[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-416671-105":3,"detail-sidebar-cat-0-en-105":85,"doc-detail-416671-en":135},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":78,"head_meta":80,"extra_data":82,"updated_unix":84},105,"en","bilateral-adrenalectomy-for-primary-bilateral-macronodular-adrenocortical-hyperplasia-with-a-novel-armc5-mutation-site-case-report","Bilateral Adrenalectomy for Primary Bilateral Macronodular Adrenocortical Hyperplasia With a Novel ARMC5 Mutation Site - Case Report","","Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) presents from subclinical disease to severe overt Cushing syndrome (CS). This case report describes a 60-year-old woman with progressive weight gain, hypokalemia, and long-standing refractory hypertension, with elevated cortisol, suppressed ACTH, and positive dexamethasone suppression tests. Imaging showed bilateral irregular macronodular adrenal masses and adrenal venous sampling without lateralization. A novel ARMC5 mutation was found, followed by staged right and left adrenalectomy leading to marked improvement in CS symptoms, biomarkers, and metabolic complications.",{"@graph":14,"@context":77},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/bilateral-adrenalectomy-for-primary-bilateral-macronodular-adrenocortical-hyperplasia-with-a-novel-armc5-mutation-site-case-report/416671/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/bilateral-adrenalectomy-for-primary-bilateral-macronodular-adrenocortical-hyperplasia-with-a-novel-armc5-mutation-site-case-report/416671.png","ImageObject",300,407,{"name":42,"@type":43},"Fans","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-11-01","2026-09-28",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",12,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69,73],{"name":60,"@type":61,"acceptedAnswer":62},"What clinical features characterized the patient’s Cushing syndrome?","Question",{"text":63,"@type":64},"The patient had progressive weight gain, hypokalemia, and refractory hypertension, with classic CS features and metabolic complications including hypertension and diabetes.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How was lateralization assessed before surgery, and what was the result?",{"text":68,"@type":64},"Adrenal venous sampling showed no lateralization, with a lateralization index \u003C 4, despite CT showing bilateral irregular macronodular masses.",{"name":70,"@type":61,"acceptedAnswer":71},"What genetic finding supported the diagnosis and guided interpretation?",{"text":72,"@type":64},"Whole-exome sequencing identified a novel ARMC5 mutation (c.534_555dup, p.Ser186Profs*19).",{"name":74,"@type":61,"acceptedAnswer":75},"How did the staged bilateral adrenalectomy affect outcomes?",{"text":76,"@type":64},"After right adrenalectomy symptoms improved but cortisol remained elevated; left adrenalectomy performed 15 months later in 2024 led to marked improvement in CS symptoms, biomarkers, and metabolic complications.","https://schema.org",{"og:url":32,"og:type":79,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":81,"canonical":32},"index,follow",{"doc_id":83,"site_id":7},416671,1790955060,{"code":4,"msg":86,"data":87},"success",[88,92,96,100,105,110,114,119,124,127,131],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},"Exam",70,"exam",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},5,"Comic",60,"comic",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},6,"Technology",50,"technology",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},7,40,"healthcare",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},8,"Research & Report",30,"research-report",{"id":120,"doc_module":4,"doc_module_name":25,"category_name":121,"show_sort_weight":122,"slug":123},9,"Religion & Spirituality",20,"religion-spirituality",{"id":122,"doc_module":4,"doc_module_name":25,"category_name":125,"show_sort_weight":122,"slug":126},"World Cup","world-cup",{"id":128,"doc_module":4,"doc_module_name":25,"category_name":129,"show_sort_weight":128,"slug":130},10,"Lifestyle","lifestyle",{"id":132,"doc_module":4,"doc_module_name":25,"category_name":133,"show_sort_weight":101,"slug":134},19,"General","general",{"code":4,"msg":86,"data":136},{"doc_id":83,"user_id":137,"nickname":42,"user_avatar":138,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":139,"file_id":140,"file_url":141,"file_type":142,"file_size":143,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":111,"language":144,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":145,"faqs":146,"seo_title":147,"seo_description":12,"update_tm":148,"read_time":149,"preview_page_count":4},5909892330395,"https://ap-avatar.wpscdn.com/davatar_6f874abed73319feea01a86fa6f0fab8","Case Report J Clin Med Res. 2025;17(12):733-739  \nBilateral Adrenalectomy for Primary Bilateral Macronodular Adrenocortical Hyperplasia With a Novel ARMC5  \nMutation Site  \nCai Guo Yua, e, Nan Nan Wub, c, e, Bin Caob, c, Hao Lin Gongb, c, Yan Mab, c, Shao Zhong Xiand, Bao Yu Zhanga, Jing Keb, c, f, Dong Zhaob, c, f  \nAbstract  \nPrimary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a heterogeneous disorder, with clinical spectrum ranging from subclinical to severe overt Cushing syndrome (CS) . Armadillo repeat containing 5 (ARMC5) mutations, found in 20-55% of cases, are often associated with more severe disease, and specific genotypes may correlate with distinct phenotypes. A 60-year-old woman was admitted with a 1-year history of progressive weight gain and hypokalemia, alongside a 13-year history of refractory hypertension. She exhibited classic CS features and metabolic complications, including hypertension and diabetes. Laboratory tests revealed elevated cortisol, suppressed adrenocorticotropic hormone (ACTH), and positive low-and high-dose dexamethasone suppression tests. Contrast-enhanced computed tomography (CT) showed bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) demonstrated no lateralization (lateralization index \u003C 4) . Wholeexome sequencing of peripheral blood leukocytes identified a novel ARMC5 mutation (c.534_ 555dup, p.Ser186Profs*19) . A right adrenalectomy was performed in 2023. Although symptoms improved, cortisol levels remained significantly elevated. Consequently, a left adrenalectomy was performed 15 months later in 2024, which led to marked improvement in her CS symptoms, biomarker levels, and metabolic complications. This case report describes a novelARMC5 mutation site in a PBMAH patient who ultimately required bilateral adrenalectomy. While AVS combined with CT can help determine  \nManuscript submitted August 31, 2025, accepted November 26, 2025 Published online December 24, 2025  \naDepartment of Endocrinology, Beijing Anzhen Hospital, Capital Medical University, Beijing 101118, China  \nbCenter for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China  \ncBeijing Key Laboratory of Diabetes Research and Care, Beijing 100000, China  \ndDepartment of Urology, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China  \neThese authors contributed equally to the article.  \nfCorresponding Authors: Jing Ke and Dong Zhao, Center for Endocrine Metabolism and Immune Diseases, Beijing Luhe Hospital, Capital Medical University, Beijing 101149, China. [Email: kejing@ccmu.edu.cn and zhaodong@ccmu.edu.cn](Email: kejing@ccmu.edu.cn and zhaodong@ccmu.edu.cn)  \ndoi: [https://doi.org/10.14740/jocmr6359](https://doi.org/10.14740/jocmr6359)  \nthe dominant side for surgery, patients with ARMC5 mutations and symmetrically sized tumors often require bilateral adrenalectomy for cure.  \nKeywords: Primary bilateral macronodular adrenocortical hyperplasia; ARMC5; Adrenal venous sampling; Cushing syndrome  \nIntroduction  \nPrimary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a clinically heterogeneous disorder characterized by bilateral adrenal macronodules > 1.0 cm with variable cortisol secretion, ranging from asymptomatic subclinical hypercortisolism to overt Cushing syndrome (CS) [1] . It is also named bilateral macronodular adrenocortical disease according to the updated World Health Organization (WHO) Classification of Endocrine and Neuroendocrine Tumors (2025) . Overt cases present with classic features including weight gain, proximal myopathy, reddish striae, facial plethora, buffalo hump, skin fragility, easy bruising, and hyperandrogenism, along with metabolic complications (hypertension, diabetes, venous thromboembolism) and skeletal manifestations (osteopenia, osteoporosis) [2] . Most symptomatic patients are diagnosed between 40 and 60 years of age, often after years of subtle progres","cbCaihnu7D9ccPlG","https://ap.wps.com/l/cbCaihnu7D9ccPlG","pdf",2258565,"English","# Abstract\n# Introduction\n## Clinical spectrum and diagnosis\n## Genetic background and ARMC5\n## Management challenges\n# Laboratory profile (Table 1)","[{\"question\":\"What clinical features characterized the patient’s Cushing syndrome?\",\"answer\":\"The patient had progressive weight gain, hypokalemia, and refractory hypertension, with classic CS features and metabolic complications including hypertension and diabetes.\"},{\"question\":\"How was lateralization assessed before surgery, and what was the result?\",\"answer\":\"Adrenal venous sampling showed no lateralization, with a lateralization index \\u003c 4, despite CT showing bilateral irregular macronodular masses.\"},{\"question\":\"What genetic finding supported the diagnosis and guided interpretation?\",\"answer\":\"Whole-exome sequencing identified a novel ARMC5 mutation (c.534_555dup, p.Ser186Profs*19).\"},{\"question\":\"How did the staged bilateral adrenalectomy affect outcomes?\",\"answer\":\"After right adrenalectomy symptoms improved but cortisol remained elevated; left adrenalectomy performed 15 months later in 2024 led to marked improvement in CS symptoms, biomarkers, and metabolic complications.\"}]","Bilateral Adrenalectomy for Primary Bilateral Macronodular Adrenocortical Hyperplasia With a Novel ARMC5 Mutation Site - Case Report | PDF",1790606276,18]