Saad-Omer, Suhail

Background: Pretibial dermopathy (PTD) is a rare, disfiguring manifestation of Graves’ disease. The shared pathophysiology with thyroid eye disease (TED), centered on fibroblast activation via a thyroid-stimulating hormone receptor and insulin-like growth factor-1 receptor (IGF-1R) complex, provides a strong rationale for using the IGF-1R inhibitor, teprotumumab. Methods: We present a case series of five patients with severe PTD and concomitant TED who were treated with teprotumumab. A review of reported cases in the literature was also conducted. Results: All patients experienced significant clinical improvement, including regression of skin thickening as well as enhanced functional capacity. Side effects included mild hearing loss, muscle cramps, and fatigue. One patient experienced a severe gastrointestinal event requiring treatment discontinuation, while those experiencing a recurrence of PTD, responded to a second course of therapy. Conclusions: Teprotumumab showed promising efficacy in the treatment of PTD. Further studies are needed to confirm its durability and safety.

Abstract Immune checkpoint inhibitors (ICI) have transformed cancer therapy but can induce a spectrum of endocrine complications. Acquired generalized lipodystrophy (AGL) is a rare adverse effect, leading to severe metabolic derangements including insulin-resistant diabetes, dyslipidemia, and hepatic steatosis. Marked hypoleptinemia is noted in these patients, and leptin-replacement therapy is known to be beneficial in patients with other forms of AGL. Though rare, T-cell lymphoma has been reported in patients with AGL on leptin therapy, and there has been much debate on the association between hyperleptinemia and cancer. The safety and efficacy of leptin therapy in patients with ICI-induced AGL and cancer are therefore not clear. We report a 66-year-old woman with metastatic lung adenocarcinoma who developed multiple endocrine disorders including AGL with metabolic abnormalities following pembrolizumab therapy. Initiation of daily metreleptin led to marked improvement in dyslipidemia, glycemic control, and hepatic steatosis, with no evidence of cancer recurrence after 2 years of leptin-replacement therapy. While further studies are warranted to establish the long-term efficacy and safety of leptin in ICI-induced AGL patients with a history of malignancy, this case report provides useful information for the management of these rare, challenging patients.

Abstract Disclosure: S. Saad-Omer: None. M. Stan: None. M.R. Castro: None. J. Brito: None. J.E. Hallanger-Johnson: None. M.M. Ryder: None. Background: Thyroid fine needle aspiration (FNA) is a widely utilized diagnostic tool for evaluating thyroid nodules. The Bethesda System for Reporting Thyroid Cytopathology (BSRTC) provides a standardized framework for classifying cytologic findings and guiding management. This study retrospectively reviews thyroid FNA cases at a large academic institution to analyze the distribution of Bethesda classifications.Methods: A retrospective review was conducted of all thyroid FNA cases done in the department of Endocrinology at a large academic institution performed from January 1st 2019 to October 3rd 2023. Thyroid FNA results were divided into categories according to the Bethesda classification system, such as benign, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS), follicular neoplasm (FN), suspicious for malignancy, malignancy and non-diagnostic. FNA results that were not able to be classified were labelled as other.Results: A total of 3,291 thyroid FNA cases were included in the analysis. The distribution of cases across the Bethesda categories revealed a significant proportion of benign findings, with 73.6% classified as benign. This was followed by 8.1% follicular neoplasm, 6.56% Papillary Thyroid Cancer, 6.62% Non-diagnostic, 2.4% Atypical, and 2.3% Suspicious. 0.5% of FNA results were classified as other.Conclusion: Overall our cohort was found to have similar findings in terms of benign and confirmed PTC nodules compared to recent literature; however, the rate of atypical and non-diagnostic nodules was found to be lower. Presentation: Monday, July 14, 2025

Abstract Disclosure: Y. Ahmed: None. S.M. Saad-Omer: None. R.M. Castro: None. M. Rivera: None. M.N. Stan: None. Background: Fine-needle aspiration (FNA) is a cornerstone in the evaluation of thyroid nodules. Its accuracy during long term follow up is not well established though. Our project aims to address that. Objective: To assess long-term accuracy of FNA results at Mayo Clinic Rochester including diagnostic classifications, procedural and cytologic variables, and concordance with surgical pathology. Methods: We conducted a retrospective cohort study of patients who underwent thyroid FNA at Mayo Clinic Rochester in 2014, to allow for the long-term follow-up. Descriptive statistics summarized patient demographics, nodule characteristics, and procedural factors. Cross-tabulation was used to evaluate concordance between FNA cytology and surgical pathology. This is an interim analysis. Results: Among 199 patients (from 741 FNAs that year), the mean age was 58.6 ± 14.1 years, and 73.7% were female. The average BMI was 29.6 ± 6.4 kg/m². Most had non-toxic multinodular goiter (69.3%) or non-toxic solitary nodules (27.6%). Nodules were 45% solid, 8% cystic, and 47% mixed, with a mean size of 2.3 cm. FNA results were predominantly benign (Bethesda II, 80%), followed by malignant (Bethesda VI, 8%), suspicious for follicular neoplasm (Bethesda IV, 7.5% ), non-diagnostic (Bethesda I, 3%), and suspicious for malignancy (Bethesda V,1%). There were no cases read as Bethesda III (AUS) in 2014. Of the 16 Bethesda VI cases, 15 had surgery; 14 were confirmed malignant, and 1 was benign (Hurthle cell adenoma). Both Bethesda V cases that underwent surgery were benign. Of the 15 Bethesda IV cases, 12 had surgery; 11 were benign and 1 was malignant and 3 had long term follow up (2 benign, and one malignant based on the available data). Overall the malignancy rate for Bethesda IV was 13.3%. Surgery was performed in 12 Bethesda II cases, with final pathology available for 11; 9 were confirmed benign, while 2 were malignant. In the other 147 cases of benign FNAs that didn’t undergo surgery we have not identified any indication of necessity for surgery during the mean of 9 years of follow-up, presumably indicating their benign character. Overall malignancy rate for this group was 1.3%. We had only 6 non diagnostic FNAs (Bethesda I), with all of them during follow up proven benign (2 by surgery, 2 by repeat FNA and 2 by long term follow up). Conclusion: Long term follow up data (over 9 years) support the continued reliability of Bethesda II and VI , while conversely raising questions about the significance of the Bethesda V classification. The malignancy rate in Bethesda IV (likely including the Bethesda III category at the time) is consistent with our institutional data, although it remains lower than that reported by other institutions. We’re currently enriching our cohort to verify and strengthen our conclusions. Presentation: Monday, July 14, 2025