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Human chorionic gonadotropin (hCG)-induced hyperthyroidism has been previously reported as a rare paraneoplastic syndrome in non-seminomatous germ cell tumours and usually presents with mild symptoms or subclinical thyrotoxicosis. We present a case of a young adult man who consulted with abdominal pain, nausea and emesis. On admission, he was found to be tachycardic, febrile, anxious and with icteric sclera and tenderness to palpation in the right upper abdomen. A right scrotal mass was also noted. Initial studies revealed transaminitis, hyperbilirubinaemia, suppressed thyroid-stimulating hormone and elevated free T4. Scrotal biopsy confirmed diagnosis of testicular choriocarcinoma with an elevated hCG level of 6074 mIU/mL, which was corrected to 6 760 713 mIU/mL when reassessed with dilution. The clinical scenario reflected hCG-induced thyrotoxicosis concerning for thyroid storm. Euthyroid state was restored after initiation of chemotherapy and a short course of methimazole. Unfortunately, the patient passed away due to progression of his malignant disease. This case suggests that when choriocarcinoma is suspected, the use of iodinated contrast agents should be limited to avoid precipitation of thyroid storm or worsening of hCG-induced hyperthyroidism. Moreover, if the clinical picture does not support a primary aetiology of hyperthyroidism and hCG is not concordantly elevated, reassessment of hCG by dilution should be considered as hCG assays are subject to prozone effect.

Abstract Disclosure: S. Paknikar: None. D. Toro Tobon: None. J. Durski: None. H. Alkhateeb: None. M.M. Ryder: None. Introduction: Radioactive iodine (RAI) therapy-induced myelosuppression is a dose-limiting toxicity for RAI avid metastatic differentiated thyroid cancers. We describe a patient with exceptionally RAI avid metastatic follicular thyroid cancer (FTC) who underwent autologous stem cell cryopreservation (ASCC) to enable high dose I-131 treatments. Case: A 60-year-old woman with T1bN0M0 FTC underwent two-stage thyroidectomy and three doses of I-131 between 2002-2007 (434 mCi cumulative activity) due to incomplete biochemical response. She presented to our institution in 2015 with rising thyroglobulin (Tg) levels and lung nodules that were intensely RAI avid. She enrolled in a clinical trial of selumetinib versus placebo (for 1 month) followed by 150 mci I-131. She had a profound response with an 80% reduction in Tg and 50% tumor shrinkage. The following year her Tg rose to 8381 ng/mL and she developed biopsy proven, well differentiated metastatic FTC in the hip and liver. Lenvatinib treatment resulted in partial tumor and Tg response but was halted due to grade 3/4 toxicities. Tumor genomic interrogation revealed NRAS, PIK3CA, and TSH-R activating mutations, providing a causal explanation of her intensely RAI avid and responsive disease. Repeat I-131 therapy was facilitated by GM-CSF stimulated ASCC (8.57 x10(6) CD34+ cells/kg for two cycles) as a tool to help mitigate future potential RAI-induced myelosuppression. The patient received 295 mci I-131 followed by a 98% decrease in Tg and 20-25% shrinkage of liver metastases. Transient pancytopenia ensued but did not require autologous stem cell transplantation (ASCT). Due to insurance issues, the patient was lost to follow-up for two years. She returned with cachexia from severe, untreated thyrotoxicosis due to widespread functional, thyroxine producing metastatic disease. Anti-thyroid drug therapy (ATD) restored euthyroid status with significant clinical improvement. A non-stimulated I-123 whole body scan showed diffuse RAI avid disease with 88% whole body radioiodine retention at 48h. She received 125 mci I-131 with initial tumor response but with progression of bone marrow, calvaria, and retinal metastases. Six months later, a final dose of 253 mCi I-131 (cumulative activity 1,370 mCi) resulted in mixed tumor responses. Unfortunately, resection of a RAI refractory calvaria lesion postoperatively resulted in serious complications. ASCT and salvage treatments could not be pursued due to her impaired functional status. The patient pursued hospice care and passed away 20 years after her diagnosis. Conclusion: We characterize a patient with NRAS, PIK3CA and TSH-R mutant metastatic, thyroxine-producing FTC whose recurrences over 20 years retained intense RAI avidity and response to I-131 therapy. In cases with potential benefit from multiple high dose RAI therapies, ASCT may be a tool to mitigate I-131-induced myelosuppression. Presentation: 6/1/2024

Background Self-monitoring of blood glucose (SMBG) has been shown to reduce hemoglobin A1C (HbA1C). Accordingly, guidelines recommend SMBG up to 4–10 times daily for adults with type 2 diabetes (T2DM) on insulin. For persons not on insulin, recommendations are equivocal. Newer technology-enabled blood glucose monitoring (BGM) devices can facilitate remote monitoring of glycemic data. New evidence generated by remote BGM may help to guide best practices for frequency and timing of finger-stick blood glucose (FSBG) monitoring in uncontrolled T2DM patients managed in primary care settings. This study aims to evaluate the impact of SMBG utility and frequency on glycemic outcomes using a novel BGM system which auto-transfers near real-time FSBG data to a cloud-based dashboard using cellular networks. Methods Secondary analysis of the intervention arm of a comparative non-randomized trial with propensity-matched chart controls. Adults with T2DM and HbA1C >  9% receiving care in five primary care practices in a healthcare system participated in a 3-month diabetes boot camp (DBC) using telemedicine and a novel BGM to support comprehensive diabetes care management. The primary independent variable was frequency of FSBG. Secondary outcomes included frequency of FSBG by insulin status, distribution of FSBG checks by time of day, and hypoglycemia rates. Results 48,111 FSBGs were transmitted by 359 DBC completers. Participants performed 1.5 FSBG checks/day; with 1.6 checks/day for those on basal/bolus insulin. Higher FSBG frequency was associated with greater improvement in HbA1C independent of insulin treatment status ( p  = 0.0003). FSBG frequency was higher in patients treated with insulin ( p  = 0.003). FSBG checks were most common pre-breakfast and post-dinner. Hypoglycemia was rare (1.2% < 70 mg/dL). Conclusions Adults with uncontrolled T2DM achieved significant HbA1C improvement performing just 1.5 FSBGs daily during a technology-enabled diabetes care intervention. Among the 40% taking insulin, this improvement was achieved with a lower FSBG frequency than guidelines recommend. For those not on insulin, despite a lower frequency of FSBG, they achieved a greater reduction in A1C compared to patients on insulin. Low frequency FSBG monitoring pre-breakfast and post-dinner can potentially support optimization of glycemic control regardless of insulin status in the primary care setting. Trial registration Trial registration number : NCT02925312 (10/19/2016).

Abstract Disclosure: K.N. Rachmasari: None. A. Osman: None. D. Toro Tobon: None. S.B. Lund: None. D.J. Merlino: None. A.R. Hsu: None. M.M. Ryder: None. Background: In low-risk papillary thyroid cancer (PTC), radioactive iodine (RAI) remnant ablation has shown no impact on disease recurrence rates, which are overall low. The role of adjuvant RAI in intermediate risk disease (i.e. T3, N1) remains unproven with no randomized clinical trials to objectively assess efficacy. Thus, in our institution, its use is highly heterogenous. We retrospectively investigated the effects of adjuvant RAI on recurrence and recurrence free survival (RFS) in patients with PTC and positive cervical lymph nodes (CLN). Methods: We performed a retrospective review of patients who underwent surgery at Mayo Clinic Rochester, MN for PTC between January 2007 and December 2016. Adult patients with Tx-T3 disease according to the 8th edition of American Joint Committee on Cancer (AJCC) were identified. Patients with positive CLN (N1) and a minimum follow up of 36 months were included. Demographics, clinicopathologic characteristics, use of RAI therapy and recurrence were analyzed. Results: A total of 367 patients with PTC, Tx-3, N1, M0 were identified, of which 187 received adjuvant RAI and 180 did not. Most patients were female (63.8%), with a median age of 44 years (IQR 34-54), and a median follow up of 77 months (IQR 58.5-101.5). There were no differences in age, type of surgery, histology, multifocality, and follow up period between the RAI and no RAI subgroups. Adjuvant Thyrogen-stimulated or thyroid hormone withdrawal-based RAI was recommended at the discretion of the treating provider and/or per patient preference. Diagnostic I-123 whole body scans were performed in all patients and mostly demonstrated remnant uptake. The median dose of I-131 was 75 mCi (range 50-100). Recurrence was defined by new occurrence of disease after at least a year of absence of clinical, biochemical, and imaging evidence of disease since initial surgery. Within the entire cohort, 35 (9.5%) developed recurrence with a median time of 41 months (28-59.5). Overall, recurrence rate and RFS were not significantly different between both subgroups (p = 0.2). A subanalysis was performed in patients with clinically detectable nodal disease (n = 161), defined by abnormal cervical lymph node on preoperative neck ultrasound with or without positive fine needle aspiration biopsy. Overall recurrence rates were 17 (10.6%) in this group. There were no differences in recurrence rates and RFS in those that received RAI versus those that did not (p = 0.8). Conclusions: In patients with intermediate risk PTC defined by nodal disease and/or T3 disease, recurrences were not different between patients that did or did not receive adjuvant I-131 therapy postoperatively. A randomized, noninferiority study of adjuvant I-131 compared to no I-131 postoperatively for N1 disease is needed to determine the benefit of near total thyroidectomy and adjuvant I-131 for this cohort. Presentation: 6/3/2024

Abstract Disclosure: D. Toro-Tobon: None. H. Billings: None. I. Bancos: None. Background: Mentorship is crucial for training physicians' career development, yet evidence of its impact on endocrinology trainees is lacking. We assessed the current state of mentorship in endocrine fellowship training in the United States. Methods: We conducted a cross-sectional study between June and September 2023. Endocrine fellows were invited to complete an online questionnaire describing their mentorship experience and its influence on burnout, satisfaction, and scholarly productivity. Results: Of 153 participants (mean age 34, 69% women, 47% White, 20% Hispanic/Latino), 73% had a mentor. Having a mentor was not associated with age, gender identity, race, or ethnicity. Those without mentors were more commonly in two-year fellowships (63% vs. 81%, p=0.04), had less access to formal mentorship programs (48% vs. 21%, p<0.01), cited insufficient faculty availability for mentoring (11% vs. 26%, p=0.01), and encountered more challenges finding mentors in their training programs (11% vs. 38%, p<0.001). Mentored participants exhibited increased post-fellowship interest in academic practice (69% vs. 50%, p<0.01), higher involvement in clinical research (65% vs. 49%, p=0.01), more fellowship-dedicated scholarly time (36% vs. 22%, <0.001), a greater median number of publications (4.6 vs. 1.8, p<0.01) and abstracts (7 vs. 3.7, p<0.01), were more likely to have submitted a grant (29% vs. 5%, p=0.03) and had higher satisfaction with training (92% vs. 64%, p<0.001). Mentors were mostly chosen by mentees (70%) and shared gender identity (61%) but often had a different race or ethnicity (71.8%). The majority found mentorship relationships satisfactory (87%), contributing to increased academic productivity (84%) and reduced mentee burnout and stress levels (60%). In bivariate analysis, all mentor attributes significantly influenced higher academic productivity and mentee satisfaction. The most divergent for academic productivity were improved communication, alignment with expectations, inspiration for goal attainment, and effective networking. For mentorship satisfaction, distinctions were found in communication enhancement, goal-oriented assistance, knowledge/skill enrichment, and personalized career path development. Traits like active listening and adapting communication styles were not linked to decreased burnout, but actively supporting work-life balance independently correlated with reduced burnout. Conclusion: Mentorship positively affects endocrine fellows' scholarly productivity and career development. Yet, a significant number lack mentors or access to programs. Mentor attributes, like effective communication, goal alignment, and networking support boost productivity and satisfaction. However, reducing mentee burnout hinges on actively fostering work-life balance. Presentation: 6/3/2024

Abstract Context Levothyroxine is one of the most prescribed medications in the United States. Objective This study explores the appropriateness of levothyroxine prescriptions. Methods A retrospective multicenter study was conducted on adult patients who were prescribed levothyroxine for the first time between 2017 and 2020 at three academic centers in the United States. We classified each case of levothyroxine initiation into one of three mutually exclusive categories: appropriate (clinically supported), indeterminate (clinically unclear), or nonevidence based (NEB, not clinically supported). Results A total of 977 participants were included. The mean age was 55 years (SD 19), there was female (69%) and White race predominance (84%), and 44% had possible hypothyroid symptoms. Nearly half of the levothyroxine prescriptions were considered NEB (528, 54%), followed by appropriate (307, 31%) and indeterminate (118, 12%). The most common reason for NEB prescription was an index thyrotropin (TSH) value of less than 10 mIU/L without previous TSH or thyroxine values (131/528, 25%), for appropriate prescription, was overt hypothyroidism (163/307, 53%), and for an indeterminate prescription was a nonconfirmed subclinical hypothyroidism with TSH greater than or equal to 10 mIU/L (no confirmatory testing) (51/118, 43%). In multivariable analysis, being female (odds ratio [OR]: 1.3; 95% CI, 1.0-1.7) and prescription by a primary care provider (OR: 1.5; 95% CI, 1.2-2.0) were associated with NEB prescriptions. Conclusion There is a considerable proportion of NEB levothyroxine prescriptions. These results call for additional research to replicate these findings and to explore the perspective of those prescribing and receiving levothyroxine.

Disclosure: D. Toro-Tobon: None. J.C. Morris: None. C. Hilger: None. C.S. Peskey: None. D.M. Jolanta: None. M.M. Ryder: None. Objective: Patients with metastatic differentiated thyroid cancer (DTC) that are radioactive iodine (RAI) refractory (RAIR) have a poor prognosis. Redifferentiation therapy (RDT) has emerged as a potential approach to restore RAI avidity in this disease. The aim of this study was to examine the efficacy and predictors of RAI restoration in RAIR disease, as well as examine the outcomes of patients re-treated with high dose RAI following RDT. Methods: A retrospective review was conducted of 33 patients with RECIST-progressive metastatic RAIR-DTC who underwent RDT between 2017 and 2022 at the Mayo Clinic. All patients underwent genomic profiling, and either MEK inhibitor alone or combination BRAF-MEK inhibitors were prescribed for 4 weeks. At week 3, Thyrogen-stimulated I-123 whole body scans were performed. Those with increased RAI avidity in metastatic foci received high dose I-131 therapy using a previously published modified dosimetry protocol. Baseline and clinicopathologic outcomes were comprehensively reviewed. Results: Of the 33 patients, 12 of 23 (52%) with papillary thyroid cancers (PTC), 4 of 4 (100%) with follicular variant PTCs (FV-PTC), and 7 of 7 (100%) with follicular thyroid cancers (FTC) had restored RAI avidity following RDT using dabrafenib/trametinib (7 for BRAF mutant disease) or trametinib monotherapy (12 for RAS mutant disease). All 11 (100%) RAS mutant tumors (2 PTC, 3 FV-PTC, and 6 FTC) had RAI avidity restoration compared to 7 (36%) with BRAF mutant disease (6 PTC, and 1 FV-PTC). Of the 19 patients (57%) with restored RAI avidity (responders), 18 (94%) received I-131 with a median dose of 294 mCi. The median thyroglobulin (Tg) in responders was 294 mIU/L as compared to 29 mIU/L in non-responders. Following RDT-facilitated I-131 treatment, 94.7% achieved RECIST defined objective response (complete or partial response, stable disease, non-complete response/non-progressive disease) with a median progression free survival of 18 months and an overall survival of 30 months. Overall, patients with FTC (p=0.01), RAS mutation (p<0.001), Tg of 294 mIU/L or more (p=0.03), largest tumor diameter of 1.7 cm or less (p=0.05), bone metastasis (p=0.007), and without locoregional nodal disease (p=0.04), were more likely to demonstrate restored RAI avidity following RDT. Of the entire cohort, 2 (6%) patients experienced histologic transformation to anaplastic thyroid cancer and 5 (15%) patients died, all had had RAI restoration and received high-dose RAI following RDT. Conclusion: RDT has the potential to restore RAI avidity and induce RECIST responses following I-131 therapy in select patients with RAIR-DTC, particularly those with RAS mutations and ‘follicular’ phenotypes. Further studies are needed to better characterize the long-term survival and/or safety outcomes of high-dose RAI following RDT, particularly whether it could be associated with histologic transformation. Presentation Date: Saturday, June 17, 2023

Literature suggests patients with thyroid cancer have unmet informational needs in many aspects of care. Patients often turn to online resources for their health-related information, and generative artificial intelligence programs such as ChatGPT are an emerging and attractive resource for patients. To assess the quality of ChatGPT's responses to thyroid cancer-related questions. Four endocrinologists and 4 endocrine surgeons, all with expertise in thyroid cancer, evaluated the responses to 20 thyroid cancer-related questions. Responses were scored on a 7-point Likert scale in areas of accuracy, completeness, and overall satisfaction. Comments from the evaluators were aggregated and a qualitative analysis was performed. Overall, only 57%, 56%, and 52% of the responses \"agreed\" or \"strongly agreed\" that ChatGPT's answers were accurate, complete, and satisfactory, respectively. One hundred ninety-eight free-text comments were included in the qualitative analysis. The majority of comments were critical in nature. Several themes emerged, which included overemphasis of diet and iodine intake and its role in thyroid cancer, and incomplete or inaccurate information on risks of both thyroid surgery and radioactive iodine therapy. Our study suggests that ChatGPT is not accurate or reliable enough at this time for unsupervised use as a patient information tool for thyroid cancer.

Abstract Purpose Overuse of thyroid ultrasound (TUS) has contributed to rising thyroid cancer diagnoses and is projected to increase US healthcare costs from $1.5 billion to $3.5 billion by 2030. This study evaluated the healthcare cost of inappropriately ordered TUS in a national multicenter academic system. Methods This is a secondary cost analysis of a retrospective cohort study across 4 Mayo Clinic sites (Rochester, MN; Jacksonville, FL; Scottsdale, AZ; and the Midwest Mayo Clinic Health System). Adult patients (≥18 years) undergoing their first TUS between January 1, 2017, and December 31, 2021, with at least 1 year of follow-up were included. TUS indications were classified as appropriate or inappropriate using a guideline-based natural language processing algorithm. The primary outcome was a comparison of adjusted 1-year all-cause healthcare costs. A secondary analysis calculated the direct procedural costs of the inappropriate TUS cascade. Results Among 6984 patients (mean age 56 [SD 16.4]; 76.2% female; 90.9% White), 546 (7.8%) underwent TUS for inappropriate indications. These patients were younger (mean age 53.0 vs 56.3 years, P < .0001) but otherwise demographically similar. Adjusted total healthcare costs over 90 days and 1 year were comparable: $4842 vs $5794 and $13 748 vs $14 257 for inappropriate vs appropriate TUS, respectively. The inappropriate TUS cascade, including an estimated 56 subsequent biopsies and 22 thyroidectomies, resulted in a minimum of $576 134 in direct procedural costs. Conclusion While adjusted total costs were similar, inappropriate TUS represents potentially avoidable spending and remains a viable target for cost-reduction strategies. Reducing low-value imaging remains a critical target for cost-saving interventions.

Abstract Disclosure: L. Miller-Wilson: Employee of Immunovant, Inc. N. Princic: Employee of Merative. K. Evans: Employee of Merative. N. Atreja: Employee of Immunovant, Inc. K. Tollefsen: Employee of Immunovant, Inc.. D. Toro-Tobón: None. Objectives: Graves’ disease (GD) is an autoimmune condition responsible for most cases of hyperthyroidism in the United States. An estimated 20%-50% of patients with GD will also develop thyroid eye disease (TED). Current treatments for GD focus on managing hyperthyroidism, but frequent monitoring, dose adjustments, and the high rate of relapse after discontinuation of antithyroid drugs can increase treatment costs and complicate long-term management. This study describes healthcare resource utilization (HCRU) and costs among patients with GD, with and without TED. Methods: This retrospective analysis utilized claims data from the Merative™ MarketScan® Research Databases. Individuals aged ≥18 years with ≥2 claims for a GD diagnosis from January 1, 2017-December 31, 2023 were included (first claim = index). To ensure a newly diagnosed cohort, patients with a history of GD-specific treatment or a GD diagnosis in the 12 months preceding the index were excluded. The final GD cohort was stratified into patients who had evidence of TED at any time during the 12-month pre-index period through 90 days post-index, and those who did not. Propensity score matching was used to balance patients with GD (with and without TED) with non-GD controls (1:3) on demographic and baseline clinical characteristics. Both GD cases (with and without TED) and controls were required to have ≥12 months of post-index follow-up. HCRU and costs were compared between cases and controls during a fixed 12-month post-index period. Categorical outcomes were compared using chi-squared tests, while continuous endpoints were compared using paired t-tests. Results: The analysis included 1,767 GD cases with TED matched with 5,301 controls (mean age, 53.1 years [standardized mean difference (SMD), 0.00]; 77% female [SMD, 0.00]; mean Charlson comorbidity score, 0.9 [SMD, 0.02]) and 43,120 GD cases without TED matched with 129,360 controls (mean age, 49.8 years [SMD, 0.00]; 78% female [SMD, 0.00]; mean Charlson comorbidity score, 0.7 [SMD, 0.01]). Compared with matched controls, patients with GD and TED had 78% more inpatient visits (0.16 vs 0.09), 104% more outpatient visits (65.06 vs 31.86), and 43% more prescriptions (30.21 vs 21.13) during the 12-month post-index period, while patients with GD without TED had 75% more inpatient visits (0.14 vs 0.08), 83% more outpatient visits (52.15 vs 28.48), and 38% more prescriptions (24.27 vs 17.56) (p<0.001 for all). Annual mean healthcare costs were 305% higher ($56,584 vs. $13,981) among GD patients with TED and 65% higher ($19,913 vs $12,076) in those without TED compared with matched controls. Conclusion: Patients with GD had significantly higher HCRU and healthcare costs than matched controls in the 12 months following diagnosis, and this difference was notably greater among GD patients who also had TED. More effective treatments are needed to address the health and financial burden of GD. Presentation: Monday, July 14, 2025