Lithium Therapy–Associated Thyroid Alterations Mimicking Thyroid Malignancy: A Diagnostic Pitfall

Abstract

Lithium is a commonly used mood stabilizer in managing bipolar disorder. While its therapeutic benefits are well-documented, its potential to induce thyroid-related disorders has long been recognized. Hypothyroidism is the most common thyroid dysfunction associated with lithium, though lithium-induced thyroiditis remains a rare and often overlooked complication. In this report, we describe a thyroid nodule initially diagnosed as “high-grade thyroid carcinoma” due to severe histomorphologic changes at an outside institution, which was later reclassified at our review as an iatrogenic effect of long-term lithium therapy. Preoperative fine needle aspiration, interpreted as “atypical follicular neoplasm (Bethesda Category IV),” prompted a diagnostic right lobectomy. No molecular testing was performed. The lobectomy was misinterpreted as carcinoma, leading to completion thyroidectomy. Histologic features included intersecting fibrosis, patchy lymphocytic inflammation, hyperplastic changes with pseudopapillary formation, nuclear pleomorphism with hyperchromasia, and giant cell formation, but notably absent were mitotic activity and necrosis, which are required for poorly differentiated or differentiated high-grade thyroid carcinoma under the 2022 WHO criteria. The patient's long history of lithium therapy was instrumental in recognizing the functional origin of the thyroid changes, which, if identified earlier, could have prevented unnecessary completion surgery. This report highlights the evolving diagnostic criteria for thyroid tumors, illustrating how lithium-associated thyroiditis can mimic malignancy and lead to overtreatment if historical context is not considered.