Clinical characteristics of thyroid abnormalities induced by sunitinib treatment in Japanese patients with renal cell carcinoma.
Sunitinib is a multi-targeted tyrosine kinase inhibitor that is effective for advanced renal cell carcinoma. However, sunitinib often causes hypothyroidism. In this study, we report eight cases with thyroid dysfunction that occurred during sunitinib treatment for advanced renal cell carcinoma. In seven cases, mild hypothyroidism developed early in the first treatment cycle, and recovered spontaneously. Transient hyperthyroidism was observed during the second or third treatment cycles and was preceded by a rapid increase in thyroglobulin levels. (99m)Tc scintigraphy in the hyperthyroid state showed decreased thyroidal uptake of (99m)TcO(4)(-), suggesting destructive thyroiditis. Hypothyroidism subsequently developed, requiring levothyroxine replacement therapy. Ultrasonography showed a hypoechogenic pattern of the parenchyma and decreased intrathyroidal blood flow. The thyroid glands ultimately became atrophic, which may progress to permanent hypothyroidism. These findings suggest that sunitinib-induced hypothyroidism may occur frequently and may be a consequence of thyroiditis with transient thyrotoxicosis. The marked decrease in thyroid size due to reduced capillary blood flow induced by VEGF receptor inhibition may cause delayed and/or permanent hypothyroidism. Therefore, thyroid function should be monitored in all patients treated with sunitinib.
Sato
Shuichi
S
Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan. dem_sato@med.kurume-u.ac.jp
Muraishi
Kazuhisa
K
Tani
Junichi
J
Sasaki
Yuko
Y
Tokubuchi
Ichiro
I
Tajiri
Yuji
Y
Yamada
Kentaro
K
Suekane
Shigetaka
S
Miyajima
Jiro
J
Matsuoka
Kei
K
Hiromatsu
Yuji
Y
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001284:Atrophy; D002292:Carcinoma, Renal Cell / Q000188:drug therapy*; D018450:Disease Progression; D005260:Female; D006801:Humans; D006980:Hyperthyroidism / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D007037:Hypothyroidism / Q000139:chemically induced* / Q000473:pathology; D007211:Indoles / Q000009:adverse effects* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D009929:Organ Size / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000009:adverse effects* / Q000627:therapeutic use; D012039:Regional Blood Flow / Q000187:drug effects; D000077210:Sunitinib; D013961:Thyroid Gland / Q000098:blood supply / Q000187:drug effects* / Q000473:pathology; D013966:Thyroiditis / Q000139:chemically induced; D013971:Thyrotoxicosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology
D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011758:Pyrroles; D000077210:Sunitinib