Журнал клинических случаев

Rectal and Liver Metachronous Cancers and Sorafenib-Induced Thyroid Dysfunction.

Abstract

Ancuta Augustina Gheorghisan Galateanu, Mara Carsote, Dan Peretianu, Cristina Iosif, Dana Terzea and Catalina Poiana

Background: The tyrosine kinase inhibitor, a new treatment option in hepatic carcinoma, may associate thyroid dysfunction like spontaneously remitting thyrotoxicosis followed by hypothyroidism. Case report: A 66-year Caucasian female was first diagnosed and operated for a moderately differentiated rectal adenocarcinoma of 5 centimeters. Immunohistochemistry showed positive VEGF receptor 2 (Flk-1, KDR), VEGF receptor 1(Flt-1), and a Ki67 of 30%. 4 years later a hepatic adenocarcinoma (clear cells variant) was diagnosed. After surgery, daily 400 mg of sorafenib was introduced. Three months later mild symptomatic thyrotoxicosis was seen: palpitations, fatigue, and mild bilateral pedal clonus. Thyroid-stimulating hormone (TSH) was suppressed (0.044 μIU/mL, normal levels between 0.4 and 4.5 μIU/mL), and free levothyroxine (fT4) elevated. The TSH receptor antibody, the antithyreoglobulin and antithyreoperoxidase antibodies were negative. Thyroid ultrasound pointed hypoechogenic, inhomogeneous aspects. She received beta-blocker and within two months thyrotoxicosis remitted but TSH progressively increased suggesting hypothyroidism with level less 5 μIU/mL so no replacement levothyroxine therapy was added yet. Discussions: The exact mechanism of the tyrosine kinase inhibitors-related thyroid malfunction is not fully understood. Non-autoimmune destructive thyroiditis of unknown trigger causes thyrotoxicosis and later hypothyroidism as seen in our case. The clinical features vary from one person to another. The hormone replacement is rarely necessary. The baseline cancer seems irrelevant for thyroid toxicity. In our unusual case the patient had a history of two metachronous cancers. The thyroid follow up is essential during each patient therapy yet a specific pattern of follow-up is not precisely designed. Conclusion: The tyrosine kinase inhibitor-induced thyroid dysfunction includes both thyrotoxicosis and hypothyroidism. We emphasize the idea of periodic endocrine evaluation in oncologic patient treated with this class of drugs.