Engineering a HEK-293T exosome-based delivery platform for efficient tumor-targeting chemotherapy/internal irradiation combination therapy.

Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvß3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvß3-overexpressing tumors.

CTLA-4 gene polymorphisms associate with efficacy of postoperative radioiodine-131 for differentiated thyroid carcinoma.

AIM: To investigate the association of CTLA-4 polymorphisms with efficacy of postoperative radioiodine-131 (I-131) treatment for differentiated thyroid carcinoma (DTC). METHODS: A total of 324 DTC patients and 350 healthy individuals were enrolled in our study. Patients received I-131 remnant ablation following surgical resection. Based on the treatment efficacy, patients were divided into the effective (n = 183) and ineffective groups (n = 141). CTLA-4 polymorphisms (+49A>G, CT60A>G and -318C>T) were genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: AG + AA genotype distribution and A allele frequency of +49A>G and CT60A>G polymorphisms were higher in the effective group than the ineffective group. CONCLUSION: +49A>G and CT60A>G polymorphisms were associated with the efficacy of postoperative I-131 treatment for DTC; and they might be bioindicators related to the prognosis of I-131 treatment.

Radioiodine Therapy: Alternative for the Treatment of Complicated Thyroid Ectopia.

Thyroid ectopy is the presence of thyroid tissue outside its normal cervical location. Clinical manifestations of thyroid ectopy are varied. The latter complications can be life-threatening. Emergency treatment is often surgical or endoscopic. We report a case of a 26-year-old man with tracheal thyroid ectopy, complicated by respiratory distress, in whom conventional treatments were not feasible. The patient was treated with radioiodine-131 administered in liquid form. The final control showed the complete resolution of the intra-tracheal mass. Intra-tracheal thyroid ectopy is a rare anomaly in which surgery is the traditional treatment. In certain cases where surgery is not feasible or refused, treatment with iodine-131 is a safe and effective alternative for the removal of ectopic thyroid tissue. The aim of our work is to show the significant efficiency of radioiodine therapy as an alternative for the treatment of complicated thyroid ectopia.

Vitamin D receptor polymorphisms associate with the efficacy and toxicity of radioiodine-131 therapy in patients with differentiated thyroid cancer.

BACKGROUND: Radioiodine-131 (I-131) therapy is the common postoperative adjuvant therapy for differentiated thyroid cancer (DTC) However, methods to evaluate the efficacy and toxicity of I-131 on DTC are still lacking. OBJECTIVE: To evaluate the association between vitamin D receptor (VDR) gene polymorphisms and the efficacy and toxicity of I-131 in DTC patients. METHODS: A total of 256 DTC patients who received I-131 therapy were enrolled. The patients were divided into effective group and ineffective group. 4 single nucleotide polymorphisms (SNPs) (rs7975232, rs731236, rs1544410 and rs10735810) of VDR were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) Cell counting kit-8 (CCK-8) and flow cytometry were used to detect the proliferation and apoptosis of thyroid cancer cells. RESULTS: Patients in effective group had more CC genotype of rs7975232 and GG genotype of rs10735810 compared with patients in ineffective group They were also independent factors for influencing the efficacy of I-131. PTC-1 and FTC-133 cells transfected with CC genotype of rs7975232 showed lower proliferative activity and higher apoptosis rate after being treated with I-131 In addition, patients with CC genotype at rs7975232 had fewer adverse reactions after I-131 treatment. CONCLUSIONS: VDR gene polymorphisms may be associated with the efficacy and toxicity of I-131 in DTC patients, which will help to personalize the treatment for patients.

Radioiodine-131 Therapy Used for Differentiated Thyroid Cancer Can Impair Titanium Dental Implants: An In Vitro Analysis.

BACKGROUND: The aim was to assess, in vitro, the effects of radioiodine-131 (I-131) on the structure of titanium implants. MATERIAL AND METHODS: A total of 28 titanium implants were divided into 7 groups (n = 4) and irradiated at 0, 6, 12, 24, 48, 192 and 384 hours. At the end of the experiment, each sample was investigated via scanning electron microscopy (SEM) and electrochemical measures. RESULTS: The control sample revealed a smooth and compact surface. The small micro-sized porosity is slightly visible at the macroscopic level, but the precise details cannot be observed. A mild exposure to the radioactive solution for 6 to 24 h showed a good preservation of the macro-structural aspects such as thread details and surface quality. Significant changes occurred after 48 h of exposure. It was noticed that the open-circuit potential (OCP) value of the non-irradiated implants move toward more noble potentials during the first 40 min of exposure to the artificial saliva and then stabilizes at a constant value of -143 mV. A displacement of the OCP values toward more negative values was observed for all irradiated implants; these potential shifts are decreasing, as the irradiation period of the tested implants increased. CONCLUSION: After exposure to I-131, the structure of titanium implants is well preserved up to 12 h. The eroded particles start to appear in the microstructural details after 24 h of exposure and their numbers progressively increase up to 384 h after exposure.

Radioiodine treatment in hyperthyroid cats: insights into the characteristics of owners and their cats, and owner motivation and perceptions.

OBJECTIVES: Radioiodine (131I) therapy is the most appropriate treatment option for many hyperthyroid cats, as it is minimally invasive and often curative. Nevertheless, 131I treatment is not always pursued by owners. Hence, it is important to obtain more insight into owner satisfaction during and after 131I treatment, and their decision-making process. In this study, we describe the characteristics of owners and their hyperthyroid cats referred for 131I therapy, and determine owners' motivation and how they experienced the 131I treatment of their cat. METHODS: A survey was sent to owners whose cats underwent 131I therapy (n = 1071) between 2010 and 2017 at Ghent University. The survey contained 35 questions with tick-box or free-text answer options concerning family situation, pet insurance, previous therapy, comorbidities, motivation for 131I therapy and owner perception of this treatment. RESULTS: In total, 438 owners completed 94% or more of the questionnaire. Over half of the cats (55%) had received previous medical, dietary or surgical treatment. Motivations for changing the initial therapy to 131I therapy included difficulties in administering medication (31%), insufficient improvement in clinical signs (23%), side effects (16%) and following the referring veterinarian's advice (16%). Almost a fifth of owners (18%) were not informed about the existence of 131I therapy by their veterinarian and found information on 131I treatment online or through friends. Hospitalising their cat was very distressing for 17% of owners. Most owners (92%) were satisfied with the treatment. Reasons for dissatisfaction were insufficient communication, iatrogenic hypothyroidism, persistent hyperthyroidism and comorbidities post-treatment. CONCLUSIONS AND RELEVANCE: Our study stresses the importance of communication regarding the possible outcome of 131I treatment, the importance of managing underlying comorbidities before treatment and anticipating the stress of owners during their cat's hospitalisation period. The results of this study could help in improving client communication when advising on 131I treatment.

Effect of Lugol's solution on 131I therapy efficacy in Graves' disease.

PURPOSE: Lugol's solution could control thyroid function and suppress 131I uptake in hyperthyroidism. This study aimed to investigate the appropriate time to withdraw Lugol's solution before 131I therapy (RIT) in Graves' disease (GD) patients, and how this should influence 131I uptake and RIT outcome. METHODS: Two groups (125 cases and 1805 cases) of GD patients received RIT, who were pre-treated with and without Lugol's solution (RI-CI group and RI group). The RI-CI group was further divided into the following sub-groups depending on the duration span between Lugol's solution withdrawal and RIT: sub-group A, 4-7 d (n = 49); sub-group B, 8-14 d (n = 41); and sub-group C, 15-30 d (n = 35). The highest radioactive iodine uptake rate (RAIUmax), effective half-life (Teff), TRAb, and free triiodothyronine (FT3) and free thyroxine (FT4) levels were compared, and therapeutic outcome was evaluated. RESULTS: There were no significant differences in RAIUmax, TRAb, and Teff among the four sub-groups (P > 0.05). Both FT3 and FT4 levels in sub-groups A and B were lower than those in group RI and sub-group C (P < 0.05). The outcome of non-hyperthyroidism (euthyroidism + hypothyroidism) in groups RI-CI and RI was significantly different at post-RIT month 1 and 3 (P < 0.05). However, intergroup differences at 6 and 12 months were not significant (P > 0.05). CONCLUSIONS: Withdrawal of Lugol's solution 4-7 or 8-14 d before RIT does not influence 131I uptake and RIT efficacy in GD. Moreover, in order to avoid a rapid increase in thyroid hormone levels at the same time, Lugol's solution should be withdrawn 4-7 d before RIT.

Evaluation of radioiodinated ethopabate as a potential tumor targeting agent.

Overexpression of folate synthesis and folate receptor in a wide variety of tumors was reported. As a result, folate derivatives have emerged as a potential candidate for tumor imaging and therapy. Ethopabate is a structural analogue of para-aminobenzoic acid (PABA), a precursor of folic acid. Ethopabate was radiolabeled with radioiodine-131 (131I) via direct electrophilic substitution reaction. Several factors that might affect the radiolabeling yield were studied. Paper chromatography was utilized for testing and evaluation of [131I]iodoethopabate, and HPLC was used as a co-chromatographic tool to confirm the radiochemical yield. The biodistribution of [131I]iodoethopabate in normal and tumor-bearing mice was investigated. The radioiodination of ethopabate resulted in a radiochemical yield of 93.70 ± 0.19%. The biodistribution data revealed that [131I]iodoethopabate was taken up by tumors with promising target/non-target (T/NT) ratios. Where, the tumor to-blood ratios were 3.30 ± 0.40 and 4.06 ± 0.10 at 1 and 4 h post injection, respectively. As a result of these findings, [131I]iodoethopabate appears to have excellent tumor uptake and adequate stability to be used for diagnostic purpose in the future.

The Value of 99mTc-MIBI SPECT/CT in the Postoperative Assessment of Patients with Differentiated Thyroid Carcinoma.

BACKGROUND: The therapeutic approaches of differentiated thyroid carcinoma (DTC) are surgery, ablation therapy with the postoperative use of radioiodine-131 (131I), and thyroid-stimulating hormone (TSH) suppression therapy. After the surgical therapy, the patient should be assessed for remnants/metastases. OBJECTIVE: The purpose of this research was to investigate the role of technetium-99m-methoxyisobutylisonitrile (99mTc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) in the postoperative management of patients with DTC. METHODS: The study comprised 22 DTC patients (13 women, 9 men; mean age 46.55 ± 13.27 y) who underwent a total thyroidectomy previously. All patients were investigated for thyroid remnants/ metastases by99mTc-MIBI SPECT/CT, posttherapy 131I whole-body scan (WBS) and ultrasound (US). Serum TSH, thyroglobulin and anti-Tg antibody levels were measured. Results of imaging modalities and laboratory measurements were compared with each other. RESULTS: 99mTc-MIBI SPECT/CT, 131I WBS and US respectively demonstrated thyroid remnants in 15 (68.18%), 22 (100%) and 14 (63.63%) of all patients and metastatic lymph nodes in 8 (100%), 6 (75%) and 6 (75%) of the 8 patients with lymph node metastases.99mTc-MIBI SPECT/CT also demonstrated lung metastases in 2 patients (9.09% of all patients). The same result was obtained with 131I WBS. CONCLUSION: The findings of this study show that 99mTc-MIBI SPECT/CT can be effective for detecting metastases in patients with DTC who underwent surgery prior to 131I therapy.

Effect of COVID-19 pandemic on diagnosis and treatment of thyroid cancer in Brazil.

Introduction: The COVID-19 pandemic delayed the diagnosis, treatment, and follow-up visits of patients with thyroid cancer. However, the magnitude with which these restrictions affected the Brazilian health care is still unknown. Methods: Retrospective analysis of thyroid cancer-related procedures performed in the Brazilian public health system from 2019 to 2021. Data were retrieved from the Department of Informatics of the Unified Health System (DATASUS). The following procedures were evaluated: fine-needle aspiration biopsies (FNABs), oncologic thyroidectomies, and radioiodine (RAI) therapies for thyroid cancer. The year of 2019 served as baseline control. Results: Compared with 2019, FNABs, oncologic thyroidectomies, and RAI therapies performed in 2020 decreased by 29%, 17% and 28%, respectively. In 2021, compared with 2019, FNABs increased by 2%, and oncologic thyroidectomies and RAI therapies decreased by 5% and 25%, respectively. Most pronounced reductions were observed in the first months of the pandemic. In April 2020, FNABs decreased by 67%, oncologic thyroidectomies by 45%, and RAI therapies by 75%. In 2021, RAI therapies were the only procedure with a statistically significant decrease. Conclusion: The restrictions to public health care during the COVID-19 pandemic resulted in a significant reduction in diagnostic and treatment procedures for thyroid cancer in Brazil. The effects of these transitory gaps in thyroid cancer care, due to COVID-19, are still unclear.

The Side Effects of Therapeutic Radioiodine-131 on the Structure of Enamel and Dentin in Permanent Human Teeth.

Radioiodine-131 (I-131) is an essential therapy for patients with differentiated thyroid carcinomas (DTC). Generally, I-131 is safe and well tolerated, but patients may present early or late complications in the oral and maxillofacial areas. Thus, the aim of this study was to evaluate in-vitro, the alteration of enamel and dentin after I-131 exposure using histopathological assessment, scanning electron microscopy (SEM) and atomic force microscopy (AFM). For I-131 irradiation, an in-vitro protocol was used that simulates the procedure for irradiation therapy performed for patients with DTCs. A total of 42 teeth were divided into seven groups (n = 6) and irradiated as follows: control, irradiation groups (3, 6, 12, 36, 48 h, 8 days). Histological changes were observed at 48 h (enamel surface with multifocal and irregular areas) and at 8 days (enamel surface with multiple, very deep, delimited cavities). SEM imaging revealed the enamel destruction progresses along with the treatment time increasing. The alterations are extended into the enamel depth and the dislocated hydroxyapatite debris is overwhelming. The enamel-dentine interface shows small gaps after 6 h and a very well developed valley after 12 h; the interface microstructure resulted after 8 days is deeply altered. The AFM imaging shows that I-131 affects the protein bond between hydroxyapatite nano-crystals causing loss of cohesion, which leads to significant increasing of nano-particles diameter after 6 h. In conclusion, both enamel and dentin appear to be altered between 12 and 48 h and after 8 days of treatment are extended in depth.

Improved Patient Dosimetry at Radioiodine Therapy by Combining the ICRP Compartment Model and the EANM Pre-Therapeutic Standard Procedure for Benign Thyroid Diseases.

Radioactive iodine is commonly used for the treatment of different thyroid conditions since the 1940s. The EANM has developed a standard pre-therapeutic procedure to estimate patient specific thyroid uptake at treatment of benign thyroid diseases. The procedure which models the time dependent fractional thyroid uptake is based on a two-compartment fitting system, one representing the thyroid and the other the blood. The absorbed dose is however only estimated for the thyroid and not for any other organ in the body. A more detailed biokinetic model for iodine is given by the ICRP and includes an iodide transport in the whole body. The ICRP model has 30 different compartments and 48 transfer coefficients to model the biokinetics of iodide and to model different transfer for inorganic iodide and organic iodine. The ICRP model is a recirculation iodine model, and the optimization is performed on the whole model and not exclusively on the thyroid as in the EANM procedure. Combining the EANM method and the ICRP model gives both patient specific estimations of thyroid uptake and retention and include most organs in the body. The new software gives both an improved patient specific dosimetry for the thyroid and an estimation of the absorbed dose to non-target organs and tissues like kidneys, urinary bladder, stomach wall, and uterus. Using the method described in this paper, the repercussions on the daily routines will be minimal.

Radioiodination and in vivo assessment of the potential of newly synthesized pyrrolizine-5-carboxamides derivative in tumor model.

Recently, pyrrolizine derivatives have been reported to possess numerous anticancer activities. In a previous study, (EZ)-6-((4-chlorobenzylidene)-amino)-7-cyano-N-(p-tolyl)-2,3-dihydro-1H-pyrrolizine carboxamide (EZPCA) compound was synthesized and the cytotoxic activity of EZPCA toward COX-2 enzyme (overexpressed in cancer cells) was reported. In order to assess the suitability of this compound as a promising pilot structure for in vivo applications, EZPCA was radiolabeled with radioiodine-131 (131I) and various factors affecting radiolabeling process were studied. Quality control studies of [131I]iodo-EZPCA were performed using paper chromatography and HPLC was used as a co-chromatographic technique for confirming the radiochemical yield. Biodistribution studies of [131I]iodo-EZPCA were undertaken in normal and tumor bearing mice. The radiochemical yield percentage of [131I]iodo-EZPCA was 94.20 ± 0.12%. The biodistribution results showed evident tumor uptake of [131I]iodo-EZPCA with promising target/non-target (T/NT) ratios. As a conclusion, these data suggest that [131I]iodo-EZPCA had high binding efficiency, high tumor uptake and sufficient stability to be used be used in diagnostic studies.

Epidemiology, Natural History, Risk Factors, and Prevention of Graves' Orbitopathy.

GO is the most frequent extrathyroidal manifestation of Graves' disease, although it may rarely occur in euthyroid/hypothyroid patients with chronic autoimmune thyroiditis. It is a relatively infrequent disorder, and men tend to have more severe ocular involvement at an older age. The prevalence of GO is lower than in the past among patients with recent onset Graves' hyperthyroidism, and moderate-to-severe forms requiring aggressive treatments are no more than 5-6% of all cases of GO. After an initial inflammatory (active) phase and a phase of stabilization (plateau phase), GO tends to improve and eventually inactivates (inactive or burnt-out phase). Minimal-to-mild GO often remits spontaneously, but complete restitutio ad integrum almost never occurs when GO is more than mild. Several risk factors contribute to its development on a yet undefined genetic background. Cigarette smoking is the most important of them. Early diagnosis, control and removal of modifiable risk factors, early treatment of mild forms of GO may effectively limit the risk of progression to more severe forms, which have a profound and dramatic impact on the quality of life of affected individuals, and remain a therapeutic challenge, often requiring long-lasting and multiple medical and surgical therapies.

A rare case of minimally invasive follicular thyroid cancer with intraluminal superior vena cava and right atrium metastases.

Follicular thyroid cancers are known to spread hematogenously to the bones and lungs and rarely presenting with massive angioinvasion. We report a case of a middle-aged female who had undergone total thyroidectomy for minimally invasive follicular thyroid cancer with angioinvasion in 2014. She was noted to have a large tumor thrombus extending from the superior vena cava to the right atrium on whole body scan post-Iodine-131 (131I) remnant ablation therapy. We discuss the various imaging modalities, treatment options, and difficulties in managing such massive angioinvasion in patients with well-differentiated thyroid cancers.

Impact factors for the outcome of the first 131I radiotherapy in patients with papillary thyroid carcinoma after total thyroidectomy.

OBJECTIVE: To investigate the impact factors of the outcome of the first 131I treatment in patients with papillary thyroid carcinoma (PTC) after total thyroidectomy. METHODS: Three hundred and fifty-three patients [256 females, 97 males, average age (43.58 ± 12.33 years)] with PTC after total thyroidectomy who underwent 131I treatment from July 2014 to August 2017 were retrospectively analyzed. Curative efficacy of 131I treatment was assessed 6 months afterward. Therapeutic outcome was determined according to thyrotropin (TSH)-stimulated thyroglobulin (sTg) level, 131I diagnostic whole-body scan (Dx-WBS) after 131I treatment and other imaging modalities. Twelve possible factors affecting the therapeutic outcome of 131I treatment including patients' gender, age, interval between surgery and 131I treatment, primary tumor size and extrathyroidal extension (ETE), number and range of primary tumor lesions, result of 99mTcO4- thyroid scan, number of metastatic lymph nodes (LN), pre-treatment laboratory measurements [TSH, sTg and Tg antibody (TgAb)], therapeutic dose of 131I and result of 131I post-treatment whole-body scan (Rx-WBS) were analyzed using univariate and multivariate logistic regression. The receiver operator characteristic (ROC) curve and diagnostic cutoff value were analyzed to evaluate the predictive value of the significant quantitative impact factors for the outcome of 131I treatment. RESULTS: The curative rate of the first 131I treatment in patients with PTC after total thyroidectomy was 62.32% (220/353). Univariate analysis indicated that gender, age, number and range of primary tumor lesions, number of metastatic LN, pre-treatment sTg and TgAb, therapeutic dose of 131I and result of 131I Rx-WBS (all P < 0.05) were significant factors affecting the outcome of 131I treatment. Multivariate analysis revealed that the numbers of metastatic LN (regression coefficient = 1.170) and sTg (regression coefficient = 0.280) were significant impact factors (all P < 0.001). The regression equation was: Logit P = - 3.997 + 1.170 × number of metastatic LN + 0.280 × sTg (χ2 = 210.68, P < 0.001). Taking sTg as a predictive factor for the outcome of the first 131I treatment, the area under the curve (AUC) of ROC for sTg was 0.917 (95% CI 0.890-0.944). The cutoff value of sTg was 2.69 ng/mL with a sensitivity of 92.48% (123/133) and specificity of 74.09% (163/220). CONCLUSION: Patients with PTC after total thyroidectomy with low pre-treatment sTg level and few lymph node metastases are more likely to be cured by the first 131I treatment.

Differentiated Thyroid Cancer, From Active Surveillance to Advanced Therapy: Toward a Personalized Medicine.

Differentiated thyroid cancer (DTC) is the most frequent endocrine malignancy and represents the most rapidly increasing cancer diagnosis worldwide. In the last 20 years, this increase has been mostly due to a higher detection of small papillary thyroid cancers, with doubtful effects on patients' outcome. In fact, despite this growth, cancer-related death remained stable over the years. The growing detection of microcarcinomas associated to the indolent behavior of these cancers led to the development of strategies of active surveillance in selected centers of different countries. Moreover, toward a more personalized approach in the management of DTC patients, surgical treatments became more conservative, favoring less extensive options in patients at low risk of recurrence. The rise in lobectomy in low-risk cases and the need to avoid further therapies, with controversial impact on recurrences and cancer-related death in selected intermediate risk cases, led to reconsider the use of radioiodine treatment, too. Since clinicians aim to treat different patients with different modalities, the cornerstone of DTC follow-up (i.e., thyroglobulin, thyroglobulin autoantibodies, and neck ultrasound) should be interpreted consistently with this change of paradigm. The introduction of novel molecular target therapies (i.e., tyrosine kinase inhibitors), as well as a better understanding of the mechanisms of immune checkpoint inhibitor therapies, is radically changing the management of patients with advanced DTC, in whom no treatment option was available. The aim of this review is to analyze the most recent developments of the management of DTC, focusing on several key issues: active surveillance strategies, initial treatment, dynamic risk re-stratification, and therapeutic options in advanced DTC.

Clinical outcomes and associated factors of radioiodine-131 treatment in differentiated thyroid cancer with cervical lymph node metastasis.

Cervical lymph node metastasis (CLNM) is common in differentiated thyroid cancer (DTC). Radioiodine-131 (131I) treatment is recommended for the removal of residual thyroid tissue following thyroidectomy. To date, the effect of 131I therapy on the outcomes of patients with DTC with CLNM is unclear. The aim of the present study was to evaluate the final outcome of patients with DTC with CLNM according to 131I administration, and to analyze the factors that may affect clinical outcomes. A total of 357 patients with DTC with CLNM were recruited and divided into three groups: Those who received 2, 3 or 4 doses of 131I therapy, respectively. Successful ablation was defined as levels of stimulated serum thyroglobulin <2 ng/ml in the absence of CLNM. The rates of successful ablation were 80.35 (229/285), 76.36 (42/55) and 70.59% (12/17) for patients who received 2, 3 and 4 doses, respectively. The patients with DTC with CLNM who were <45 years old, with tumor sizes <2 cm, solitary nodules and TNM stage I-II disease exhibited significantly higher rates of successful ablation compared with the patients who were ≥45 years old, with tumor size ≥2 cm, multiple nodules and stage III-IV disease. Multivariate analyses revealed that tumor size, number of nodules and TNM stage were independent risk factors associated with successful ablation in patients with DTC with CLNM who received 2 doses of 131I therapy. 131I administration is a useful therapy to eradicate cervical lymph node metastasis in patients with DTC, and may be preferentially indicated in patients with DTC with CLNM who are aged <45 years, with tumor sizes <2 cm, solitary nodules and lower TNM stages, in order to control and prevent recurrence and/or metastases.

Effects of Radioiodine Treatment on Salivary Gland Function in Patients with Differentiated Thyroid Carcinoma: A Prospective Study.

Complaints of a dry mouth (xerostomia) and sialoadenitis are frequent side effects of radioiodine treatment in differentiated thyroid cancer (DTC) patients. However, detailed prospective data on alterations in salivary gland functioning after radioiodine treatment (131I) are scarce. Therefore, the primary aim of this study was to prospectively assess the effect of high-activity radioiodine treatment on stimulated whole saliva flow rate. Secondary aims were to study unstimulated whole and stimulated glandular (i.e., parotid and submandibular) saliva flow rate and composition alterations, development of xerostomia, characteristics of patients at risk for salivary gland dysfunction, and whether radioiodine uptake in salivary glands on diagnostic scans correlates to flow rate alterations. METHODS: In a multicenter prospective study, whole and glandular saliva were collected both before and 5 mo after radioiodine treatment. Furthermore, patients completed the validated xerostomia inventory. Alterations in salivary flow rate, composition, and xerostomia inventory score were analyzed. Salivary gland radioiodine uptake on diagnostic scans was correlated with saliva flow rate changes after radioiodine treatment. RESULTS: Sixty-seven patients (mean age ± SD, 48 ± 17 y; 63% women, 84% underwent ablation therapy) completed both study visits. Stimulated whole saliva flow rate decreased after ablation therapy (from 0.92 [interquartile range, 0.74-1.25] to 0.80 [interquartile range, 0.58-1.18] mL/min, P = 0.003), as well as unstimulated whole- and stimulated glandular flow rates (P < 0.05). The concentration of salivary electrolytes was similar at both study visits, whereas the output of proteins, especially amylase (P < 0.05), was decreased. The subjective feeling of dry mouth increased (P = 0.001). Alterations in saliva flow rate were not associated with semiquantitatively assessed radioiodine uptake in salivary glands on diagnostic scans. For the small cohort of patients undergoing repeated radioiodine therapy, we could not demonstrate alterations in salivary parameters. CONCLUSION: We prospectively showed that salivary gland function is affected after high-activity radioiodine ablation therapy in patients with DTC. Therefore, more emphasis should be placed on salivary gland dysfunction during follow-up for DTC patients receiving high-activity radioiodine treatment.

Predictive value of pyramidal lobe, percentage thyroid uptake and age for ablation outcome after 15 mCi fixed dose of radioiodine-131 in Graves' disease.

PURPOSE: The purpose was to find out the efficacy of fixed 15 mCi radioactive iodine-131 (RAI) dose and predictive values of various factors for inducing hypothyroidism in Graves' disease (GD). MATERIALS AND METHODS: Retrospective study conducted from January 2012 till August 2014. Patients with GD who had a technetium-99m thyroid scan, thyroid antibodies, received fixed 15 mCi RAI and did follow endocrine clinics for at least 6 months were selected. RAI was considered successful if within 6 months of RAI therapy patients developed hypothyroidism. RESULTS: Of the 370 patients with GD who had RAI during study period, 210 (57%) qualified study criteria. Mean age of patients was 48 ± 15 years with female: male ratio of 69:31, positive thyroid antibodies in 61%, means thyroid uptake of 15.09 ± 11.23%, and presence of pyramidal lobe in 40% of total population. Hypothyroidism was achieved in 161 (77%) patients while 49 (23%) patients failed to achieve it (remained either hyperthyroid or euthyroid on antithyroid medication). Patients who became hypothyroid were significantly younger with higher proportion of presence of thyroid antibodies and pyramidal lobe and lower percentage thyroid uptake than those who failed. Multiple logistic regression analysis revealed that age (odds ratio; OR = 2.074), pyramidal lobe (OR = 3.317), thyroid antibodies (OR = 8.198), and percentage thyroid uptake (OR = 3.043) were found to be significant prognostic risk factors for post-RAI hypothyroidism. Gender was found to have nonsignificant association with the development of hypothyroidism. Receiver operating characteristic analysis revealed age <42 years and thyroid uptake <15% as threshold values for the development of post-RAI hypothyroidism. CONCLUSION: We conclude that fixed (15 mCi) RAI dose is highly effective in rendering hypothyroidism in patients with GD. Age (≤42 years), thyroid uptake (≤15%) and presence of pyramidal lobe are strong predictors of hypothyroidism and must be considered for selecting optimal RAI dose.