Thyroid Dysfunction in Patients with Metastatic Carcinoma Treated with Sunitinib: Is Thyroid Autoimmunity Involved?

Pani, Filippo Eros; Atzori, Francesco; Baghino, Germana; Boi, Francesco; Tanca, Luciana; Ionta, Maria Teresa; Mariotti, Stefano

doi:10.1089/thy.2015.0170

Cited by 39 publications

(21 citation statements)

References 28 publications

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“…First, the follow-up period was only 24 weeks, and therefore we cannot exclude the possibility that the patients who had positive antithyroid Abs but not thyroid dysfunction during the observation period will develop destructive thyroiditis or hypothyroidism in the future. Indeed, a previous study suggested that long-term observations are necessary to clarify the role of autoimmune mechanisms underlying hypothyroidism development in patients treated with sunitinib [ 26 ]. However, it has been reported that most nivolumab-induced adverse events occurred within the first 16 weeks of treatment [ 9 ] and that irAEs in the thyroid mostly developed within the first 3 months [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

Kobayashi

Iwama

Yasuda

et al. 2018

Journal of the Endocrine Society

163

112

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ContextImmune checkpoint inhibitors, including anti–programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. However, these medicines can cause immune-related adverse events (irAEs), including endocrinopathies.ObjectiveThis study examined the incidence of endocrine irAEs induced by nivolumab.Patients and Main Outcome MeasuredSixty-six patients treated with nivolumab at Nagoya University Hospital were prospectively evaluated for pituitary hormones, thyroid function, antithyroid antibodies (Abs), and glucose levels every 6 weeks after the initiation of nivolumab for 24 weeks.ResultsFour out of 66 patients developed destructive thyroiditis, and three patients developed hypothyroidism requiring levothyroxine replacement. The prevalence of positive anti-thyroglobulin Abs (TgAbs) and/or anti–thyroid peroxidase Abs (TPOAbs) at baseline was significantly higher in the group that developed destructive thyroiditis (3/4) compared with the group that did not develop thyroiditis (3/62; P = 0.002). There were no significant differences in other clinical variables between the groups. There were no endocrine irAEs other than destructive thyroiditis during the 24 weeks. The prevalence of TgAbs and/or TPOAbs at baseline was not associated with the development of other irAEs, including pneumonitis, colitis, or skin reactions.ConclusionsOur real-world data showed that destructive thyroiditis was an endocrine irAE that was frequently induced by nivolumab and was significantly associated with positive TgAbs and/or TPOAbs before treatment. Our findings indicate that evaluating these Abs before treatment may help identify patients with a high risk of thyroidal irAEs and may have important clinical benefit.

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Section: Discussionmentioning

confidence: 99%

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

Kobayashi

Iwama

Yasuda

et al. 2018

Journal of the Endocrine Society

163

112

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“…In this view also thyroid dysfunction has been evaluated in patients treated with sunitinib. In renal cell carcinoma patients receiving sunitinib the development of antithyroid peroxidase (TPOAb) autoantibodies along with severe hypothyroidism was associated with a longer progression free survival (PFS)16. In the TRIBUTE (Toxicity during Regorafenib Induction and Benefit Under Treatment Extension) analysis we evaluated the potential role of off target effects as early surrogate markers of clinical outcome in patients with colorectal cancer treated with regorafenib with the final aim to improve the early identification of patients more likely to benefit from such a treatment approach and optimise adverse events management.…”

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confidence: 99%

Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

Prete

Prochilo

Puzzoni

et al. 2017

Sci Rep

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Regorafenib is an orally administered multikinase inhibitor indicated for the treatment of heavily pretreated metastatic colorectal cancer patients with good performance status, albeit less than 50% treated patients achieve disease stabilisation or better at the first radiological evaluation. In addition to that a particularly broad spectrum of toxicities (experienced as G3 or more NCI CTCAE graded by 50% of patients treated) have led to reconsider its widespread use in the majority of patients. We retrospectively collected data about the magnitude of off-target effects experienced during the first 8-weeks of regorafenib monotherapy and analysed their correlation with overall survival, progression free survival and disease control rate. Our findings suggest that skin rash (Exp (B): 0.52, p = 0.0133) or hypothyroidism (Exp (B): 0.11, p = 0.0349) were significantly correlated with improved overall survival at multivariate regression analysis. It was also demonstrated a statistically significant role of diarrhea as predictor of improved survival but its independent prognostic role was lost at multivariate analysis (Exp (B): 0.63, p = 0.162). This is the first analysis showing a potential correlation between the onset of these forms of side effects and regorafenib efficacy, however sample size limitations and the retrospective nature of our analysis prevent us from drawing definitive conclusions.

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“…13 Several mechanisms may play a role in TKI-induced hypothyroidism including decreased thyroid gland capillary density, induction of type 3 deiodinase activity, inhibition of iodine uptake, inhibition of peroxidase activity, altered thyroid hormone transport, decreased thyroid hormone synthesis, and in some patients, thyroid autoimmunity resulting in thyroid failure. [14][15][16][17][18] Studies performed in rats exposed to sunitinib showed changes in thyroid gland capillary density, which was both structural and functional in nature. These changes were hypothesized to be caused by the antiangiogenic effects of vascular endothelial growth factor (VEGF) receptor inhibition and increased concentrations of circulating endothelin-1.…”

mentioning

confidence: 99%

Effects of Toceranib Phosphate on the Hypothalamic‐Pituitary‐Thyroid Axis in Tumor‐Bearing Dogs

Hume

Rizzo

Balkman

2017

Veterinary Internal Medicne

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BackgroundThyroid dysfunction is associated with the use of tyrosine kinase inhibitors (TKI) in people.Hypothesis/ObjectivesTo determine whether dysfunction in the hypothalamic‐pituitary‐thyroid axis occurs in dogs receiving the TKI, toceranib phosphate.AnimalsForty‐three client‐owned dogs with cancer.MethodsProspective, observational study. Concentrations of total thyroxine (TT4), free thyroxine (FT4), total triiodothyronine (TT3), and thyroid‐stimulating hormone (TSH) were evaluated on day 0, 30, and 90. Dogs also were evaluated for the presence of thyroglobulin autoantibodies.ResultsThe proportion of dogs with low TT4, low FT4, low TT3, high TSH, or primary hypothyroidism (increased TSH and decreased TT4, FT4 or both) did not change over 90 days. Hormone concentrations remained within laboratory reference intervals, but FT4 (P = 0.0032) and TSH (P < 0.0001) changed over time. Mean FT4 was 1.22 ng/dL (95% confidence interval [CI], 1.10–1.34) on day 0 and 1.00 ng/dL (95% CI, 0.86–1.16) on day 90. Mean TSH was 0.17 ng/mL (95% CI, 0.13–0.23) on day 0 and 0.34 ng/mL (95% CI, 0.24–0.48) on day 90. Furthermore, TT4/TT3 ratio also changed over time (P = 0.0086). Mean TT4/TT3 ratio was 2.57 (95% CI, 2.26–2.88) on day 0 and 2.02 on day 90 (95% CI, 1.61–2.44). Thyroglobulin autoantibodies were not detected in any dog.Conclusions and Clinical ImportanceToceranib phosphate can disrupt the hypothalamic‐pituitary‐thyroid axis in dogs. Periodic evaluation of TT4, FT4, TT3, and TSH should be carried out in dogs receiving long‐term treatment with this medication.

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Thyroid Dysfunction in Patients with Metastatic Carcinoma Treated with Sunitinib: Is Thyroid Autoimmunity Involved?

Cited by 39 publications

References 28 publications

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

Patients With Antithyroid Antibodies Are Prone To Develop Destructive Thyroiditis by Nivolumab: A Prospective Study

Off-target effects and clinical outcome in metastatic colorectal cancer patients receiving regorafenib: The TRIBUTE analysis

Effects of Toceranib Phosphate on the Hypothalamic‐Pituitary‐Thyroid Axis in Tumor‐Bearing Dogs

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