Received Radioactive Iodine Research Articles

Cobimetinib plus atezolizumab for RAS and NF1/2-mutated poorly differentiated thyroid carcinoma.

6106 Background: Poorly differentiated thyroid carcinomas (PDTC) are a subset of thyroid cancers characterized by high-grade pathologic features. They hold an intermediate position on the spectrum of follicular-derived thyroid cancers. Due to their more aggressive clinical behavior, PDTCs typically exhibit shorter responses to the usual kinase inhibitors (KIs) used in advanced differentiated thyroid cancers and develop resistance earlier on. In fact, median progression free survival (PFS) with single-agent lenvatinib in patients with PDTC in the SELECT trial (n=28) was 14.8 months. Although there are increasing data to support the use of immunotherapy plus KI combinations in anaplastic thyroid cancer, evidence demonstrating the efficacy of this strategy in PDTC is sparse. We aimed to study the safety and efficacy of atezolizumab combined with KIs in PDTC. Methods: We enrolledpatientswith PDTC in a single-center phase II prospective trial of atezolizumab plus mutation-determined targeted therapy (NCT03181100). Patients with RAS or NF- mutated tumors were treated with atezolizumab plus the MEK inhibitor (MEKi) cobimetinib. Primary outcome was median overall survival (mOS). Best response to therapy was assessed per RECIST v1.1; survival by the Kaplan-Meier method. Results: Eight patients with RAS/NF-mutated PDTC were enrolled. Median age at treatment start was 68.5 years. All patients had distant metastatic disease at time of enrollment. Prior to study entrance, 7/8 patients (88%) had surgical resection of the primary tumor, 6/8 (75%) radioactive iodine, 2/8 (25%) external beam radiation to the neck, and 3/8 (38%) bridging cytotoxic chemotherapy. All patients were naïve to KIs. Six (75%) patients had RAS mutations (1 HRAS, 3 KRAS, 2 NRAS) and 3 (38%) had NF mutations (2 NF1, 1 NF2). One patient’s tumor harbored both KRAS and NF2 mutations at baseline. PD-L1 score was positive in 3/4 evaluable specimens. Median duration of follow-up was 65 months. Best response to therapy was stable disease in 6/8 (75%), partial response in 1/8 (12.5%) and progressive disease in 1/8 (12.5%). mOS was 23 months (95% CI, 12.8 – 33.2) and median PFS was 7 months (95% CI, 2.4 – 11.6). 4/8 patients received radioactive iodine (RAI) while on systemic therapy. Median dose of RAI was 149 millicuries (range, 108 – 153). mOS was significantly longer in patients who received RAI (32 vs 16 months; p= 0.034). The combination of cobimetinib + atezolizumab was overall well tolerated, with an expected adverse event profile. Conclusions: In patients with metastatic PDTC driven by RAS or NFmutations, combination of the anti-PD-L1 atezolizumab with MEKi cobimetinib showed some clinical efficacy, although PFS was shorter than with single-agent lenvatinib. However, SELECT trial did not delineate responses by driver mutations. This combination could thus be considered in selected patients at high risk of complications with antiangiogenic KIs. Clinical trial information: NCT03181100 .

Risk Stratification of Differentiated Thyroid Cancer at King Abdullah Specialized Children's Hospital Endocrinology Clinic in Riyadh, Saudi Arabia.

Background Papillary thyroid cancer (PTC), a well-differentiated form of cancer, accounts for the majority of thyroid malignancies, and the incidence of PTC is on the rise. While the rate of PTC recurrence is considered to be low, there are broad spectrums of clinical and biological behavior that can lead to disease recurrence. The American Thyroid Association (ATA) risk stratification system for differentiated thyroid cancer is used as a prognostic tool to guide decision-making and management strategies most likely to achieve a favorable outcome. Aim This study aimed to estimate the prevalence of PTC recurrence in each category of the ATA risk stratification system and determine the appropriate iodine dose to be administered at the King Abdulaziz Medical City Endocrinology Clinic in Riyadh, Saudi Arabia. Methods A cross-sectional retrospective chart review was conducted on adult patients with PTC who underwent thyroidectomy procedures at the King Abdullah SpecializedChildren'sHospital(KASCH) Endocrinology Clinic in Riyadh between 2015 and 2023. IBM SPSS (Statistical Package for the Social Sciences) version 25 (IBM Corp., Armonk, NY) was used for data analysis. Results Of the 697 patients included in the study, 82.4% were females. About 5% had suffered from PTC recurrence, and 54.4% had low-risk stratification. In addition, more than half (52.1%) had received radioactive iodine (RAI). The recurrence of PTC was significantly associated with age (P = 0.019), ATA risk stratification (P = 0.0001), RAI therapy (P = 0.001), and iodine dosage (P = 0.013). Conclusion Both low PTC recurrence rates and low-risk stratification were observed among the PTC patients. The risk factors relating to PTC recurrence included high-risk stratification, advanced age, RAItherapy, and the dosage of RAI administered.

FRI572 Teprotumumab In Unexplored Presentation Of Thyroid Eye Disease

Abstract Disclosure: M.T. Torres Torres: None. A.N. Gonzalez Bossolo: None. M.M. Mangual Garcia: None. Thyroid eye disease (TED) is an autoimmune disease of the orbital soft tissue associated with facial disfigurement, diminished quality of life, and potentially vision-threatening consequences that can occur in 40% of patients with Graves’ disease (GD). All the therapies for this condition were off-label with questionable long-term effects until 2020 when the Federal Drug Administration approved teprotumumab, a human monoclonal antibody against insulin-like growth factor-1 receptor, for the treatment of TED. Randomized placebo-controlled trials have demonstrated that teprotumumab reduces proptosis, diplopia, and Clinical Activity Score (CAS) in patients with active TED of less than 1.3 years of duration who were treatment-naïve or previously treated with < 1g of methylprednisolone equivalent therapy. Data on the efficacy of teprotumumab on cases of longer TED duration or previously treated with eye surgery or > 1g of methylprednisolone equivalent therapy for TED is limited as these patients were excluded from the trials. A 76-year-old nonsmoker male with long-standing hyperthyroidism due to GD, glaucoma, and type 1 diabetes mellitus was referred by ophthalmologist due to TED. He received radioactive iodine (RAI) for treatment of GD after failure to Methimazole therapy. After RAI, he reported progressively worsening bilateral eye edema, redness, pain, vision loss, and diplopia requiring hospitalization for an emergent orbital decompressive surgery and intravenous steroid therapy due to sight-threatening Grave’s orbitopathy. He was discharged home with oral prednisone taper down until it was discontinued 6 months later with mild improvement of symptoms. Physical exam was remarkable for bilateral strabismus, orbital chemosis, conjunctival injection and redness, eyelid swelling, limited eye motion, severely impaired visual acuity and color vision, no proptosis, and a CAS of 5 suggesting active TED. Laboratories showed biochemical euthyroidism and controlled glycemia. Teprotumumab was started 2 years and 8 months after symptom onset with marked improvement of inflammatory signs and symptoms, eye motion, visual acuity, diplopia, intraocular pressure, and CAS score decrease to 1 point suggesting inactive disease within 4 weeks of therapy without adverse side effects. This case describes the positive effects of teprotumumab in a patient with characteristics not previously studied such as active TED of longer duration than in clinical trials, previous treatment with orbital surgery or > 1g of methylprednisolone equivalent therapy, and increased IOP. Rather than drawing conclusions, our goal is to create awareness and promote further research of teprotumumab and novel agents in patients with TED with previously uncharacterized presentations as it may have important implications for their management including significant improvement in their quality of life. Presentation: Friday, June 16, 2023

Impact of lymphovascular invasion on otherwise low-risk papillary thyroid carcinomas: a retrospective and observational study

PurposePresence of venous vascular invasion is a criterion of intermediate risk of recurrence in papillary thyroid carcinoma (PTC). However, the presence and type of vascular invasion (lymphatic or venous) is often underreported and its impact on PTCs without other risk features remains unknown. The aim of this study was to evaluate the impact of both lymphatic and venous invasion on the risk of recurrence/persistence on otherwise low-risk PTCs.MethodsRetrospective study including patients with otherwise low-risk PTCs but with vascular invasion, diagnosed between 2013 and 2019. The persistence/recurrence during the follow-up was evaluated. Pathology was reviewed to confirm the presence of lymphovascular invasion and determine the type of invasion.ResultsA total of 141 patients were included. Lymphovascular invasion was confirmed in 20.6%. After surgery, 48.9% (N = 69) of the patients received radioactive iodine (RAI). The median follow-up time was 4 [3–6] years. Overall, 6 (4.2%) patients experienced persistent/recurrent disease in the neck, including 3 with lymphovascular invasion, confirmed as “only lymphatic”. Overall, patients with tumors harboring lymphovascular invasion had sensibly more persistent/recurrence disease compared with those without lymphovascular invasion (10.3% vs 2.7%, p = 0.1), especially in the subgroup of patients not treated with RAI (20% vs 1.6%, p = 0.049) [OR 15.25, 95% CI 1.24-187.85, p = 0.033].ConclusionLymphovascular invasion, including lymphatic invasion only, is associated with a sensibly higher risk of persistent/recurrent disease in otherwise low-risk PTCs, namely in patients not treated with RAI. Lymphatic invasion could have a role in risk-stratification systems for decision making.

Papillary thyroid carcinoma with fibromatosis-like stroma: a case report and review of the literature

BackgroundPapillary thyroid carcinoma (PTC) is a common neoplasia with multiple variants. One of these extremely rare and poorly described variants is PTC with fibromatosis-like stroma (PTC-FMS), a peculiar entity distinguished by its predominant mesenchymal component. This paper reviews the literature, discusses the diagnostic challenges, and the clinical and surgical implications of this type of tumor which has fewer than 30 cases reported in the literature.Case presentationWe reported a case of PTC-FMS found in a 41-year-old Italian woman, who came to our Institute with a recent growth in the form of a mass on the neck. Further immunohistochemical examination showed β-catenin aberrant staining both in the nuclei and cytoplasm of the mesenchymal cells. The patient underwent total thyroidectomy and received radioactive iodine (RAI) 2 months after surgery.ConclusionGiven the possibility of recurrence of PTC-FMS and the ineffectiveness of RAI therapy, complete surgical resection represents the main treatment for this type of tumor. Despite the fact that the specific nature of these lesions has yet to be determined, guidelines for classical PTC should be followed.

Linear association between radioactive iodine dose and second primary malignancy risk in thyroid cancer.

We aimed to investigate whether the risk of second primary malignancy (SPM) in patients with thyroid cancer (TC) receiving radioactive iodine (RAI) therapy rises in a cumulative, dose-dependent manner compared with those not undergoing RAI. Using the Korean National Health Insurance Service National Health Information Database (2002-2019), we investigated hazard ratios of SPM associated with RAI in TC. SPM was defined as a second primary malignancy diagnosed at least 1 year after TC diagnosis. Of 217 777 patients with TC (177 385 women and 40 392 men; mean [SD] age, 47.2 [11.6] years), 100 448 (46.1%) received RAI therapy. The median (IQR) follow-up duration was 7.7 (5.5-10.3) years, and the median (IQR) cumulative RAI dose was 3.7 (1.9-5.6) GBq. From 2004 to 2019, SPM incidence rates were 7.30 and 6.56 per 1000 person-years in the RAI and non-RAI groups, respectively, with an unadjusted hazard ratio of 1.09 (95% confidence interval = 1.05 to 1.13); this rate remained at 1.08 (95% confidence interval = 1.04 to 1.13) after adjustment for multiple clinical confounding factors. Notably, SPM risk increased significantly, from 3.7 GBq with full adjustments, and a strong linear association between cumulative RAI dose and SPM was observed in the restricted cubic spline analysis. Regarding cancer subtypes, myeloid leukemia and salivary gland, trachea, lung and bronchus, uterus, and prostate cancers were the most significantly elevated risks in patients who underwent RAI therapy. This study identified that SPM risk increased linearly in a dose-dependent manner in patients with TC undergoing RAI therapy compared with those not undergoing RAI therapy.

Retrospective Evaluation of the Efficiency of Therapeutic Plasmapheresis in Thyrotoxic Patients

Background: Therapeutic plasma exchange (TPE) is a treatment method that can be used to provide euthyroidism before permanent treatment in patients with severe thyrotoxicosis, in cases of thyroid storm and in cases where antithyroid drug (ATD) cannot be used due to side effects or ineffectiveness. This study presented our results and experience on TPE in thyrotoxic patients.
 Material and Methods: The data of 10 patients who underwent plasmapheresis for thyrotoxicosis in Bursa Uludag University Faculty of Medicine Endocrinology Clinic were retrospectively analyzed and compared with the literature.
 Results: Ten patients, 6 female and 4 male, were included. The cause of hyperthyroidism was Graves’ disease in 8 patients and toxic multinodular goiter (TMNG) in 2 patients. It was observed that the reason for applying plasmapheresis in the patients was primarily due to toxic hepatitis. The mean number of plasmapheresis required to maintain euthyroidism was 4 (1-8). While no difference was found between the thyroid-stimulating hormone (TSH) results before and after TPE, free T4 (fT4) and free T3 (fT3) values were statistically significantly lower after TPE. It was observed that the leukocytes were considerably higher after TPE and the sodium and calcium values were markedly lower after TPE in the patients. After TPE, 7 patients underwent total thyroidectomy, 1 patient received radioactive iodine (RAI) treatment, and 2 were discharged with ATD treatment.
 Conclusions: TPE is an effective and safe treatment option that can be applied in cases where it is necessary to provide rapid euthyroidism before permanent treatments or non-thyroid surgical procedures or to treat life-threatening thyrotoxicosis. It requires experience in application and follow-up and provides rapid euthyroidism when performed in experienced centres.

Clinical Management of End-Stage Renal Disease Patients on Dialysis Receiving Radioactive Iodine Treatment.

Radioactive iodine (RAI) is used to treat thyroid cancer patients with a clear paradigm for most patients. End-stage renal disease (ESRD) patients pose several challenges when undergoing RAI treatment, primarily due to the lack of renal clearance. We retrospectively report our experience with RAI treatment in a cohort of patients with ESRD and provide a set of recommendations on aspects such as the need for adjusted dose activity, balancing scheduling between RAI therapy and dialysis, and radiation safety precautions. In this study, we report on 5 patients (6 cases), with ESRD on dialysis, treated with RAI for thyroid cancer. Retention measurements to determine individual biological clearance of RAI from the patient's body before and after dialysis sessions were assessed using external exposure dose rates measured at 1 m. Delayed biological clearance of RAI, after the first hemodialysis session, resulted in a longer RAI effective half-life as a consequence of longer retention periods, consistent with observations reported in scientific literature. To achieve a much closer radiation exposure compared with a nondialysis patient, one would recommend administering ~20%-30% of the dose activity normally administered to a thyroid cancer patient based on their medical history, histopathology, and uptake with the appropriate dialysis schedule. Special precautions should be taken with the administration of RAI in ESRD patients by adjusting the prescribed dose activity, dialysis sessions, and paying special attention to wastes. Pooling data from multiple centers may be useful to build a consensus and substantiated recommendations.

A multicenter, prospective study to observe the initial management of patients with differentiated thyroid cancer in China (DTCC study)

BackgroundTo assess the gaps between the initial management of patients with differentiated thyroid cancer (DTC) in real clinical practice and the recommendations of the 2012 Chinese DTC guidelines.MethodsThis multicenter, prospective study was conducted at nine tertiary hospitals across China. Eligible patients were those having intermediate or high-risk DTC after first-time thyroidectomy. During 1 year of follow-up, comprehensive medical records were collected and summarized using descriptive statistics.ResultsOf 2013 patients, 1874 (93.1%) underwent standard surgery according to the guidelines (including total lobectomy plus isthmusectomy and total/near total thyroidectomy), and 1993 (99.0%) underwent lymph node dissection; only 56 (2.8%) had postoperative complications. Overall, 982/2013 patients (48.8%) received radioactive iodine (RAI) therapy after thyroidectomy. Of all enrolled patients, 61.4% achieved the target serum thyroid-stimulating hormone level, with a median time to target of 234.0 days (95% CI: 222.0–252.0). At 1 year of follow-up, proportions of patients with excellent response, incomplete structural response, biochemical incomplete response, and indeterminate response were 34.6, 11.2, 6.6, and 47.5%, respectively; recurrence or metastasis occurred in 27 patients (1.3%). During the overall study period, 209 patients (10.4%) had at least one adverse event: 65.1% of cases were mild, 24.9% moderate, and 10.1% severe.ConclusionsThis was the first large-scale prospective study of how patients with DTC in China are treated in actual practice. Initial DTC management is generally safe and adheres to the 2012 Chinese guidelines but could be improved, and the level of guideline adherence did not produce the anticipated treatment response at 1 year of follow-up.

"Cardiovascular Pathology in Women Who Received Radioactive Iodine Exposure During Pregnancy as a Result of the Chernobyl Accident"

Stojarov AN1*, Khrustalev VV2 and Adzintsova-Stazharava DA3 Author Affiliations 1Department of Radiation Medicine and Ecology, Belarusian State Medical University, Minsk, Belarus 2Department of General Chemistry, Belarusian State Medical University, Minsk, Belarus 3Department of Obstetrics and Gynecology, Belarusian State Medical University, Minsk, Belarus Received: July 10, 2021 | Published: July 20, 2021 Corresponding author: Stojarov AN, Department of Radiation Medicine and Ecology, Belarusian State Medical University, Belarus DOI: 10.26717/BJSTR.2021.37.005984

The value of serum thyroglobulin alteration after ultrasonography-guided fine-needle biopsy of suspicious cervical lymph nodes in the diagnosis of metastasis in patients with differentiated thyroid cancer.

It is known that serum thyroglobulin (TG) can increase after fine-needle biopsy of thyroid nodules. We aimed to determine whether TG is increased after ultrasonography (US)-guided fine needle capillary biopsy (FNC) of suspicious cervical lymph nodes (LNs) in thyroidectomised patients and investigate the possible association between change in TG and cytology results. Data of 188 patients who underwent FNC of suspicious cervical LNs were retrospectively evaluated. Demographical, laboratory and ultrasonography features of LNs were noted. TG levels before FNC (TGb-FNC ), after FNC (TGa-FNC ), TGa-FNC /TGb-FNC ratio and the number of patients with increased TG were determined. Patients were grouped as benign, nondiagnostic, suspicious for malignancy and malignant according to the cytological results. TGa-FNC , TGb-FNC /TGa-FNC and rate of patients with increased TG were significantly higher in malignant cytology group than other groups (P<.001). The optimal cut-off level of TG increase that was predictive for malignancy was 7.6% with a sensitivity of 73.7% and specificity of 85.2%. TG increase was not associated with age, sex, Thyroid-stimulating hormone (TSH) level, anti-TG positivity and US features of LNs while significantly lower in patients who received radioactive iodine (RAI) treatment. Among 31 patients with positive anti-TG, TGb-FNC /TGa-FNC , and rate of patients with increased TG were higher in malignant compared to benign and nondiagnostic cytology groups. Serum TG increment and rate of patients with increased TG after FNC of suspicious cervical LNs were higher in patients with malignant cytology than with all other cytology results both in all study group and in sub-group of anti-TG positive patients. Increase in TG after FNC might be an additional tool for determining LN metastasis.

Oncological outcomes in differentiated thyroid cancer in South East Scotland

BackgroundDifferentiated thyroid cancer (DTC) is increasing in incidence but little is known about oncological outcomes for patients treated in the UK. Internationally there is a move toward conservative treatment of DTC. However, this is based on evidence from outside the UK. The aim of this study was to analyse oncological outcomes for a contemporary cohort of patients treated in a UK centre. MethodsReview of 470 consecutive prospectively recorded cases of DTC from the South East of Scotland endocrine MDT 2009–2018. Data on patient, tumour and treatment details as well as recurrence and survival details were extracted from the electronic patient record. ResultsOf 470 patients female:male ratio was 3.4:1, median age at presentation was 48 years (range 16–86 years). Overall 193 (41%), 134 (29%), 119 (25%) and 22 (5%) patients were p T1, T2, T3, and p T4 respectively. 385 patients (82%) were pN0, 31 patients (7%) were pN1a and 53 patients (11%) were pN1b. 19 patients (4%) were M1. Of 470 patients 350 (74%) had papillary thyroid carcinoma, 120 patients (26%) had follicular carcinoma. Surgical management was lobectomy, isthumusectomy, total thyroidectomy and lobectomy then completion thyroidectomy in 14%,1%, 41% and 43% cases respectively. 64% patients received radioactive Iodine (RAI) therapy. With a median follow-up of 70 months (range 4–124 months), 5 years overall survival and disease specific survival were 96.7% and 98.5% respectively. The 5 year local recurrence free survival (LRFS), regional recurrence free survival (RRFS), locoregional recurrence free survival (LRRFS), distant recurrence free survival (DRFS) and any recurrence free survivals were 100%, 95.8%, 95.8%, 98.3% and 95% respectively. ConclusionOncological outcomes for patients treated with DTC were excellent, in keeping with experience from international groups, suggesting that a move towards conservative treatment in the UK seems reasonable.

Annual Hazard Rate of Recurrence in Middle Eastern Papillary Thyroid Cancer over a Long-Term Follow-Up.

Simple SummaryTumor recurrence is a relatively common event in papillary thyroid cancer (PTC). The aim of this study was to analyze the time-varying pattern of recurrence in PTC using annual hazard function and establish a predictive model for early and late recurrences. We found a double-peaked pattern of annual hazard of recurrence, with the risk being highest during the first 5 years after surgery. We also found distinct clinico-pathological parameters that could independently predict the occurrence of early recurrence (first 5 years) as compared to late recurrence (after 5 years). Overall, this study highlights the importance of long-term follow-up of PTC patients. Furthermore, the findings of our study could help in establishing individualized treatment and surveillance plans in PTC patients.Predicting the pattern of recurrence in papillary thyroid cancer (PTC) is necessary to establish optimal surveillance and treatment strategies. We analyzed changes in hazard rate (HR) for tumor recurrence over time in 1201 unselected Middle Eastern PTC patients. The changes in risk were further analyzed according to clinical variables predictive of early (≤5 years) and late (>5 years) recurrence using Cox regression analysis to identify patient populations that remain at risk. Tumor recurrence was noted in 18.4% (221/1201) patients. The annualized hazard of PTC recurrence was highest during the first 5 years (2.8%), peaking between 1 and 2 years (3.7%), with a second smaller peak between 13 and 14 years (3.2%). Patients receiving radioactive iodine (RAI) therapy had lower recurrence hazard compared to those who did not (1.5% vs. 2.7%, p = 0.0001). Importantly, this difference was significant even in intermediate-risk PTC patients (0.7% vs. 2.3%; p = 0.0001). Interestingly, patients aged ≥55 years and having lymph node metastasis were at persistent risk for late recurrence. In conclusion, we confirmed the validity of the double-peaked time-varying pattern for recurrence risk in Middle Eastern PTC patients and our findings could help in formulating individualized treatment and surveillance plans.

Analysis of Pattern of Laryngotracheal Invasion by Papillary Thyroid Carcinoma and Their Management: Our Experience.

To analyse the pattern of laryngotracheal invasion (LTI) by papillary-thyroid-carcinoma (PTC) and outcomes of their management. We undertook a retrospective chart review to study patterns of LTI by PTC and to evaluate outcomes of surgical modalities used to treat PTC with LTI. Out of 246cases of PTC, 26-cases had LTI (male-12, female-14, mean-age-55.6years, range 42-73years). Common clinical presentation were neck swelling, respiratory distress/stridor and vocal cord paralysis in 100%, 8 (30.8%) and 10 (38.5%) cases respectively. PTC was staged according to AJCC-TNM staging system (T4a-24, T4b-02, N1a-12, N1b-14, M0-25, and M1-01). CT-scan showed obvious LTI and tracheal narrowing in 11(42.3%) and 18(69.2%) cases respectively. All cases underwent total thyroidectomy with central-compartment-clearance. Unilateral and bilateral lateral-neck-dissection was performed in 08 and 06cases respectively. Pattern of Intra-operative LTI were as follows: trachea-13cases, trachea and cricoid-05cases, thyroid cartilage-6cases, trachea, cricoid and thyroid cartilage-2 cases and intra-luminal involvement in 4cases. Modified Shin's staging was used to stage LTI. LTI were superficial, deep-extra-luminal and intra-luminal in 13, 09 and 04cases respectively. LTI was managed by shave-excision, window-resection of trachea, sleeve-resection of trachea and anastomosis, partial laryngectomy and total-laryngectomy in 13,02,04,05 and 2 cases respectively. All patients received radio-active-iodine (RAI) and TSH-suppression-therapy post-operatively. Mean follow-up period was two-years (range 18-30months). One-case had radio-iodine non-avid local recurrence with lung metastases one-year post-operatively. Shave-excision is adequate for tumours not infiltrating into outer perichondrium. Tracheal-resection and total/partial laryngectomy may be required in cases with laryngo-tracheal cartilage or intra-luminal involvement. Adequate surgical excision along with postoperative RAI and TSH-suppression-therapy gives good loco-regional disease control in PTC with LTI.

Long-term outcome of differentiated thyroid cancer in children and young adults: risk stratification by ATA criteria and assessment of pre-ablation stimulated thyroglobulin as predictors of disease persistence.

Differentiated thyroid cancer (DTC) has an increasing incidence in childhood and adolescence but long-term outcome data are limited. We aimed to identify possible risk factors associated with disease persistence, with special focus on the usefulness of ATA risk stratification system and pre-ablation stimulated thyroglobulin (Tg) levels. We retrospectively studied 103 patients, 79 females (76.7%), aged 15.6 ± 3.2 years (range 5-21 years) who underwent total thyroidectomy for DTC. Patients were classified by ATA risk stratification criteria as low, intermediate, and high risk for recurrence. All, except five with papillary microcarcinoma, received radioactive iodine (RAI) treatment. At diagnosis, 44.7% of patients had cervical lymph node and 7.8% pulmonary metastases. Amongst the 72 patients with long-term follow-up data, 31.9% had persistent disease. Lymph node as well as pulmonary metastases and increased pre-ablation stimulated thyroglobulin (Tg) levels were associated with persistent disease. The risk of persistent disease was significantly higher in both the intermediate- (OR 17.95; 95% CI 2.66-120.94, p < 0.01) and high-risk (OR 17.65; 95% CI 4.47-69.74, p < 0.001) groups. ROC curve analysis showed that a pre-ablation Tg level higher than 14 ng/ml had a sensitivity of 94.7% to predict persistence, corresponding to a positive (PPV) and negative predictive values (NPV) of 66.7% and 93.8%, respectively. ATA risk stratification was validated in our population of children and young adults with DTC. Moreover, pre-ablation stimulated Tg levels of <14 ng/ml were associated with a low risk of long-term persistence and may therefore serve as a marker to identify patients who may need less intensive surveillance.

SUN-512 Graves’ Disease Induced Renal Tubular Acidosis

Thyroid gland can affect kidney function in different ways. Thyroxine as a master hormone of metabolism and growth works in many cellular levels include the renal tubules.We present a 34-year-old Emirati gentleman who presented with multiple episodes of hypokalemic periodic paralysis. Blood test revealed thyrotoxic state, with highly positive serology for thyroid peroxidase, anti-thyroglobulin and thyrotropin receptor antibodies. Thyroid uptake scan confirmed homogenous diffuse uptake consistent with toxic diffuse goitre [Graves’ disease]. In view of recent fracture, bone profile and DXA scan were done. Investigations revealed vitamin D deficiency and below expected for age bone mass density.The patient was started on symptomatic treatment with propranolol, IV and oral potassium along with IVF hydration. Routine blood work during admission showed a persistent normal anion Gap metabolic acidosis, serum bicarb 15 mmol/l. 24 hours urine electrolytes revealed normal potassium, sodium, high magnesium, low calcium and PH levels. Biochemical lab results suggested type 1 renal tubular acidosis. As the patient had hypokalaemia, high urine magnesium and low urine calcium and limbs weakness, Gitleman Syndrome was considered in the differential diagnosis. Whole Exome Sequencing (CentoXome GOLD®) was sent which came back negative. The following gene panels were studied: Renal tubular acidosis panel: ATP6V0A4, ATP6V1B1, CA2, EHHADH, HNF4A, SLC34A1, SLC4A1, SLC4A4. Bartter Syndrome panel: ATP6V1B1, BSND, CA2, CASR, CLCNKA, CLCNKB, CLDN16, CLDN19, FXYD2, HSD11B2,KCNJ1, KCNJ10, KLHL3, NR3C2, SCNN1A, SCNN1B, SCNN1G, SLC12A1, SLC12A2, SLC12A3, SLC4A1, SLC4A4, WNK1. Gene related to Gitelman syndrome: SLC12A3Renal tubular acidosis was treated with KCL 600mg PO TID, Na bicarb 1200mg PO BID and spironolactone 25 mg PO OD. The patient received radioactive iodine (RAI) as the ultimate treatment for Graves’ disease. He developed hypothyroidism post RAI ablation and commenced on levothyroxine. Improvement of the metabolic acidosis was noticed in line with improvement of thyroid function. Na bicarb and spironolactone tablets were stopped eventually as the patient was euthyroid clinically and biochemically.Overt hyperthyroidism is associated with accelerated bone remodelling, leading to hypercalciuria, which can predispose to nephrocalcinosis and renal tubular damage, and therefore causes type 1 renal tubular acidosis. Once the patient becomes euthyroid, bone remodelling and urine calcium return to normal levels and that would correct the renal acidosis.This case report serves to highlight the effect of Graves’ disease on renal tubules which may result in type 1 renal tubular acidosis. This effect could be reversible with normalization of thyroid function.

Is routine dissection of central lymph node and radio-active iodine therapy, necessary for papillary thyroid carcinoma, T1-2 N0? A randomized controlled trial

Backgroundprophylactic central neck dissection (pCND) is a subject of discussion for papillary thyroid carcinoma T1-2 N0, our study proves that pCND should be recommended as it is associated with less postoperative residual tumour with increasing recurrence-free survival. ObjectiveThe primary endpoint is the recurrence free survival, study exclusively compares the outcome of surgical ablation with and without CND in PTC T1-2N0. Another endpoint is whether patients with residual disease, need to receive repeated radioactive iodine ablation or completion surgery. Subject and methodA Randomized controlled trial multi-centre study, assigned the patients into two arms, Group I was the control arm underwent total thyroidectomy only, whereas the other arm, included Total thyroidectomy and central neck dissection. Univariate and multivariate analysis was performed to declare risk group for recurrence. Recurrence Free Survival was the main issue of the study and calculated as the time elapsed from the date of surgery to the date of relapse; patients with residual and uTg 0.2–2 ng/ml received radio-active iodine (RAI) therapy versus completion surgery. ResultsLoco-regional recurrence cases were found more in male patients aged more than 45 years old. Size of the primary tumour and the extent of surgery was a significant factor for RFS, patients with PCND in group II, had lower loco-regional recurrence and longer RFS, mean RFS was 25 months with (95%CI) is (23.61–26.38 months). Recurrence was high in the controlled group 38.1%. ConclusionN0 patients will benefit by total thyroidectomy and pCND. pCND is recommended to decreases the residual tumour, increase the RFS. Completion surgery versus RAI for postoperative recurrence needs more number of patients.

Direct bilirubin level is an independent risk factor for atrial fibrillation in thyrotoxic patients receiving radioactive iodine therapy.

This study aimed to indicate the risk factors of atrial fibrillation (AF) in thyrotoxic patients receiving radioactive iodine (RAI) therapy after antithyroid drug and other medication. This study was a retrospective cohort study. Thyrotoxic patients were divided into two groups, with or without AF. Clinical features were retrospectively analyzed. Univariate and multivariate analyses of data from thyrotoxic patients were performed to evaluate the probability of AF. The following clinical factors were found to be correlated with AF: age, gender, duration of hyperthyroidism, coronary artery disease, hypertension, and levels of platelets, creatinine, uric acid (UA), and certain liver enzymes. According to the multiple logistic regression model, age and levels of UA, direct bilirubin (DBIL), and gamma-glutamyl transpeptidase (GGT) were important risk factors for predicting AF. ROC analysis showed that DBIL levels were predictive of AF, with a specificity of 0.813, a sensitivity of 0.767, and an area under the curve of 0.8515 (P < 0.001). Older age and levels of UA, DBIL, and GGT influenced the occurrence of AF in thyrotoxic patients receiving RAI. DBIL level was an important factor in predicting AF in patients with hyperthyroidism. Thus, thyrotoxic patients who have the above-mentioned risk factors should undergo routine pulse palpation should be considered for active antithyroid drug therapy.

Long-term Outcomes and Prognostic Factors in Patients with Differentiated Thyroid Cancer and Distant Metastases

Distant metastatic spread is the most frequent cause of thyroid cancer-related death. The objective of this study was to evaluate overall and disease-related survival of patients with differentiated thyroid cancer (DTC) and distant metastases (DM) attending a single medical center and to investigate variables predictive of better long-term outcomes. The Rabin Medical Center Thyroid Cancer Registry was searched for patients with DM from DTC. The cohort included 138 patients (58.7% female) diagnosed at age 54.7 ± 19.5 years. Mean primary tumor size was 33.9 ± 26 mm. Most patients (57.7%) were stage T3/T4; 48.7% had extrathyroidal extension; 53.5% had lymph node metastases. Histopathology yielded papillary and follicular thyroid carcinoma in 66.7% and 13.8%, respectively, and intermediate/poorly differentiated carcinoma in 19.6%. All but 2 patients underwent total thyroidectomy, and 133/138 (96.4%) received radioactive iodine (RAI) therapy. DM were synchronous in 55.1%. The mean follow-up was 8.2 years from detection of metastases. The common sites of metastases were the lungs (85.6% of patients), bones (39.9%), brain (5.8%) and liver (3.6%). At last follow-up, resolution was documented in 24.6% of patients, improvement/stable disease in 31.6%, and structurally progressive disease in 43.4%. By the end of the study, 40.6% of patients died, 23.2% of DTC. Improved overall survival and disease progression were associated with younger age, lung-only DM, and metastatic RAI avidity. Patients with DTC and DM treated by standard-of-care approaches frequently achieve favorable long-term outcomes. Novel therapies might be necessary in only a minority of these patients, and the reported prognostic factors can aid in their identification. CR = complete response; DM = distant metastases; DTC = differentiated thyroid cancer; ETE = extra-thyroidal extension; M0 = detected during follow-up; M1 = detected at diagnosis; MSKCC = Memorial Sloan Kettering Cancer Center; NED = no evidence of disease; OS = overall survival; PFS = progression free survival; PTC = papillary thyroid cancer; RAI = radioactive iodine; Tg = thyroglobulin.

Higher body weight and distant metastasis are associated with higher radiation exposure to the household environment from patients with thyroid cancer after radioactive iodine therapy.

There were insufficient data regarding radiation exposure to the household environment from patients with thyroid cancer who received radioactive iodine (RAI) therapy in Asia; we therefore performed the present study at the Chang Gung Memorial Hospital in Keelung, Taiwan.Patients with papillary or follicular thyroid cancer who received 3.7 GBq (100 mCi) RAI were enrolled in this prospective hospital-based study. The enrolled patients were asked to place a thermoluminescent dosimeter in the living room, bedroom, and bathroom of their houses for 4 weeks to measure radiation exposure to the household environment.A total of 43 patients (18 men and 25 women; mean age 51 ± 13 years) who received 3.7 GBq (100 mCi) RAI completed the study. The mean value of total radiation exposure over 4 weeks from the patients to the bedroom, bathroom, and living room (eliminating the background radiation factor) was 0.446 ± 0.304 (0.088–1.382) mSv. We divided the patients into 2 groups: those with more than and less than the mean value of total radiation exposure to the bedroom, bathroom, and living room. Factors associated with the higher amount of radiation exposure from the patients to the household environment were patient body weight (P = .025, univariate analysis; P = .037, multivariate analysis, odds ratio [95% confidence interval] 1.067 [1.004–1.134]) and distant metastases based on 131I post-therapy scanning (P = .041, univariate analysis; P = .058, multivariate analysis, odds ratio [95% confidence interval] 6.453 [0.938–44.369]); age, sex, body mass index, renal function, serum stimulated thyroglobulin level, and recombinant human thyroid-stimulating hormone use were not associated with the amount of radiation exposure from the patients to the household environment.Higher body weight and distant metastases may be the best predictors for higher radiation exposure to the household environment from patients with thyroid cancer after RAI therapy.