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Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab

CONTEXT: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. OBJECTIVE: To assess the incidence and characteristics of...

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Autores principales: de Filette, Jeroen, Jansen, Yanina, Schreuer, Max, Everaert, Hendrik, Velkeniers, Brigitte, Neyns, Bart, Bravenboer, Bert
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Endocrine Society 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095250/
https://www.ncbi.nlm.nih.gov/pubmed/27571185
http://dx.doi.org/10.1210/jc.2016-2300
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author de Filette, Jeroen
Jansen, Yanina
Schreuer, Max
Everaert, Hendrik
Velkeniers, Brigitte
Neyns, Bart
Bravenboer, Bert
author_facet de Filette, Jeroen
Jansen, Yanina
Schreuer, Max
Everaert, Hendrik
Velkeniers, Brigitte
Neyns, Bart
Bravenboer, Bert
author_sort de Filette, Jeroen
collection PubMed
description CONTEXT: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. OBJECTIVE: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. DESIGN AND SETTING: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. (18)Fluorodeoxyglucose uptake on positron emission tomography/computed tomography ((18)FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. PATIENTS: Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. MAIN OUTCOME MEASURES: Patient characteristics, thyroid function (TSH, free T(4)), thyroid autoantibodies, and (18)FDG-PET/CT. RESULTS: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased (18)FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. CONCLUSIONS: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased (18)FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates.
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spelling pubmed-50952502016-11-28 Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab de Filette, Jeroen Jansen, Yanina Schreuer, Max Everaert, Hendrik Velkeniers, Brigitte Neyns, Bart Bravenboer, Bert J Clin Endocrinol Metab Original Articles CONTEXT: Immune checkpoint blockade is associated with endocrine-related adverse events. Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized. OBJECTIVE: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction. DESIGN AND SETTING: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center. (18)Fluorodeoxyglucose uptake on positron emission tomography/computed tomography ((18)FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis. PATIENTS: Ninety-nine patients with advanced melanoma (age, 26.3–93.6 years; 63.6% females) who received at least one administration of pembrolizumab. MAIN OUTCOME MEASURES: Patient characteristics, thyroid function (TSH, free T(4)), thyroid autoantibodies, and (18)FDG-PET/CT. RESULTS: Eighteen adverse events of thyroid dysfunction were observed in 17 patients. Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism. Isolated hypothyroidism was present in six patients. Levothyroxine therapy was required in 10 of 15 hypothyroid patients. Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases. Diffuse increased (18)FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism. CONCLUSIONS: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab. Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations. Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy. Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased (18)FDG uptake by the thyroid gland. The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates. Endocrine Society 2016-11 2016-08-29 /pmc/articles/PMC5095250/ /pubmed/27571185 http://dx.doi.org/10.1210/jc.2016-2300 Text en http://creativecommons.org/licenses/by-nc/4.0/ This article is published under the terms of the Creative Commons Attribution-Non Commercial License (CC-BY-NC; http://creativecommons.org/licenses/by-nc/4.0/).
spellingShingle Original Articles
de Filette, Jeroen
Jansen, Yanina
Schreuer, Max
Everaert, Hendrik
Velkeniers, Brigitte
Neyns, Bart
Bravenboer, Bert
Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
title Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
title_full Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
title_fullStr Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
title_full_unstemmed Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
title_short Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
title_sort incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095250/
https://www.ncbi.nlm.nih.gov/pubmed/27571185
http://dx.doi.org/10.1210/jc.2016-2300
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