Destructive thyroiditis presenting as thyrotoxicosis followed by hypothyroidism during lenvatinib therapy for hepatocell
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CASE REPORT
Destructive thyroiditis presenting as thyrotoxicosis followed by hypothyroidism during lenvatinib therapy for hepatocellular carcinoma Maito Suoh1 · Hideki Fujii1 · Yuki Nagata2 · Kohei Kotani1 · Atsushi Hagihara1 · Masaru Enomoto1 · Akihiro Tamori1 · Masaaki Inaba2 · Norifumi Kawada1 Received: 29 October 2019 / Accepted: 16 February 2020 © Japanese Society of Gastroenterology 2020
Abstract Hypothyroidism is a common adverse event of lenvatinib therapy for hepatocellular carcinoma (HCC), whereas thyrotoxicosis has rarely been reported in clinical trials. A 74-year-old man complaining of abdominal pain was found to have liver tumors and paraaortic lymphadenopathy. The intrahepatic lesions were diagnosed as HCC by angiography and treated with transcatheter arterial chemoembolization. Although localized prostate cancer was discovered incidentally, the etiology of paraaortic lymphadenopathy was assumed to be metastatic HCC. Lenvatinib 12 mg/day was started when his thyroid function tests were almost normal but was interrupted because of thyrotoxicosis. The patient was negative for tested thyroid autoantibodies. Color Doppler ultrasonography detected reduced thyroid blood flow, suggesting destructive thyroiditis. Although he resumed lenvatinib at 8 mg/day once his serum level of free thyroxine normalized, thyrotoxicosis recurred. Subsequently, he suffered hypothyroidism, which exacerbated despite levothyroxine replacement. Lenvatinib was discontinued as it was ineffective against the paraaortic lymph node metastasis, and external-beam radiotherapy was performed. After the completion of radiotherapy, the thyroid dysfunction significantly improved. In summary, lenvatinib for HCC can induce transient thyrotoxicosis followed by hypothyroidism, which is compatible with destructive thyroiditis. During lenvatinib therapy, close monitoring of thyroid function and appropriate management of thyrotoxicosis as well as hypothyroidism are essential. Keywords Hepatocellular carcinoma · Lenvatinib · Destructive thyroiditis · Thyrotoxicosis · Hypothyroidism
Introduction Lenvatinib is an oral tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor (VEGFR) 1–3, fibroblast growth factor receptor (FGFR) 1–4, plateletderived growth factor receptor (PDGFR) α, RET, and KIT [1, 2]. In 2018, a phase 3 global multicenter randomized controlled study (the REFLECT trial) showed that lenvatinib as the first-line systemic therapy is non-inferior to sorafenib in * Norifumi Kawada [email protected]‑cu.ac.jp 1
Department of Hepatology, Osaka City University Graduate School of Medicine, 1‑4‑3, Asahimachi, Abeno‑ku, Osaka 545‑8585, Japan
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, 1‑4‑3, Asahimachi, Abeno‑ku, Osaka 545‑8585, Japan
2
terms of overall survival (OS) in patients with unresectable HCC [3]. Therefore, lenvatinib is currently recommended as the first-line chemotherapeutic agent for unresectable HCC in addition to s
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