{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T09:15:55Z","timestamp":1767172555412,"version":"build-2238731810"},"reference-count":18,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,26]],"date-time":"2021-05-26T00:00:00Z","timestamp":1621987200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Med Case Reports"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The clinical characteristics and complications of Cushing syndrome (CS) are well known and described in the literature. Nevertheless, rare, atypical presentations may go unnoticed. Osteonecrosis is a well-documented complication of glucocorticoid therapy. However, endogenous hypercortisolism is a rare, but relevant, cause of bone avascular necrosis. We describe the case of a woman with CS undiagnosed for 2 years after presenting with femoral avascular necrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Case presentation<\/jats:title>\n                    <jats:p>A 38-year-old Caucasian woman was referred for evaluation of secondary amenorrhea, associated with oral contraception withdrawal in the context of deep venous thrombosis (DVT). She had a previous right hip arthroplasty for treatment of avascular necrosis of the femoral head, diagnosed after 3 years of progressive right hip pain and limited mobility. She also had high blood pressure (HBP) of 5 years\u2019 duration, and reported weight gain (4 kg in 2 years). There was no history of infertility (gravida 2, para 2). Physical examination revealed buffalo hump, truncal obesity, facial plethora, muscular atrophy and proximal myopathy, and easy bruising (under anticoagulant treatment for DVT). Workup showed abnormal overnight dexamethasone suppression test (DST) (serum cortisol 21.5 \u00b5g\/dL; normal &lt; 1.8 \u00b5g\/dL), elevated 24-hour urinary free cortisol (UFC) (728.9 \u00b5g\/day; reference range 36.0\u2013137.0 \u00b5g\/day), and suppressed plasma adrenocorticotropic hormone (ACTH) (&lt; 1.0 pg\/mL), findings consistent with ACTH-independent CS. Urinary metanephrines and catecholamines were normal, and the remaining analytical study showed no major changes, apart from glycated hemoglobin (HbA1c) of 6.8%. Adrenal computed tomography (CT) scan showed a 25 mm lesion in the left adrenal gland, with density non-suggestive of adenoma. The patient underwent unilateral adrenalectomy and started steroid replacement. Histology revealed an adrenal cortex adenoma. Three months after surgery the patient presented with resolution of HBP and hypercortisolism (UFC 37.4 \u00b5g\/day; reference range 36.0\u2013137.0 \u00b5g\/day).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In some cases, CS signs may go unnoticed and the diagnosis postponed. Avascular necrosis is a rare presenting feature of endogenous hypercortisolism, and, if left untreated, complete collapse of the femoral head may ensue, rendering the need for hip replacement in up to 70% of patients. Suspicion and recognition of atypical features is therefore important in avoiding complications and delay in treatment of CS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13256-021-02882-7","type":"journal-article","created":{"date-parts":[[2021,5,25]],"date-time":"2021-05-25T19:07:16Z","timestamp":1621969636000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Avascular femoral necrosis as part of Cushing syndrome presentation: a\u00a0case report"],"prefix":"10.1186","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-9689","authenticated-orcid":false,"given":"Daniela","family":"Salazar","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9sar","family":"Esteves","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Jo\u00e3o","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Pedro","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiago","family":"Pimenta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Portugal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide","family":"Carvalho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,5,26]]},"reference":[{"issue":"4","key":"2882_CR1","doi-asserted-by":"publisher","first-page":"385","DOI":"10.5301\/HIP.2011.8538","volume":"21","author":"A Rajpura","year":"2011","unstructured":"Rajpura A, Wright AC, Board TN. Medical management of osteonecrosis of the hip: a review. Hip Int. 2011;21(4):385\u201392. https:\/\/doi.org\/10.5301\/HIP.2011.8538.","journal-title":"Hip Int."},{"issue":"7","key":"2882_CR2","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1097\/00007611-198607000-00011","volume":"79","author":"KA Phillips","year":"1986","unstructured":"Phillips KA, Nance EP Jr, Rodriguez RM, Kaye JJ. Avascular necrosis of bone: a manifestation of Cushing\u2019s disease. South Med J. 1986;79(7):825\u20139. https:\/\/doi.org\/10.1097\/00007611-198607000-00011.","journal-title":"South Med J."},{"issue":"4","key":"2882_CR3","doi-asserted-by":"publisher","first-page":"225","DOI":"10.4103\/aam.aam_75_17","volume":"17","author":"N Belmahi","year":"2018","unstructured":"Belmahi N, Boujraf S, Larwanou MM, El Ouahabi H. Avascular necrosis of the femoral head: an exceptional complication of Cushing\u2019s disease. Ann Afr Med. 2018;17(4):225\u20137. https:\/\/doi.org\/10.4103\/aam.aam_75_17.","journal-title":"Ann Afr Med."},{"issue":"9","key":"2882_CR4","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1210\/jcem.84.9.5992","volume":"84","author":"CA Koch","year":"1999","unstructured":"Koch CA, Tsigos C, Patronas NJ, Papanicolaou DA. Cushing\u2019s disease presenting with avascular necrosis of the hip: an orthopedic emergency. J Clin Endocrinol Metab. 1999;84(9):3010\u20132. https:\/\/doi.org\/10.1210\/jcem.84.9.5992.","journal-title":"J Clin Endocrinol Metab."},{"issue":"6","key":"2882_CR5","first-page":"413","volume":"61","author":"M Premkumar","year":"2013","unstructured":"Premkumar M, Dhanwal DK, Mathews S, Garg A, Sahoo S, Mahamine K, et al. Avascular osteonecrosis of femoral head in a postoperative patient of pituitary Cushing\u2019s disease. J Assoc Phys India. 2013;61(6):413\u20135.","journal-title":"J Assoc Phys India"},{"issue":"10","key":"2882_CR6","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1136\/ard.46.10.783","volume":"46","author":"IP Wicks","year":"1987","unstructured":"Wicks IP, Calligeros D, Kidson W, Bertouch JV. Cushing\u2019s disease presenting with avascular necrosis of the femoral heads and complicated by pituitary apoplexy. Ann Rheum Dis. 1987;46(10):783\u20136. https:\/\/doi.org\/10.1136\/ard.46.10.783.","journal-title":"Ann Rheum Dis."},{"issue":"2","key":"2882_CR7","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1007\/s11845-011-0717-1","volume":"181","author":"A Saeed","year":"2012","unstructured":"Saeed A, Bannan L. Avascular necrosis of femoral heads post-adrenal surgery for Cushing\u2019s syndrome: a rare presentation. Ir J Med Sci. 2012;181(2):263\u20134. https:\/\/doi.org\/10.1007\/s11845-011-0717-1.","journal-title":"Ir J Med Sci"},{"issue":"10","key":"2882_CR8","doi-asserted-by":"publisher","first-page":"1111","DOI":"10.3928\/0147-7447-20041001-25","volume":"27","author":"J Takada","year":"2004","unstructured":"Takada J, Nagoya S, Kuwabara H, Kaya M, Yamashita T. Rapidly destructive coxarthropathy with osteonecrosis and osteoporosis caused by Cushing\u2019s syndrome. Orthopedics. 2004;27(10):1111\u20133 (PMID: 15553956).","journal-title":"Orthopedics"},{"issue":"2","key":"2882_CR9","doi-asserted-by":"publisher","first-page":"120","DOI":"10.5371\/hp.2019.31.2.120","volume":"31","author":"J-S Ha","year":"2019","unstructured":"Ha J-S, Cho H-M, Lee H-J, Kim S-D. Bilateral avascular necrosis of the femoral head in a patient with asymptomatic adrenal incidentaloma. Hip Pelvis. 2019;31(2):120\u20133. https:\/\/doi.org\/10.5371\/hp.2019.31.2.120.","journal-title":"Hip Pelvis."},{"key":"2882_CR10","doi-asserted-by":"publisher","first-page":"160015","DOI":"10.1530\/EDM-16-0015","volume":"2016","author":"A Pazderska","year":"2016","unstructured":"Pazderska A, Crowther S, Govender P, Conlon KC, Sherlock M, Gibney J. Spontaneous resolution of avascular necrosis of femoral heads following cure of Cushing\u2019s syndrome. Endocrinol Diabetes Metab Case Rep. 2016;2016:160015. https:\/\/doi.org\/10.1530\/EDM-16-0015.","journal-title":"Endocrinol Diabetes Metab Case Rep"},{"key":"2882_CR11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/00003086-197311000-00011","volume":"97","author":"JM Cerletty","year":"1973","unstructured":"Cerletty JM, Ziebert AP, Mueller KH. Avascular necrosis of the femoral head as presenting manifestation of Cushing\u2019s disease. Clin Orthop Relat Res. 1973;97:69\u201373. https:\/\/doi.org\/10.1097\/00003086-197311000-00011.","journal-title":"Clin Orthop Relat Res."},{"issue":"5","key":"2882_CR12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.medcli.2016.03.042","volume":"147","author":"F Camporro","year":"2016","unstructured":"Camporro F, Bulacio E, Magaldi IG. Bilateral osteonecrosis of the hip secondary to endogenous Cushing\u2019s syndrome due to a recently-diagnosed carcinoid tumour of the lung. Medicina Clinica. 2016;147(5):228. https:\/\/doi.org\/10.1016\/j.medcli.2016.03.042.","journal-title":"Medicina Clinica."},{"issue":"5","key":"2882_CR13","doi-asserted-by":"publisher","first-page":"1526","DOI":"10.1210\/jc.2008-0125","volume":"93","author":"LK Nieman","year":"2008","unstructured":"Nieman LK, Biller BM, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al. The diagnosis of Cushing\u2019s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2008;93(5):1526\u201340. https:\/\/doi.org\/10.1210\/jc.2008-0125.","journal-title":"J Clin Endocrinol Metab."},{"key":"2882_CR14","doi-asserted-by":"publisher","first-page":"449","DOI":"10.2174\/1874325001206010449","volume":"6","author":"KL Chan","year":"2012","unstructured":"Chan KL, Mok CC. Glucocorticoid-induced avascular bone necrosis: diagnosis and management. Open Orthop J. 2012;6:449\u201357. https:\/\/doi.org\/10.2174\/1874325001206010449.","journal-title":"Open Orthop J."},{"key":"2882_CR15","first-page":"252","volume":"32","author":"DS Hungerford","year":"1983","unstructured":"Hungerford DS. Pathogenesis of ischemic necrosis of the femoral head. Instr Course Lect. 1983;32:252\u201360 (PMID: 6546072).","journal-title":"Instr Course Lect"},{"key":"2882_CR16","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1007\/bf00442735","volume":"100","author":"N Cheng","year":"1982","unstructured":"Cheng N, Burssens A, Mulier JC. Pregnancy and post-pregnancy avascular necrosis of the femoral head. Arch Orthop Traumat Surg. 1982;100:199\u2013210. https:\/\/doi.org\/10.1007\/bf00442735.","journal-title":"Arch Orthop Traumat Surg."},{"issue":"1","key":"2882_CR17","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/s0049-0172(05)80026-5","volume":"23","author":"CC Chang","year":"1993","unstructured":"Chang CC, Greenspan A, Gershwin ME. Osteonecrosis: current perspectives on pathogenesis and treatment. Semin Arthritis Rheum. 1993;23(1):47\u201369. https:\/\/doi.org\/10.1016\/s0049-0172(05)80026-5.","journal-title":"Semin Arthritis Rheum."},{"issue":"5","key":"2882_CR18","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.2106\/JBJS.E.01041","volume":"88","author":"MA Mont","year":"2006","unstructured":"Mont MA, Jones LC, Hungerford DS. Nontraumatic osteonecrosis of the femoral head: ten years later. J Bone Joint Surg Am. 2006;88(5):1117\u201332. https:\/\/doi.org\/10.2106\/JBJS.E.01041.","journal-title":"J Bone Joint Surg Am"}],"updated-by":[{"DOI":"10.1186\/s13256-021-03105-9","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000}}],"container-title":["Journal of Medical Case Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-021-02882-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13256-021-02882-7\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13256-021-02882-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T10:29:41Z","timestamp":1632392981000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmedicalcasereports.biomedcentral.com\/articles\/10.1186\/s13256-021-02882-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,26]]},"references-count":18,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2882"],"URL":"https:\/\/doi.org\/10.1186\/s13256-021-02882-7","relation":{},"ISSN":["1752-1947"],"issn-type":[{"value":"1752-1947","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,26]]},"assertion":[{"value":"25 December 2019","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 April 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 May 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 September 2021","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1186\/s13256-021-03105-9","URL":"https:\/\/doi.org\/10.1186\/s13256-021-03105-9","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Our institutional review board approved the search of electronic medical records for this paper. The patient involved gave consent for the use of her medical records.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"287"}}