Abstract:
Diagnosis: Hyperfunctional or hot thyroid nodules are autonomously functioning and produce thyroid hormone independently of pituitary regulation. Hot nodules account for approximately 5-10% of palpable thyroid nodules. Some patients may remain asymptomatic, though some may present with signs of thyrotoxicosis including palpitations, weight loss, heat intolerance, tremors, and anxiety. Laboratory findings typically report suppressed thyroid-stimulating hormone (TSH) with normal to elevated triiodothyronine (T3) and thyroxine (T4) levels. These nodules are diagnosed using radionuclide thyroid scintigraphy which reveal a focal area of increased uptake compared to the remainder of the gland. This case presents a patient with a history of a partial thyroidectomy resulting in hypothyroidism that was maintained on thyroid hormone for over 20 years, who subsequently developed a hyperfunctioning nodule in the setting of both thyroid peroxidase (TPO) and thyroid-stimulating immunoglobulin (TSI) antibodies.
Description: We present a 65 year-old female with a history of left-lobe thyroidectomy in the 1990s due to a suspicious nodule. After resection it was confirmed the nodule was of benign pathology. Due to the surgery she subsequently developed postoperative hypothyroidism and was well-maintained on a 100 mcg dose of levothyroxine for over 20 years. 1 year ago, due to a decrease in her TSH levels, her levothyroxine dose was incrementally decreased to 25 mcg daily by her primary care physician. Despite the decrease in her thyroid hormone dosage, she persisted to be in a hyperthyroid state and presented to the ER in August of 2025 with signs of thyrotoxicosis. She complained of dizziness, palpitations, and anxiety, and was found to have new-onset atrial fibrillation with rapid ventricular response (RVR). Laboratory studies at that time confirmed persistent hyperthyroidism while still on low-dose levothyroxine, which was now further decreased to 25 mcg three times weekly. Despite being clinically stabilized on this dosage, her lab TSH values continued to show levels consistent with hyperthyroidism. The patient was referred to endocrinology where her levothyroxine was stopped. After being discontinued for 8 weeks, TSH remained suppressed at 0.09 mIU/L. This prompted a series of labs including autoantibodies and a thyroid ultrasound. Subsequently, the patient was found to be positive for TSI and TPO antibodies which are found in Graves and Hashimoto’s disease respectively. Thyroid ultrasound revealed a 2.3 cm nodule in the remaining right lobe, and radionuclide uptake scan demonstrated focal increased uptake consistent with a hot nodule. Currently the patient has been initiated on methimazole, however, the final dosage is yet to be established pending further clinical and laboratory evaluation.
Conclusion: This case illustrates how hyperthyroid disease may present unexpectedly in patients with a history of hypothyroidism receiving stable replacement therapy and emphasizes the importance of routine reassessment of thyroid function in this population. Delayed recognition of true hyperthyroid pathology is common, as symptoms are frequently attributed to medication over-supplementation. This case also highlights the rare overlap of autoimmune thyroid disease with concurrent TSI and TPO positivity in the setting of nodular thyroid disease, a phenomenon that has seldom been described in the literature.
