A Case of Sunitinib-Induced Destructive Thyroiditis

Sunitinib is a multi-targeted tyrosine-kinase inhibitor used for gastrointestinal stromal tumors and renal cell carcinoma (RCC). Several recent studies have reported sunitinib-induced hypothyroidism and thyroid dysfunction; however, the underlying mechanisms are not clear. Here, we report a patient with metastatic RCC, who developed destructive thyroidtis due to sunitinib treatment. The course followed in this case may be useful in understanding the clinical course of sunitinib-induced thyroiditis.

Interferon-Alpha-Induced Destructive Thyroiditis Followed by Graves' Disease in a Patient with Chronic Hepatitis C: A Case Report

Interferon-induced thyroiditis (IIT) is a major clinical problem for patients receiving interferon-alpha (IFN-alpha) therapy. But, destructive thyroiditis followed by Graves' disease associated with IFN-alpha therapy is very rarely reported. Herein, we report a rare case of pegylated IFN-alpha (pegIFN-alpha) induced destructive thyroiditis followed by Graves' disease in a patient with HCV infection. A 31-yr-old woman suffered from chronic active hepatitis C and was treated with pegIFN-alpha and ribavirin for 12 months. Results of a thyroid function test and autoantibody levels were normal before IFN-alpha therapy was initiated. Destructive thyrotoxicosis appeared seven months after the initiation of IFN-alpha therapy, followed by Graves' thyrotoxicosis two months after the cessation of therapy. The diagnoses of destructive thyroiditis and Graves' disease were confirmed by the presence of TSH receptor antibodies in addition to Tc-99m scintigraphy findings. The patient's antithyroglobulin antibody titer increased gradually during IFN-alpha therapy and remained weakly positive after IFN-alpha therapy was discontinued.

Thyroid hormonal disturbances related to treatment of hepatitis C with interferon-alpha and ribavirin

OBJECTIVE: To characterize thyroid disturbances induced by interferon-alpha and ribavirin therapy in patients with chronic hepatitis C. INTRODUCTION: Interferon-alpha is used to treat chronic hepatitis C infections. This compound commonly induces both autoimmune and non-autoimmune thyroiditis. METHODS: We prospectively selected 26 patients with chronic hepatitis C infections. Clinical examinations, hormonal evaluations, and color-flow Doppler ultrasonography of the thyroid were performed before and during antiviral therapy. RESULTS: Of the patients in our study, 54 percent had no thyroid disorders associated with the interferon-alpha therapy but showed reduced levels of total T3 along with a decrease in serum alanine aminotransferase. Total T4 levels were also reduced at 3 and 12 months, but free T4 and thyroid stimulating hormone (TSH) levels remained stable. A total of 19 percent of the subjects had autoimmune interferon-induced thyroiditis, which is characterized by an emerge of antithyroid antibodies or overt hypothyroidism. Additionally, 16 percent had non-autoimmune thyroiditis, which presents as destructive thyroiditis or subclinical hypothyroidism, and 11 percent remained in a state of euthyroidism despite the prior existence of antithyroidal antibodies. Thyrotoxicosis with destructive thyroiditis was diagnosed within three months of therapy, and ultrasonography of these patients revealed thyroid shrinkage and discordant change in the vascular patterns. DISCUSSION: Decreases in the total T3 and total T4 levels may be related to improvements in the hepatocellular lesions or inflammatory changes similar to those associated with nonthyroidal illnesses. The immune mechanisms and direct effects of interferon-alpha can be associated with thyroiditis. CONCLUSION: Interferon-alpha and ribavirin induce autoimmune and non-autoimmune thyroiditis and hormonal changes (such as decreased total T3 and total T4 levels), which occur despite stable free T4 and TSH levels. A thyroid hormonal evaluation, including the analysis of the free T4, TSH, and antithyroid antibody levels, should be mandatory before therapy, and an early re-evaluation within three months of treatment is necessary as an appropriate follow-up.

La tiroiditis bifásica: un patrón fisiopatológico en las tiroiditis

La disfunción tiroidea es una observación común en el curso evolutivo de las tiroiditis. En las fases avanzadas de la tiroiditis crónica autoinmune es muy frecuente el hallazgo de hipotiroidismo clínico o subclínico, como consecuencia del reemplazo glandular por la fibrosis y atrofia resultantes. El hipotiroidismo permanente también es una secuela común en la tiroiditis silente y poco frecuente en la tiroiditis subaguda. Por otra parte, se conoce como “tiroiditis destructiva”, al proceso inflamatorio tiroideo acompañado de destrucción del epitelio glandular y tirotoxicosis transitoria, que usualmente ocurre en los primeros meses de evolución de las tiroiditis subaguda y silente o, en un porcentaje menor, durante el curso de la tiroiditis crónica autoinmune. Desórdenes que tienen diferente patogénesis, como, la tiroiditis subaguda, vinculada con las infecciones virales, o las tiroiditis silente o posparto y la enfermedad de Hashimoto, reconocidos procesos autoinmunes, son responsables de fenómenos fisiopatológicos similares que dan origen a la “tiroiditis bifásica”. De manera característica, estos casos desarrollan secuencialmente, tirotoxicosis pasajera que va seguida de hipotiroidismo transitorio y recuperación. En dos muestras venezolanas, la tirotoxicosis pasajera y el hipotiroidismo transitorio con el patrón de la tiroiditis bifásica se observó, respectivamente, en 86 % y 27 % de los casos de tiroiditis subaguda y, el patrón bifásico, en los cuatro casos de tiroiditis silente o posparto. En la muestra de tiroiditis crónica autoinmune, no se observó ningún caso de tiroiditis bifásica. Los mecanismos fisiopatológicos de la tiroiditis bifásica son consecuencia directa de la inflamación tiroidea y la autoinmunidad, que también implica a los anticuerpos estimulantes o bloqueadores del receptor de la hormona estimulante de la tiroides.

La observación de este patrón funcional y su reversibilidad, constituye indudablemente un comportamiento sui generis en las enfermedades de las glándulas endocrinas, en las que hiper o hipofunción espontáneas, suelen ocurrir aislada y permanentemente. Por eso, parece justificado presentar sendos casos típicos de tiroiditis subaguda, silente y crónica autoinmune, en los cuales, el patrón de la tiroiditis bifásica fue el hallazgo más relevante de su evolución clínica.

Thyroid dysfunction is commonly observed in the clinical course of thyroiditis. Clinical or subclinical hypothyroidism frequently occurred in chronic autoimmune thyroiditis as a consequence of progressive glandular replacement by fibrosis and atrophy. Also, permanent hypothyroidism is a common sequel of silent thyroiditis, unusual in subacute thyroiditis. Thyroid inflammatory process associated to destruction of glandular epithelium and transitory thyrotoxicosis is known as “destructive thyroiditis”, which frequently occurred in the first months of subacute or silent thyroiditis evolution or, in a little percentage, during the course of chronic autoimmune thyroiditis. Disorders with different pathogenesis, as subacute thyroiditis which is entailed with viral infections or, silent-postpartum or chronic autoimmune thyroiditis, known autoimmune diseases, are responsible of similarly pathophysiological phenomena which originated “biphasic thyroiditis”. Characteristically, these cases developed sequentially transitory thyrotoxicosis, which is followed by transient hypothyroidism and recovery. In two Venezuelan samples, transitory thyrotoxicosis and hypothyroidism with biphasic patron were observed, respectively, in 86 % and 27 % of thyroiditis subacute cases and, the biphasic patron, in the four cases with silent or postpartum thyroiditis. In the sample of chronic autoimmune thyroiditis, no cases of biphasic thyroiditis were observed.

The pathophysiological mechanisms of biphasic thyroiditis are direct consequence of thyroidal inflammation and autoimmunity, which also imply the effects of stimulating or blocking antibodies for the stimulant thyroid hormone receptor. Undoubtedly, this functional patron and its reversibility, constitutes a sui generis behavior in the endocrine glands diseases, in which spontaneous hyper or hypo function usually occurred isolated and permanently. These reasons justify the report of these typical cases of subacute, silent and chronic autoimmune thyroiditis, in which, the patron of biphasic thyroiditis was the most relevant finding of his clinical evolution.