Mannavola Deborah, Coco Paola, Vannucchi Guia, Bertuelli Rossella, Carletto Marco, Casali Paolo G, Beck-Peccoz Paolo, Fugazzola Laura
Department of Medical Sciences, University of Milan and Endocrine Unit, Fondazione Policlinico Istituto di Ricovero e Cura a Carattere Scientifico, 20122 Milan, Italy.
J Clin Endocrinol Metab. 2007 Sep;92(9):3531-4. doi: 10.1210/jc.2007-0586. Epub 2007 Jun 26.
Sunitinib (sunitinib malate; SU11248; Sutent; Pfizer Inc., New York, NY) is a multitarget inhibitor of tyrosine kinases for the treatment of some human cancers. A myxedematous coma in a patient treated with sunitinib for a gastrointestinal stromal tumor was unexpectedly observed.
Our objective was to evaluate the effect of sunitinib on thyroid function in 24 patients with gastrointestinal stromal tumors.
This was a prospective, observational cohort study.
The study was performed at two tertiary care hospitals.
A total of 24 patients receiving the following cycles of therapy were included in the study: 4-wk daily treatment at the dose of 50 mg orally (ON) and 2-wk withdrawal (OFF).
Thyroid function tests, ultrasonography, and iodine-123 ((123)I) thyroidal uptake were performed at the end of several ON and OFF periods.
After one to six cycles of treatment, 46% of patients developed hypothyroidism. Initially, TSH levels were elevated at the end of ON periods and normalized at the end of OFF periods, but a worsening in following cycles was always observed. Neither echographic alterations nor variations in thyroglobulin and antithyroid autoantibodies were found during the ON and OFF periods. On the contrary, (123)I uptake was significantly reduced at the end of ON periods, with partial or total normalization at the end of OFF periods.
A high prevalence of hypothyroidism, very severe in some cases, was observed during sunitinib. Significant variations in (123)I uptake strongly suggest that the underlying mechanism is an impaired iodine uptake. The absence of thyroid autoimmunity, the lack of a preceding transient hyperthyroidism, and the normal echographic pattern exclude autoimmune and/or destructive mechanisms. Patients on sunitinib should be strictly monitored for the appearance of hypothyroidism and promptly treated.
舒尼替尼（苹果酸舒尼替尼；SU11248；索坦；辉瑞公司，纽约州纽约市）是一种酪氨酸激酶多靶点抑制剂，用于治疗某些人类癌症。意外观察到一名接受舒尼替尼治疗胃肠道间质瘤的患者发生黏液性水肿昏迷。
我们的目的是评估舒尼替尼对24例胃肠道间质瘤患者甲状腺功能的影响。
这是一项前瞻性观察队列研究。
该研究在两家三级医疗医院进行。
共有24例接受以下治疗周期的患者纳入研究：每日口服50 mg，持续4周（服药期），然后停药2周（停药期）。
在几个服药期和停药期结束时进行甲状腺功能测试、超声检查和碘-123（¹²³I）甲状腺摄取检查。
经过1至6个周期的治疗，46%的患者出现甲状腺功能减退。最初，服药期结束时促甲状腺激素（TSH）水平升高，停药期结束时恢复正常，但在随后的周期中总是观察到病情恶化。在服药期和停药期均未发现超声改变，也未发现甲状腺球蛋白和抗甲状腺自身抗体的变化。相反，服药期结束时¹²³I摄取显著降低，停药期结束时部分或完全恢复正常。
在使用舒尼替尼期间观察到甲状腺功能减退的高发生率，在某些情况下非常严重。¹²³I摄取的显著变化强烈提示其潜在机制是碘摄取受损。缺乏甲状腺自身免疫、无前驱短暂性甲状腺功能亢进以及正常的超声表现排除了自身免疫和/或破坏性机制。应严格监测使用舒尼替尼的患者是否出现甲状腺功能减退，并及时进行治疗。
