{"markup":"\u003C?xml version=\u00221.0\u0022 encoding=\u0022UTF-8\u0022 ?\u003E\n    \u003Chtml version=\u0022HTML+RDFa+MathML 1.1\u0022\n    xmlns:content=\u0022http:\/\/purl.org\/rss\/1.0\/modules\/content\/\u0022\n    xmlns:dc=\u0022http:\/\/purl.org\/dc\/terms\/\u0022\n    xmlns:foaf=\u0022http:\/\/xmlns.com\/foaf\/0.1\/\u0022\n    xmlns:og=\u0022http:\/\/ogp.me\/ns#\u0022\n    xmlns:rdfs=\u0022http:\/\/www.w3.org\/2000\/01\/rdf-schema#\u0022\n    xmlns:sioc=\u0022http:\/\/rdfs.org\/sioc\/ns#\u0022\n    xmlns:sioct=\u0022http:\/\/rdfs.org\/sioc\/types#\u0022\n    xmlns:skos=\u0022http:\/\/www.w3.org\/2004\/02\/skos\/core#\u0022\n    xmlns:xsd=\u0022http:\/\/www.w3.org\/2001\/XMLSchema#\u0022\n    xmlns:mml=\u0022http:\/\/www.w3.org\/1998\/Math\/MathML\u0022\u003E\n  \u003Chead\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_itu2PgFdrjV-docKmLK8Jn5oXe_05RgvQh73eOhI_mE.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/js\/js_I8yX6RYPZb7AtMcDUA3QKDZqVkvEn35ED11_1i7vVpc.js\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\n(function(i,s,o,g,r,a,m){i[\u0022GoogleAnalyticsObject\u0022]=r;i[r]=i[r]||function(){(i[r].q=i[r].q||[]).push(arguments)},i[r].l=1*new Date();a=s.createElement(o),m=s.getElementsByTagName(o)[0];a.async=1;a.src=g;m.parentNode.insertBefore(a,m)})(window,document,\u0022script\u0022,\u0022\/\/www.google-analytics.com\/analytics.js\u0022,\u0022ga\u0022);ga(\u0022create\u0022, \u0022UA-15605596-27\u0022, {\u0022cookieDomain\u0022:\u0022auto\u0022});ga(\u0022set\u0022, \u0022page\u0022, location.pathname + location.search + location.hash);ga(\u0022send\u0022, \u0022pageview\u0022);ga(\u0027create\u0027, \u0027UA-189672-26\u0027, \u0027auto\u0027, {\u0027name\u0027: \u0027hwTracker\u0027});\r\nga(\u0027hwTracker.send\u0027, \u0027pageview\u0027);\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022\u003E\n\u003C!--\/\/--\u003E\u003C![CDATA[\/\/\u003E\u003C!--\njQuery.extend(Drupal.settings, {\u0022basePath\u0022:\u0022\\\/\u0022,\u0022pathPrefix\u0022:\u0022\u0022,\u0022highwire\u0022:{\u0022markup\u0022:[{\u0022requested\u0022:\u0022full-text\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/20\\\/28\u0022},{\u0022requested\u0022:\u0022long\u0022,\u0022variant\u0022:\u0022full-text\u0022,\u0022view\u0022:\u0022full\u0022,\u0022pisa\u0022:\u0022spmdc;14\\\/20\\\/28\u0022}],\u0022ac\u0022:{\u0022spmdc;14\\\/20\\\/28\u0022:{\u0022access\u0022:{\u0022reprint\u0022:true,\u0022full\u0022:true},\u0022pisa_id\u0022:\u0022spmdc;14\\\/20\\\/28\u0022,\u0022atom_uri\u0022:\u0022\u0022,\u0022jcode\u0022:\u0022spmdc\u0022}}},\u0022googleanalytics\u0022:{\u0022trackOutbound\u0022:1,\u0022trackMailto\u0022:1,\u0022trackDownload\u0022:1,\u0022trackDownloadExtensions\u0022:\u00227z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip\u0022,\u0022trackUrlFragments\u0022:1},\u0022ajaxPageState\u0022:{\u0022js\u0022:{\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/jquery.cluetip.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.hoverIntent.js\u0022:1,\u0022sites\\\/all\\\/libraries\\\/cluetip\\\/lib\\\/jquery.bgiframe.min.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_at_symbol.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/highwire\\\/highwire\\\/plugins\\\/highwire_markup_process\\\/js\\\/highwire_article_reference_popup.js\u0022:1,\u0022sites\\\/all\\\/modules\\\/contrib\\\/google_analytics\\\/googleanalytics.js\u0022:1,\u00220\u0022:1}}});\n\/\/--\u003E\u003C!]]\u003E\n\u003C\/script\u003E\n\u003Clink type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EStudies have identified subclinical hypercortisolism in patients with adrenal incidentalomas, which is associated with greater rates of cardiovascular disease, type 2 diabetes mellitus, and mortality. This article discusses the genetics of bilateral macronodular adrenal hyperplasia, subclinical Cushing syndrome, as well as hypercortisolism in adrenal incidentaloma.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003Eadrenal disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cdiv class=\u0022section\u0022 id=\u0022sec-1\u0022\u003E\n         \n         \u003Cp id=\u0022p-2\u0022\u003EStudies have identified subclinical hypercortisolism in patients with adrenal incidentalomas, which is associated with greater rates of cardiovascular disease, type 2 diabetes mellitus (T2DM), and mortality. Jerome Yves Bertherat, MD, PhD, Paris Descartes University, Paris, France, described the genetics of bilateral macronodular adrenal hyperplasia (BMAH), a cause of hypercortisolism. The development of BMAH has been associated with several known genes, including somatic mutations of GNAS [Weinstein LS et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 1991] and duplication of PRKACA (resulting in MAH) [Beuschlein F et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2014], as well as genes associated with multiple tumor syndromes such as Menin, APC [Gaujoux S et al. \u003Cem\u003EClin Cancer Res\u003C\/em\u003E 2011], and fumarate hydratase [Matyakhina L et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2005].\u003C\/p\u003E\n         \u003Cp id=\u0022p-3\u0022\u003EProf. Bertherat hypothesized that 1 copy of an unknown gene receives a \u201chit,\u201d or germline mutation, and later, a somatic mutation occurs in the second copy, resulting in the development of BMAH. To evaluate this hypothesis, the group searched for a gene that may be affected by a germline and somatic mutation. A single-nucleotide polymorphism array was used to perform a genome-wide screening for chromosomal aberrations by comparing leukocyte and BMAH tumor DNA. Loss of heterozygosity at chromosome 16p was detected in 24% of tumor samples from patients with BMAH [Assie G et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2013]. Whole-genome sequencing of 5 leukocyte-tumor DNA pairs was undertaken and found that the armadillo repeat containing 5 (ARMC5) gene, located on chromosome 16p11.2, was mutated in 4 of 5 leukocyte samples and 3 of 5 tumor samples. Further analysis of the entire cohort of patients with BMAH demonstrated that 55% of patients harbored inactivating heterozygous ARMC5 mutations. In addition, recent studies have identified ARMC5 mutations in multiple families with BMAH, including a large family from Brazil (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Alencar GA et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2014; Gagliardi L et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Mutation of ARMC5 Resulting in BMAH in a Large Family\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-34454353\u0022 data-figure-caption=\u0022Mutation of ARMC5 Resulting in BMAH in a Large Family\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16443\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EMutation of ARMC5 Resulting in BMAH in a Large Family\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003ECT=computed tomography; DST=dexamethasone suppression test; PMAH=primary macronodular adrenal hyperplasia.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003EReproduced from Alencar GA et al. ARMC5 mutations are a frequent cause of primary macronodular adrenal hyperplasia. \u003Cem\u003EJ Clin Endocrinol Metab.\u003C\/em\u003E 2014;99(8):E1501\u2013E1509. With permission from The Endocrine Society.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-5\u0022\u003EA genotype-phenotype study in a cohort of European patients with BMAH who harbored wild-type or mutated ARMC5 found several meaningful, clinical differences. A significantly greater number of patients with mutated ARMC5 had clinical Cushing syndrome (71%) compared with patients with wild-type ARMC5 (35%; p = .006). In addition, patients with mutated ARMC5 had greater rates of hypertension (p = .009), T2DM (p = .093), and food response (p \u0026lt; .001). Serum adrenocorticotropic hormone (ACTH) levels were significantly higher in patients with mutated ARMC5 (p = .003), as were dexamethasone (1 mg) response (p \u0026lt; .001) and midnight plasma cortisol levels (p = .019). Furthermore, patients with mutated ARMC5 had greater body weight, larger adrenal size, and larger number of nodules identified by computed tomographic (CT) scan.\u003C\/p\u003E\n         \u003Cp id=\u0022p-6\u0022\u003EProf. Bertherat concluded that ARMC5 is a novel tumor suppressor gene that is frequently mutated in patients with BMAH, likely causing impaired steroidogenesis; however, further studies are needed to assess the function of ARMC5 and its impact on patient management.\u003C\/p\u003E\n         \u003Cp id=\u0022p-7\u0022\u003EMassimo Terzolo, MD, S. Luigi Hospital, Orbassano, Italy, proposed that subclinical Cushing syndrome (SCS) in adrenal incidentaloma is a clinical entity. Adrenal incidentalomas are present in up to 5% of patients who undergo abdominal CT scans. Patients with adrenal incidentalomas do not typically display overt Cushing syndrome features but may have low-grade cortisol oversecretion. These patients may be considered to have SCS, in which specific symptoms of Cushing such as easy bruising, facial plethora, striae, and proximal myopathy are absent, but aspecific symptoms such as obesity, hypertension, T2DM, and osteoporosis are present [Nieman LK et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2008].\u003C\/p\u003E\n         \u003Cp id=\u0022p-8\u0022\u003EA systematic review found that across many studies, the frequency of SCS ranged from 5% to 45% [Terzolo M et al. \u003Cem\u003EEur J Endocrinol\u003C\/em\u003E 2011]. Diagnostically, SCS may be identified by a failure to suppress on the dexamethasone suppression test (DST), elevated urinary free cortisol (UFC), low-suppressed ACTH, and elevated midnight serum cortisol (MSC). For example, 55% of patients with SCS have positive results on DSTs using a cutoff of 50 nmol\/L, 8.8% have elevated MSC, 27% have suppressed ACTH, and 4.6% have an elevated UFC. However, the diagnosis can be challenging with the potential for false-positives, technical limitations of diagnostic testing, and the presence of a minimal degree of cortisol excess in these patients.\u003C\/p\u003E\n         \u003Cp id=\u0022p-9\u0022\u003ERecently, SCS has been associated with metabolic syndrome and osteoporosis; however, cause and effect has not yet been definitively proved because of small sample sizes, poor study design, and a lack of data from hard end points. One study in which SCS was defined as 1 mg-DST cortisol \u0026gt; 5 mg\/dL found that patients with adrenal incidentaloma and SCS (5.5%) had greater rates of hypertension, T2DM, coronary heart disease, osteoporosis, and osteoporotic fractures compared with patients who did not have SCS (\u003Ca id=\u0022xref-table-wrap-1-1\u0022 class=\u0022xref-table\u0022 href=\u0022#T1\u0022\u003ETable 1\u003C\/a\u003E) [Di Dalmazi G et al. \u003Cem\u003EEur J Endocrinol\u003C\/em\u003E 2012].\u003C\/p\u003E\n         \u003Cdiv id=\u0022T1\u0022 class=\u0022table pos-float\u0022\u003E\u003Cdiv class=\u0022table-inline\u0022\u003E\u003Cdiv class=\u0022callout\u0022\u003E\u003Cspan\u003EView this table:\u003C\/span\u003E\u003Cul class=\u0022callout-links\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022\/\u0022 class=\u0022table-expand-inline\u0022 data-table-url=\u0022\/highwire\/markup\/16446\/expansion?postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\u0026amp;table-expand-inline=1\u0022 html=\u00221\u0022 fragment=\u0022#\u0022 external=\u00221\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView inline\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022\/highwire\/markup\/16446\/expansion?width=1000\u0026amp;height=500\u0026amp;iframe=true\u0026amp;postprocessors=highwire_figures%2Chighwire_math%2Chighwire_inline_linked_media\u0022 class=\u0022colorbox colorbox-load table-expand-popup\u0022 rel=\u0022gallery-fragment-tables\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView popup\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16446\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cdiv class=\u0022table-caption\u0022\u003E\u003Cspan class=\u0022table-label\u0022\u003ETable 1.\u003C\/span\u003E \n               \u003Cp id=\u0022p-10\u0022 class=\u0022first-child\u0022\u003ERates of Cardiovascular Disease Among Patients With Adrenal Incidentalomas\u003C\/p\u003E\n            \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-19\u0022\u003EAnother study found that patients with adrenal incidentalomas with 1 mg-DST cortisol \u0026gt; 1.8 mg\/dL demonstrated a greater mean visceral\/subcutaneous fat ratio and visceral\/total volume fat ratio compared with patients who had lower cortisol levels [Debono M et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2013]. A recent study with \u2265 5 years of follow-up found that 11.6% of patients had SCS, with an additional 8.2% of patients developing SCS during the follow-up period [Morelli V et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2014]. The study defined SCS as 1 mg-DST cortisol \u0026gt; 5 mg\/dL or at least 2 of the following: ACTH \u0026lt; 10 pg\/mL, increased UFC, and 1 mg-DST cortisol \u0026gt; 3.0 mg\/dL. In addition, at baseline, the presence of bilateral adenomas was greater in these patients, as was the presence of T2DM, hypertension, and cardiovascular events, rates of which increased substantially by the end of follow-up.\u003C\/p\u003E\n         \u003Cp id=\u0022p-20\u0022\u003EIn a study of cardiovascular events and mortality in patients with adrenal incidentalomas, patients with SCS or an intermediate phenotype had greater rates of all-cause mortality (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) and cardiovascular mortality compared with patients with nonsecretory adenomas [Di Dalmazi G et al. \u003Cem\u003ELancet Diabetes Endocrinol\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022All-Cause Mortality Among Patients With Adrenal Incidentalomas\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-34454353\u0022 data-figure-caption=\u0022All-Cause Mortality Among Patients With Adrenal Incidentalomas\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16444\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n               \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003EAll-Cause Mortality Among Patients With Adrenal Incidentalomas\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EReproduced from Di Dalmazi G et al. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing\u0027s syndrome: a 15-year retrospective study. \u003Cem\u003ELancet Diabetes Endocrinol.\u003C\/em\u003E 2014;2:396\u2013405. With permission from Elsevier.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-22\u0022\u003EProf. Terzolo concluded by stating that there is consistent evidence of autonomous cortisol secretion with evidence indicating an association between greater cortisol autonomy and clinical adverse effects; however, it remains difficult to determine which patients have adrenal autonomy that translates into clinically meaningful cortisol overproduction.\u003C\/p\u003E\n         \u003Cp id=\u0022p-23\u0022\u003EMiguel Debono, MD, MRCP, PhD, University of Sheffield, Sheffield, United Kingdom, discussed whether hypercortisolism in adrenal incidentaloma should be treated. The dilemma in treating these patients is that although SCS is associated with cardiovascular risk and events, osteoporosis, and mortality, many diagnostic tests lack specificity, and therefore false positives are possible. Evidence-based data indicate that even very mild to mild secreting phenotypes are associated with an increased risk for cardiovascular disease, including coronary heart disease, as well as T2DM (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E) [Di Dalmazi et al. \u003Cem\u003EEur J Endocrinol\u003C\/em\u003E 2012]. Accumulated visceral fat also occurs more frequently in patients with mild hypercortisolism when compared with patients with nonsecretory adenomas [Debono M et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2013].\u003C\/p\u003E\n         \u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Cardiovascular Risk Factors Among Patients With Adrenal Incidentalomas\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-34454353\u0022 data-figure-caption=\u0022Cardiovascular Risk Factors Among Patients With Adrenal Incidentalomas\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/20\/28\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/16445\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n               \u003Cp id=\u0022p-24\u0022 class=\u0022first-child\u0022\u003ECardiovascular Risk Factors Among Patients With Adrenal Incidentalomas\u003C\/p\u003E\n            \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003EReproduced with permission from M. Debono, MD. Adapted from Di Dalmazi et al. Progressively increased patterns of subclinical cortisol hypersecretion in adrenal incidentalomas differently predict major metabolic and cardiovascular outcomes: a large cross-sectional study. \u003Cem\u003EEur J Endocrinol.\u003C\/em\u003E 2012;166:669\u2013677.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\n         \u003Cp id=\u0022p-25\u0022\u003EMoreover, in both pre- and postmenopausal women with adrenal incidentalomas, mild hypercortisolism is associated with a greater number of fractures [Chiodini I et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2004], and recent data show that hypercortisolism may be associated with increases in all-cause and cardiovascular mortality compared with patients with nonsecreting adenomas [Di Dalmazi G et al. \u003Cem\u003ELancet Diabetes Endocrinol\u003C\/em\u003E 2014].\u003C\/p\u003E\n         \u003Cp id=\u0022p-26\u0022\u003EHowever, surgical studies in patients with adrenal incidentalomas and hypercortisolism, diagnosed using conventional tests, show conflicting results, suggesting difficulties with diagnosis; in some cases, no improvement is observed after surgery, raising the question of false positives, and in other instances, although some patients are diagnosed with \u201cnonfunctioning\u201d adenomas, they do still improve after surgical intervention, indicating that tests may lack sensitivity for milder cases [Chiodini I et al. \u003Cem\u003EJ Clin Endocrinol Metab\u003C\/em\u003E 2010]. Therefore, Dr. Debono called for improved diagnostic strategies, which would require longitudinal, prospective, observational, and interventional studies to identify glucocorticoid biomarkers. In addition, randomized, prospective trials evaluating surgical intervention are also needed.\u003C\/p\u003E\n         \u003Cp id=\u0022p-27\u0022\u003EThe presence of hypercortisolism in patients with adrenal incidentalomas is becoming more recognized, despite the absence of specific Cushing syndrome symptoms. However, the dilemma of surgical intervention in these patients continues, because of the risk associated with the disease and the potential for false positives.\u003C\/p\u003E\n      \u003C\/div\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/20\/28.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_tables.js?nzoyj2\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}