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array:24 [ "pii" => "S2254887422000364" "issn" => "22548874" "doi" => "10.1016/j.rceng.2022.01.003" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "2019" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "copyrightAnyo" => "2022" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2022;222:458-67" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0014256522000200" "issn" => "00142565" "doi" => "10.1016/j.rce.2022.01.003" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "2019" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2022;222:458-67" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">ORIGINAL</span>" "titulo" => "Prevalencia y fenotipo de la hiperplasia suprarrenal macronodular bilateral primaria con secreción autónoma de cortisol: un estudio de 98 pacientes" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "458" "paginaFinal" => "467" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Prevalence and phenotype of primary bilateral macronodular adrenal hyperplasia with autonomous cortisol secretion: A study of 98 patients" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1804 "Ancho" => 1902 "Tamanyo" => 274114 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Población a estudio y criterios de inclusión</p> <p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">IS: incidentalomas suprarrenales; HSMBP: hiperplasia suprarrenal macronodular bilateral primaria; PSD: prueba de supresión con dexametasona.</p> <p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">*Solo uno de los tres pacientes con síndrome de Cushing florido tenía HSMBP.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "N. Bengoa-Rojano, M. Fernández-Argüeso, J.I. Botella-Carretero, E. Pascual-Corrales, M. Araujo-Castro" "autores" => array:5 [ 0 => array:2 [ "nombre" => "N." "apellidos" => "Bengoa-Rojano" ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Fernández-Argüeso" ] 2 => array:2 [ "nombre" => "J.I." "apellidos" => "Botella-Carretero" ] 3 => array:2 [ "nombre" => "E." "apellidos" => "Pascual-Corrales" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Araujo-Castro" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2254887422000364" "doi" => "10.1016/j.rceng.2022.01.003" "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/S2254887422000364?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000200?idApp=WRCEE" "url" => "/00142565/0000022200000008/v1_202209290544/S0014256522000200/v1_202209290544/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2254887422000777" "issn" => "22548874" "doi" => "10.1016/j.rceng.2022.06.004" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "2047" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2022;222:468-78" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Factors associated with mortality due to SARS-CoV-2 in the population over 75 years of age in the Community of Madrid" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "468" "paginaFinal" => "478" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Factores asociados con la mortalidad por SARS-CoV-2 en la población mayor de 75 años de la Comunidad de Madrid" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1876 "Ancho" => 2925 "Tamanyo" => 208508 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0040" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Factors associated with mortality during the first wave (before July 1, 2020, 7,466 deaths (black)) and subsequent waves (July 1, 2020 to January 31, 2021, 3,588 deaths (gray)) in the total Madrid population older than 75 years (587,603 subjects), in 41,603 subjects with confirmed SARS-CoV-2 infection, and in 22,362 patients hospitalized due to this infection.</p> <p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">COPD: chronic obstructive pulmonary disease.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.M. Mostaza, M.A. Salinero-Fort, J. Cardenas-Valladolid, F. Rodríguez-Artalejo, M. Díaz-Almirón, P. Vich-Pérez, F.J. San Andrés-Rebollo, I. Vicente, C. Lahoz" "autores" => array:9 [ 0 => array:2 [ "nombre" => "J.M." "apellidos" => "Mostaza" ] 1 => array:2 [ "nombre" => "M.A." "apellidos" => "Salinero-Fort" ] 2 => array:2 [ "nombre" => "J." "apellidos" => "Cardenas-Valladolid" ] 3 => array:2 [ "nombre" => "F." "apellidos" => "Rodríguez-Artalejo" ] 4 => array:2 [ "nombre" => "M." "apellidos" => "Díaz-Almirón" ] 5 => array:2 [ "nombre" => "P." "apellidos" => "Vich-Pérez" ] 6 => array:2 [ "nombre" => "F.J." "apellidos" => "San Andrés-Rebollo" ] 7 => array:2 [ "nombre" => "I." "apellidos" => "Vicente" ] 8 => array:2 [ "nombre" => "C." "apellidos" => "Lahoz" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256522000820" "doi" => "10.1016/j.rce.2022.06.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000820?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887422000777?idApp=WRCEE" "url" => "/22548874/0000022200000008/v1_202210061413/S2254887422000777/v1_202210061413/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2254887422000558" "issn" => "22548874" "doi" => "10.1016/j.rceng.2022.03.009" "estado" => "S300" "fechaPublicacion" => "2022-10-01" "aid" => "2037" "copyright" => "Elsevier España, S.L.U. and Sociedad Española de Medicina Interna (SEMI)" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Rev Clin Esp. 2022;222:443-57" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Analysis of the effectiveness and safety of short-stay units in the hospitalization of patients with acute heart failure. Propensity Score SSU-EAHFE" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "443" "paginaFinal" => "457" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Análisis de la efectividad y seguridad de las unidades de estancia corta en la hospitalización de pacientes con insuficiencia cardíaca aguda. <span class="elsevierStyleItalic">Propensity Score</span> UCE-EAHFE" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "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" => 1741 "Ancho" => 2508 "Tamanyo" => 314867 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Patient inclusion flowchart.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">EAHFE: Epidemiology of Acute Heart Failure in Emergency departments; AHF: acute heart failure; SSU: short stay unit.</p> <p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">*The propensity score for SSU admission was calculated via a multiple logistic regression using all variables included in <a class="elsevierStyleCrossRefs" href="#tbl0005">Tables 1, 2</a>, and <a class="elsevierStyleCrossRef" href="#tbl0015">3</a> as covariates and includes data on demographics, comorbidity, chronic at-home treatment, baseline functional status, triggering factor of the decompensation, and severity of the decompensation.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "C. Sánchez-Marco, J. Jacob, P. Llorens, B. Rodríguez, F.J. Martín-Sánchez, S. Herrera, L.E. Castillero-Díaz, P. Herrero, V. Gil, Ò. Miró" "autores" => array:11 [ 0 => array:2 [ "nombre" => "C." "apellidos" => "Sánchez-Marco" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Jacob" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Llorens" ] 3 => array:2 [ "nombre" => "B." "apellidos" => "Rodríguez" ] 4 => array:2 [ "nombre" => "F.J." "apellidos" => "Martín-Sánchez" ] 5 => array:2 [ "nombre" => "S." "apellidos" => "Herrera" ] 6 => array:2 [ "nombre" => "L.E." "apellidos" => "Castillero-Díaz" ] 7 => array:2 [ "nombre" => "P." "apellidos" => "Herrero" ] 8 => array:2 [ "nombre" => "V." "apellidos" => "Gil" ] 9 => array:2 [ "nombre" => "Ò." "apellidos" => "Miró" ] 10 => array:1 [ "colaborador" => "on behalf of the investigators of the AHF-SEMES group" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0014256522000649" "doi" => "10.1016/j.rce.2022.03.011" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0014256522000649?idApp=WRCEE" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2254887422000558?idApp=WRCEE" "url" => "/22548874/0000022200000008/v1_202210061413/S2254887422000558/v1_202210061413/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Prevalence and phenotype of primary bilateral macronodular adrenal hyperplasia with autonomous cortisol secretion: a study of 98 patients" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "458" "paginaFinal" => "467" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "N. Bengoa-Rojano, M. Fernández-Argüeso, J.I. Botella-Carretero, E. Pascual-Corrales, M. Araujo-Castro" "autores" => array:5 [ 0 => array:3 [ "nombre" => "N." "apellidos" => "Bengoa-Rojano" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "M." "apellidos" => "Fernández-Argüeso" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "J.I." "apellidos" => "Botella-Carretero" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Pascual-Corrales" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 4 => array:4 [ "nombre" => "M." "apellidos" => "Araujo-Castro" "email" => array:1 [ 0 => "marta.araujo@salud.madrid.org" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 3 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario Ramón y Cajal, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Centro de Investigación Biosanitaria en Red de Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Madrid. Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Facultad de Medicina, Universidad de Alcalá, Alcalá de Henares (Madrid). Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Prevalencia y fenotipo de la hiperplasia suprarrenal macronodular bilateral primaria con secreción autónoma de cortisol: un estudio de 98 pacientes" ] ] "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" => 1808 "Ancho" => 1937 "Tamanyo" => 253563 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Study population and inclusion study population.</p> <p id="spar0001" class="elsevierStyleSimplePara elsevierViewall">AIs: adrenal incidentalomas; PBMAH: primary bilateral macronodular adrenal hyperplasia; DST: dexamethasone suppression test.</p> <p id="spar0002" class="elsevierStyleSimplePara elsevierViewall">*Only 1 of the 3 patients with overt Cushing's syndrome had PBMAH.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Primary bilateral macronodular adrenal hyperplasia (PBMAH) is a rare cause of Cushing’s syndrome and is frequently diagnosed as bilateral adrenal incidentalomas (AIs) with mild autonomous cortisol excess (MACE)1. It is a highly heterogeneous entity, both in terms of the severity of cortisol excess and the morphological appearance of the adrenals. Moreover, no consensus has yet been reached regarding its definition. However, most authors agree that PBMAH diagnosis should be based on the presence of possible autonomous cortisol secretion (ACS) or ACS due to bilateral adrenal hyperplasia associated with the presence of one or more AIs greater than 1 cm in each adrenal gland.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Its reported prevalence is usually low<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–7</span></a> and it represents less than 2.0% of the cases of endogenous Cushing’s syndrome.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">It is well known that 3–5% of the general population may harbour AIs,<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> 15% of which are bilateral. These latter may have associated possible ACS or ACS in up to 40% of cases.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10,11</span></a> Therefore, the actual prevalence of PBMAH is expected to be higher than that reported in series of patients with Cushing’s syndrome. Furthermore, few data exist on the clinical, hormonal, and radiological features of this entity which may differ from those presented by other adrenal lesions associated with MACE that do not meet PBMAH criteria.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The aim of our study was to evaluate the prevalence of PBMAH in a large series of 730 patients with AIs and to analyse the clinical (including cardiometabolic comorbidities), hormonal, and radiological phenotype of these patients. We then compared them with the characteristics of patients with bilateral adrenal hyperplasia and bilateral adrenal nodules with possible ACS or ACS that does not meet the criteria for PBMAH definition (non-PBMAH).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient cohorts</span><p id="par0020" class="elsevierStylePara elsevierViewall">Patients were selected from the ADRENAL INCIDENTALOMA database. Patients with AIs were identified through an electronic search of the Biochemical database of our hospital. All 1 mg dexamethasone suppression tests (DST) performed between 2013 and 2019 were identified.</p><p id="par0025" class="elsevierStylePara elsevierViewall">Only those patients who met the inclusion criteria for the ADRENAL INCIDENTALOMA database were included. The inclusion and exclusion criteria were previously published.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Included patients were between 18 and 90 years old, with incidentally discovered unilateral and/or bilateral AIs with a diameter of at least 10 mm. Exclusion criteria were: (i) known diagnosis of hereditary syndromes associated with adrenal tumours; (ii) chronic treatment with glucocorticoids or drugs that affect dexamethasone metabolism; (iii) current treatment with oral hormonal contraceptives (treatment should be suspended for at least 6 weeks before performing the functionality study), and (iv) AIs identified during further investigation of extra-adrenal primary cancer.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Only patients with MACE (possible ACS or ACS) and bilateral AIs with or without hyperplasia were included in this study, so patients with primary aldosteronism, pheochromocytoma, and overt Cushing’s syndrome were excluded. Patients with missing information in the hormonal or radiological study were not included either (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">The study was approved by the local ethics committee of our hospital (approval date: 23 September 2019).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Clinical definitions</span><p id="par0040" class="elsevierStylePara elsevierViewall">AI was defined as the presence of an asymptomatic adrenal lesion greater than 1 cm detected on imaging tests not performed in the context of suspected adrenal disease (such as further investigation of extra-adrenal primary cancer or other abdominal diseases).<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The definitions of hypertension, type 2 diabetes (T2DM), obesity, and dyslipidaemia were the same as stated in previous research.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> Cardiovascular disease was defined as ischemic heart disease or heart failure, and cerebrovascular disease as transient ischemic attack or acute stroke. Moreover, the presence of active smoking was analysed.</p><p id="par0045" class="elsevierStylePara elsevierViewall">For the MACE definition, the most sensitive criterion was used to optimize the identification of patients with AI with increased cardiometabolic risk, considering that there was possible ACS when cortisol post-DST was >1.8 µg/dL and ≤5.0 µg/dL in the absence of specific data for hypercortisolism12, and ACS was confirmed when cortisol post-DST was >5.0 µg/dL9. PBMAH diagnosis was based on the presence of possible ACS or ACS due to bilateral adrenal hyperplasia associated with the presence of one or more AIs greater than 1 cm in each adrenal gland.<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1,2</span></a> Those patients with possible ACS or ACS and bilateral AIs without hyperplasia or with one of the AIs <1 cm were classified as non-PBMAH.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Biochemical and hormonal study</span><p id="par0050" class="elsevierStylePara elsevierViewall">All patients underwent a 1 mg DST as the first step in the hormonal AI evaluation (n = 98). This test involved measuring cortisol in the morning (8:00–9:00 am) after the administration of 1 mg of dexamethasone the night before at 23:00 pm. Moreover, measurements of adrenocorticotropic hormone (ACTH) (n = 85), dehydroepiandrosterone sulphate (DHEA-S) (n = 62), late-night salivary cortisol (n = 76) and 24 -h urinary free cortisol (UFC) (n = 73) were performed based on the physicians’ clinical judgment. Both 17-OH progesterone and basal serum cortisol were measured in 58 and 76 patients, respectively. The DST was repeated at the follow-up visit in 75 patients. All hormonal analyses were performed on an empty stomach. Moreover, an intermediate DST was performed between the first and last visit in 48 patients. Other hormones were also tested at the discretion of the treating physician. A biochemical study including fasting plasma glucose, total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides, was performed in most of the patients. Lastly, HbA1c was measured in 43 patients.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study of aberrant receptors</span><p id="par0055" class="elsevierStylePara elsevierViewall">An aberrant receptors study was performed on five patients. The protocol of our centre was performed on an outpatient basis over four consecutive or non-consecutive days. On the first day, 250 μg of cosyntropin was administered intravenously to serve as a reference for the cortical response capacity. A wandering test was also performed that same day, taking a baseline sample and repeating the extraction after two walking hours. The second day, a mixed meal test was conducted with a meal of 450 kcal comprising 46% carbohydrates, 32% fat and 22% protein. On the third day intravenous administration of 100 μg of GnRH and intravenous administration of 200 μg of TRH were given. On the fourth day the patients received an intravenous dose of 1 mg of glucagon, then 4 μg of desmopressin and, lastly, an oral dose of 10 mg of metoclopramide (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In all tests, baseline and serial measurements of cortisol, aldosterone, and DHEA-S were taken. A change of less than 25% in cortisol levels was defined as no response, a 25–49% change as partial response, and a 50% or greater change as a positive response to the test.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Laboratory assays</span><p id="par0065" class="elsevierStylePara elsevierViewall">The following assays were employed: serum and urine cortisol were measured by chemiluminescence assays in ARCHITECT i2000 systems from Abbott Diagnostics with an intra-assay coefficient of variation (CV) <10%; the normal range for serum cortisol was 3.7–19.4 µg/dL and 140 µg/24 h for urine cortisol. ACTH was measured by chemiluminescence in the IMMULITE® 2000 Siemens system with an intra-assay CV of <10%, and in LIAISON® XL DiaSorin from 2019 with an intra-assay CV of <10%.</p><p id="par0070" class="elsevierStylePara elsevierViewall">DHEA-S was measured by chemiluminescence assay in the IMMULITE® 2000 Siemens system with an intra-assay CV of < 15%; the normal range was established by sex and age (female: 18–24 years, 150–3402 ng/mL; 25–34 years, 150–2982 ng/mL; 35–49 years, 150–2582 ng/mL; 50–59 years, 260–2000 ng/mL; 60–69 years, 130–1300 ng/mL; and 70–79 years, 170–900 ng/mL. Male: 20–29 years, 2800–6400 ng/mL; 30–39 years, 1200–5200 ng/mL; 40–49 years, 950–5300 ng/mL; 50–59 years, 700–3100 ng/mL; 60–69 years, 420–2900 ng/mL; and 70–79 years, 280–1750 ng/mL). Salivary cortisol was measured in Cobas 6000 Roche by electrochemiluminescence with an intra-assay CV of <10% and a normal range lower than 5.74 nmol/L.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Radiological study</span><p id="par0075" class="elsevierStylePara elsevierViewall">Abdominal computed tomography (CT) or MRI were performed in all patients at diagnosis (CT and MRI in 53 patients, only CT in 38, and only MRI in 7 patients). The size of the largest adenoma was included in the analyses. Moreover, we calculated the total adenomatous mass as the sum of the largest diameters of both adrenal incidentalomas.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> Lipidic content was analysed in 85 patients, and the presence of necrosis, haemorrhage, or other atypical radiological features were described in all AIs. During follow-up, radiological studies were repeated in 89 patients (CT and MRI in 8 patients, only CT in 52, and only MRI in 27 patients).</p><p id="par0080" class="elsevierStylePara elsevierViewall">In 15 patients in whom unilateral adrenalectomy had been considered, norcholesterol scintigraphy (potassium iodide was administered before the radiopharmaceutical administration) was performed, evaluating grade and laterality of the uptake.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Statistical analysis</span><p id="par0085" class="elsevierStylePara elsevierViewall">All statistical analyses were performed with STATA.15. The Shapiro–Wilk test was used to check the normality assumption and Levene's test to evaluate the homogeneity of variance. Categorical variables are expressed as percentages and absolute values. Quantitative variables are expressed as mean ± standard deviation or median and interquartile range (IQR) depending on the normal distribution of the variable.</p><p id="par0090" class="elsevierStylePara elsevierViewall">Odds ratios (with 95% confidence intervals) and mean differences were calculated as measures of association using a logistic regression model, and the β coefficient using a linear regression model. For variables following the normal distribution, we used Student’s t-test to compare differences between two groups. The chi-squared test was performed to compare categorical variables between independent groups.</p><p id="par0095" class="elsevierStylePara elsevierViewall">In all cases, a two-tailed <span class="elsevierStyleItalic">p</span>-value <0.05 was considered statistically significant.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Differential phenotype of patients with PBMAH and non-PBMAH</span><p id="par0100" class="elsevierStylePara elsevierViewall">Ninety-eight patients were enrolled in the study, 31 patients with PBMAH (31.6%) and 67 with non-PBMAH (68.4%). Patients with PBMAH presented a higher prevalence of ACS compared to non-PBMAH (32.3% vs. 10.5%, <span class="elsevierStyleItalic">p</span> = 0.008). This finding could be explained by the larger tumour size and total adenomatous mass in patients with PBMAH compared to non-PBMAH, since differences in the prevalence of ACS disappeared after adjusting by tumour size (adjusted OR 2.3, 95% CI: 0.65–8.27) or by total adenomatous mass (OR 2.3, 95% CI: 0.47–11.21) (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Moreover, a positive correlation was found between total adenomatous mass (r = 0.45, <span class="elsevierStyleItalic">p</span> < 0.001), but not with tumour size (r=0.19, <span class="elsevierStyleItalic">p</span> = 0.084). Nevertheless, no significant differences were found in the cardiometabolic profile of both groups. The only observed difference in the hormonal profile was the presence of lower DHEAS levels in patients with PBMAH (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). Patients with ACS and PBMAH (n = 10) tended to have a higher prevalence of dyslipidaemia than patients with PBMAH and possible ACS (n = 21) (80% vs. 42.9%, <span class="elsevierStyleItalic">p</span> = 0.052), but no differences were found in the prevalence of hypertension (70% vs. 71%, <span class="elsevierStyleItalic">p</span> = 0.935), type 2 diabetes (20% vs. 57%, <span class="elsevierStyleItalic">p</span> = 0.052), and obesity (50% vs. 16%, <span class="elsevierStyleItalic">p</span> = 0.064).</p><p id="par0110" class="elsevierStylePara elsevierViewall">Norcholesterol scintigraphy was performed in 9 patients with PBMAH and 6 patients with non-PBMAH. In all patients, bilateral uptake was observed, with the exception of one patient with non-PBMAH with no uptake<span class="elsevierStyleBold">.</span></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Follow-up study</span><p id="par0115" class="elsevierStylePara elsevierViewall">Two patients with PBMAH underwent unilateral adrenalectomy of the largest adenoma, improving their cardiometabolic comorbidities and cortisol secretion. These two patients had ACS, were young (55 and 60 years) and had several comorbidities potentially related to the ACS. Two patients with non-PBMAH died (one due to an infection and the other with no identified cause).</p><p id="par0120" class="elsevierStylePara elsevierViewall">After a median follow-up of 33.7 months (range 3.7–194.8), 7 out of 58 patients (12.1%) with possible ACS developed ACS. A total of 10 patients developed dyslipidaemia, 5 type 2 diabetes, 5 cardiovascular disease, 4 obesity, and 2 high blood pressure. No new cases of cerebrovascular events were reported. No differences in the risk of developing comorbidities or tumour growth were observed between PBMAH and non-PBMAH (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Results of the study of aberrant receptors in PBMAH</span><p id="par0125" class="elsevierStylePara elsevierViewall">An aberrant receptors study was performed in 5 patients with PBMAH. The reasons for not performing the study in the other 26 patients with PBMAH were unknown. It was negative in 2 patients, positive in the metoclopramide test in 2 patients (cortisol increase of 63% in one and 40–50% in the other patient), and positive for metoclopramide and the mixed meal test in the last patient (cortisol increase of 48% and 62%, respectively). The patient with the positive mixed meal test was treated with 120 µg/month of lanreotide with no response, and one of the patients with a positive metoclopramide test received amitriptyline with no response either. Two patients (one of the patients with a negative study and one with a positive response to the metoclopramide test) underwent unilateral adrenalectomy.</p></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0130" class="elsevierStylePara elsevierViewall">The prevalence of PBMAH in patients with AIs and with bilateral AIs and subtle hypercortisolism in our series was 4.2% and 31.6%, respectively. The prevalence of PBMAH has not been determined in other studies despite the fact that 15% of AIs are bilateral<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and up to 40% of bilateral lesions are associated with ACS.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Song et al.<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> reported a cohort of 1049 patients with AIs and showed that only 1 patient (0.1%) had PBMAH. Lomte et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> retrospectively analysed a cohort of 70 patients with bilateral adrenal masses and found that only 3 patients (4.3%) harboured PBMAH. The prevalence of PBMAH in our cohort is higher than in both of those studies. This may be explained by the fact that in the cohort of Song et al.,<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> PBMAH diagnosis was established by histology (the number of biopsied masses was low, only 12) and not on the basis of the secretory profile and radiological features. The differences with the study by Lomte et al.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> can be attributed to the higher prevalence of familial pheochromocytoma (40%) and tuberculosis (27.1%), which is more prevalent in India than in our country.</p><p id="par0140" class="elsevierStylePara elsevierViewall">Patients with PBMAH presented a fourfold prevalence of ACS than those non-PBMAH, but these differences were related to the larger tumour size and total adenomatous mass in patients with PBMAH. The ACS prevalence in AIs is widely variable in the previously reported studies.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,15,16</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">In two observational studies performed in the Italian population, the prevalence of ACS varied from 9.2% in a multicentre cohort with more than 1000 patients with AIs<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> to 29% in a small group of 41 patients with AIs and typical adrenal adenoma imaging.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> However, none of the previous studies compared the prevalence of ACS in PBMAH vs. other bilateral AIs without PBMAH definition criteria. Therefore, we believe that larger prospective, multicentre studies should be carried out to confirm our findings.</p><p id="par0150" class="elsevierStylePara elsevierViewall">As an interesting point, despite the higher prevalence of ACS in patients with PBMAH than non-PBMAH, ACTH levels tended to be higher in patients with PBMAH. This finding could be related to the presence of local production of ACTH by the steroidogenic cells themselves. In fact, aberrant hormone receptors have been shown to regulate the paracrine secretion of ACTH, creating an autocrine/paracrine loop that promotes adrenal growth and steroid secretion in PBMAH.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Regarding tumour size and ACS risk, there is some discrepancy in previous studies about the prevalence of ACS and the size of AIs. In accordance with our findings, Vassiliadi et al.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> found significantly larger sizes and cortisol levels after DST in bilateral AIs when compared with unilateral lesions. Besides, the ACS was diagnosed in more patients with bilateral AIs than unilateral (41.5% vs. 12.2%, respectively), even when various criteria were used to define the ACS.</p><p id="par0160" class="elsevierStylePara elsevierViewall">In another small retrospective study with 33 bilateral AIs (5 of them PBMAH), those subjects with positive responses to the aberrant receptor study had bigger adenomas, higher cortisol levels after DST, higher night cortisol levels and a tendency towards lower levels of ACTH.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> According to these results, it seems that the significantly larger size of the bilateral lesions could justify the higher frequency of ACS in this group. Perhaps the larger tumour size in bilateral AIs rather unilateral could be related to a longer duration of the disease in bilateral tumours, which may also explain the higher risk of ACS.</p><p id="par0165" class="elsevierStylePara elsevierViewall">On the other hand, Morelli et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> performed a prospective study with 175 patients with unilateral AIs and 38 with bilateral AIs (30 of them corresponding to PBMAH), and although the maximum diameter of the adrenal lesions was significantly higher in the bilateral than the unilateral forms, the magnitude of hypercortisolism was similar in both unilateral and bilateral AIs.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Despite the higher prevalence of ACS in patients with PBMAH than in non-PBMAH, no differences in the cardiometabolic risk were observed between them. To our knowledge, no previous study has analysed this issue. Previous AIs series focusing on the different phenotypes of unilateral and bilateral AIs have described similar results.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19–21</span></a> In fact, the lack of association of bilateral AIs with ACS-related comorbidities was observed in some studies reporting an association between the prevalence of ACS and bilaterality of AIs.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">19,20</span></a> This finding could be related to the presence of different sensitivities to hypercortisolism in patients with bilateral AIs.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> In this sense, Majnik et al.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> found that the prevalence of T2DM in patients with bilateral AIs (40.9%) was significantly higher compared with unilateral adrenal tumours (23.2%). This could be related to the higher prevalence of the N363S variant in bilateral Ais, suggesting a role in the pathogenesis in bilateral AIs. However, the studies that focused on the role of single-nucleotide polymorphisms (SNP) of the glucocorticoid (GC) receptor gene in the risk of ACS in AIs found controversial results.<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Some authors showed an association between SNPs of the GC receptor and ACS risk<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24,25</span></a> while others<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22,23,26</span></a> found that the presence of SNPs of the GC receptor did not influence the development of Cushing’s disease, or adrenal dependent Cushing’s syndrome. Thus, few data are available in patients with AIs to confirm the hypothesis that a single polymorphic variant could influence cortisol secretion and risk of comorbidities, and even less about the differences in SNPs of the GC receptor prevalence in bilateral and unilateral AIs.</p><p id="par0180" class="elsevierStylePara elsevierViewall">The aberrant receptors study was positive in 60% of patients with PBMAH, with the metoclopramide test the most frequently altered. Previous studies have also described that aberrant receptors are highly prevalent in PBMAH.<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27–29</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Hsiao et al.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> showed that the most frequent response to aberrant receptor expression tests in 14 patients with PBMAH was vasopressin (45.5%); Mircescu et al.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> described AVP administration and upright posture test (in 3 of 6 patients with PBMAH) as the most affected test; Libé et al.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> showed in a prospective study of 32 patients with PBMAH that the most frequently observed responses were to upright posture (67%) and metoclopramide (56%) tests. Therefore, most studies, including ours, supported that vasopressin and serotonin receptors are probably the more prevalent functional receptors in PBMAH, which is in line with previous reports.<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">The presence of abnormal receptors can lead to innovative pharmacological therapies as alternatives to adrenalectomy, including suppression of the ligands or the use of specific receptor antagonists.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> However, it should be noted that the medical treatment was not effective in either of the two patients in our study. Libé et al.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> found inhibition of cortisol secretion by octreotide in the three Cushing’s syndrome patients who positively responded to the mixed meal test, in all the glucagon responsive patients, and in 12 out of 13 (92%) patients with ACS. In accordance with this, previous studies demonstrated a correction of hypercortisolism with chronic subcutaneous octreotide administration in patients with food-dependent Cushing’s syndrome,<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32,33</span></a> with endogenous GIP level inhibition thought to be the possible underlying mechanism.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Moreover, long-term control of hypercortisolism has also been obtained by ectopic ᵦ-adrenergic receptor blockade with propranolol<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28,34</span></a> and by inhibition of LH secretion with leuprolide acetate.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28,35</span></a> Other medical treatment included angiotensin II receptor or serotonin receptor antagonists.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> In contrast, Albiger et al.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> reported on the follow-up of 16 patients with PBMAH and Cushing’s syndrome, one case with food-dependent CS treated with octreotide LAR, and two patients with a positive postural test treated with propranolol with a limited clinical response despite marked improvement in biochemical values. Thus, surgery is the current recommended therapy for PBMAH.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> However, adrenal steroidogenesis inhibitors remain a valid option for nonsurgical candidates.</p><p id="par0200" class="elsevierStylePara elsevierViewall">In general, in patients with ACS and PBMAH without abnormal receptors, unilateral adrenalectomy is the treatment of choice. It should be considered in patients with comorbidities potentially associated with ACS (type 2 diabetes, hypertension, and/or osteoporosis), especially if they are poorly controlled and if the patient is young. Adrenalectomy leads to significant improvement in the control of diabetes and high blood pressure.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">38</span></a> Regarding follow-up for these patients, it should be performed following the current European guidelines for the management of AIs.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">One of the major strengths of our study is that it includes a large number of subjects who were consecutively evaluated in our centre between 2013 and 2019, as well as the long-term follow-up period. Moreover, this is the first study focusing on the differential phenotype of PBMAH compared to other bilateral AIs with associated MACE. The limitations are mainly related to the retrospective nature of the study, and the possible bias induced by individual decisions to perform adrenalectomy or the medical treatment of comorbidities. In addition, information from the last visit was not available for all patients, so a follow-up bias should be considered.</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conclusions</span><p id="par0210" class="elsevierStylePara elsevierViewall">PBMAH is relatively common in patients with incidentally detected bilateral adrenal lesions with associated subtle hypercortisolism. The higher prevalence of ACS in PBMAH compared to non-PBMAH is related to larger tumour size and total adenomatous mass in patients with PBMAH, but no differences in the cardiometabolic profile were observed between the two groups.</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Ethical approval</span><p id="par0215" class="elsevierStylePara elsevierViewall">All procedures performed on the study participants were conducted in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.</p></span><span id="sec0081" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0141">Funding</span><p id="par0221" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs1">SENDIMAD</span>: SENDIMAD GRANT for Support for Research in Endocrinology, Nutrition and Diabetes 2019.</p><p id="par0228" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleGrantSponsor" id="gs2">IRYCIS</span>: Intramural invitation for aid for research projects from novice researchers, associate clinical researchers, and/or emerging groups from Ramón y Cajal University Hospital 2019.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0220" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres1778583" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aim" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ 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"identificador" => "sec0081" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-11-01" "fechaAceptado" => "2022-01-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1561534" "palabras" => array:4 [ 0 => "Autonomous cortisol secretion" 1 => "Adrenal incidentalomas" 2 => "Primary bilateral macronodular adrenal hyperplasia" 3 => "Subclinical hypercortisolism." ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1561535" "palabras" => array:4 [ 0 => "Secreción autónoma de cortisol" 1 => "Incidentalomas suprarrenales" 2 => "Hiperplasia suprarrenal macronodular bilateral primaria" 3 => "Hipercortisolismo leve" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Aim</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">This study evaluated prevalence of primary bilateral macronodular adrenal hyperplasia (PBMAH). It also analyzed the differential phenotype of patients with PBMAH compared to other bilateral adrenal lesions that do not meet the definition of PBMAH.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">We reviewed the medical records of 732 patients diagnosed with an adrenal incidentaloma at our center. Ninety-eight patients with subclinical hypercortisolism were included in the analysis. We defined PBMAH as the presence of plasma cortisol > 1.8 μg/dL after an over-night 1-mg dexamethasone test, bilateral adrenal hyperplasia, and bilateral adrenal nodules > 1 cm.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">A total of 31 patients had PBMAH. Patients with PBMAH showed greater prevalence of autonomous cortisol secretion (plasma cortisol > 5.0 μg/dL after an overnight 1-mg dexamethasone test) than patients without PBMAH (OR 4.1, 95%CI 1.38-12.09, <span class="elsevierStyleItalic">p</span> = 0.010). Tumor size and total adenomatous mass were significantly greater in patients with PBMAH compared to patients without PBMAH (30.2 ± 12.16 vs. 24.3 ± 8.47 mm, <span class="elsevierStyleItalic">p</span> = 0.010 and 53.9 ± 20.8 vs. 43.3 ± 14.62 mm, <span class="elsevierStyleItalic">p</span> = 0.023), respectively. A greater proportion of patients with PBMAH had diabetes compared to patients without PBMAH (45.2% vs. 25.4%, <span class="elsevierStyleItalic">p</span> = 0.05).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">PBMAH is present in one-third of patients with adrenal incidentaloma and subclinical hypercortisolism. Patients with PBMAH showed greater autonomous cortisol secretion, bigger tumor size, and higher rates of diabetes than those without PBMAH.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Aim" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Se evaluó la prevalencia de hiperplasia suprarrenal macronodular bilateral primaria (PBMAH). También se analizó el fenotipo diferencial de los pacientes con PBMAH en comparación con otras lesiones suprarrenales bilaterales que no cumplían con la definición de PBMAH.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Revisamos las historias clínicas de 732 pacientes diagnosticados de incidentaloma suprarrenal en nuestro centro. Se incluyeron 98 pacientes con hipercortisolismo subclínico para el análisis. Se definió PBMAH como la presencia de cortisol plasmático > 1,8 μg/dL después de una prueba de 1 mg de dexametasona durante la noche, hiperplasia suprarrenal bilateral y nódulos suprarrenales bilaterales > 1 cm.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Un total de 31 pacientes tenían PBMAH. Los pacientes con PBMAH mostraron una mayor prevalencia de secreción autónoma de cortisol (cortisol plasmático > 5,0 μg/dL después de la prueba de 1 mg de dexametasona durante la noche) que los pacientes sin PBMAH (OR 4,1, IC del 95%: 1,38-12,09, p = 0,010). El tamaño del tumor y la masa adenomatosa total fueron significativamente mayores en pacientes con PBMAH en comparación con los pacientes sin PBMAH (30,2 ± 12,16 vs. 24,3 ± 8,47 mm, p = 0,010 y 53,9 ± 20,8 vs. 43,3 ± 14,62 mm, p = 0,023), respectivamente. Una mayor proporción de pacientes con PBMAH tenían diabetes en comparación con los pacientes sin PBMAH (45,2% vs. 25,4%, p = 0,05).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">PBMAH está presente en un tercio de los pacientes con incidentaloma suprarrenal e hipercortisolismo subclínico. Los pacientes con PBMAH mostraron una mayor secreción autónoma de cortisol, mayor tamaño del tumor y diabetes que aquellos sin PBMAH.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Bengoa-Rojano N, Fernández-Argüeso M, Botella-Carretero JI, Pascual-Corrales E, Araujo-Castro M. Prevalencia y fenotipo de la hiperplasia suprarrenal macronodular bilateral primaria con secreción autónoma de cortisol: un estudio de 98 pacientes. Rev Clin Esp. 2022;222:458–467.</p>" ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1808 "Ancho" => 1937 "Tamanyo" => 253563 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Study population and inclusion study population.</p> <p id="spar0001" class="elsevierStyleSimplePara elsevierViewall">AIs: adrenal incidentalomas; PBMAH: primary bilateral macronodular adrenal hyperplasia; DST: dexamethasone suppression test.</p> <p id="spar0002" class="elsevierStyleSimplePara elsevierViewall">*Only 1 of the 3 patients with overt Cushing's syndrome had PBMAH.</p>" ] ] 1 => array:8 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 653 "Ancho" => 2175 "Tamanyo" => 135431 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0010" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Protocol for the study of aberrant receptors.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0015" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">ACS: autonomous cortisol secretion; ACTH: adrenocorticotropic hormone; BMI: body mass index; DHEA-S: dehydroepiandrosterone sulfate; DST: dexamethasone suppression test; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; LNSC: late-night salivary cortisol; PBMAH: primary bilateral macronodular adrenal hyperplasia; UFC: urinary free cortisol.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PBMAH(n = 31) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-PBMAH (n = 67) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p-</span>value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><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">Female (%) \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">56.7 \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">55.2 \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">0.895 \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">Age (años) \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">65.0 ± 10.5 \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">66.1 ± 9.70 \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">0.621 \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">Active smoking (%) \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">39.3 \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">47.0 \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">0.493 \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">BMI (kg/m<span class="elsevierStyleSup">2</span>) \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">28.2 ± 6.04 \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">28.2 ± 5.17 \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">0.981 \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">Systolic blood pressure (mmHg) \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">137.4 ± 16.39 \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">140.4 ± 17.28 \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">0.478 \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">Diastolic blood pressure (mmHg) \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">77.4 ± 9.39 \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">79.8 ± 8.17 \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">0.257 \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">Any comorbidity (%) \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">86.7 \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">91.0 \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">0.512 \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">Hypertension (%) \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">71.0 \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">65.7 \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">0.603 \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">Type 2 diabetes (%) \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">45.2 \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">25.4 \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">0.050 \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">Dyslipidaemia (%) \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">54.8 \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">55.2 \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">0.972 \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">Obesity (%) \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">25.9 \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">35.9 \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">0.461 \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">Cerebrovascular disease (%) \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">1.5 \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">0.494 \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">Cardiovascular disease (%) \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">24.1 \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">16.4 \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">0.374 \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">Possible ACS (%) \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">67.7 \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">89.5 \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">0.008<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">Confirmed ACS (%) \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">32.3 \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">10.5 \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">0.008<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">Fasting plasma glucose (mg/dL) (n = 97) \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">111.2 ± 39.01 \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">106.8 ± 27.03 \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">0.515 \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">HbA1c (%) (n = 43) \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">7.1 ± 2.12 \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">6.1 ± 0.84 \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">0.030<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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 cholesterol (mg/dL) (n = 92) \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">176.0 ± 54.0 \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">198.2 ± 45.10 \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">0.043<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">LDL-c (mg/dL) (n = 74) \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">106.8 ± 39.93 \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">122.9 ± 39.13 \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">0.110 \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">HDL-c (mg/dL) (n = 74) \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">50.5 ± 15.47 \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">53.5 ± 15.79 \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">0.463 \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">Triglycerides (mg/dL) (n = 92) \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">114.8 ± 57.0 \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">104.5 ± 41.49 \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">0.331 \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">Cortisol after 1 mg DST (μg/dL) (n = 98) \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">4.7 ± 2.98 \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">3.5 ± 3.25 \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">0.073 \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">Cortisol after repeated 1 mg DST (μg/dL) (n = 98) \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">6.6 ± 3.62 \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">5.2 ± 6.00 \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">0.315 \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">UFC (μg/24 h) (n = 73) \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">50.5 ± 39.17 \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">60.8 ± 74.62 \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">0.446 \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">UFCx2 (μg/24 h) (n = 50) \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">42.4 ± 24.29 \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">45.5 ± 45.56 \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">0.758 \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">ACTH (pg/mL) (n = 85) \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">23.6 ± 48.57 \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">14.0 ± 9.70 \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">0.150 \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">DHEA-S (μg/dL) (n = 62) \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">337.1 ± 202.9 \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">494.6 ± 377.31 \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">0.039<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">LNSC (μg/dL) (n = 76) \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">5.2 ± 3.15 \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">5.0 ± 4.75 \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">0.850 \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">Tumour rich in lipidic content (%) (n = 87) \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">82.1 \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">82.5 \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">0.972 \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">Tumour size (mm) \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">30.2 ± 12.16 \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">24.3 ± 8.47 \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">0.010<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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 adenomatous mass (mm) \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">53.9 ± 20.8 \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">43.3 ± 14.62 \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">0.023<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \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">Calcification, haemorrhage, or other atypical features (%) \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">25.9 \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">20.7 \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">0.590 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Statistically significant results.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Baseline characteristics of patients with PBMAH and non-PBMAH.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0020" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Δ: mean increase during the follow-up period (mean value in last visit–mean value in initial visit); 95% CI: 95% confidence interval; ACS: autonomous cortisol secretion; ACTH: adrenocorticotropic hormone; BMI: body mass index; DST: dexamethasone suppression test; FPG: fasting plasma glucose; HDL-c: high-density lipoprotein cholesterol; HR: hazard ratio; LDL-c: low-density lipoprotein cholesterol; LNSC: late-night salivary cortisol; NA: not applicable; PBMAH: primary bilateral macronodular adrenal hyperplasia; UFC: urinary free cortisol.</p>" "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PBMAH (n = 31) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Non-PBMAH (n = 67) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">HR [95% CI], <span class="elsevierStyleItalic">p-</span>value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><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">New comorbidities (%) \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">84.2 (n = 16) \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">90.7 (n = 39) \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">HR 0.8 [0.45–1.47], <span class="elsevierStyleItalic">p</span> = 0.493 \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">New hypertension (%) \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">11% (n = 2) \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">NA \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">New type 2 diabetes (%) \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">6.3 (n = 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">9.5 (n = 4) \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">HR 0.4 [0.04–3.61], <span class="elsevierStyleItalic">p</span> = 0.370 \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">New dyslipidaemia (%) \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">15.4 (n = 2) \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">29.6 (n = 8) \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">HR 0.5 [0.10–2.17], <span class="elsevierStyleItalic">p</span> = 0.289 \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">New obesity (%) \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">5.3 (n = 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">9.1 (n = 3) \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">HR 0.7 [0.08–7.10], <span class="elsevierStyleItalic">p</span> = 0.787 \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">New obesity (%) \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">5.0 (n = 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">8.5 (n = 4) \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">HR 0.5 [0.06–4.88], <span class="elsevierStyleItalic">p</span> = 0.565 \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">ACS development (%) \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">18.8 (n = 3) \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">9.5% (n = 4) \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">HR1.5 [0.35–7.01], <span class="elsevierStyleItalic">p</span> = 0.564 \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">ΔFPG (mg/dL) (n = 92) \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">−1.3 ± 33.39 \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">1.8 ± 23.10 \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"><span class="elsevierStyleItalic">p</span> = 0.597 \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">ΔHbA1c (%) (n = 25) \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">−0.5 ± 1.04 \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">0.3 ± 1.03 \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"><span class="elsevierStyleItalic">p</span> = 0.087 \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">ΔLDL (mg/dL) (n = 48) \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">−9.8 ± 29.85 \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">−12.7 ± 40.00 \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"><span class="elsevierStyleItalic">p</span> = 0.809 \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">ΔHDL (mg/dL) (n = 49) \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">1.9 ± 10.77 \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">2.6 ± 9.39 \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"><span class="elsevierStyleItalic">p</span> = 0.816 \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">ΔTriglycerides (mg/dL) (n = 81) \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">4.9 ± 47.11 \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">7.7 ± 55.08 \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"><span class="elsevierStyleItalic">p</span> = 0.821 \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">ΔDST (mg/dL) (n = 75) \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">0.6 ± 2.47 \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">−0.0 ± 1.64 \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"><span class="elsevierStyleItalic">p</span> = 0.197 \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">ΔUFC (μg/24 h) (n = 30) \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">7.3 ± 41.21 \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">−28.2 ± 33.36 \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"><span class="elsevierStyleItalic">p</span> = 0.014<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \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">ΔACTH (pg/mL) (n = 50) \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">−2.6 ± 16.00 \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">−3.5 ± 11.61 \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"><span class="elsevierStyleItalic">p</span> = 0.804 \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">ΔLNSC (μg/dL) (n = 43) \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">2.7 ± 12.39 \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">1.0 ± 8.84 \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"><span class="elsevierStyleItalic">p</span> = 0.611 \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">ΔTumor size (%) >5 mm (n = 51) \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">12.5 (n = 2) \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">14.3 (n = 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">HR 0.7 [0.12–3.57], <span class="elsevierStyleItalic">p</span> = 0.614 \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">ΔTumor size (mm) (n = 51) \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">0.4 ± 4.75 \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">0.7 ± 3.98 \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"><span class="elsevierStyleItalic">p</span> = 0.855 \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">ΔTotal adenomatous mass (mm) (n = 51) \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">0.6 ± 6.66 \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">0.6 ± 7.26 \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"><span class="elsevierStyleItalic">p</span> = 0.997 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Statistically significant results.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Follow-up differences between PBMAH and non-PBMAH.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:38 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis and management of primary bilateral macronodular adrenal hyperplasia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.A. 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