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.

Successful treatment of erythropoietin-producing advanced renal cell carcinoma after targeted therapy using sunitinib: Case report and review of the literature.

In general, only ≤5% of patients with renal cell carcinoma (RCC) develop paraneoplastic erythropoietin (EPO) overproduction-induced polycythemia. However, a number of reports on EPO-producing RCC are available. The present study aimed to report the first case of a patient demonstrating a therapeutic effect on EPO-producing advanced RCC, subsequent to targeted pre-surgical sunitinib therapy, with a review of the literature. The patient involved was a 62-year-old male who presented with a malformation of the left scrotum. Examination revealed a tumor of 73 mm in diameter along with lymph node metastasis. The histological examination indicated a clear cell RCC containing viable cells as well as hemorrhage and necrosis. EPO in cancer cells was confirmed by immunohistochemistry. Subsequently, a case of EPO-producing RCC with polycythemia was diagnosed. The EPO-producing RCC was successfully treated following targeted presurgical therapy with sunitinib.

The Interaction between female sex hormone receptors and osteopontin in a rat hyperoxaluric model.

It is well known that the incidence of urinary stones is higher in men than women. Although it is believed that the lower incidence of urinary stones in women is due to a protective effect of estrogen, the mechanisms remain unclear. To clarify the relation between female sex hormones and stone matrix protein, we examined the interaction of estrogen receptor-α (ERα), estrogen receptor-related receptor-α (ERRα), and stone matrix protein osteopontin (OPN) in a rat hyperoxaluric model and in primary cultured rat kidney cells. Adult female Wistar rats were divided into 6 groups. Groups 1 and 4 consisted of normal females, Groups 2 and 5 consisted of ovariectomized females, and Groups 3 and 6 consisted of ovariectomized females receiving female sex hormone supplements. Groups 1-3 were administered distilled water, while groups 4-6 were administered 0.5% ethyleneglycol (EG). Moreover, rat kidney primary cultured cells were examined after treatment with female sex hormones under various conditions. The expressions of ERα, ERRα and OPN-mRNA in whole kidney and primary cultured cells were examined using Real-Time PCR. The expressions of OPN and ERRα-mRNA were suppressed by ovariectomy. Supplementation with female sex hormones increased the expression of OPN and ERRα-mRNA. In contrast, the expression of ERα-mRNA was increased by ovariectomy and suppressed by supplementation with female sex hormones. The results of the mRNA expression in primary cultured cells matched those in the hyperoxaluric model rats. Although the reason for the difference in expression between ERα and ERRα-mRNA is unclear, estrogen may regulates OPN expression through ERα and/or ERRα, either independently or in combination. Moreover, the decrease of OPN induced by removal of estrogen may increase urinary stones in postmenopausal women.