Stan, Marius

Abstract Disclosure: D. Hamadi: None. A. Algeciras-Schimnich: None. M. Stan: None. Background: Thyroid hormone-binding proteins (TBPs)—thyroxine-binding globulin (TBG), transthyretin, and albumin—play a critical role in transporting thyroid hormones in the bloodstream. Rare genetic alterations in these proteins can lead to discordant thyroid function test (TFT) results, potentially mimicking thyroid dysfunction despite a clinically euthyroid state. This study retrospectively evaluates the clinical scenarios that warrant TBP testing. Methods: Data was extracted from the electronic medical record (EMR) at the Mayo Clinic in Rochester, MN. The study included patients who had Thyroid-binding protein electrophoresis (TBPE) ordered between 2016 to 2023. Results: A total of 138 patients were included (53% female; median age: 58 years) of which 42% had TBP abnormalities. TBP testing was frequently ordered by endocrinology (33%), followed by cardiology (9%) and family medicine (7%). Discrepancies between thyroid-stimulating hormone (TSH) and total T4 (TT4) were identified in 41 patients of which 75% had abnormal TBP. Among these, eleven were diagnosed with familial dysalbuminemic hyperthyroxinemia (FDH), including one with a known family history. Additionally, five patients were diagnosed with thyroid hormone resistance—one of whom had previously been misdiagnosed with Graves’ disease. Three patients were found to have TSH-secreting tumors, and three were receiving infusion therapy with patisiran with resulting TBP abnormalities. The remaining cases involved binding protein abnormalities, most commonly presenting as elevated TBG. Conclusion: This study identified varied clinical utilization for TBP testing, from very appropriate indications to cases of doubtful clinical utility. TBP abnormalities were clinically meaningful in 22% of cases, supporting the utility of testing in select scenarios. Specifically, TBP testing should be reserved for situations with a clear discrepancy between clinical presentation and TFT results—particularly discordant TSH and total T4 levels. In such contexts, TBP assessment is valuable in preventing misdiagnoses and avoiding unnecessary treatments, especially since individuals with TBP mutations are typically clinically euthyroid. Presentation: Sunday, July 13, 2025

Abstract Thyroid dysfunction in pregnancy has been associated with hypertensive disorders of pregnancy and poor maternal and fetal outcomes. In this article, we describe two cases of significant thyroid dysfunction leading to new diagnoses of chronic hypertension in pregnancy and review physiologic changes in the thyroid gland, placenta and maternal cardiovascular system during pregnancy.

AbstractThe course and pathogenesis of Graves’ disease and Graves’ ophthalmopathy are interdependent, influencing each other’s therapeutic choices. Multiple factors including geographic location, access to medical services, patient and physician preferences influence the management of these conditions. Graves’ disease is classically managed with one of three treatment options – antithyroid drugs, radioactive iodine, and thyroidectomy. In recent years, there has been a shift towards antithyroid drugs, including long term therapy with these agents, given the advantage of avoiding hypothyroidism and the apparent safety of this approach. In addition, new therapies are (slowly) emerging, focusing on immunomodulation. Technological advances are opening doors to non-pharmaceutical interventions that aim to deal with both structural thyroid abnormalities as well as biochemical abnormalities of hyperthyroidism. Graves’ ophthalmopathy management is guided by its activity and severity status, with treatment options including smoking cessation, control of hyperthyroidism, local eye measures, glucocorticoids, selenium, orbital radiotherapy, and surgery. In addition to these established treatment choices, new immunotherapy-based approaches are being tested. Some of them (tocilizumab and teprotumumab) are very promising but further evaluation is needed before we can establish their role in clinical care. Agents identified as beneficial in Graves’ disease management will likely be tested in Graves’ ophthalmopathy as well. In the coming years, our main clinical responsibility will be to find the proper balance between the benefits and potential risks of these incoming therapies, and to identify the subgroups of patients where this ratio is most likely to favor a safe and successful therapeutic outcome.

Background: Thyroid lymphoma is a relatively rare disease often posing a diagnostic challenge. Reaching the final diagnosis can be delayed if insufficient biopsy material is obtained for immunohistochemistry analysis. The aim of this study was to evaluate the clinical, biochemical, and radiological features of thyroid lymphoma. Methods: A retrospective analysis was conducted of all Mayo Clinic patients evaluated between 2000 and 2014 who had a tissue biopsy positive for thyroid lymphoma. Results: Seventy-five subjects had biopsy-proven thyroid lymphoma, and 62.7% were primary thyroid lymphomas. The median age at diagnosis was 67 years (range 20–90 years). A total of 50.7% were male, and 54.7% had a history of Hashimoto's thyroiditis. Presenting symptoms included neck mass (88%), dysphagia (45.3%), and hoarseness (37.3%). The typical ultrasound appearance consisted of a solid, hypoechoic mass with increased vascularity and variable edge characteristics. Fine-needle aspiration (FNA) biopsies were abnormal in 70.7% of cases, and 42% indicated a specific lymphoma subtype. The diagnosis was confirmed in 53.3% by core biopsy, in 21.3% by thyroidectomy (partial or total), in 12% through incisional biopsy, and in 12% by lymph node biopsy. Core biopsy had a higher sensitivity compared with FNA (93% vs. 71%, p = 0.006). Conclusion: A rapidly enlarging neck mass in the setting of Hashimoto's thyroiditis should raise suspicion for thyroid lymphoma. Radiologically, this usually presents as a large, unilateral, thyroid-centered mass, hypoechoic by ultrasound, and expanding into adjacent soft tissues. Core-needle biopsy should be the first diagnostic test to expedite reaching the final diagnosis and decrease patient burden of additional tests and interventions.