Impact of Teprotumumab on Clinical Practice in Thyroid Eye Disease.

BACKGROUND: Following its Food and Drug Administration approval in January 2020, we examined the impact of teprotumumab on thyroid eye disease (TED) clinical practices. METHODS: Across 3 referral centers from January 1, 2018, to December 30, 2022, we retrospectively analyzed demographics, clinical features, treatment choices, and insurance status of patients with active, moderate to severe TED. RESULTS: Of 74 patients recommended for medical therapy, 53% received collaborative recommendations from endocrinologists and ophthalmologists in a TED clinic. Prior to teprotumumab availability, 19 patients were recommended medical therapy, and all received medical therapy (100%), which consists of corticosteroids (14, 73.7%) or tocilizumab (5, 26.3%). After teprotumumab became available, out of 55 patients that were recommended medical therapy, only 41 (74.6%) received medical therapy, mostly teprotumumab (33, 60%), followed by corticosteroids (5, 9.1%) or tocilizumab (3, 5.4%), while 14 (25.4%) did not receive medical therapy. Discordance between physicians' recommendations and therapy received or lack thereof was explained by patients' refusal (9, 64.3%), mostly due to side effect concerns (8, 88.9%), and insurance denial (5, 35.7%). Teprotumumab use was mostly associated with otic changes (10, 30.3%), weight loss (9, 27.3%), and hyperglycemia (6, 18.2%), but 2 (6.1%) patients developed serious infections. Corticosteroids were associated with insomnia (4, 21.1%), and 1 patient in the tocilizumab group had an infusion reaction requiring hospitalization. CONCLUSION: Teprotumumab introduction increased TED therapy evaluations, yet not all received recommended treatment due to safety concerns or accessibility issues. Enhancing collaborative care, medication accessibility, and adverse effect management is crucial.

Posterior hypothalamic involvement on pre-operative MRI predicts hypothalamic obesity in craniopharyngiomas.

PURPOSE: Hypothalamic obesity (HO) is a complication associated with craniopharyngioma (CP). Attempts have been made to perioperatively predict the development of this complication, which can be severe and difficult to treat. METHODS: Patients who underwent first transsphenoidal surgical resection in a single center between February 2005 and March 2019 were screened; those who have had prior surgery or radiation, were aged below 18 years, or did not have follow up body mass index (BMI) after surgery were excluded. Primary end point was BMI within 2 years post-surgery. Hypothalamic involvement (HI) was graded based on preoperative and postoperative imaging with regards to anterior, posterior, left and right involvement. Data on baseline demographics, pre-operative and post-operative MRI, and endocrine function were collected. RESULTS: 45 patients met the inclusion and exclusion criteria. Most patients in our cohort underwent gross total resection (n = 35 patients). 13 patients were from no HI or anterior HI only group and 22 patients were classified as both anterior (ant) and posterior (post) HI group. There was no significant difference between the two groups in the gross total, subtotal or near total resection. Pre-operative BMI and post-operative BMI were significantly higher in patients who had ant and post HI on pre-operative MRI (p < 0.05 and p < 0.01, respectively). Similarly, post-operative BMI at 13-24 months was also significantly higher in the ant and post HI group on post-op MRI (p < 0.01). There was no significant difference between the two groups in terms of baseline adrenal insufficiency, thyroid insufficiency, gonadal insufficiency, IGF-1 levels, hyperprolactinemia, and diabetes insipidus. Diabetes insipidus was more common following surgery among those who had anterior and posterior involvement on pre-operative MRI (p < 0.05). CONCLUSIONS: HO appears to be predetermined by tumor involvement in the posterior hypothalamus observed on pre-operative MRI. Posterior HI on pre-operative MRI was also associated with the development of diabetes insipidus after surgery.

The Epidemiology of Thyroid Eye Disease in Olmsted County, Minnesota, 2005-2020.

Objective: To describe the epidemiology of thyroid eye disease (TED). Methods: A population-based cohort of all Olmsted County, Minnesota, residents who had newly diagnosed TED between January 1, 2005, and December 31, 2020, was identified through the medical diagnostic index of the Rochester Epidemiology Project. Individuals aged 18 years and older were included. Incidence rates and point prevalence were calculated. Baseline disease characteristics and progression of disease were described. Results: We identified 83 incident patients, of whom 75 (90.4%) were female. The overall age and sex adjusted incidence for the U.S. population were 5 cases/100,000 person-years. Females had higher incidence (8.9 cases/100,000 person-years) compared with men (1 case/100,000 person-years). The distribution of peak incidence rates by 5-year age groups differed between male and female, in which females had peak incidence rates in the age groups 60-64 years and 80-84 years (18.3 cases and 18 cases/100,000 person-years, respectively), while male had peak incidence rate in the age group 70-74 years (5.7 cases/100,000 person-years). No clear trend was identified for the yearly incidence between 2005 and 2020. The overall estimated point prevalence per 100,000 was 65 (CI, 53.3-78.7). Prevalence was 114.5 (CI, 92.6-139.9) for females and 13.8 (CI, 6.8-24.6) for males (p < 0.001). Factors associated with disease progression were severity of soft tissue involvement (hazard ratio [HR] 7.7; CI, 2-29.8) and presence of diplopia (HR 2.5, CI, 1.2-5.1). Conclusions: Incidence rates for TED remained stable over the past two decades, yet lower than that in the previous study from our population. Females continue to have the peak incidence rate a decade earlier than males, and the majority of disease burden is present after the age of 50 years. Appropriate resources should be devoted to furthering education, management, and research into this condition.

Exploring Radiofrequency Ablation for T1 Papillary Thyroid Cancer in the United States: Mayo Clinic Experience.

OBJECTIVE: To report the efficacy, safety, and feasibility of radiofrequency ablation (RFA) for T1 papillary thyroid carcinoma (PTC) in a large referral center in the United States. PATIENTS AND METHODS: We conducted a retrospective study of 8 patients who underwent RFA for T1 PTC at Mayo Clinic in Rochester Minnesota, between July 1, 2020, and February 28, 2023. The RFA technique and the type of anesthesia are described. Thyroid function, changes in ablated zone, and adverse events were analyzed for up to 24 months after the procedure. RESULTS: Of the 8 patients included in the study, 7 were female and 1 was male with a mean ± SD age of 53±16.4 years. Thyroid status was unaffected in 7 of the 8 patients. The median duration of RFA was 6 minutes (range, 2 to 14.5 minutes) with energy delivered at between 25 and 45 W. The mean ± SD volume of small PTCs was 0.3±0.2 mL, and the mean largest diameter was 9.5±3.3 mm (range, 6 to 15 mm). The mean ± SD ablated volume at 3 to 6 months was larger than the target lesion (0.8±0.7 mL), with a reduction in mean ± SD ablated volume of 0.4±0.4 mL at 7 to 12 months and 0.1±0.06 mL at 13 to 18 months. The ablated zone almost disappeared at 19 to 24 months (0.04±0.04 mL). There were no major adverse events during or after the RFA procedure. CONCLUSION: This is the first reported series of T1 PTC treated with RFA in the United States. Early postablation imaging revealed that the ablated region was larger than the target lesions, followed by a serial decrease in size. Therefore, RFA at centers with such expertise appears to be a safe and effective treatment for small PTCs. Further studies are needed to evaluate its long-term efficacy and the risk of recurrence.

Improving Intravenous and Subcutaneous Insulin Overlap During Treatment of Diabetic Ketoacidosis: A Quality Improvement Project.

Objective: To reduce the frequency of insufficient overlap of intravenous (IV) and subcutaneous (SC) insulin during the treatment of diabetic ketoacidosis (DKA) as a quality improvement project. Patients and Methods: Rates of insufficient IV and SC insulin overlap (< 2-hour overlap, SC insulin given after IV insulin discontinuation, or no SC insulin given after IV insulin discontinuation) were assessed in adults with DKA treated with IV insulin at a large tertiary care referral center in Rochester, Minnesota, from July 1, 2021, to March 15, 2023. After a preintervention analysis period, an electronic medical record-based best practice advisory was introduced to notify hospital providers discontinuing IV insulin if SC long-acting insulin had not been given in the previous 2-6 hours. Demographic characteristics and clinical outcomes before and after intervention were compared. Results: A total of 352 patient encounters were included (251 in the preintervention phase and 101 in the postintervention phase). The rate of insufficient IV to SC insulin overlap decreased from (88 of 251) 35.1% before intervention to (20 of 101) 19.8% after intervention (P=.005). The rate of posttransition hypoglycemia (<70 mg/dL; to convert to mmol/L, multiply by 0.0259) decreased from (27 of 251) 10.7% to (4 of 101) 4% after intervention (P=.04). Rates of posttransition hyperglycemia (>250 mg/dL), rebound DKA, length of hospital stay, and duration of IV insulin therapy were similar before and after intervention. Conclusion: Using quality improvement methodology, the rates of insufficient IV to SC insulin overlap during treatment of DKA in a large tertiary care referral center were measured and reduced through an electronic medical record-based best practice advisory targeting hospital providers.

Medical Therapy in Patients with Moderate to Severe, Steroid-Resistant, Thyroid Eye Disease.

Background: Corticosteroid therapy is often employed in thyroid eye disease (TED), but its efficacy is variable. Teprotumumab and tocilizumab have been considered as effective alternatives. This study aims to evaluate their clinical outcomes and safety in patients with steroid-resistant TED. Methods: A retrospective case-control study was conducted between 2018 and 2022 within a national multicenter health system. Thirty-seven patients with moderate to severe steroid-resistant TED treated with teprotumumab or tocilizumab (cases) were compared with steroid-naïve patients treated with similar therapy (controls). Due to lack of steroid-naïve patients treated with tocilizumab, a control subgroup for tocilizumab was not included in the analysis. Demographic and clinical characteristics were described. Proptosis, diplopia, clinical activity score (CAS), and disease severity (European Group on Graves' orbitopathy classification) were evaluated at weeks 0, 12, 24, and 52 after therapy initiation. Results: Thirty-one patients received teprotumumab (13 cases and 18 controls) and 6 received tocilizumab (cases). The mean age was 57 years (standard deviation ±14.3), median duration of TED was 11.5 months (interquartile range [IQR]: 7.2-17.7), and median excess proptosis was 4 mm (IQR: 2-8) above the upper limit of normal for sex and race. At week 24, in the teprotumumab cases, 81% had proptosis response (reduction of ≥2 mm), 45.5% resolution of diplopia, 85.7% disease inactivation (CAS <3), and 58.3% reverted to mild disease severity. There were comparable results in teprotumumab controls, with no significant differences between subgroups. In the tocilizumab cases, 50% had a proptosis response, 16.7% resolution of diplopia, 100% disease inactivation, and 75% returned to mild disease. In the teprotumumab cases, there was a trend toward worsening proptosis and diplopia between weeks 24 and 52. In the same time frame, the tocilizumab cases had a trend toward worsening diplopia, disease activity, and severity. In the teprotumumab subgroup, 46.2% experienced otic changes and 23.1% hyperglycemia. In the tocilizumab subgroup, there were no reported adverse events. Conclusions: Teprotumumab and tocilizumab improved inflammation in patients with moderate to severe TED who had failed previous steroid therapy. Additionally, the teprotumumab cases demonstrated similar improvement in proptosis and diplopia to the teprotumumab controls. Further evaluation, particularly regarding the long-term response and side effect profile, of these medications in steroid-resistant TED is needed.

Thyroid eye disease or Graves' orbitopathy: What name to use, and why it matters.

There is currently no universally accepted name for inflammatory disease of the eye and orbit associated with thyroid autoimmune disease. Variability in terminology impedes the evaluation of scientific literature and clinical collaboration and can affect patients' understanding of a disease process. The goals of this perspective article are 1. To compare the frequency of different terms used for eye disease associated with autoimmune thyroid disease in the scientific literature between 2000, 2010 and 2020 publications; 2. To investigate potential associations of terminology with author and journal specialty, and multidisciplinary vs. mono-disciplinary author teams; 3. To determine preferential terms used by professional societies; and 4. To propose standardized terminology based on our data analysis. The methods for this study included review of all English language articles listed in PubMed, with publication dates in the years 2000, 2010 and 2020, that included one of 6 terms currently used to describe eye disease associated with autoimmune thyroid disease. Characteristics pertaining to authors, journals, and article type were recorded. Results showed that the most used term in the 2000 literature was Graves' Ophthalmopathy (61%). In the 2010 literature, Graves' Orbitopathy (31%) became most common, followed by Graves' Ophthalmopathy (30%). Between 2010 and 2020, thyroid eye disease (37%) became the most common term, followed by Graves' Orbitopathy (35%). This perspective article proposes "thyroid eye disease" (TED) as the preferred name for this entity and discusses supporting terminology patterns and trends over time in scientific literature and in professional societies.