Scientific letter
Subacute thyroiditis by dasatinib
Tiroiditis subaguda por dasatinib
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"nombre" => "Maria del Carmen" "apellidos" => "Vázquez Friol" "email" => array:1 [ 0 => "Maria.del.Carmen.Vazquez.Friol@sergas.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Iria" "apellidos" => "Bravo Blázquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Cristina" "apellidos" => "Tejera Pérez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Medicina Interna, Complejo Hospitalario Universitario de Ferrol, Xerencia de Xestión Integrada de Ferrol, Sergas, A Coruña, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Complejo Hospitalario Universitario de Ferrol, Xerencia de Xestión Integrada de Ferrol, Sergas, A Coruña, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tiroiditis subaguda por dasatinib" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Dasatinib is a tyrosine kinase inhibitor (TKI) used as a second-line treatment for Philadelphia chromosome-positive chronic myeloid leukemia.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Unlike other TKIs, hypothyroidism is considered a rare side effect: hyperthyroidism and thyroiditis are rare secondary events. We report the case of a patient with chronic myeloid leukaemia treated with dasanitib who developed dasatinib-induced subacute thyroiditis.</p><p id="par0010" class="elsevierStylePara elsevierViewall">This is a 44-year-old male, diagnosed with chronic myeloid leukaemia, undergoing treatment with 100 mg of dasatinib daily with major molecular response criteria. The patient presented with a 1-moth history of pharyngeal discomfort and dysphagia for solids, which also associated fever, anterior cervical pain, palpitations and about 5 kg weight loss. He had been treated with several cycles of antibiotherapy, without clinical improvement. At the time of the initial assessment, he was receiving amoxicillin-clavulanic treatment.</p><p id="par0015" class="elsevierStylePara elsevierViewall">A painful and diffusely enlarged thyroid gland stood out as a clear symptom, without other findings. Blood tests showed elevated levels of C-reactive protein and a high erythrocyte sedimentation rate, as well as a suppressed TSH (0.01 μIU/mL) and an increased T4L (2.2 ng/dL), with negative anti-peroxidase and anti-thyroglobulin antibodies. The previous thyroid profile was normal.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Hospital admission was decided, and treatment was instituted with 600 mg of Ibuprofen every 8 h and 10 mg of propranolol every 12 h. Initially, antibiotic coverage was maintained with amoxicillin-clavulanate, which was discontinued once the microbiological studies were negative. After assessment by Haematology, dasatinib treatment was also discontinued.</p><p id="par0025" class="elsevierStylePara elsevierViewall">During hospitalization, a cervical ultrasound showed a diffuse increase in the thyroid gland with a decrease in its vascularization and the presence of a region in the right thyroid lobe suggestive of thyroiditis, without abscesses or lymphadenopathy.</p><p id="par0030" class="elsevierStylePara elsevierViewall">In addition, the study was completed with a thyroid scintigraphy, which showed absence of thyroid gland uptake.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The clinical progression was satisfactory, so he was discharged with a diagnosis of subacute thyroiditis secondary to dasatinib, based on the Naranjo causality algorithm,<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> according to which said causal relationship was considered probable (5 points) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Treatment with non-steroidal anti-inflammatory drugs and beta-blockers was maintained and multidisciplinary outpatient follow-up was scheduled for Endocrinology and Haematology. One month after admission, T4L levels were normal, although TSH remained slightly decreased. The thyroid profile developed towards a subclinical hypothyroidism, for which hormone replacement therapy was prescribed in increasing doses. Haematologically, dasatinib was replaced by nilotinib; the patient remained in major molecular response.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">TKIs, especially first-generation TKIs, are associated with thyroid dysfunction in 30%–40% of patients; in half of the cases it is a subclinical dysfunction.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Several pathophysiological mechanisms have been proposed that justify these alterations: direct induction of destructive thyroiditis, increased hormone clearance, capillary regression induced by vascular endothelial growth factor inhibition and iodine uptake impairment.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Thyroid dysfunction is rare with second-generation TKIs such as dasatinib, especially the one developing in the form of thyroiditis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The thyroid effects of TKIs can manifest themselves after the first year from the start of treatment, but they usually appear within the first 6  months. A recent review recommends performing a TSH determination at the start of treatment, which should be repeated every 6  weeks for the first 6  months and then every 3–6 months for a year.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Biannual <span class="elsevierStyleItalic">screening</span> is recommended beyond the first 18  months. Systematic determination of antithyroid antibodies is not recommended.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Treatment of TKI-induced subacute thyroiditis should be done with anti-inflammatories and beta-blockers; in most cases it is not necessary to modify the treatment with TKI.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Regarding progression, it is unknown whether the percentage of patients who achieve a normal thyroid profile is similar to that of patients with thyroiditis not associated with TKIs.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">We consider it important to know the thyroid effects of these drugs as well as to emphasize the need for thyroid function monitoring and to start treatment, if appropriate, to improve the quality of life and prognosis of these patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Vázquez Friol MC, Bravo Blázquez I, Tejera Pérez C. Tiroiditis subaguda por dasatinib. Med Clin (Barc). 2020;155:270–271.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Did the adverse reaction recur after administering a placebo? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">−1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Was the drug detected in blood (or other fluids) at toxic concentrations? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Was the reaction more severe when the dose was increased or less severe when reduced? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Did the patient have a similar reaction caused by the same or a similar drug in any previous exposure? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Was the adverse event confirmed by any type of objective evidence? \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">+1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Total score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2532283.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Naranjo Causality Algorithm.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:5 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "FT_06363004.pdf [Internet]. 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"fecha" => "2018" "volumen" => "28" "paginaInicial" => "437" "paginaFinal" => "444" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000015500000006/v2_202102250949/S2387020620303697/v2_202102250949/en/main.assets" "Apartado" => array:4 [ "identificador" => "43311" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Scientific letters" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015500000006/v2_202102250949/S2387020620303697/v2_202102250949/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020620303697?idApp=UINPBA00004N" ]
