Management of Low-Risk Differentiated Thyroid Cancer

ObjectiveTo summarize the definitions of and management recommendations for low-risk thyroid cancer made by the American and European Thyroid Associations and synthesize this information with the recent literature, including systematic evaluations of tumor staging systems guiding therapy.MethodsThe American Thyroid Association and European Thyroid Association guidelines were compared and pertinent literature since 2005 was reviewed.ResultsOf papillary thyroid microcarcinomas (PTMC), up to 50% breach the thyroid capsule, 64% have lymph node metastases, up to 43% are multifocal, and as many as 2.8% have distant metastases. Locoregional and distant recurrences are, respectively, as high as 5.9% and 1.5%. As many as 1 in 4 patients with a papillary thyroid carcinoma 1.5 cm or smaller develop persistent disease. Cancer-related mortality rates are usually less than 1%, but are as high as 2% in some reports. Tumor staging systems are too inaccurate to guide therapy.ConclusionIt is unlikely that many patients will forgo treatment after understanding their risk, especially when total thyroidectomy and radioiodine (¹³¹I) therapy can reduce the PTMC recurrence or persistence disease rate to zero. Preoperatively diagnosed PTMC should be treated with total or near-total thyroidectomy, regardless of tumor size. For very low-risk patients with unifocal PTMC smaller than 1 cm that is removed by chance during surgery to treat benign thyroid disease, lobectomy alone without ¹³¹I therapy may be sufficient therapy if there are no concerning histologic features and no tumor extension beyond the thyroid, metastases, history of head and neck irradiation, or positive family history—any of which requires total or near-total thyroidectomy and remnant ablation with 30 mCi. (Endocr Pract. 2007;13:498-512)     

Early and Late Toxicity of Radioiodine Therapy: Detection and Management

ObjectiveTo review the early and late toxicity associated with radioiodine (¹³¹I) therapy, highlighting the need for early detection and, where possible, preventive measures.MethodsWe performed a literature search on MEDLINE using the terms radioiodine, ¹³¹I toxicity, complications, Graves disease, and thyroid cancer and chose the most relevant studies for this review. Where appropriate, we refer to our own published series of patients as well.ResultsUptake of ¹³¹I into the salivary glands, lacrimal glands, fetal thyroid, and adult thyroid accounts for the early toxic effects of radioiodine therapy. Delayed radiation effects to the gonads, bone marrow, and cell nuclei give rise to late complications. Toxicity may also arise from uptake into metastatic tumors located at vulnerable sites, including the spinal cord, brain, and lungs.ConclusionAlthough radioiodine therapy for benign and malignant thyroid disorders is usually well tolerated, clinicians involved in the management of thyroid disorders need to be aware of the potential toxicity of radioiodine and take all measures to reduce these effects to a minimum. (Endocr Pract. 2010;16:1064-1070)     

Ultrasonographic Differentiation of Cervical Lymph Nodes in Patients with Papillary Thyroid Carcinoma After Thyroidectomy and Radioiodine Ablation: A Prospective Study

ObjectiveThe objective of the present study was to validate an ultrasound (US) classification of cervical lymph nodes (LNs) in patients with papillary thyroid cancer (PTC) after thyroidectomy and radioactive iodine (¹³¹I) ablation.MethodsWe performed a prospective study in which the patients were submitted to thyroidectomy and ¹³¹I ablation and then followed until neck US revealed LN(s) ≥ 5 mm. A total of 288 LNs from 112 patients with PTC were evaluated. Patient management was based on LN characteristics grouped according to the classification system studied here.ResultsThe presence of microcalcifications and/or cystic degeneration of cervical LNs were highly suggestive of a metastatic etiology (specificity of 99.4%). In contrast, the most sensitive finding for LNs affected by PTC was the absence of an echogenic hilum (sensitivity of 100%). In the absence of these findings (microcalcifications, cystic degeneration, echogenic hilum), a metastatic etiology was the most likely in the case of a round LN (specificity of 89%). The differentiation of a spindle-shaped LN without a visible hilum by Doppler analysis permitted us to dichotomize an initial probability of metastases of 13% in 25% (with peripheral vascularization) versus 3.3% (without peripheral vascularization).ConclusionsOur results confirm that the classification proposed for cervical LNs in patients with PTC is valid for determining patient management following initial therapy. (Endocr Pract. 2014;20:293-298)     

Radioactive Iodine Therapy Without Recent Antithyroid Drug Pretreatment For Hyperthyroidism Complicated By Severe Hyperbilirubinemia Due To Hepatic Dysfunction: Experience Of A Chinese Medical Center

Objective: The objective of this work is to report our experience with ¹³¹I therapy without recent antithyroid drug (ATD) pretreatment for refractory severe hyperthyroidism complicated by hyperbilirubinemia due to hepatic dysfunction.Methods: Five patients with refractory severe hyperthyroidism were treated with ¹³¹I at 90 to 120 μCi/g-thyroid (total activity, 6.2 to 10.1 mCi). The patients previously had received ATD treatment from 2 months to 12 years and discontinued ATDs from 2 months to 4 years before ¹³¹I treatment due to treatment failure or severe jaundice. Prior to ¹³¹I therapy, the patients were asked to take a low-iodine diet and were treated with bisoprolol fumarate, digoxin, furosemide, S-adenosylmethionine, polyene phosphatidylcholine, and plasma exchange as supportive treatment for related clinical conditions. Four of the patients also received lithium carbonate in conjunction with their ¹³¹I treatment. The patients were followed for 4 to 9 years after ¹³¹I therapy.Results: After ¹³¹I treatment, jaundice disappeared completely within 3 to 4 months in all patients, and liver function tests returned to normal. Concurrent atrial fibrillation and heart failure, leukopenia and thrombocytopenia, or thrombocytopenia and left cardiac enlargement improved remarkably in 3 patients during the follow-up period. Three to 45 months after ¹³¹I treatment, hypothyroidism was noted in the patients and they were treated with L-thyroxine replacement therapy.Conclusion:¹³¹I therapy without recent ATD pretreatment for refractory severe hyperthyroidism complicated by serious jaundice appears to be safe and effective, with good long-term results. It may be the preferred therapy for such patients and should be used as early as possible.Abbreviations:ATD = antithyroid drugFT₄ = free thyroxinePTU = propylthiouracilRAIU = radioactive iodine uptakeTSH = thyroid-stimulating hormone     

Insular Variant of Poorly Differentiated Thyroid Carcinoma

ObjectiveTo present a case of an insular variant of poorly differentiated thyroid carcinoma (PDTC) and to review the literature related to diagnosis, natural history, and treatment of this unusual form of thyroid cancer.MethodsWe present the clinical, laboratory, and pathologic findings of the study patient and review Englishlanguage literature related to PDTC published between 1970 and the present.ResultsPDTC is a controversial and rare epithelial thyroid cancer, intermediate between differentiated thyroid carcinoma and anaplastic thyroid carcinoma that exhibits increased aggressiveness, propensity to local recurrence, distant metastases, and increased mortality. PDTC warrants aggressive management with total thyroidectomy followed by radioactive iodine ablation and potentially additional therapy for residual or recurrent disease. Some carcinomas do not take up radioactive iodine, and dedifferentiated clones of distant metastases may evolve. It is unclear whether chemotherapy is beneficial. Use of additional imaging modalities, including positron emission tomography, 18-fludeoxyglucose positron emission tomography/computed tomography, 18-fludeoxyglucose positron emission tomography/computed tomography/magnetic resonance imaging, ¹²⁴I positron emission tomography/computed tomography, positron emission tomography/magnetic resonance imaging fusion studies, and recombinant human thyrotropin-stimulated radioactive iodine uptake for cancer surveillance are discussed.ConclusionsPDTC is an unusual and aggressive form of thyroid cancer. Fine-needle aspiration cytology may not yield sufficient information to specifically diagnose PDTC. Aggressive management with total thyroidectomy and neck dissection followed by high-dose radioactive iodine remnant ablation is standard. Iodine I 131 whole body scanning is often the initial test for tumor surveillance, with other imaging modalities applied as needed. (Endocr Pract. 2011;17:115-121)     

A comparison of the dissolution profiles for several commercially available [131I]sodium iodide capsules

The dissolution profiles for [¹³¹I]sodium iodide diagnostic capsules from three commercial vendors were studied. The ¹³¹I release rate in water was rapid for capsules from Vendors A and C. The dissolution profile for the Vendor B product resembled that of a sustained release capsule. The data from the study indicates the potential for differences in the bioavailability of ¹³¹I from the sodium iodide diagnostic capsules.     

Reliability of Early Iodine 123 Uptake for Treatment of Graves Disease in Children

ObjectiveTo determine the reliability of early radioiodine uptake (RAIU) in calculation of the radioiodine ablation dose for pediatric patients with Graves disease.MethodsThis retrospective review of medical records involved 22 pediatric patients with Graves disease, who had undergone early (4 to 8 hours) and late (24 to 26 hours) RAIU studies and were treated with iodine 131 (¹³¹I). Quantitative data are reported as mean ± standard error of the mean. Early and late RAIU and actual administered versus calculated ¹³¹I ablation doses were compared by using the paired t test. The correlation between early and late RAIU was assessed by curvilinear regression analysis. Significance was assessed at P < .05.ResultsMean early RAIU was 57.1% ± 18.2%, and mean late RAIU was 72.1% ± 14.4% (P < .05). Curvilinear regression analysis showed the following: late RAIU = 7.13 + 1.71 × (early RAIU) - 0.01 × (early RAIU)²; r² = 0.75. The mean ablation dose of ¹³¹I based on late RAIU was 9.3 ± 2.0 mCi. The calculated radioiodine dose would have been, on average, 32% higher (12.3 ± 3.8 mCi; P < .05) had early RAIU been used.ConclusionIn children, early RAIU can be much lower than late RAIU. This may be misleading for ablation dose calculations. Therefore, late RAIU should be used to avoid overtreatment in children with Graves disease.(Endocr Pract. 2011;17:541-545)     

Risk Factors for Nonremission and Progression-Free Survival after I-131 Therapy in Patients with Lung Metastasis from Differentiated Thyroid Cancer: A Single-Institute,Retrospective Analysis in Southern China

Objective: Prognostic factors related to progression-free survival (PFS) have not received much attention in the literature regarding iodine-131 (¹³¹I) therapy for patients with differentiated thyroid cancer and lung metastases. We sought to explore the factors associated with PFS and nonremission in a group of patients with differentiated thyroid cancer and pulmonary metastases at initial diagnosis and to investigate the impact of ¹³¹I therapy on pulmonary function and peripheral blood counts in the same cohort of patients.Methods: The medical records of 1,050 patients with differentiated thyroid cancer treated at the Zhujiang Hospital of Southern Medical University from January 2006 to January 2015 were retrospectively reviewed. Among them, 107 patients fulfilled the inclusion criteria.Results: Multivariate Cox regression analysis indicated that age ≥45 years and ¹³¹I nonavidity were independent risk factors for disease progression. Multivariate logistic regression analysis revealed that pulmonary nodule size ≥1 cm and ¹³¹I nonavidity were the strongest risk factors predicting nonremission. Varying cumulative ¹³¹I dosage had no association with posttreatment pulmonary function or peripheral blood cell counts.Conclusion: Similar to earlier studies, our results confirm that ¹³¹I nonavidity was associated with an increased risk of disease progression and greater odds of nonremission. In addition, patients with differentiated thyroid cancer and lung metastases with pulmonary nodules ≥1 cm had a reduced likelihood of achieving remission. Furthermore, special attention is needed when monitoring patients over 45 years at a higher risk of disease progression.Abbreviations:CI = confidence intervalDTC = differentiated thyroid cancer¹⁸F-FDG = fluoro-18 fluorodeoxyglucoseFEF = forced expiratory flowFTC = follicular thyroid cancerFVC = forced vital capacityGR = granulocytesHb = hemoglobinHR = hazard ratio¹³¹I = iodine-131LN = lymph nodeOR = odds ratioOS = overall survivalPET/CT = positive positron emission tomography/computed tomographyPFS = progression-free survivalPT = partial thyroidectomyPTC = papillary thyroid cancerRAI = radioactive iodineRBC = red blood cellTg = thyroglobulinTgAb = thyroglobulin antibodyTSH = thyroid-stimulating hormoneTT = total thyroidectomyWBC = white blood cellsWBS = whole body scan     

Synthesis and in vitro evaluation of radioiodinated indolequinones targeting NAD(P)H: Quinone oxidoreductase 1 for internal radiation therapy

NAD(P)H: quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase and is highly expressed in many human solid cancers. Because NQO1 can be induced immediately after exposure to ionizing radiation, we aimed to develop an NQO1-targeted radiolabeled agent to establish a novel internal radiation therapy that amplifies the therapeutic effects when combined with external radiation therapy. We designed three NQO1-targeted radioiodinated compounds including two ether linkage compounds ([¹²⁵I]1 and [¹²⁵I]2) and a sulfide linkage compound ([¹²⁵I]3) based on the selective binding of indolequinone analogs to the active site of NQO1 by the stacking effect. These compounds were successfully prepared using an oxidative iododestannylation reaction with high radiochemical yields and purity. In NQO1-expressing tumor cells, [¹²⁵I]1 and [¹²⁵I]2 were readily metabolized to p-[¹²⁵I]iodophenol or m-[¹²⁵I]iodophenol and [¹²⁵I]I⁻, whereas over 85% of the initial radioactivity of [¹²⁵I]3 was observed as an intact form at 1 h after incubation. The cellular uptake of [¹²⁵I]3 was significantly higher than those of [¹²⁵I]1 and [¹²⁵I]2. The uptake of [¹²⁵I]3 was specific and was dependent on the expression of NQO1. These data suggest that the novel NQO1-targeted radioiodinated compound [¹²⁵I]3 could be used as a novel internal radiation agent for the treatment of cancer.     

Effect of Post-Surgical Rai Therapy on Parathyroid Function in Patients with Differentiated Thyroid Cancer

Objective: Radiotherapy with radioactive iodine (RAI) has become a common treatment for postsurgical differentiated thyroid carcinoma (DTC). The objective of this study was to determine the effect of RAI therapy following surgery on the function of the parathyroid glands in DTC patients.Methods: A total of 81 DTC patients who received RAI therapy after surgery were enrolled in the study. The size of the residual thyroid was detected by technetium-99m (^99mTc)-pertechnetate thyroid scan (^99mTc thyroid scan) before RAI therapy. The iodine uptake ability of residual thyroid was evaluated by iodine-131 (¹³¹I) whole-body scan (WBS). All patients were treated with an activity of 3.7 GBq (100 mCi) ¹³¹I. Parathyroid hormone (PTH), serum calcium, phosphorus, and magnesium were evaluated at 1 day before treatment, and at 1 month and 3 months after treatment.Results: The results show that there was no statistically significant difference in blood PTH level observed (P>.05) between 3 time points (pre-treatment, 1 month post-treatment and 3 months post-treatment). The serum calcium and phosphorus did not change significantly (P>.05), but serum magnesium level was elevated after treatment (P<.05). There were no significant differences between PTH changes and sex, age, scores of ^99mTc thyroid scan, scores of ¹³¹I WBS, Tumor (T) stage, and Node (N) stage.Conclusion: RAI therapy following surgery did not significantly affect parathyroid function in DTC patients.Abbreviations: ATA = American Thyroid Association; DTC = differentiated thyroid carcinoma; FT3 = free triiodothyronine; FT4 = free thyroxine; 131I = iodine-131; PTH = parathyroid hormone; RAI = radioiodine; 99mTc = Technetium-99m; TG = thyroglobulin; TNM = Tumor Node Metastasis; TSH = thyroid-stimulating hormone; WBS = whole-body scan     

Tall-Cell Variant Papillary Thyroid Carcinoma Arising from Struma Ovarll

ObjectiveTo present a case of tall-cell variant (TCV) papillary thyroid carcinoma (PTC) arising from Struma ovarii (SO) and to discuss special considerations in the management of this patient.MethodsThe clinical presentation and relevant pathologic features of a patient with PTC-TCV developing from SO are described, and a concise review of literature regarding this topic is also presented.ResultsA 36-year-old woman with a history of stable right ovarian dermoid cyst presented with amenorrhea and was found to have a significantly enlarged right ovary with multiple cysts. Following laparoscopic cystectomy, pathology revealed mature cystic teratoma (SO) with associated PTC-TCV. Based on this finding, she underwent right salpingo-oophorectomy, right pelvic lymph node dissection, and partial omentectomy. Pathology was negative for extra-ovarian disease, and her tumor was staged as pT1pN0M0. Total thyroidectomy was performed in preparation for radioactive iodine (RAI) therapy. A diagnostic iodine-131 (I-131) scan showed residual uptake in the neck with faint uptake in the lower left quadrant of the abdomen and was followed by therapy with 90 mCi of I-131. The patient had an unremarkable course with no clinical or biochemical evidence of disease recurrence to date.ConclusionsThis is to our knowledge the first reported case of TCV-PTC arising from SO. The presence of this aggressive variant of PTC factored into our decision to proceed with thyroidectomy and I-131 ablation, despite the lack of conclusive evidence in the literature. Recent discoveries on the natural history of thyroid-derived TCV-PTC were critical in choosing the appropriate management for this patient’s disease. (Endocr Pract. 2014;20:e24-e27)     

Synthesis and biological effects of new hybrid compounds composed of benzylguanidines and the alkylating group of busulfan on neuroblastoma cells

¹³¹Iodine-labelled (meta-iodobenzyl)guanidine ([¹³¹I]-mIBG) and busulfan [butane-1,4-diylbis(methanesulfonate)] are well-established pharmaceuticals in neuroblastoma therapy. We report the design, synthesis, and testing of hybrid molecules—mBBG and pBBG—which combine key structural features of (meta-iodobenzyl)guanidine and busulfan: they contain a benzylguanidine moiety for accumulating in neuroblastoma cells via the noradrenaline transporter and, in the meta- or para-position, respectively, one of the two identical alkylating motives of busulfan for killing cells. Uptake and toxicity of hybrids mBBG and pBBG in human neuroblastoma cells compared favorably to their ancestors [¹³¹I]-mIBG and busulfan.     

Frequency of Flame Sensor Activation in Public Places after Administration of Radioactive Iodine to Treat Graves Disease: A Recent Survey

Objective: Ultraviolet (UV)-perception-type flame sensors detect gamma rays emitted from iodine 131 (¹³¹I). Explaining the possibility of flame sensor activation to patients when they receive ¹³¹I to treat Graves disease or other ablative purposes is important. We investigate the current situation of flame sensor activation after radioactive iodine (RAI) therapy.Methods: A total of 318 patients (65 males and 253 females) with Graves disease who received RAI therapy at our clinic between November 2007 and June 2014 participated in this study. Patients were given both written and oral explanations regarding the possibility of flame sensor activation. Participants were surveyed with a questionnaire. The following question was asked: “Did the fire alarm (flame sensor) go off when you used a restroom in places like shopping centers within a few days after your isotope therapy?” To those who answered “yes,” we asked where the fire alarm had gone off.Results: Of the 318 patients, 19 (6.0%) answered “yes,” 2 of whom were male while 17 were female. Of the 299 (94.0%) patients who answered “no,” 63 were male and 236 were female. As to the place of restroom sensor activation, shopping centers were reported by 9 patients; supermarkets by 5; airports by 2; and a bookstore, the Kyushu Shinkansen (bullet train), and a hospital by 1 each.Conclusion: Explaining to patients the possibility of flame sensor activation after RAI therapy is important to avoid some complications, especially in security-sensitive areas.Abbreviations:¹³¹I = iodine 131RAI = radioactive iodineUV = ultra-violet     

¿Está de acuerdo nuestra conducta ante el nódulo tiroideo y cáncer diferenciado de tiroides con la guía norteamericana y el consenso europeo?

IntroductionThe aim of this study was to assess the approaches of specialists in Spain to patients with thyroid nodules and differentiated thyroid carcinoma and to compare them with the American guideline and European consensus.Material and methodsWe performed a cross-sectional study based on a questionnaire addressed to clinical endocrinologists specialized in thyroid cancer and specialists in nuclear medicine throughout Spain.ResultsA total of 177 questionnaires were completed, representing an overall response rate of 85%; 74% of responses were from endocrinologists and 24% from physicians active in nuclear medicine; 82% of respondents worked in third-level hospitals, 10% in second level hospitals and the remainder in private practice. Most used ultrasonography and cytology to assess thyroid nodules and collaborated with a group of surgeons expert in thyroid surgery. The majority preferred total or subtotal thyroidectomy in tumors with a diameter of 1 cm or more, and systematic lymph node dissection. Only 43 (24%) preferred prophylactic central lymph node dissection. Eighty-one respondents (45%) would still use whole body scan with ¹³¹I or ¹²³I before ¹³¹I ablation. Follow-up was based on cervical echography and thyroglobulin determination; however, 101 (57%) respondents continued to use diagnostic whole body scan in the follow-up.ConclusionThe approaches of the respondents were mainly in accordance with the guideline and consensus, although some variations were found, especially in the use of whole body scan with ¹³¹I before ablation and in follow-up.     

Factors Associated With Radioactive Iodine Therapy–Acquired Nasolacrimal Duct Obstruction

ObjectiveTo identify factors associated with radioactive iodine (RAI)-acquired nasolacrimal duct obstruction (NLDO).MethodsRetrospective chart review and telephone surveys of patients who received RAI therapy for thyroid carcinoma at an academic institution were conducted. Telephone surveys were used to screen for post-RAI NLDO diagnoses. Databases were reviewed for documented NLDO, demographics, RAI dose, total number of RAI treatments, and sialadenitis. Routine post-RAI whole-body scintigraphy (WBS) images were analyzed for the presence or absence of ¹³¹I sodium iodide (I-131) in the nasolacrimal duct. Intranasal I-131 activity was graded as none, low, moderate, and high; those with moderate or high activity were considered to have “increased” activity. Logistic and ordinal logistic regression models were used to evaluate the associations with NLDO while adjusting for I-131 dose.ResultsOf the 209 patients who completed the survey, 15 (7%) had NLDO diagnoses. Increased intranasal I-131 activity on WBS, presence of nasolacrimal I-131 WBS activity, presence of documented post-RAI sialadenitis, and history of >1 RAI treatment were associated with the development of NLDO from univariate analyses (P ≤ .013). After adjusting for the administered dose of I-131, the presence of sialadenitis and nasolacrimal I-131 activity on WBS were the remaining 2 factors significantly associated with NLDO development (P < .001 and P = .01, respectively).ConclusionsThe presence of sialadenitis and nasolacrimal I-131 activity on WBS are I-131 dose-independent correlative factors for RAI-associated NLDO. Patients with these characteristics should be counseled on their increased risk of NLDO after RAI therapy for thyroid carcinoma.     

Pre-Ablation Thyroglobulin and Thyroglobulin to Thyroid-Stimulating Hormone Ratio may be Associated with Pulmonary Metastases in Children with Differentiated Thyroid Cancer

Objective: Pediatric differentiated thyroid cancer (DTC) frequently presents with extensive disease. We studied the value of pre-ablation thyroglobulin (Tg) and Tg normalized to thyroid-stimulating hormone (TSH) levels in predicting distant metastases in pediatric patients with DTC.Methods: This is a retrospective cohort study of patients <21 years old who underwent thyroidectomy followed by ¹³¹I ablation for DTC at 3 university hospitals over 20 years. Tg levels and the Tg/TSH ratio following surgery but prior to ¹³¹I ablation were assessed. The presence of distant metastatic disease was determined from the postablation whole-body scan.Results: We studied 44 patients with a mean age of 15.2 years (range 7 to 21 years) and mean tumor size of 2.8 cm. Eight patients had distant metastases and had a higher mean pre-ablation Tg value compared to patients without distant metastases (1,037 μg/L versus 93.5 μg/L, P<.01). The pre-ablation Tg/TSH ratio was also associated with the presence of distant metastases: 12.5 ± 18.8 μg/mU in patients with distant metastases versus 0.7 ± 1.8 μg/mU in patients without (P<.01). A nomogram to predict distant metastases yielded areas under the receiver operating characteristic curve of 0.85 for Tg and 0.83 for Tg/TSH ratio.Conclusion: After initial thyroidectomy, elevated preablation Tg and Tg/TSH ratio are associated with distant metastatic disease in pediatric DTC. This may inform the decision to ablate with ¹³¹I, as well as the dosage.Abbreviations:ATA = American Thyroid AssociationCI = confidence intervalDTC = differentiated thyroid cancerOR = odds ratioROC = receiver operating characteristicTg = thyroglobulin     

Long-Term Outcomes of Radioiodine Therapy for Juvenile Graves Disease with Emphasis on Subsequently Detected Thyroid Nodules: A Single Institution Experience from Japan

Objective: To investigate the long-term outcomes of radioiodine therapy (RIT) for juvenile Graves disease (GD) and the ultrasonographic changes of the thyroid gland.Methods: All of 117 juvenile patients (25 males and 92 females, aged 10 to 18 &lsqb;median 16] years) who had undergone RIT for GD at our clinic between 1999 and 2018 were retrospectively reviewed. Each RIT session was delivered on an outpatient basis. The maximum ¹³¹I dose per treatment was 13.0 mCi, and the total ¹³¹I dose per patient was 3.6 to 29.8 mCi (median, 13.0 mCi). ¹³¹I administration was performed once in 89 patients, twice in 26, and three times in 2 patients. Ultrasonography of the thyroid gland was regularly performed after RIT. The duration of follow-up after the initial RIT ranged from 4 to 226 (median 95) months.Results: At the latest follow-up more than 12 months after RIT (n = 111), the patients' thyroid functions were overt hypothyroidism (91%), subclinical hypothyroidism (2%), normal (5%), or subclinical hyperthyroidism (2%). New thyroid nodules were detected in 9 patients, 4 to 17 years after initial RIT. Patients with newly detected thyroid nodules underwent RIT with lower doses of ¹³¹I and had larger residual thyroid volumes than those without nodules. None of the patients were diagnosed with thyroid cancer or other malignancies during the follow-up period.Conclusion: Over a median follow-up period of 95 months (range, 4 to 226 months), RIT was found to be effective and safe in juvenile GD. However, cumulative evidence from further studies is required to confirm the long-term safety of RIT for juvenile GD.Abbreviations: ATD = antithyroid drug; GD = Graves disease; KI = potassium iodide; LT4 = levothyroxine; MMI = methimazole; PTU = propylthiouracil; RAIU = radio-active iodine uptake; RIT = radioiodine therapy; ^99mTc = technetium-99m; TSH = thyrotropin     

Influence of the external and internal radioactive contamination of the body and the clothes on the results of the thyroidal 131I measurements conducted in Belarus after the Chernobyl accident—Part 2: Monte Carlo simulation of response of detectors near the thyroid

This paper describes the calculation of the response of the most common types of radiation detectors that were used within the first few weeks after the Chernobyl accident to determine the activity of ¹³¹I in the thyroids of Belarusian subjects of an epidemiologic study of thyroid cancer. The radiation detectors, which were placed against the necks of the subjects, measured the exposure rates due to the emission of gamma rays resulting from the radioactive decay of ¹³¹I in their thyroids. Because of the external and internal radioactive contamination of the monitored subjects, gamma radiation from many radionuclides in various locations contributed to the exposure rates recorded by the detectors. To estimate accurately the contribution from gamma rays emitted from various internal and external parts of the body, the calibration factors of the radiation detectors, expressed in kBq per µR h^− 1, were calculated, by means of Monte Carlo simulation, for external irradiation from unit activities of 17 radionuclides located on 19 parts of the body, as well as for internal irradiation from the same 17 radionuclides in the lungs, from caesium radionuclides distributed uniformly in the whole body, and from ¹³¹I in the thyroid. The calculations were performed for six body sizes, representative of the age range of the subjects. In a companion paper, the levels of external and internal contamination of the body were estimated for a variety of exposure conditions. The results presented in the two papers were combined to calculate the ¹³¹I activities in the thyroids of all 11,732 Belarusian study subjects of an epidemiologic study of thyroid cancer and, in turn, their thyroid doses.

     

Graves Ophthalmopathy After Radiation Treatment of Thyroid Cancer

ObjectiveTo describe a patient with metastatic thyroid cancer who developed Graves ophthalmopathy after treatment with radioiodine (I 131) and external beam radiation.MethodsWe present a case report that includes clinical, laboratory, and radiologic findings and a brief review of the literature.ResultsA 49-year-old woman who had had a total thyroidectomy and neck dissection followed by I 131 treatment 5 years earlier for papillary thyroid cancer presented for follow-up management after recent neck dissection for recurrent disease. Because she had thyroglobulin antibodies, she was again treated with I 131 after preparation with recombinant human thyroid-stimulating hormone. A post-treatment scan revealed uptake in the right iliac crest. A fludeoxyglucose F 18 positron emission tomography/computed tomography fusion scan revealed osseous metastases in the right pelvis, and external beam radiotherapy was delivered to this area. Approximately 5 months later, she developed periocular swelling and excessive tearing. Magnetic resonance imaging of the orbits revealed enlargement of the extraocular muscles. Serum thyroid-stimulating immunoglobulins were greatly elevated.ConclusionThis case corroborates an earlier report to suggest that radiation-associated thyroid injury in a patient with thyroid cancer may be followed by Graves ophthalmopathy and appearance of thyroid-stimulating immune-globulins in the serum. (Endocr Pract. 2008;14:419-421)     

Genome-Wide Analysis of Barrett's Adenocarcinoma. A First Step Towards Identifying Patients at Risk and Developing Therapeutic Paths

BACKGROUND: Barrett's esophagus metaplasia is the key precursor lesion of esophageal adenocarcinoma. The aim of this study was to find a subset of markers that may allow the identification of patients at risk for esophageal adenocarcinoma, and to determine genes differentially expressed in esophageal squamous cell carcinoma. METHODS: Laser capture microdissection technique was applied to procure cells from defined regions. Genome-wide RNA profiling was performed on esophageal adenocarcinoma (n = 21), Barrett's esophagus (n = 20), esophageal squamous carcinoma (n = 9) and healthy esophageal biopsies (n = 18) using the Affymetrix Human Genome U133plus 2.0 array. Microarray results were validated by quantitative real-time polymerase chain reaction in a second and independent cohort and by immunohistochemistry of two putative markers in a third independent cohort. RESULTS: Through unsupervised hierarchical clustering and principal component analysis, samples were separated into four distinct groups that match perfectly with histology. Many genes down-regulated in esophageal cancers belong to the epidermal differentiation complex or the related GO-group “cornified envelope” of terminally differentiated keratinocytes. Similarly, retinol metabolism was strongly down-regulated. Genes showing strong overexpression in esophageal carcinomas belong to the GO groups extracellular region /matrix such as MMP1, CTHRC1, and INHBA. According to an analysis of genes strongly up-regulated in both esophageal adenocarcinoma and Barrett's esophagus, REG4 might be of particular interest as an early marker for esophageal adenocarcinoma. CONCLUSIONS: Our study provides high quality data, which could serve for identification of potential biomarkers of Barrett's esophagus at risk of esophageal adenocarcinoma progression.