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A) Imagen macroscópica de glándula tiroidea, cara anterior, con un peso de 182 g. B) Imagen histológica de áreas pseudonodulares por fibrosis (hematoxilina eosina, 40X). C) Imagen de inmunohistoquímica con IgG (400X). D) Imagen de inmunohistoquímica con IgG4 (400X).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Pamela Benítez Valderrama, Alejandro Castro Calvo, Laura Rodrigañez Riesco, Rita Regojo Zapata, Paola Parra Ramírez" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Pamela" "apellidos" => "Benítez Valderrama" ] 1 => array:2 [ "nombre" => "Alejandro" "apellidos" => "Castro Calvo" ] 2 => array:2 [ "nombre" => "Laura" "apellidos" => "Rodrigañez Riesco" ] 3 => array:2 [ "nombre" => "Rita" "apellidos" => "Regojo Zapata" ] 4 => array:2 [ "nombre" => "Paola" "apellidos" => "Parra Ramírez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2530018022002335" "doi" => "10.1016/j.endien.2022.11.034" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2530018022002335?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2530016422001124?idApp=UINPBA00004N" "url" => "/25300164/00000070000000S2/v1_202305101755/S2530016422001124/v1_202305101755/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2530018022002438" "issn" => "25300180" "doi" => "10.1016/j.endien.2022.01.014" "estado" => "S300" "fechaPublicacion" => "2023-06-01" "aid" => "1298" "copyright" => "SEEN and SED" "documento" => "article" "crossmark" => 1 "subdocumento" => "crp" "cita" => "Endocrinol Diabetes Nutr. 2023;70 Supl 2:62-4" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Scientific letter</span>" "titulo" => "Thyroid gland metastases: 3 cases that illustrate their clinical, radiological and pathological characteristics" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "62" "paginaFinal" => "64" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Metástasis en la glándula tiroidea. Tres casos ilustrativos de su presentación clínica, radiológica y anatomopatológica" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 710 "Ancho" => 2182 "Tamanyo" => 170609 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Thyroid ultrasound. Enlarged right thyroid lobe with no clear nodularity. Heterogeneous echogenicity with a "tiger-striped" appearance. Lobe measuring 39<span class="elsevierStyleHsp" style=""></span>mm in length. (B) CT scan of the neck. Generalised enlargement of the thyroid gland with a heterogeneous appearance. Bilateral pathological cervical lymphadenopathy. Decreased tracheal calibre.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Irene de Lara-Rodríguez, Ana R. Romero-Lluch, Suset Dueñas-Disotuar, Esteban Castillo-Sánchez-Heredero, Elena Navarro-González" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Irene" "apellidos" => "de Lara-Rodríguez" ] 1 => array:2 [ "nombre" => "Ana R." 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Benítez Valderrama, Alejandro Castro Calvo, Laura Rodrigañez Riesco, Rita Regojo Zapata, Paola Parra Ramírez" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Pamela" "apellidos" => "Benítez Valderrama" "email" => array:1 [ 0 => "alexapamela.benitez@salud.madrid.org" ] "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" => "Alejandro" "apellidos" => "Castro Calvo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Laura" "apellidos" => "Rodrigañez Riesco" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "Rita" "apellidos" => "Regojo Zapata" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "Paola" "apellidos" => "Parra Ramírez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Otorrinolaringología, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario La Paz, Madrid, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tiroiditis de Hashimoto variante fibrosante como manifestación de enfermedad por IgG4, simulando un linfoma tiroideo: reporte de un caso" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1276 "Ancho" => 2183 "Tamanyo" => 639719 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Macroscopic and histological imaging of total thyroidectomy specimen. (A) Macroscopic image of thyroid gland, anterior face, weighing 182<span class="elsevierStyleHsp" style=""></span>g. (B) Histological image of pseudonodular areas due to fibrosis (haematoxylin and eosin, 40×). (C) Immunohistochemistry image with IgG (400×). (D) Immunohistochemistry image with IgG4 (400×).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In 2001, a new subtype of autoimmune pancreatitis was reported and recognised as IgG4-related disease (IgG4-RD).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> It was characterised by the formation of lesions/masses due to diffuse lymphoplasmacytic infiltration of IgG4-positive cells, tissue sclerosing fibrosis, hypergammaglobulinaemia with a predominant increase in serum IgG4 levels and dysfunction of the compromised organ.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The list of compromised organs rapidly expanded, with involvement of the salivary glands, bile ducts, orbit, lymph nodes, retroperitoneal tissue, etc.</p><p id="par0010" class="elsevierStylePara elsevierViewall">Moreover, thyroid involvement or IgG4-related thyroid disease (IgG4-RTD) was first described by Li et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> in 2009, manifesting as a single entity or as a part of multisystem involvement in IgG4-RD. We report the case of a patient with IgG4-RTD mimicking thyroid lymphoma.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The patient was a 47-year-old Caucasian man, with no history of thyroid disease or cervical radiation, who consulted for a four-month history of non-painful, rapidly growing anterior cervical tumour associated with progressive dysphonia, dysphagia and dyspnoea. Physical examination revealed grade III goitre without palpable nodules. An initial neck ultrasound showed a markedly enlarged thyroid gland with hypoechoic areas and thin hyperechoic septa featuring increased vascularisation on colour Doppler imaging, suggestive of thyroiditis. Laboratory results were consistent with overt primary hypothyroidism of autoimmune origin (thyroid-stimulating hormone [TSH] 100.9<span class="elsevierStyleHsp" style=""></span>μIU/ml [normal range (NR) 0.55–4.78], free thyroxine [T4] 0.38<span class="elsevierStyleHsp" style=""></span>ng/dl [NR 0.89–1.76] and peroxidase antibodies 443,012 IU/ml [NR<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>60]), so treatment with levothyroxine was started. One month after the onset of signs and symptoms, the patient presented with right thyroid lobe (RTL) enlargement spreading to the ipsilateral submandibular region. Computed tomography (CT) of the neck showed a large goitre affecting the RTL (4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4.6<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>cm [AP<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>T<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>L]; left thyroid lobe [LTL] 4.3<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>cm), with spread towards the retropharyngeal space compressing the larynx and the ipsilateral pyriform sinus, associated with displacement of the glottal and supraglottal portion, including the vocal cords. Due to the mass’s rapid growth, fine needle aspiration biopsy was performed, yielding results consistent with Hashimoto’s thyroiditis. However, given that thyroid lymphoma was suspected, a decision was made to perform open glandular biopsy, which revealed a pattern of thyroiditis, inflammatory myofibroblastic tumour or IgG4-related sclerosing disease.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The case was presented to the Endocrine Tumours Committee. It was decided to order IgG4 521<span class="elsevierStyleHsp" style=""></span>mg/dl (NR 3–200), beta-2 microglobulin 2.6<span class="elsevierStyleHsp" style=""></span>mg/l (NR 1.1–2.5) and lactate dehydrogenase (LDH) 247 IU/l (NR 100–190) plus a positron emission tomography/computed tomography (PET/CT) scan with 18F-fluorodeoxyglucose (<span class="elsevierStyleSup">18</span>F-FDG), which corroborated the presence of a large goitre with diffuse uptake in relation to lymphocytic thyroiditis. In light of the rapid growth and the compressive symptoms reported, it was decided to perform a total thyroidectomy. The only post-operative complication was a seroma that required drainage on two occasions. Pathology showed a thyroid gland weighing 182<span class="elsevierStyleHsp" style=""></span>g (NR 25–30<span class="elsevierStyleHsp" style=""></span>g) with IgG4-related fibrous variant of Hashimoto’s thyroiditis (with IgG4 staining >28 plasma cells per high-power field and IgG4/IgG ratio <30%, without observing areas of diffuse lymphoid proliferation through antigen receptor rearrangement analysis) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). IgG4 values decreased by 55% (290<span class="elsevierStyleHsp" style=""></span>mg/dl) two weeks after the operation and normalised two months later. Two years after surgery, the patient has not presented with compromise of other organs or systems and maintains normal IgG4 serum levels.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Our case represents a clear example of IgG4-RTD, a recently recognised benign thyroid disease that may mimic a neoplastic condition. The link between thyroid compromise and IgG4-RD was initially suggested based on the observation that hypothyroidism was highly prevalent in patients with autoimmune pancreatitis.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Taking these observations as a starting point, Li et al.<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> found that patients with Hashimoto’s thyroiditis could be subcategorised as patients with IgG4 (+) or IgG4 (–) infiltrates, with the former characterised by fibrosis and lymphoplasmacytic infiltration and the apparent absence of systemic extrathyroid involvement. Typically, patients with IgG4-RTD had higher rates of hypothyroidism, had high levels of thyroid peroxidase (TPO) antibodies, were younger, were mostly male and had disease with a surprisingly progressive course compared to patients with IgG4 (–) disease.<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4,5</span></a> Thus, the case reported had the typical characteristics of this condition.</p><p id="par0030" class="elsevierStylePara elsevierViewall">At present, it is known that IgG4-RTD can encompass cases of (a) chronic autoimmune thyroiditis, (b) a fibrotic variant of this disease, (c) Riedel’s thyroiditis and (d) some uncommon cases of Graves’ disease.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Regarding diagnosis of IgG4-RTD, although there are mixed criteria, the most commonly accepted criteria are those of the Japan Thyroid Association and the Japan Endocrine Society, which include: (1) gland enlargement, (2) hypoechoic lesions on ultrasound, (3) elevated serum IgG4 levels (≥135<span class="elsevierStyleHsp" style=""></span>mg/dl), (4) thyroid histopathology findings such as infiltration of >20 IgG4+ plasma cells per high-power field and a proportion of IgG4+/IgG+ plasma cells >30%) and (5) involvement of other organs.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> As such, a patient is considered to have definitive IgG4-RTD when criteria 1–4 are met, probable IgG4-RTD when criteria 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2+4 or 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2+5 are met and possible IgG4-RTD when criteria 1<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2+3 are met.</p><p id="par0040" class="elsevierStylePara elsevierViewall">On the one hand, it should be stressed that histopathological findings are the most important elements for demonstrating IgG4+ plasma cell infiltration and for ruling out malignancy or other entities. On the other hand, it is important to note that elevated serum IgG4 levels are not sufficient by themselves to diagnose this entity, since elevated IgG4 is also characteristic of other diseases.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Although histology in the case reported revealed a proportion of IgG4+/IgG+ plasma cells <30%, based on meeting all the other criteria, the clinical presentation, the epidemiological data and the fact that lymphoid clonality had been ruled out, the patient was considered to have definitive IgG4-RTD.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Concerning treatment, glucocorticoids and immunomodulators such as azathioprine, mycophenolate mofetil and methotrexate are treatments of choice in IgG4-RD.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> However, thyroid gland enlargement with significant compression of adjacent organs, constrictive symptoms or suspected malignancy lend themselves to a surgical strategy.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, knowledge of this condition is indispensable given that it will help physicians to decide the best strategy for diagnosis and treatment, since many of these lesions involve a mass raising clinical suspicion of malignancy, and in some cases unnecessary surgery may be avoided.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Funding</span><p id="par0055" class="elsevierStylePara elsevierViewall">This research has not received specific funding from public sector agencies, the commercial sector or non-profit organisations.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest in relation to the publication of this scientific article.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Funding" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Conflicts of interest" ] 2 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1276 "Ancho" => 2183 "Tamanyo" => 639719 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Macroscopic and histological imaging of total thyroidectomy specimen. 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