy or thyroidectomy may be considered. A total thyroidectomy would provide the advantage of following Tg for cancer surveillance of both thyroid and ovarian malignancies. There is scant evidence on the treatment of malignant struma ovarii. A few small case series and a pooled review of 57 cases of low-risk (confined to the ovary) malignant struma ovarii in which 50 patients did not undergo thyroidectomy/I-131 ablation showed only a 7.5% recurrence rate at 25 years (Marti et al Thyroid 2012 Apr; 22 (4): 400-406). Hence, this study recommends reserving prophylactic thyroidectomy for patients with extra-ovarian extension or metastases. Treatment of malignant struma ovarii may be extrapolated from those used in differentiated thyroid cancer; high-risk lesions would be those measuring &amp;gt;4cm, have local or distant invasion, or have a BRAF mutation (indicating an aggressive tumor). In conclusion, conservative measures of the thyroid gland with a suspicious nodule may be acceptable in patients with noninvasive malignant struma ovarii, provided strict adherence to cancer surveillance of Tg with both thyroid and pelvic sonography. Presentation: No date and time listed

Preparation of flexible biobased non-isocyanate polyurethane (NIPU) foams using the transurethanization approach

A new process for the preparation of non-isocyanate polyurethane (NIPU) flexible foams has been implemented. Biobased amino-telechelic NIPU oligomers were prepared by an organo-catalyzed transurethane polycondensation reaction of fatty biscarbamates with fatty diols and diamines. The obtained oligomers were reacted with a biobased multi-epoxide molecule as crosslinking agent, in the presence of a poly(hydromethylsiloxane) or its copolymer as foaming agent and surfactant. The crosslinking and foaming reactions were monitored by rheometric, volumetric and FTIR studies. The foams can be obtained in <30 min at 100 °C or in 14.5 h at room temperature. The prepared foams displayed cell diameters in the range of 210 to 430 μm associated with densities in the range of 130 to 400 kg/m3. They also exhibited thermal stabilities above 300 °C, as well as a soft character attested by negative Tg values ranging from −10 to −28 °C, and low values of the Young modulus varying from 1.0 × 104 Pa to 6.3 × 104 Pa. The recovery time, hysteresis loss and the firmness of these foams were found to be dependent on their chemical structures.

Low correlation between serum thyroglobulin and 131I radioiodine whole body scintigraphy: implication for postoperative disease surveillance in differentiated thyroid cancer

PurposeTo evaluate postoperative serum thyroglobulin (Tg) as a reliable tumor marker in low-risk differentiated thyroid cancer (DTC). MethodsTwo hundred and three patients met the selection criteria of >18 years old; who had undergone total or near total thyroidectomy; had a postoperative Tg, and had undergone 131I pre ablation whole body scan (PA-WBS). The primary endpoint was the correlation between Tg level and functional remnant thyroid tissues. Outcomes were categorized as concordant and discordant. Concordant results were positive Tg (>1 ng/ml) with positive PA-WBS or negative Tg (<1 ng/ml) with negative PA-WBS. Discordant results were negative Tg with a positive PA-WBS or positive Tg with a negative PA-WBS. To increase the sensitivity of Tg detection, we evaluated Tg in patients with high thyroid stimulating hormone (TSH) with serum level >30 mU/l on thyroxine withdrawal protocol. ResultsOne hundred ten patients (54.1%) had discordant results (p < 0.05) with positive PA-WBS and Tg <1 ng/ml, while 93 patients (45.9%) had concordant results. For concordant results, 88 patients had positive PA-WBS and Tg >1 ng/ml, and 5 patients had negative PA-WBS and Tg <1 ng/ml. There was no patient with Tg >1 ng/ml and negative PA-WBS. There were 74 patients with high TSH (>30 mU/l) on abstention (thyroxine withdrawal protocol). Twenty-four (32.5%) had discordant results (p < 0.001) and 50 (67.5%) had concordant results. ConclusionThere is low correlation between postoperative Tg and PA-WBS. The sole use of Tg as a serum biomarker for postoperative disease status may not be reliable.

Glass Transition Temperatures of Copolymers: Molecular Origins of Deviation from the Linear Relation

The glass transition temperature (Tg) is an important material parameter in determining polymer properties. The main molecular structure factors affecting Tg are chain stiffness and cohesive energy, causing polymers to exhibit the complex micro-structure dependence of Tg. The composition dependence of the Tgs of binary random copolymers mainly shows as three cases: the linear relation, the negative deviation (or concave curve), or the positive deviation (convex curve). The study of the Tg’s composition dependence can guide the design of copolymer materials with desirable properties. On the other hand, it can provide insights into understanding the precise nature of the glass transition. In this study, the root cause of the Tg deviation from the linear relation in random copolymers was revealed, and new molecular origins were proposed. First, the theoretical basis of why there exists a linear Tg relation for copolymers was clarified, and the influence of the specific polar interactions between components was discussed briefly. More importantly, it has been identified that the negative Tg deviation is related to copolymers composed of the mono-substituted (M-type) monomer and asymmetrical di-substituted (AD-type) monomer, and the positive Tg deviation is related to copolymers composed of the M-type monomer and symmetrical di-substituted (SD-type) monomer. The molecular origin of the Tg deviations from the linear relation is the destruction of the special conformational structures (e.g., the locally rigid conformational structure in the AD-type homopolymer or the dynamic flexible structure in the SD-type homopolymer) caused by copolymerization. The behaviors for more complex binary copolymers (AD–AD, SD–SD, and AD–SD types) were also discussed. Finally, the variation in Tg of a statistical copolymer as a function of composition was summarized.

Change in Antithyroglobulin Antibody Levels is a Good Predictor of Responses to Therapy in Antithyroglobulin Antibody-Positive Pediatric Papillary Thyroid Carcinoma Patients.

Objective Antithyroglobulin antibodies (TgAbs) could be used as a surrogate tumor marker of TgAb-positive-differentiated thyroid carcinoma. This study aims to determine whether the change in TgAb levels over time could be used as a predictor of responses to therapy in pediatric papillary thyroid carcinoma (PTC) patients. Methods We retrospectively analyzed the records of 48 pediatric PTC patients with TgAb levels ≥50 IU/ml 6 months after initial 131I treatment. Suppressed thyroglobulin (Tg) levels 6 months after initial 131I treatment were used to divide the patients into positive Tg (P-Tg, Tg ≥ 0.2 ng/ml) and negative Tg (N-Tg, Tg < 0.2 ng/ml) groups. Responses to therapy were classified as the acceptable response (AR) group and the not acceptable response (NAR) group. Results Of 48 enrolled patients with 58 months (range, 24–143 months) of follow-up, 28 patients had NAR and 20 patients had AR. TgAb levels were decreasing ≥50% in 28 patients, decreasing <50% in 8 patients, and increasing in 12 patients. Multivariate analysis showed that high initial risk stratification and TgAb levels decreasing <50% or increasing were significantly associated with NAR (p < 0.05). Changes in Tg levels were also associated with NAR in the P-Tg group (p < 0.05). Conclusion Changes in TgAb levels over time could be used as a predictor of responses to therapy in TgAb-positive pediatric PTC patients. Changes in Tg levels over time are also associated with NAR to therapy in both TgAb-positive and Tg-positive pediatric PTC patients.

Can ultrasensitive thyroglobulin immunoassays avoid the need for ultrasound in thyroid cancer follow-up?

Differentiated thyroid cancer (DTC) is the most common endocrine neoplasm, with a rising incidence and a long life expectancy. It has recently been suggested that patients with low- and intermediate-risk DTC with a good response to treatment at one year could be followed up using only highly sensitive immunoassays for thyroglobulin (Tg). The aim of this study was to examine the serum Tg levels in a series of DTC patients with histologically proven persistent or recurrent diseases. The study involved 50 consecutive patients being routinely followed up at our center, whose clinical, histological, and biochemical data were retrospectively collected. The false-negative rate of ultrasensitive serum Tg assay was 14.3% (5/35) overall, and limited to anti-thyroglobulin autoantibodies (TgAb)-negative patients. Among them, only one patient had an excellent response to treatment at one-year follow-up and was diagnosed with a 4 mm recurrence, after more than seven years of periodic ultrasounds. The size of the neck lesion documented in the histological report was slightly larger in patients with detectable as opposed to negative Tg values (P < 0.05). Serum highly sensitive Tg is undetectable in a proportion of patients with a proven persistent or recurrent DTC. The reasons behind this phenomenon are still unknown. However, in low/intermediate-risk patients cured at one-year follow-up, highly sensitive Tg without neck US seems an appropriate strategy for patients' management.

Predictors of Response to Therapy Among Post Thyroidectomy Adult Filipino Patients with Papillary Thyroid Carcinoma Based on the 2015 American Thyroid Association Guidelines

ObjectiveTo identify factors independently associated with incomplete response to therapy based on the 2015 ATA guidelines in surgically treated Filipino patients with papillary thyroid carcinoma (PTC).MethodologyThis is a retrospective cohort study of adults aged 21-74 years with papillary thyroid carcinoma (PTC) treated with surgery with or without radioactive iodine therapy (RAI) in Makati Medical Center from 2013 to 2017. We collected the following factors through a review of charts: age at diagnosis, gender, family history of thyroid cancer, date of surgery, tumor size, capsular/lymphovascular invasion, lymph node/distant metastases, stage, risk of recurrence, dose of post-surgical RAI therapy, initial post-treatment serum Thyroglobulin (Tg) and anti-Tg antibody levels (Negative Tg level: suppressed non-stimulated Tg <0.2 ng/mL or TSH-stimulated Tg <1 ng/mL; Positive Tg level: suppressed Tg ≥1 ng/mL or a TSH-stimulated Tg ≥10 ng/mL or rising anti-Tg antibody levels), thyroid stimulating hormone suppression, post-operative imaging studies and levothyroxine dose. Response to therapy was checked 6-24 months post-therapy.ResultsWe analyzed a total of 115 patients with PTC who underwent thyroidectomy. Patients who had family history of thyroid cancer were less likely to have an incomplete or indeterminate response (p=0.045). None of the patients with excellent response had lymphovascular invasion. Having a positive Tg (p=0.001) and positive anti-Tg post-operatively (p<0.001) were strongly associated with incomplete or indeterminate response.ConclusionPatients who were positive for thyroglobulin and anti-thyroglobulin post-operatively were strongly associated with incomplete or indeterminate response to therapy in PTC.

Clinicopathological features and outcome of thyroglobulin elevation and negative iodine scintigraphy (TENIS) patients with negative neck ultrasound: Experience from a thyroid carcinoma clinic in India.

ABSTRACTManagement of differentiated thyroid carcinoma (DTC) patients with thyroglobulin (Tg) elevation and negative iodine scintigraphy (TENIS) and negative neck ultrasound scan causes considerable diagnostic and therapeutic dilemma, especially in resource-poor settings. The aim of this study was to evaluate clinicopathological features and outcome of TENIS patients with negative neck US attending a thyroid cancer clinic in India. From a DTC database of 722 containing 193 TENIS patients, subjects with negative neck US and negative Tg antibody (TgAb) were selected retrospectively and analyzed using appropriate statistical methods. The study group included 64 patients (male – 17, female – 47, mean age – 44.7 ± 12.8 years) with 54 papillary and 10 follicular thyroid carcinomas, American Thyroid Association (ATA) recurrence risk categorization (2009) – low – 16, intermediate – 28, and high – 2 0. Most of the patients became TENIS within 1 year of diagnosis with median Tg level of 6.5 ng/mL (1.2–996 ng/mL) and mean follow-up of 7.8 years. On follow-up, Tg dropped spontaneously in 27 patients, more among the low and intermediate-risk categories. For those with high or increasing Tg level, further imaging (fluorodeoxyglucose positron emission tomography/computed tomography) was done and 14 out of 18 were positive. Treatment included empiric radioactive iodine therapy-16, external beam radiation therapy (EBRT)-7, and lymph node dissection (LND)-10. A favorable outcome was seen in 36 patients and unfavorable in 28. Distant metastases were associated with unfavorable outcome and poor survival. Progression-free survival was significantly better in the Tg group of <10 at the time of TENIS (111 months) compared to the Tg group >10 (72 months). Tg level dropped spontaneously in nearly half the patients, especially if levels were <10 and more so among the low-risk category. Distant metastasis was predictive of unfavorable outcomes. Along with Tg level, the ATA risk category might help to predict clinical course and reduce unnecessary expensive imaging in resource-poor settings.

A Subtype of Papillary Thyroid Carcinoma Bone Metastasis With Excellent Response to RAI-Therapy

Introduction: Bone metastases from differentiated thyroid cancer are generally resistant to radioactive iodine (RAI) therapy and are associated with poor prognosis, except for RAI-avid bone metastases with no structural correlate on imaging studies. Case: A 59 y/o woman presented for the evaluation of non-toxic multinodular goiter. Thyroid US showed a 2.7 cm nodule meeting FNAB criteria and no suspicious cervical lymph nodes. Cytology reported a Bethesda IV category with ThyroSeq V3 positive for chromosomal copy number alterations and a high Na+/I− symporter (NIS) expression (27%) with an ~ 60% probability of cancer. The patient underwent left lobectomy with isthmusectomy without neck dissection. Surgical pathology showed a 3.5 cm papillary thyroid carcinoma with extensive angioinvasion (≥4 vessels), negative margins, no ETE, and did not contain a BRAF V600E mutation. Completion thyroidectomy, in anticipation of RAI treatment, showed no additional tumor. Post-operative Tg after 6 weeks was unexpectedly high at 69 ng/mL (negative Tg Ab, TSH 5.7 uIU/ml) which prompted a rhTSH I-123 RAI WBS with SPECT/ CT and a diagnostic chest CT to uncover possible distant metastases. There was RAI uptake in the thyroid bed and right anterolateral 9thrib without a CT correlate (no osteolytic lesion) but with a signal abnormality on MRI. She was categorized as T2NxM1, 8th Edition AJCC Stage IVB, and ATA high risk. She was treated with 148.3 mCi I-131. Unfortunately, 6 months later the Tg was elevated and rising (Tg 38.4 ng/mL, negative Tg Ab, TSH 0.05 uIU/ml). A second diagnostic I-123 WBS with SPECT/ CT showed a new recurrence in the neck but no uptake in the rib lesion on planar images or other distant sites. Because of the unusually high Tg without any RAI-avid metastatic disease, an 18-FDG PET/CT was ordered to search for non-RAI avid disease. This showed disease confined to the neck and increased sclerosis of the rib lesion without increased FDG-uptake consistent with treated disease status post-RAI. There were no other distant hypermetabolic lesions. The left thyroid bed lesion was biopsied and consistent with Bethesda VI cytology and she will soon undergo left central neck dissection with tumor resection. Discussion: RAI-avid bone metastases without structural correlate on high-resolution imaging are a subtype of bone metastases located in the marrow. They do not present as the typical lytic lesions from cortical destruction. They often resolve following RAI treatment, do not cause skeletal-related complications, and do not significantly affect prognosis. The combination of high NIS expression and increased vascularity in the bone marrow (as opposed to the protected microenvironment in the bone cortex) makes them vulnerable to RAI treatment. Recognition of this subset of bone lesions may prevent overtreatment with high doses of RAI treatment and avoid the use of bisphosphonates or external beam radiation.

Long-term follow-up of differentiated thyroid carcinoma in children and adolescents.

Objectives The aims were to analyze the clinical features, response to treatment, prognostic factors and long-term follow-up of children and adolescents with differentiated thyroid carcinoma (DTC). Methods Eighty patients with DTC were studied retrospectively. All underwent total or near-total thyroidectomy, and in 75 cases, ablative iodine therapy was recommended. Patients were assessed periodically by tests for serum thyroglobulin levels and whole-body iodine scans. Age, gender, initial clinical presentation, histology, tumor stage, postoperative complications, radioiodine treatment protocol, treatment response, thyroglobulin (Tg), recurrence and long-term disease progression were evaluated. Results Seventy patients completed >2 years of follow-up (23 males, 47 females; median age: 14 years; range: 3-18years). Sixty-two patients showed papillary DTC and eight, follicular DTC. Sixty-five percent presented nodal metastasis and 16%, pulmonary metastasis at diagnosis. Six months after first radioiodine treatment, 36.2% of patients were free of disease. Seven recurrences were documented. At the end of follow-up, overall survival was 100%, and 87.2% of patients were in complete remission. Nine patients had persistent disease. We found a significant association between stage 4 and persistent disease. Hundred percent of patients with negative Tg values at 6months posttreatment were documented free of disease at the end of the follow-up. The analysis of disease-free survival based on radioiodine treatment protocols used showed no statistically significant differences. Conclusions DTC in children and adolescents is frequently associated with presence of advanced disease at diagnosis. Despite this, complete remission was documented after treatment in most cases, with a good prognosis in the long-term follow-up. Negative posttreatment thyroglobulin and stage 4 at diagnosis were significant prognostic variables.

Follow-up of differentiated thyroid cancer

The management of differentiated thyroid carcinoma has shown considerable changes in recent years, moving away from a fixed therapy regimen towards individual treatment strategies. The aim of our work (literature research) is to present current developments in the follow-up of differentiated thyroid cancer.For the management of individual follow-up, an initial evaluation and, at later time points, the re-evaluation of the risk of recurrence is crucial. The performance of I-131-diagnostics after radioiodine therapy can provide essential information and can be seen as a survey of a new baseline situation, in order to be able to draw a comparison in case of a rising Thyreoglobulin (Tg).The measurement of Tg with a highly sensitive assays shows a high negative predictive value. Negative Tg measurements with these assays seem to indicate complete remission even with Tg antibodies being present. An increasing Tg value in follow-up implies further diagnostic work-up, primarily neck ultrasonography. Sonographically suspicious findings should be subjected to fine needle biopsy, whereby in addition to cytological processing, determination of Tg from the sample can be recommended. If the suspicious lesion cannot be displayed sonographically and Tg values keep rising, computed tomography (CT) and magnetic resonance imaging (MRI) of the neck region can provide further information. FDG-PET/CT has also shown an excellent performance in this setting.The previously fixed therapy regimen has been realigned towards an individual treatment management. Current studies and guidelines lead to a repetitive recurrence risk evaluation and the adjustment of the aftercare planning to the individual risks with appropriately selected examination methods and personalized intervals of assessment.

MON-448 Detection of Thyroid Cancer Recurrence in Patients with Positive Thyroglobulin Antibody Receiving Immunoglobulin Therapy

Introduction: Differentiated thyroid cancers such as papillary and follicular thyroid cancer make up more than 90% of all thyroid cancers. The presence of thyroglobulin autoantibodies makes interpretation of the thyroglobulin level unreliable, as it could be falsely low or falsely high. Studies have shown that rising thyroglobulin antibody levels, could be used to monitor for disease recurrence in patients with negative thyroglobulin and imaging studies. However, there are challenges in detecting recurrence in patients with normal thyroglobulin level and thyroid imaging studies, who are on lifelong immunoglobulin therapy and who have increasing thyroglobulin antibody levels.Clinical case: A 63 yr old female was found to have an incidental left thyroid nodule at age 48yrs from a carotid ultrasound. She underwent US guided FNA of the thyroid nodule and was found to have papillary thyroid cancer. She had total thyroidectomy a month later, with removal of a 1.4cm primary, with no evidence of extrathyroidal extension, clear margins and no evidence of lymphovascular invasion – Stage T1bN0M0. There was left level 6 neck dissection with no carcinoma identified in the 2 lymph nodes removed. She received 105.3 mCi radioactive iodine (RAI) and whole body thyroid scan done 7 days later revealed, increased uptake involving the thyroid bed likely residual thyroid tissue. Activity was noted inferolateral to the right thyroid bed which most likely represents a lymph node. There was no evidence of distant metastasis.She was commenced on levothyroxine post operatively. Her other past medical history is significant for idiopathic urticaria and angioedema, immune deficiency disorder with low IgG and IgM and asthma. She was commenced on monthly IV immunoglobulins 5yrs post RAI therapy, due to recurrent sinusitis, rhinitis and chronic diarrhea. She was later transitioned to weekly SQ immune globulin – Hizentra which she is on till date.Over the past 15 years, serial neck ultrasounds post radioiodine ablation have been negative for recurrence. Her TSH ranged 14.91 to 0.04 (ref 0.27-4.2 uiu/ml) and thyroglobulin (Tg) titer remains <0.1 (ref <0.1). Her thyroglobulin antibody titers have trended up from <0.2 (ref <2.0) 5yrs post RAI therapy to 49 (ref <4 iu/ml)) on her most recent test this year. She is currently undergoing further work up to rule out recurrence of her cancer. In our review of the literature we found one report that showed use of Liquid Chromatography–Mass Spectrometry (LC-MS) was able to differentiate thyroid cancer recurrence in an individual with positive antithyroglobulin antibody receiving immunoglobulin therapy.Conclusion: In patients with negative Tg levels, but elevated thyroglobulin antibody while receiving immune globulin therapy, thyroglobulin antibody levels may not be a reliable indicator of thyroid cancer recurrence. Measurement of Tg levels using a LC-MS may provide some clarity.

SUN-486 Unusual Presentation of Metastatic Follicular Thyroid Cancer

Distant metastasis of follicular thyroid cancer to the bone has been well documented. However, spinal cord compression as the initial presentation of metastatic follicular thyroid cancer without any thyroid symptoms is relatively rare. Here we discuss such a case. A 78-year-old female with history of HTN and melanoma presented to the ED with a 1-month history of middle back pain that progressed to lower extremity weakness, numbness, and inability to ambulate. MRI showed a T7 vertebral mass with cord compression and edema. Metastatic work up was unremarkable except for incidental bilateral thyroid nodules, the largest on the right lobe, at 1.6 cm, with peripheral calcifications. The patient underwent T6-T7 laminectomy with vertebral decompression, partial colpectomy, and T4-T10 fusion. Pathology of the thoracic vertebral mass was positive for CAM 5.2, cytokeran 7, TTF-1, and PAX8 consistent with either metastatic pulmonary adenocarcinoma or thyroid carcinoma. The patient denied shortness of breath, dysphagia, hoarseness, or neck tenderness. She had no personal history of hyperthyroidism or hypothyroidism, or radiation exposure. She also did not have any family history of thyroid cancer. Laboratory work up was significant for TSH of 3.71 mcU/mL (0.4-4.0 mcU/mL), Free T4 1.56 ng/dL (0.7-1.9 ng/dL), thyroglobulin (Tg) 6940 ng/mL (1.6-55.0 ng/mL), and thyroglobulin antibody (Tg Ab) 20 IU/mL (0-115 IU/mL). FNA of the right thyroid nodule showed follicular neoplasm with very similar morphological features to the epidural pathology, favoring a follicular carcinoma. She underwent total thyroidectomy. Pathology showed a 1.6 x 1.1 cm follicular carcinoma with capsular and angiolymphatic invasion, but with uninvolved margins of resection. TNM staging was pT1b, pNx, pM1. She was ablated with 109 mCi of I-131 after withdrawal therapy. Whole body scan after treatment revealed radioiodine avid metastatic disease at T7 and activity in the thyroid bed compatible with residual thyroid tissue. Patient completed 10 fractions of external beam radiotherapy to the spine for a total of 30 Gy. Three months follow up lab work showed Tg 580 ng/mL and negative Tg Ab with a suppressed TSH. Thyroid bed ultrasound did not show any residual tissue or abnormal lymph nodes. Ten-year survival rates in patients with bony metastatic differentiated thyroid cancer range from 13-21% (1). Metastatic thyroid carcinoma should be considered in the differential diagnosis of every patient with new onset bony metastasis and thyroglobulin should be considered as a tumor marker in the initial work up. Research shows increased survival with I-131 avidity and complete bone metastasis resection (1). 1. Ramadan, Sami et al. “Spinal metastasis in thyroid cancer.” Head & neck oncology vol. 4 39. 25 Jun. 2012, doi:10.1186/1758-3284-4-39

Lung Metastases From Papillary Thyroid Cancer With Persistently Negative Thyroglobulin and Elevated Thyroglobulin Antibody Levels During Radioactive Iodine Treatment and Follow-Up: Long-Term Outcomes and Prognostic Indicators

Background: The lung is the most frequent site of distant metastasis from differentiated thyroid cancer (DTC). However, lung metastasis from papillary thyroid cancer (PTC) with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels is an extremely rare entity, and the prognosis is therefore elusive. We investigated the clinical characteristics, long-term outcomes, and prognostic factors of lung metastases in PTC patients with persistently negative thyroglobulin (Tg) and elevated Tg antibody (TgAb) levels during radioactive iodine (131I) treatment and follow-up.Methods: We retrospectively reviewed 10,482 patients with DTC who underwent postoperative 131I treatment from 2007 to 2017 at Shanghai Sixth's People's Hospital. The relationships between progression-free survival (PFS) and several variables were assessed by univariate and multivariate analyses using the Kaplan–Meier method and a Cox proportional hazards model, respectively.Results: Forty-seven patients with PTC were enrolled in this study (4.48‰ of all patients with DTC). The median age at the initial diagnosis of lung metastasis was 39.6 ± 15.4 years, and the patients comprised 14 male and 33 female patients (male: female ratio = 1.00:2.36). Twenty-five patients had 131I avidity and 22 had non-131I avidity. At the end of the 5-years follow-up, 12 patients exhibited progressive disease (PD), and 2 patients had died. At the end of the 10-years follow-up, 21 patients showed PD and five patients had died. The 5- and 10-year PFS rates were 74.47 and 53.32%, respectively; the 5- and 10-years overall survival (OS) rates were 95.74 and 89.36%, respectively. The timing of diagnosis of lung metastases, maximal size of lung metastases, and 131I avidity were significantly associated with the 5-years PFS rate (P = 0.035, P = 0.030, and P<0.001, respectively). Only 131I avidity was associated with the 10-years PFS rate (P < 0.001). The multivariate analyses also showed that non-131I avidity were the independent poor prognostic factors for 10-years PFS at the end of follow-up (P < 0.001).Conclusions: Lung metastases from PTC in patients with persistently negative Tg and elevated TgAb levels had an excellent prognosis and survival rate during 131I treatment and follow-up. The loss of 131I avidity remained the strongest independent predictor of a poor prognosis and survival in these patients.