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.

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.

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.