Endocrine Abstracts

The most common cause of primary hypothyroidism is Hashimoto’s disease, while the most common cause of hyperthyroidism is Graves’ disease; both conditions are autoimmune diseases. In clinical practice, the switch from hypothyroidism to hyperthyroidism is a rare phenomenon. So far, the etiology and mechanisms of conversion have not been determined. We present a case where we believe the monoclonal antibody rituximab was the primary cause of transition. A 58-year-old male patient presented to the hospital with enlarged neck lymph nodes. After undergoing a number of tests, he was diagnosed with 3 synchronous primary neoplasms: mantle cell lymphoma (B-cell lymphoma), localized colorectal cancer, and localized right kidney cancer. At the same time, he was also diagnosed with diffuse thyroid goiter and hypothyroidism (TSH 67.35 mIU/l, FT-4 3.4 pmol/l), and levothyroxine therapy was begun. First, the patient underwent surgery: a rectosigmoid colon resection and right-sided nephrectomy were performed. Due to the low grade of the lymphoma, the immunochemotherapy treatment was postponed so that the patient could receive capecitabine chemotherapy for colon cancer. At the end of capecitabine chemotherapy, the patient was euthyroid with 175 mg/day of levothyroxine, and R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristin, and prednisone) treatment for mantle cell lymphoma was started. The patient received 8 cycles of therapy within 6 months, which resulted in disease remission; however, at the end of the last cycle, the TSH values were lowered. Levothyroxine dosage was gradually reduced as a result of decreasing TSH levels, and it was completely discontinued 4 years after the end of the R-CHOP treatment. Despite discontinuation of the therapy, the patient’s TSH remained <0.005 pmol/l; unfortunately, we missed levels of thyrotropin receptor antibodies (both blocking and stimulating). The patient started losing weight and had exophthalmos, therefore, thyrostatic therapy with thiamazole was started. Initially, the patient responded well to the therapy, but over time there was a relapse of hyperthyroidism, which no longer responded to thiamazole, necessitating a total thyroidectomy. Until now, nine years following the diagnosis of three primary malignant diseases, there have not been any disease relapses. There are a variety of opposing theories described in the literature about how rituximab affects the thyroid. While it is used to treat resistant Graves’ orbitopathies, in our patient’s case, it appears that rituximab led to the resolution of the hypothyroidism and caused the hyperthyroidism. However, it remains unclear whether chemotherapeutic agents used in combination with rituximab contributed to that transition.