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Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1
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The patient is placed in a hyperextension position. 1 – first incision is made below the last rib to create a retroperitoneal space; 2 – second port, 1 cm above the iliac crest, where the 0° endoscope enters; 3 – working port located 4 cm anterior to trocar number 2.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Marcelo Hisano, Fabio Carvalho Vicentini, Miguel Srougi" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Marcelo" "apellidos" => "Hisano" ] 1 => array:2 [ "nombre" => "Fabio Carvalho" "apellidos" => "Vicentini" ] 2 => array:2 [ "nombre" => "Miguel" "apellidos" => "Srougi" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222024139?idApp=UINPBA00004N" "url" => "/18075932/00000067000000S1/v1_202212010649/S1807593222024139/v1_202212010649/en/main.assets" ] "en" => array:18 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">REVIEW</span>" "titulo" => "Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "169" "paginaFinal" => "172" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Flavia L. Coutinho, Delmar M. Lourenco, Rodrigo A. Toledo, Fabio L.M. Montenegro, Sergio P.A. Toledo" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Flavia L." "apellidos" => "Coutinho" "email" => array:1 [ 0 => "flacoutinho07@yahoo.com.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor1" ] ] ] 1 => array:4 [ "nombre" => "Delmar M." "apellidos" => "Lourenco" "sufijo" => "Jr." "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] ] ] 2 => array:3 [ "nombre" => "Rodrigo A." "apellidos" => "Toledo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] ] ] 3 => array:3 [ "nombre" => "Fabio L.M." "apellidos" => "Montenegro" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">II</span>" "identificador" => "aff2" ] ] ] 4 => array:3 [ "nombre" => "Sergio P.A." "apellidos" => "Toledo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">I</span>" "identificador" => "aff1" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Endocrine Genetics Unit (LIM-25), Endocrinology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo." "etiqueta" => "I" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Head and Neck Surgery Department, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo." "etiqueta" => "II" "identificador" => "aff2" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Tel.: 55 11 3061 7252" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 490 "Ancho" => 425 "Tamanyo" => 19303 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Mean serum levels of parathyroid hormone (PTH; mean ± SEM) before and after total parathyroidectomy (PTX) followed by autologous parathyroid implant in the non-dominant forearm in 16 cases of hyperparathyroidism associated with multiple endocrine neoplasia type 1. Serum samples were collected from both non-dominant (A) and dominant (B) forearms. These data are based on those of Coutinho et al. (<a class="elsevierStyleCrossRef" href="#bib34">34</a>).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Primary hyperparathyroidism (HPT) is a common endocrine disorder, affecting 0.3% of the general population and 1–3% of postmenopausal women (<a class="elsevierStyleCrossRef" href="#bib1">1</a>). It is characterized by hypercalcemia and elevated or inappropriately normal levels of parathyroid hormone (PTH). Most patients (80–95%) present with the sporadic form of the disease (s-HPT), whereas familial cases may be associated with multiple endocrine neoplasia type 1 (MEN1) and MEN type 2, jaw tumor syndrome, neonatal severe primary HPT, and familial isolated HPT (<a class="elsevierStyleCrossRefs" href="#bib2">2–4</a>). HPT disease associated with MEN1 (HPT/MEN1) differs in many aspects from s-HPT, including its clinical, pathological, and genetic characteristics, and it is therefore treated with different surgical protocols, and exhibits different cure rates and outcomes (<a class="elsevierStyleCrossRef" href="#bib2">2</a>),(<a class="elsevierStyleCrossRef" href="#bib5">5</a>),(<a class="elsevierStyleCrossRef" href="#bib6">6</a>). In contrast to s-HPT, HPT/MEN1 presents as a multiglandular parathyroid neoplasia (hyperplasia versus adenoma), has an earlier disease onset (20 versus 40 years of age), has a higher recurrence rate after parathyroidectomy (PTX), and is often less aggressive (<a class="elsevierStyleCrossRef" href="#bib2">2</a>),(<a class="elsevierStyleCrossRef" href="#bib5">5</a>),(<a class="elsevierStyleCrossRef" href="#bib7">7</a>). A potentially more virulent form of HPT has also been reported in association with Zollinger–Ellison syndrome (<a class="elsevierStyleCrossRef" href="#bib8">8</a>). We have found an increase in the frequency of HPT/MEN1in recent years, since familial genetic screening for the <span class="elsevierStyleItalic">MEN1</span> gene was introduced into routine use in our hospital (<a class="elsevierStyleCrossRefs" href="#bib9">9–11</a>).</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">PTX IN HPT/MEN1</span><p id="para20" class="elsevierStylePara elsevierViewall">Instead of adenomectomy, the procedure recommended for s-HPT, two basic surgical procedures have been performed for the treatment of patients with HPT/MEN1: subtotal partial parathyroidectomy (SPTX) and total parathyroidectomy (TPTX). SPTX consists of the removal of at least 3–3.5 glands, leaving a normal parathyroid remnant of 20–30 mg, whereas TPTX consists of the removal of all four glands followed by autologous heterotopic implant of parathyroid tissue in the muscles of the non-dominant forearm (<a class="elsevierStyleCrossRefs" href="#bib8">8,12–16</a>). Ultimately, in the hands of skilled surgeons, both methods have been reported to achieve euparathyroidism, maintaining correct PTH secretion and calcium metabolism, and preventing clinical complications.</p></span><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">BONE MINERAL DENSITY IN HPT/MEN1</span><p id="para30" class="elsevierStylePara elsevierViewall">Very few data on bone status in patients with HPT/MEN1 are available in the literature, which limits comparisons. Burgess et al. documented high rates of early and severe bone mineral loss in the femoral neck (FN) and lumbar spine (LS) of 29 women in a large MEN1 family from Tasmania (<a class="elsevierStyleCrossRef" href="#bib17">17</a>). Of note, the authors used analysis of the bone mineral density (BMD) to evaluate bone status in the studied cases.</p><p id="para40" class="elsevierStylePara elsevierViewall">Similarly, in 2008, we confirmed the same demineralization pattern in affected cases from an extended MEN1 family harboring a founding <span class="elsevierStyleItalic">MEN1</span> germline heterozygous mutation. We also identified the proximal one-third of the distal radius (1/3 DR) as an early and severely compromised bone site in this MEN1 family (<a class="elsevierStyleCrossRef" href="#bib18">18</a>). Patients with MEN1-related HPT usually have severe bone and kidney involvement despite a milder biochemical presentation compared with their s-HPT counterparts (<a class="elsevierStyleCrossRef" href="#bib19">19</a>).</p><p id="para50" class="elsevierStylePara elsevierViewall">In 2010, our preliminary findings were confirmed in a larger series of HPT/MEN1 cases that we were able to study. In this latter investigation, we found that urolithiasis occurred early (<30 years) and frequently (75%) and that it was usually associated with kidney-related co-morbidities (50%), as well as with renal insufficiency in the older group (>50 years) (33%). We also verified that bone mineral-related and urolithiasis-related renal complications in HPT/MEN1 were of early onset, frequent, extensive, severe, and progressive (<a class="elsevierStyleCrossRef" href="#bib20">20</a>). Notably, the trabecular bone mineral content in the studied cases was not protected, in contrast to the previously reported trend in s-HPT (<a class="elsevierStyleCrossRefs" href="#bib21">21-25</a>). Furthermore, it was recently suggested that the Menin protein, coded by the <span class="elsevierStyleItalic">MEN1</span> gene, may interfere in osteoblast differentiation (<a class="elsevierStyleCrossRefs" href="#bib26">26–28</a>), and may also have a direct demineralizing effect on trabecular bone in animal models (<a class="elsevierStyleCrossRef" href="#bib29">29</a>).</p><p id="para60" class="elsevierStylePara elsevierViewall">The impact of PTX in s-HPT has been widely studied, and significant short-term bone mineral recovery of the LS and FN has been documented (<a class="elsevierStyleCrossRef" href="#bib22">22</a>),(<a class="elsevierStyleCrossRef" href="#bib30">30</a>),(<a class="elsevierStyleCrossRef" href="#bib31">31</a>). Conversely, 1/3 DR BMD was previously thought to have no marked recovery one year after PTX (<a class="elsevierStyleCrossRef" href="#bib31">31</a>), whereas long-term mineral recovery of the LS, FN and also 1/3 DR has been documented (<a class="elsevierStyleCrossRefs" href="#bib22">22,25,30–33</a>).</p></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">BMD AFTER PTX IN HPT/MEN1</span><p id="para70" class="elsevierStylePara elsevierViewall">Data on bone mineral recovery after PTX in the specific subset of patients with HPT/MEN1 have been published in only two papers so far (<a class="elsevierStyleCrossRef" href="#bib17">17</a>),(<a class="elsevierStyleCrossRef" href="#bib34">34</a>).</p><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle60">Data from Burgess et al.</span><p id="para80" class="elsevierStylePara elsevierViewall">This first study addressed the LS and FN BMD before and after PTX in five women with HPT/MEN1. In this limited number of patients, significant recovery of BMD was seen in the femoral neck (3.2±2.9%) and lumbar spine (5.2±2.5%) after PTX (<a class="elsevierStyleCrossRef" href="#bib17">17</a>).</p></span><span id="cesec60" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">Our data</span><p id="para90" class="elsevierStylePara elsevierViewall">We assessed the BMD changes in 16 patients with HPT/MEN1 11 years after total PTX followed by autologous parathyroid implant in the forearm, using dual-energy X-ray absorptiometry (DXA, Hologic QDR-4500 S/N 45130, Waltham, MA) (<a class="elsevierStyleCrossRef" href="#bib34">34</a>). Significant improvements in BMD were verified in all cases 15 months after PTX at both the LS and FN, but not at 1/3 DR. Hence, 15 months after PTX, the LS values increased from 0.843 to 0.909 g/cm<span class="elsevierStyleSup">2</span>, with a BMD increase of +8.4±9.84% (<span class="elsevierStyleItalic">p</span> = 0.001). The FN values rose from 0.745 to 0.798 g/cm<span class="elsevierStyleSup">2</span>, and BMD increased by +6.9±3.17% (<span class="elsevierStyleItalic">p</span> = 0.0001). Conversely, no significant changes were seen in the 1/3 DR BMD values 15 months after PTX (<a class="elsevierStyleCrossRef" href="#bib34">34</a>).</p><p id="para100" class="elsevierStylePara elsevierViewall">It was noted that pre-surgical bone mineral mass was already compromised in the 16 patients with HPT/MEN1. Hence, there was a high prevalence of reduced BMD (Z-score < – 2.0) for the 1/3 DR (50%), LS (43.7%), ultradistal radius (UDR; 43.7%), FN (25%), and total femur (TF) (18.7%) in these cases.</p></span><span id="cesec70" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">BMD DATA IN s-HPT and HPT/MEN1</span><p id="para110" class="elsevierStylePara elsevierViewall">The BMD values after PTX in our study were between those reported by Burgess et al. (<a class="elsevierStyleCrossRef" href="#bib17">17</a>) in HPT/MEN1 cases, and those seen in s-HPT (<a class="elsevierStyleCrossRef" href="#bib32">32</a>). Furthermore, in contrast to the short-term and long-term 1/3 DR BMD recovery reported by Rubin et al. (<a class="elsevierStyleCrossRef" href="#bib32">32</a>) in cases with s-HPT, we could not document significant change in 1/3 DR BMD (-0.6±15.73%) during follow-up of our cases (<a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>). These data indicate a trend for potential differences in BMD recovery after surgery in patients with HPT/MEN1 compared with patients with s-HPT.</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia></span></span><span id="cesec80" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">PTH AND CALCIUM AFTER PTX IN HPT/MEN1</span><p id="para120" class="elsevierStylePara elsevierViewall">In this study, immediately after PTX, all cases presented transient signals and symptoms of hypocalcemia, associated with low serum calcium and PTH values. Therapy with oral calcium (∼2–3 g/day) and calcitriol (∼1 μg/day) supplements was instituted in all cases to achieve normal calcemia. This treatment was maintained for 4–5 months (with an average time of 8.3 months), although progressively lower therapeutic doses were needed over this time. The post-surgical pattern of increasing serum levels of PTH secreted by the parathyroid implant is shown in <a class="elsevierStyleCrossRef" href="#fig1">Figure 1</a>. A slow biochemical (calcium, PTH) recovery after successful total PTX followed by autologous parathyroid implantation was verified in this series of patients. Fully viable parathyroid implants with consistent mean PTH secretion values (32.6±9.1 ng/ml) were obtained 9 months after PTX (<a class="elsevierStyleCrossRef" href="#bib34">34</a>).</p><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="para130" class="elsevierStylePara elsevierViewall">Based on these data, we conclude that in patients with HPT/MEN1, bone demineralization is an important complication and should be routinely evaluated before PTX, and patients should be followed up for several years. Calcium and calcitriol supplementation is frequently needed for several months after PTX until efficient function of the autologous parathyroid implant is achieved.</p><p id="para140" class="elsevierStylePara elsevierViewall">In conclusion, in our experience there is a marked short-term improvement in BMD at the LS and FN in most patients with HPT/MEN1 after total PTX followed by autologous parathyroid implant into the forearm, although BMD at the 1/3 DR may take longer to recover (>18 months) after surgery. Hence, LS and FN BMDs are the better sites to investigate BMD after PTX in patients with HPT/MEN1.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:2 [ "identificador" => "xpalclavsec1581194" "titulo" => "KEYWORDS" ] 1 => array:2 [ "identificador" => "cesec10" "titulo" => "INTRODUCTION" ] 2 => array:2 [ "identificador" => "cesec20" "titulo" => "PTX IN HPT/MEN1" ] 3 => array:2 [ "identificador" => "cesec30" "titulo" => "BONE MINERAL DENSITY IN HPT/MEN1" ] 4 => array:3 [ "identificador" => "cesec40" "titulo" => "BMD AFTER PTX IN HPT/MEN1" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "cesec50" "titulo" => "Data from Burgess et al." ] 1 => array:2 [ "identificador" => "cesec60" "titulo" => "Our data" ] 2 => array:2 [ "identificador" => "cesec70" "titulo" => "BMD DATA IN s-HPT and HPT/MEN1" ] ] ] 5 => array:2 [ "identificador" => "cesec80" "titulo" => "PTH AND CALCIUM AFTER PTX IN HPT/MEN1" ] 6 => array:2 [ "identificador" => "xack638767" "titulo" => "ACKNOWLEDGMENTS" ] 7 => array:1 [ "titulo" => "REFERENCES" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "KEYWORDS" "identificador" => "xpalclavsec1581194" "palabras" => array:5 [ 0 => "Primary Hyperparathyroidism" 1 => "MEN1" 2 => "Bone Mineral Density" 3 => "Parathyroid Hormone" 4 => "Total Parathyroidectomy" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:1 [ "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><p id="spara50" class="elsevierStyleSimplePara elsevierViewall">The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm) on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months) improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara" id="cenpara10">No potential conflict of interest was reported.</p> <p class="elsevierStyleNotepara" id="cenpara20">Coutinho FL was responsible for the clinical assessment, data collection and analysis, and manuscript writing. Lourenco DM Jr is the doctor who contributed to the clinical assessment of patients with MEN1. Toledo RA is the biologist who performed the molecular diagnosis of patients in the study. Montenegro FL is the surgeon responsible for the surgical treatment of all patients in the study. Toledo SPA guided the study.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig1" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 490 "Ancho" => 425 "Tamanyo" => 19303 ] ] "descripcion" => array:1 [ "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">Mean serum levels of parathyroid hormone (PTH; mean ± SEM) before and after total parathyroidectomy (PTX) followed by autologous parathyroid implant in the non-dominant forearm in 16 cases of hyperparathyroidism associated with multiple endocrine neoplasia type 1. Serum samples were collected from both non-dominant (A) and dominant (B) forearms. These data are based on those of Coutinho et al. (<a class="elsevierStyleCrossRef" href="#bib34">34</a>).</p>" ] ] 1 => array:7 [ "identificador" => "tbl1" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">LS, lumbar spine; FN, femoral neck; 1/3 DR, distal third of radius; NA, data not evaluated.</p><p id="spara40" class="elsevierStyleSimplePara elsevierViewall">In all cases studied by Coutinho et al. (<a class="elsevierStyleCrossRef" href="#bib34">34</a>) total parathyroidectomy was followed by autologous parathyroid implant, and bone mineral density values were assessed using dual-energy X-ray absorptiometry (Hologic apparatus).</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="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col"> \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="center" valign="top" scope="col">Burgess (<a class="elsevierStyleCrossRef" href="#bib17">17</a>) (HPT/MEN1) \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="center" valign="top" scope="col">Coutinho (<a class="elsevierStyleCrossRef" href="#bib34">34</a>) (HPT/MEN1) \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="center" valign="top" scope="col">Rubin (<a class="elsevierStyleCrossRef" href="#bib32">32</a>)(s-HPT) \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">LS (%) \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="center" valign="top">5.2 \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="center" valign="top">8.4 \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="center" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">FN (%) \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="center" valign="top">3.2 \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="center" valign="top">6.9 \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="center" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">1/3 DR (%) \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="center" valign="top">NA \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="center" valign="top">–0.6 \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="center" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="top">Post-surgical mean time (months) \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="center" valign="top">18 \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="center" valign="top">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="center" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Mean percentage change in bone mineral density at three sites in patients with hyperparathyroidism associated with multiple endocrine neoplasia type 1 (HPT/MEN1) and those with sporadic HPT, after parathyroidectomy.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec10" "bibliografiaReferencia" => array:34 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Population-based screening for primary 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id="para150" class="elsevierStylePara elsevierViewall">FLC is the recipient of a CNPq doctorate fellowship (142603/2010-4), RAT is the recipient of a FAPESP post-doctorate fellowship (2009/15386-6), and SPAT is the recipient of a CNPq fellowship and grant (401990/2010-9).</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/18075932/00000067000000S1/v1_202212010649/S1807593222024140/v1_202212010649/en/main.assets" "Apartado" => null "PDF" => "https://static.elsevier.es/multimedia/18075932/00000067000000S1/v1_202212010649/S1807593222024140/v1_202212010649/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1807593222024140?idApp=UINPBA00004N" ]
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