Salivary, lacrimal and nasal (SALANS) measure to assess side effects following radioactive iodine treatment: development, psychometric properties, and factor structure.

PURPOSE: This study aimed to develop and psychometrically evaluate a patient-reported outcome measure (PROM), SAlivary, LAcrimal, NaSal (SALANS), to document patients' symptoms after radioactive iodine (RAI) treatment for differentiated thyroid cancer (DTC). METHODS: We generated and iteratively revised SALANS items based on expert input, focus group discussions and feedback from cognitive testing (n = 17). We administered an initial SALANS measure with 39 items to patients diagnosed with DTC in the past two years (n = 105). Exploratory factor analysis (EFA) examined the factor structure of the SALANS items. We assessed the consistency reliability and related the total and subscale scores of the final SALANS to existing PROMs to assess validity. RESULTS: The final SALANS consisted of 33 items and six subscales (sialadenitis, taste, xerostomia, dry eyes, epiphora, and nasal) with six factors extracted by EFA. The six subscales demonstrated good internal reliability (α range = 0.87-0.92). The SALANS total score showed good convergent validity with the Xerostomia Inventory (r = 0.86) and good discriminant validity with a measure of spirituality (r = - 0.05). The mean SALANS total score was significantly higher (d = 0.5, p < 0.04) among patients who had RAI compared to those who did not have RAI. CONCLUSION: Preliminary evidence suggests that SALANS is a novel and reliable PROM to assess the type and frequency all symptoms experienced after RAI treatment for DTC. Future work is needed to further validate and develop the scale.

Immunotherapy-Associated Hypothyroidism: Comparison of the Pre-Existing With De-Novo Hypothyroidism.

Background: Immunotherapy has revolutionized the treatment of solid malignancies, but is associated with endocrine-related adverse events. This study aims to dissect the natural course of immunotherapy-induced hypothyroidism and provide guidance regarding diagnosis and management in patients with and without pre-existing hypothyroidism. Methods: A retrospective analysis was conducted using patients who received immunotherapy between 2010-2019 within a multicenter hospital system. Participants were separated in three groups-those with pre-existing hypothyroidism, those who developed primary hypothyroidism and those with hypophysitis within a year of their first immunotherapy. Serial effects of immunotherapy on thyroid function tests (TFTs) and levothyroxine dosing were evaluated. Results: 822 patients were screened, with 85 determined to have pre-existing hypothyroidism, 48 de-novo primary hypothyroidism and 12 de-novo hypophysitis. All groups displayed fluctuations in TFTs around weeks 6-8 of treatment. In the pre-existing hypothyroidism group, the levothyroxine dose was higher at 54 weeks than at baseline with the difference showing a trend towards statistical significance (p=0.06). The observed mean levothyroxine dose was significantly lower than the mean calculated weight-based dose for all groups. This finding was most clinically significant for the de-novo hypophysitis group (mean difference: -58.3 mcg, p<0.0001). The mean 0.9 mcg/kg levothyroxine dose at week 54 for the de-novo hypophysitis group was statistically lower than the other groups (p=0.009). Conclusion: It is reasonable to screen with TFTs every 4 weeks, and space out TFTs surveillance to every 12 weeks after week 20. Our findings suggest a more conservative approach for levothyroxine dosing in those developing de-novo hypothyroidism, especially hypophysitis, such as initiating at 0.9-1.2 mcg/kg.

Metastatic Differentiated Thyroid Cancer Survival Is Unaffected by Mode of Preparation for 131I Administration.

Context: Recombinant human thyrotropin (rhTSH) is currently not Food and Drug Administration approved for the treatment of high-risk patients with differentiated thyroid cancer (DTC). Objective: The goal of our study was to compare the outcomes in higher-risk patients with metastatic DTC prepared for radioiodine (RAI) therapy with rhTSH vs thyroid hormone withdrawal (THW). Methods: A retrospective chart review was performed of patients with metastatic DTC in follow-up at MedStar Washington Hospital Center and MedStar Georgetown University Hospital from 2009 to 2017. Patients were divided according to their preparation for RAI therapy, with assessment of progression-free survival (PFS) and overall survival (OS). Results: Fifty-five patients with distant metastases (16 men, 39 women) were prepared for RAI therapy exclusively either with rhTSH (n = 27) or with THW (n = 28). There were no statistically significant differences between the groups regarding clinicopathological features and history of RAI therapies. The median follow-up time for patients with rhTSH-aided therapies was 4.2 years (range, 3.3-5.5 years) and for patients with THW-aided therapies was 6.8 years (range, 4.2-11.6 years) (P = .002). Multivariate analysis showed that the method of thyrotropin stimulation was not associated with a difference in PFS or OS. Conclusion: As has been shown previously for low-risk DTC, this study indicates that the mode of preparation for RAI therapy does not appear to influence the outcomes of patients with metastatic DTC. PFS and OS were similar for patients with THW-aided or rhTSH-aided RAI therapies.

COVID-19 and Thyroid Diseases: A Bidirectional Impact.

CONTEXT: COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has become the most lethal and rapidly moving pandemic since the Spanish influenza of 1918-1920, is associated with thyroid diseases. METHODS: References were identified through searches of PubMed and MEDLINE for articles published from Jan 1, 2019 to February 19, 2021 by use of the MeSH terms "hypothyroidism", "hyperthyroidism", "thyroiditis", "thyroid cancer", "thyroid disease", in combination with the terms "coronavirus" and "COVID-19". Articles resulting from these searches and references cited in those articles were reviewed. RESULTS: Though preexisting autoimmune thyroid disease appears unlikely to render patients more vulnerable to COVID-19, some reports have documented relapse of Graves' disease (GD) or newly diagnosed GD about 1 month following SARS-CoV-2 infection. Investigations are ongoing to investigate molecular pathways permitting the virus to trigger GD or cause subacute thyroiditis (SAT). While COVID-19 is associated with non-thyroidal illness, it is not clear whether it also increases the risk of developing autoimmune hypothyroidism. The possibility that thyroid dysfunction may also increase susceptibility for COVID-19 infection deserves further investigation. Recent data illustrate the importance of thyroid hormone in protecting the lungs from injury, including that associated with COVID-19. CONCLUSION: The interaction between the thyroid gland and COVID-19 is complex and bidirectional. COVID-19 infection is associated with triggering of GD and SAT, and possibly hypothyroidism. Until more is understood regarding the impact of coronavirus on the thyroid gland, it seems advisable to monitor patients with COVID-19 for new thyroid disease or progression of preexisting thyroid disease.

A Joint Statement from the American Thyroid Association, the European Association of Nuclear Medicine, the European Thyroid Association, the Society of Nuclear Medicine and Molecular Imaging on Current Diagnostic and Theranostic Approaches in the Management of Thyroid Cancer.

Background: The American Thyroid Association (ATA), the European Association of Nuclear Medicine, the European Thyroid Association, and the Society of Nuclear Medicine and Molecular Imaging have established an intersocietal working group to address the current controversies and evolving concepts in thyroid cancer management and therapy. The working group annually identifies topics that may significantly impact clinical practice and publishes expert opinion articles reflecting intersocietal collaboration, consensus, and suggestions for further research to address these important management issues. Summary: In 2019, the intersocietal working group identified the following topics for review and interdisciplinary discussion: (i) perioperative risk stratification, (ii) the role of diagnostic radioactive iodine (RAI) imaging in initial staging, and (iii) indicators of response to RAI therapy. Conclusions: The intersocietal working group agreed that (i) initial patient management decisions should be guided by perioperative risk stratification that should include the eighth edition American Joint Committee on Cancer staging system to predict disease specific mortality, the modified 2009 ATA risk stratification system to estimate structural disease recurrence, with judicious incorporation of molecular theranostics to further refine management recommendations; (ii) diagnostic RAI scanning in ATA intermediate risk patients should be utilized selectively rather than being considered mandatory or not necessary for all patients in this category; and (iii) a consistent semiquantitative reporting system should be used for response evaluations after RAI therapy until a reproducible and clinically practical quantitative system is validated.

Do Molecular Profiles of Primary Versus Metastatic Radioiodine Refractory Differentiated Thyroid Cancer Differ?

Management of metastatic radioiodine refractory differentiated thyroid cancer (DTC) can be a therapeutic challenge. Generally, little is known about the paired molecular profile of the primary tumor and the metastases and whether they harbor the same genetic abnormalities. The present study compared the molecular profile of paired tumor specimens (primary tumor/metastatic sites) from patients with radioiodine refractory DTC in order to gain insight into a possible basis for resistance to radioiodine. Twelve patients with radioiodine refractory metastases were studied; median age at diagnosis of 61 years (range, 25-82). Nine patients had papillary TC (PTC), one had follicular TC (FTC), and two had Hürthle cell TC (HTC). Distant metastases were present in the lungs (n = 10), bones (n = 4), and liver (n = 1). The molecular profiling of paired tumors was performed with a panel of 592 genes for Next Generation Sequencing, RNA-sequencing, and immunohistochemistry. Digital microfluidic PCR was used to investigate TERT promoter mutations. The genetic landscape of all paired sites comprised BRAF, NRAS, HRAS, TP53, ATM, MUTYH, POLE, and NTRK genes, including BRAF and NTRK fusions. BRAF V600E was the most common point mutation in the paired specimens (5/12). TERT promoter mutation C228T was detected in one case. PD-L1 expression at metastatic sites was highly positive (95%) for one patient with HTC. All specimens were stable for microsatellite instability testing, and the tumor mutation burden was low to intermediate. Therefore, the molecular profile of DTC primary and metastatic lesions can show heterogeneity, which may help explain some altered responses to therapeutic intervention.

Looking under the hood of "the Cadillac of cancers:" radioactive iodine-related craniofacial side effects among patients with thyroid cancer.

PURPOSE: Despite having a generally favorable prognosis, differentiated thyroid cancer is known to have a significant, long-term impact on the quality of life of survivors. We wished to investigate short- and long-term effects among thyroid cancer survivors following radioactive iodine therapy. METHODS: We conducted eight focus groups (N = 47) to understand patients' experiences of short- and long-term effects after radioactive iodine treatment and the impact these treatment-related side effects had on patients' quality of life. We elicited responses regarding experiences with side effects following radioactive iodine treatment, particularly salivary, lacrimal, and nasal symptoms. We transcribed audiotapes and conducted qualitative analyses to identify codes and themes. RESULTS: We identified eight broad themes from the qualitative analyses. Themes reflecting physical symptoms included dry mouth, salivary gland dysfunction, altered taste, eye symptoms such as tearing or dryness, and epistaxis. Psychosocial themes included lack of knowledge and preparation for treatment, regret of treatment, and distress that thyroid cancer is labeled as a "good cancer." CONCLUSIONS: Thyroid cancer survivors reported a wide range of radioactive iodine treatment-related effects and psychosocial concerns that appear to reduce quality of life. The psychosocial concerns reported by participants underscore the significant unmet information and support needs prior to and following RAI treatment among individuals diagnosed with thyroid cancer. IMPLICATIONS FOR CANCER SURVIVORS: Future research is needed to help both patients and physicians understand the effect of radioactive iodine on quality of life, and to better assess the benefits versus the risks of radioactive iodine therapy.

Infiltration of the thyroid gland by non-thyroid malignancy: A literature review reveals this to be an unusual cause of hyperthyroidism.

BACKGROUND: Non-thyroid malignancies that metastasize to the thyroid gland are relatively rare. At one end of the spectrum they may only be identified at the time of autopsy. At the other extreme, they may be identified during the evaluation of a progressive malignancy. Most patients who are identified as having metastases to their thyroid gland are euthyroid, but some patients may have associated hypothyroidism or hyperthyroidism. This review examines cases of hyperthyroidism associated with metastases affecting the thyroid gland. RESULTS: Twenty four articles describing 26 cases of malignancy-associated hyperthyroidism were identified, with the cases presenting with features suggestive of a thyroiditis and with goiter. The solid malignancies (19 cases) were mostly breast and lung cancer. Hematologic malignancies (7 cases) were also reported with a similar thyroiditis-like presentation. Patients underwent the traditional work-up for a thyroiditis, but frequently underwent other radiographic studies, in addition to radioactive iodine imaging, and frequently also underwent thyroid biopsy. The course in most patients (22/26 cases) was progression from hyperthyroidism to hypothyroidism, as the underlying malignancy progressed or thyroidectomy was performed, or the patient succumbed to their malignancy. Some patients (4 cases) became euthyroid with successful treatment of their malignancy. A subset of patients (5 cases) initially presented with severe thyrotoxicosis. Many affected patients succumbed to their underlying malignancy. CONCLUSION: Malignancy-associated hyperthyroidism has a similar underlying mechanism to subacute thyroiditis, in so much as there is damage or destruction of thyroid tissue. In cases of subacute thyroiditis this damage is self-limited, and there is recovery of thyroid function. In some cases of thyroiditis associated with malignancy there may be thyroid gland recovery as the underlying malignancy is treated and controlled. However, if the malignancy progresses, eventual hypothyroidism is likely to ensue.

A Survey of American Thyroid Association Members Regarding the 2015 Adult Thyroid Nodule and Differentiated Thyroid Cancer Clinical Practice Guidelines.

Background: The 2015 American Thyroid Association (ATA) clinical practice guidelines (CPGs) on management of thyroid nodules (TNs) and differentiated thyroid cancer (DTC) in adults were developed to inform clinicians, patients, researchers, and health policy makers about the best available evidence, and its limitations, relating to management of these conditions. Methods: We conducted a cross-sectional electronic survey of ATA members' perspectives of these CPGs, using a standardized survey (Clinician Guidelines Determinant Questionnaire) developed by the Guidelines International Network. A survey link was electronically mailed to members in February of 2019, with reminders sent to nonrespondents 2 and 5 weeks later. Data were descriptively summarized, after excluding missing responses. Results: The overall response rate was 19.8% (348/1761). The effective response rate was 20.2% (348/1720), after excluding a recently deceased member and individuals who had either invalid e-mail addresses or whose e-mails were returned. Of the respondents, 37.9% (132/348) were female, 60.4% (209/346) were endocrinologists, 27.5% (95/346) were surgeons, and 3.5% (12/346) were nuclear medicine specialists. The majority of respondents (71.9%; 250/348) were at a mid- or advanced-career level, and more than half were in academia (57.5%; 195/339). The majority (69.8%; 243/348) practiced in North America. The vast majority of respondents indicated that the CPGs explained the underlying evidence (92.3%; 298/323) and 92.9% (300/323) agreed or strongly agreed with the content. Most respondents stated that they regularly used the CPGs in their practice (83.0%; 268/323). Most respondents (83.0%; 268/323) also agreed or strongly agreed that the recommendations were easy to incorporate in their practice. The most popular CPG format was an electronic desktop file (78.8%; 252/320). Shorter more frequent CPGs were favored by 55.0% (176/320) of respondents, and longer traditional CPGs were favored by 39.7% (127/320). Conclusions: The clinical content and evidence explanations in the adult TN and DTC CPGs are widely accepted and applied among ATA survey respondents. Future ATA CPG updates need to be optimized to best meet users' preferences regarding format, frequency, and length.

Clinical, Pathological, and Molecular Profiling of Radioactive Iodine Refractory Differentiated Thyroid Cancer.

Background: Six to 20% of thyroid cancer (TC) patients develop distant metastases, and one-third become radioiodine refractory (RAIR). Available targeted therapies increase progression-free survival but are associated with toxicities. This study aims to characterize clinical, pathological, and molecular profiles of patients with RAIR TC. Methods: Data of TC patients seen during 2013-2017 at two tertiary care centers were retrospectively analyzed. Patients were considered RAIR according to American Thyroid Association guidelines. The control cohort was sex matched and age matched and had either regression or stable disease (by Response Evaluation Criteria in Solid Tumors) on follow-up at least three years after initial therapy. Molecular profiles on a subset of RAIR patients were reviewed. Results: Compared with 22 matched controls, 54 RAIR patients had an average age of 57 years (standard deviation [SD] = 13), 56% were male (41% in the control group); the average tumor size was 4 cm (SD = 2.5); tumors were multifocal in 54%, with involved surgical margins in 42%, focal invasion in 79%, and extrathyroidal extension (ETE) in 61%. Sixty-six percent had distant metastases at initial presentation with metastases to the lungs in 85%, bone in 56%, both sites in 43%, brain in 9%, and liver in 4%. There were no statistically significant differences between RAIR and controls in tumor size, focal invasion, ETE, and histology. The RAIR group received a higher cumulative radioactive iodine (RAI) dose and number of therapies compared with the controls (518 mCi vs. 302 mCi, p = 0.002 and 2.2 vs. 1.3 treatments, p = 0.001). Overall, patients >46 years had 4.5 times higher odds ratio (OR) of being RAIR; white race/ethnicity was associated with a reduced OR of RAIR disease (OR 0.33, p = 0.079). Molecular profiling data in the RAIR subgroup indicated that 50% of patients harbored mutations in the RAS/RAF pathway (11/22). Among 19 patients with a more extensive molecular panel, median tumor mutational burden was 5 megabase (range 3-16) and 26% (5/19) exhibited strong PD-L1 positivity. Conclusion: Among patients with metastatic differentiated thyroid carcinomas, patients with RAIR have similar histopathological and clinical characteristics as patients with RAI avid cancer. The risk of having RAIR TC is increased at age ≥46 and reduced in Caucasians.

Brain Metastases From Differentiated Thyroid Carcinoma: Prevalence, Current Therapies, and Outcomes.

BACKGROUND AND OBJECTIVE: The brain is an unusual site for distant metastases of differentiated thyroid carcinoma (DTC). The aim of this study was to document the prevalence of brain metastases from DTC at our institutions and to analyze the current therapies and the outcomes of these patients. METHODS: We performed a retrospective chart review of patients with DTC and secondary neoplasia of the brain. RESULTS: From 2002 to 2016, 9514 cases of thyroid cancer were evaluated across our institutions and 24 patients met our inclusion criteria, corresponding to a prevalence of 0.3% of patients with DTC. Fourteen (58.3%) were female and 10 (41.7%) were male. Fifteen patients had papillary thyroid cancer (PTC) (62.5%). Brain metastases were diagnosed 0 to 37 years (mean ± SD, 10.6 ± 10.4 years) after the initial diagnosis of thyroid cancer. Patients undergoing surgery had a median survival time longer than those that did not undergo surgery (27.3 months vs 6.8 months; P = 0.15). Patients who underwent stereotactic radiosurgery (SRS) had a median survival time longer than those that did not receive SRS (52.5 months vs 6.7 months; P = 0.11). Twelve patients (50%) were treated with tyrosine kinase inhibitors (TKIs), and they had a better survival than those who have not used a TKI (median survival time, 27.2 months vs 4.7 months; P < 0.05). CONCLUSION: The prevalence of brain metastases of DTC in our institutions was 0.3% over 15 years. The median survival time after diagnosis of brain metastases was 19 months. In our study population, the use of TKI improved the survival rates.

Prescribing Therapy for Hypothyroidism: Influence of Physician Characteristics.

BACKGROUND: Physician characteristics and perceptions and their effect on choice of therapies for patients with thyroid cancer have been well studied. Some data also exist about physician characteristics and prescribing treatment for subclinical hypothyroidism. The effect of physician characteristics on prescribing thyroid preparations for treating overt hypothyroidism is less studied. METHODS: Members of the American Thyroid Association were surveyed in 2017. Physicians were presented with 13 different theoretical patients with hypothyroidism and asked to choose among six therapeutic options, including levothyroxine, synthetic combination therapy, thyroid extract, and liothyronine monotherapy. The 13 patient scenarios incorporated parameters that potentially provide reasons for considering combination therapy (presence of symptoms, low serum triiodothyronine concentration, and documentation of deiodinase polymorphisms). Repeated-measures logistic regression analysis was performed to examine the prescribing of the various therapies. Data regarding the responding physicians were also collected. These data included number of years in practice, country of practice, and specialty. Multivariate repeated-measures logistic regression analysis of prescribing patterns was also conducted controlling for all patient and physician characteristics. RESULTS: Of the 389 survey respondents, 93% prescribed therapy for hypothyroidism. Fifty-three percent of respondents had been in practice for >20 years, and 23% had been in practice for 11-20 years. Sixty-four percent practiced in North America, and 18% practiced in Europe. Eight-six percent were endocrinologists, and 5% were surgeons. In multivariate analysis, physicians from North America were both more likely to prescribe any triiodothyronine-containing therapies (odds ratio [OR] = 1.8 [confidence interval (CI) 1.3-2.4]) and more likely to add liothyronine to levothyroxine therapy (OR = 1.9 [CI 1.2-2.9]). In addition, they were more likely to prescribe desiccated thyroid extract or liothyronine monotherapy (OR = 1.7 [CI 1.0-2.9]). CONCLUSIONS: A previous analysis of this survey showed that patient characteristics profoundly affect physician prescribing patterns. The current multivariate analysis shows that physician characteristics affect prescribing patterns. Whether this is due to impact upon physicians of patient-related experiences, media exposure, influence from pharmaceutical companies, educational activities, or other concerns cannot be determined. However, these results have potential importance for understanding physician-patient interactions at a time when the benefits and risks of triiodothyronine-containing therapies have not been fully documented.

A review of clinical trials: mesenchymal stem cell transplant therapy in type 1 and type 2 diabetes mellitus.

Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are widely prevalent metabolic diseases with differing pathologies. T1DM manifests due to autoimmune destruction of the pancreatic beta cells, resulting in a diminished secretion of insulin. T2DM originates from a state of insulin resistance, resulting in hyperglycemia and reduction in beta cell mass. Both diseases can cause severe health consequences. Despite the globally increasing prevalence of both T1DM and T2DM there remains to be a medically defined cure for either of these diseases. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible curative treatment method. In this review, we explain the molecular mechanisms underlying MSCs and their potential ability to treat T1DM and T2DM. We describe the capability of MSCs to differentiate into insulin-producing cells and regenerate pancreatic beta cells, as well as assess their role in modulating the immune system. Lastly, we evaluate the current literature focusing on the clinical application of MSC transplantation in T1DM and T2DM. Despite the favorable results, study designs and analyses cast doubt on the effectiveness of MSCs for the management of T1DM. Conversely, the positive metabolic effects consistently demonstrated in the literature offer hope for MSCs as a treatment for T2DM, at least in the short-term.

Update on the treatment of hypothyroidism.

PURPOSE OF REVIEW: Differentiated thyroid cancer is a malignancy that is rapidly increasing in frequency. As thyroidectomy plays a central role in the treatment of thyroid cancer, it is incumbent on physicians treating this patient group to be well versed in the intricacies of treating hypothyroidism. RECENT FINDINGS: Treatment of hypothyroidism may be refined by careful attention to dose selection, monitoring of therapy and achievement of thyrotropin goals that are specific to the individual patient's overall clinical situation. These goals are common not only to patients with a sole diagnosis of hypothyroidism, as discussed in the recent American Thyroid Association Guidelines, but also to patients with hypothyroidism in the setting of thyroid cancer. Several recent studies have illuminated our understanding of the benefits and risks of thyrotropin suppression therapy in patients with differentiated thyroid cancer. Multiple studies of combination therapy with levothyroxine and liothyronine for treating hypothyroidism have not led to a clear conclusion about its benefits over levothyroxine monotherapy. Animal studies have advanced our understanding of the altered serum and tissue milieu that characterizes levothyroxine monotherapy. Crossing the bridge from this translational research into clinical research using sustained release triiodothyronine preparations may ultimately enhance the health of our patients. SUMMARY: Continued refinement of our understanding of thyroid status and our ability to flawlessly implement thyroid hormone replacement is an active area of research.

Reassessing the NTCTCS Staging Systems for Differentiated Thyroid Cancer, Including Age at Diagnosis.

BACKGROUND: Thyroid cancer is unique for having age as a staging variable. Recently, the commonly used age cut-point of 45 years has been questioned. OBJECTIVE: This study assessed alternate staging systems on the outcome of overall survival, and compared these with current National Thyroid Cancer Treatment Cooperative Study (NTCTCS) staging systems for papillary and follicular thyroid cancer. METHODS: A total of 4721 patients with differentiated thyroid cancer were assessed. Five potential alternate staging systems were generated at age cut-points in five-year increments from 35 to 70 years, and tested for model discrimination (Harrell's C-statistic) and calibration (R(2)). The best five models for papillary and follicular cancer were further tested with bootstrap resampling and significance testing for discrimination. RESULTS: The best five alternate papillary cancer systems had age cut-points of 45-50 years, with the highest scoring model using 50 years. No significant difference in C-statistic was found between the best alternate and current NTCTCS systems (p = 0.200). The best five alternate follicular cancer systems had age cut-points of 50-55 years, with the highest scoring model using 50 years. All five best alternate staging systems performed better compared with the current system (p = 0.003-0.035). There was no significant difference in discrimination between the best alternate system (cut-point age 50 years) and the best system of cut-point age 45 years (p = 0.197). CONCLUSIONS: No alternate papillary cancer systems assessed were significantly better than the current system. New alternate staging systems for follicular cancer appear to be better than the current NTCTCS system, although they require external validation.

Long-Term Outcomes Following Therapy in Differentiated Thyroid Carcinoma: NTCTCS Registry Analysis 1987-2012.

CONTEXT: Initial treatments for patients with differentiated thyroid cancer are supported primarily by single-institution, retrospective studies, with limited follow-up and low event rates. We report updated analyses of long-term outcomes after treatment in patients with differentiated thyroid cancer. OBJECTIVE: The objective was to examine effects of initial therapies on outcomes. DESIGN/SETTING: This was a prospective multi-institutional registry. PATIENTS: A total of 4941 patients, median follow-up, 6 years, participated. INTERVENTION: Interventions included total/near-total thyroidectomy (T/NTT), postoperative radioiodine (RAI), and thyroid hormone suppression therapy (THST). MAIN OUTCOME MEASURE: Main outcome measures were overall survival (OS) and disease-free survival using product limit and proportional hazards analyses. RESULTS: Improved OS was noted in NTCTCS stage III patients who received RAI (risk ratio [RR], 0.66; P = .04) and stage IV patients who received both T/NTT and RAI (RR, 0.66 and 0.70; combined P = .049). In all stages, moderate THST (TSH maintained subnormal-normal) was associated with significantly improved OS (RR stages I-IV: 0.13, 0.09, 0.13, 0.33) and disease-free survival (RR stages I-III: 0.52, 0.40, 0.18); no additional survival benefit was achieved with more aggressive THST (TSH maintained undetectable-subnormal). This remained true, even when distant metastatic disease was diagnosed during follow-up. Lower initial stage and moderate THST were independent predictors of improved OS during follow-up years 1-3. CONCLUSIONS: We confirm previous findings that T/NTT followed by RAI is associated with benefit in high-risk patients, but not in low-risk patients. In contrast with earlier reports, moderate THST is associated with better outcomes across all stages, and aggressive THST may not be warranted even in patients diagnosed with distant metastatic disease during follow-up. Moderate THST continued at least 3 years after diagnosis may be indicated in high-risk patients.

Salivary Function after Radioiodine Therapy: Poor Correlation between Symptoms and Salivary Scintigraphy.

OBJECTIVE: Symptoms of salivary gland dysfunction frequently develop after radioactive iodine (RAI) therapy, but have generally not been correlated with assessment of salivary gland functioning. The aim of this study was to determine whether there was a correlation between salivary symptoms and salivary functioning as assessed by salivary scan parameters. METHODS: This was a non-randomized observational study. Fifteen patients receiving RAI therapy for differentiated thyroid cancer completed a questionnaire assessing their salivary and nasal symptoms prior to their therapy and 3 and 12 months after their therapy. Salivary gland scanning using technetium-99m pertechnetate was performed at the same time points. In addition, protective measures used at the time of radioiodine administration, such as use of fluids and sour candy, were also documented. Measures of salivary gland accumulation and secretion were correlated with scores of salivary and nasal symptomatology and any effects of protective measures were assessed. RESULTS: The mean number of salivary, nasal, and total symptoms at 3 months increased significantly over the number of symptoms at baseline by 3.7, 2.7, and 6.3 symptoms, respectively (p values 0.001, 0.0046, and <0.001, respectively). The mean increases in the number of salivary, nasal, and total symptoms at 12 months were non-significant at 1.3, 1.3, and 2.5 symptoms, respectively. The mean right parotid gland accumulation and secretion of radioisotope declined significantly at 3 months, compared with baseline. The changes in left parotid and right and left submandibular function were non-significant. There was no association between the increase in salivary, nasal, or total symptoms and the change in scintigraphy measures. However, the increases in nasal and total symptoms were significantly greater in those with co-existent Hashimoto's disease, compared with those without this condition (p values 0.01 and 0.04, respectively). Nasal symptoms decreased (p value 0.04) and total symptoms trended to decrease (p value 0.08) in those who used sour candies, compared with those who did not. Increasing body mass index was significantly associated with increasing nasal symptoms (p value 0.05). Greater decline in salivary parameters at 3 months compared with baseline was generally associated with heavier body weight, decreased thyroid cancer stage, absence of Hashimoto's thyroiditis, and pre-menopausal status. CONCLUSION: Salivary and nasal symptoms increased and salivary scintigraphy parameters decreased after radioiodine therapy. However, the increased symptoms did not correlate with decrements in salivary gland accumulation or secretion. Moreover, the variables associated with symptoms and changes in salivary scan parameters differed. Therefore, a better understanding of the relationship between salivary gland symptoms and functioning is needed. Factors affecting susceptibility to salivary and nasal damage after radioiodine therapy need to be better elucidated, so that modifiable factors can be identified.