SUN-336 - Graves Disease Stability Following Early Antithyroid Drug Discontinuation in A Transplant Recipient: Implications for Immunomodulatory Therapy

A 70-year-old male with Graves' disease and a history of orthotopic liver transplantation in February 2023 on immunosuppression presented to the endocrinology clinic for evaluation of hyperthyroidism. Graves' disease was diagnosed in 2022 after persistent thyroid-stimulating hormone (TSH) suppression ( < 0.02mIU/L) with elevated free thyroid hormone levels(>4ng/L) and markedly elevated thyroid-stimulating immunoglobulin (TSI) >296%. The patient was initially clinically euthyroid and elected to defer antithyroid drug (ATD) therapy. Due to progressive biochemical hyperthyroidism, methimazole was initiated in January 2023 at 30 mg daily. In April of 2023, after normalization of free thyroxine levels with persistently suppressed TSH, the dose was reduced to 10 mg daily.

In July 2023, methimazole was discontinued due to neutropenia during a hospitalization (absolute neutrophil count 840). Concurrently, mycophenolate mofetil was held, while tacrolimus was continued. Following resolution of neutropenia, mycophenolate was reintroduced in January 2024.

Despite early discontinuation of ATD therapy in July 2023, the patient has remained clinically stable. At follow-up visits, he denied symptoms of thyrotoxicosis including palpitations, tremors, anxiety, or heat intolerance and has maintained near-normal biochemical thyroid function.

Graves disease is an autoimmune disorder mediated by thyroid-stimulating immunoglobulins that activate the thyrotropin receptor, resulting in sustained hyperthyroidism. Recurrence following ATD withdrawal is common, particularly among patients with high-risk features. This patient possessed several established predictors of relapse, including male sex, active smoking history, markedly elevated TSI levels, and a high Graves’ Recurrent Events After Therapy (GREAT) score, classifying him as GREAT class III, a group associated with high recurrence risk.

Despite these unfavorable prognostic indicators, the patient demonstrated sustained biochemical and clinical stability after a short course of methimazole. This atypical disease course suggests that immunosuppression and modulation influenced disease activity. Graves disease is driven by dysregulated B- and T-cell interactions, and emerging therapies increasingly target immune pathways rather than thyroid hormone synthesis alone. Investigational strategies include antigen-specific immune tolerance induction, CD40–CD154 pathway blockade, and thyrotropin receptor–blocking monoclonal antibodies.

In this case, the post-transplant immune milieu and chronic immunosuppressive exposure may have attenuated autoimmune thyroid activity, counterbalancing his otherwise high recurrence risk. This observation supports growing interest in immune-targeted therapies as potential disease-modifying approaches for Graves disease, particularly in patients with high relapse risk or contraindications to standard therapy.

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