The incidence and mechanism of sunitinib-induced thyroid atrophy in patients with metastatic renal cell carcinoma

• Published in: British journal of cancer Vol. 104; no. 2; pp. 241 - 247
• Main Authors: SHINOHARA, N, TAKAHASHI, M, KAMISHIMA, T, IKUSHIMA, H, OTSUKA, N, ISHIZU, A, SHIMIZU, C, KANAYAMA, H, NONOMURA, K
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 18.01.2011
• Subjects: Adult; Aged; Antineoplastic Agents - adverse effects; Antineoplastic Agents - therapeutic use; Atrophy; Biological and medical sciences; Cancer research; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - pathology; Clinical Study; Cohort Studies; Drug dosages; Female; Growth factors; Humans; Hypothyroidism; Indoles - adverse effects; Indoles - therapeutic use; Kidney cancer; Kidney Neoplasms - drug therapy; Kidney Neoplasms - pathology; Kidneys; Male; Medical research; Medical sciences; Medicine; Metastasis; Neoplasm Metastasis; Nephrology. Urinary tract diseases; Pyrroles - adverse effects; Pyrroles - therapeutic use; Thyroid Function Tests; Thyroid gland; Thyroid Gland - diagnostic imaging; Thyroid Gland - drug effects; Thyroid Gland - pathology; Thyroid Gland - physiopathology; Tomography; Tomography, X-Ray Computed; Toxicity; Tumors; Tumors of the urinary system; University graduates; Japan; Endocrinopathy; Antineoplastic agent; Endocrine gland; Carcinoma; Thyroid gland; Metastasis; Epidemiology; Mechanism; Incidence; Atrophy; Sunitinib; Cancerology; Grawitz tumor; Advanced stage; Antiangiogenic agent; Protein-tyrosine kinase; Kidney disease; Human; Urinary system disease; Enzyme; Tyrosine kinase inhibitor; Transferases; Thyroid diseases; Enzyme inhibitor; Malignant tumor; Hypothyroidism; thyroid atrophy; renal cell carcinoma; Kidney cancer; Multikinase inhibitor; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6606029

To elucidate the incidence and mechanisms of sunitinib-induced thyroid atrophy, we investigated serial volumetric and functional changes, and evaluated histological changes of the thyroid gland in metastatic renal cell carcinoma patients who received sunitinib. Thyroid volume (by computed tomography volumetry) and thyroid function were measured at baseline, during the treatment, and at post-treatment periods. Histological evaluation of the thyroid gland was performed in four autopsied patients. The median reduction rate in thyroid volume at last evaluation during sunitinib treatment was 30% in all 17 patients. The incidence of hypothyroidism during sunitinib treatment was significantly higher in the high reduction rate group (n=8; more than 50% reduction in volume) than in the low reduction rate group (n=9; less than 50% reduction in volume). Half of the patients in the high reduction rate group exhibited a transient thyroid-stimulating hormone suppression, suggesting thyrotoxicosis during sunitinib treatment. Histological evaluation demonstrated atrophy of thyroid follicles and degeneration of follicular epithelial cells without critical diminution of vascular volume in the thyroid gland. Thyroid atrophy is frequently observed following sunitinib treatment and may be brought about by sunitinib-induced thyrotoxicosis or the direct effects of sunitinib that lead to degeneration of thyroid follicular cells.