{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T09:13:26Z","timestamp":1777886006945,"version":"3.51.4"},"reference-count":38,"publisher":"Journal of the ASEAN Federation of Endocrine Societies (JAFES)","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J ASEAN Fed Endocr Soc"],"abstract":"<jats:p>Introduction. Adrenal incidentalomas (AIs) are frequently discovered during imaging performed for unrelated conditions. While most are benign and non-functional, a subset demonstrates hormonal activity or malignant potential. This study aimed to describe the clinical and radiological characteristics, natural history and predictors of mild autonomous cortisol secretion (MACS) in a Malaysian cohort.\nMethodology. This retrospective multicentre study reviewed medical records of 251 patients with AIs from three tertiary hospitals in Malaysia. Data on demographics, imaging findings, hormonal evaluations, histopathological diagnoses and longitudinal follow-up, including serial imaging and hormonal assessments, were collected and analysed.\nResults. The median age of the cohort was 58 years (IQR 19), with a slight female predominance (53%). The population was predominantly Malay (n = 126, 50.2%), followed by Chinese (36.3%) and Indian (12.7%). The median follow-up duration was 39 months.\nMost AIs were non-malignant (92%) and non-functioning (72%). Bilateral lesions were present in 9.6% of patients. Among non-malignant AIs, 27% were functioning, with higher rates of hypertension and osteoporosis, larger tumour size and greater tumour density. Adrenalectomy was more commonly performed in the functioning group, mainly for MACS and pheochromocytoma. In contrast, 94% of benign non-functioning AIs were managed conservatively, with no cases of malignant transformation and only one case developing hormonal activity over a median follow-up of 30 months. Among the 20 malignant AIs, 12 were primary adrenal carcinomas. Malignant AIs were associated with larger size, overt Cushing\u2019s syndrome, higher Hounsfield units, lower contrast washout and increased mortality.\nMACS was identified in 12.7% of the cohort. It was associated with bilateral lesions, larger tumour size, and higher prevalence of diabetes, dyslipidaemia, obesity and osteoporosis. On multivariate analysis, only bilaterality and osteoporosis remained significant predictors of MACS.\nConclusion. This study reinforces that most benign non-functioning AIs carry minimal risk of progression, supporting less intensive follow-up in stable cases. Bilaterality and osteoporosis were identified as independent predictors of MACS, emphasizing the importance of targeted hormonal and bone health monitoring in these patients.<\/jats:p>","DOI":"10.15605\/jafes.041.01.5143","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T03:21:25Z","timestamp":1777605685000},"source":"Crossref","is-referenced-by-count":0,"title":["Retrospective Study of Clinical Characteristics, Natural History and Predictive Factors for Mild Autonomous Cortisol Secretion (MACS) in Patients with Adrenal Incidentalomas in Malaysia"],"prefix":"10.15605","author":[{"given":"Vanusha","family":"Devaraja","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Subashini","family":"Rajoo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vijaya Mala","family":"Valayatham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Foo Siew","family":"Hui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6244","published-online":{"date-parts":[[2026,4,30]]},"reference":[{"key":"85164","doi-asserted-by":"crossref","unstructured":"Kloos RT, Gross MD, Francis IR, et al. Incidentally discovered adrenal masses. Endocr Rev. 1995;16(4):460-84. https:\/\/pubmed.ncbi.nlm.nih.gov\/8521790 https:\/\/doi.org\/10.1210\/edrv-16-4-460","DOI":"10.1210\/edrv-16-4-460"},{"key":"85165","doi-asserted-by":"crossref","unstructured":"Grumbach MM, Biller BMK, Braunstein GD, et al. Management of the clinically inapparent adrenal mass (\"incidentaloma\"). Ann Intern Med. 2003;138(5):424-9. https:\/\/pubmed.ncbi.nlm.nih.gov\/12614096 https:\/\/doi.org\/10.7326\/0003-4819-138-5-200303040-00013","DOI":"10.7326\/0003-4819-138-5-200303040-00013"},{"key":"85166","doi-asserted-by":"crossref","unstructured":"Lam KY, Lo CY. A critical examination of adrenal tuberculosis and a 28-year autopsy experience of active tuberculosis. Clin Endocrinol (Oxf). 2001;54(5):633-9. https:\/\/pubmed.ncbi.nlm.nih.gov\/11380494 https:\/\/doi.org\/10.1046\/j.1365-2265.2001.01266.x","DOI":"10.1046\/j.1365-2265.2001.01266.x"},{"key":"85167","doi-asserted-by":"crossref","unstructured":"Fassnacht M, Arlt W, Bancos I, et al. Management of adrenal incidentalomas: European society of endocrinology clinical practice guideline in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol. 2016;175(2):G1-G34. https:\/\/pubmed.ncbi.nlm.nih.gov\/27390021 https:\/\/doi.org\/10.1530\/EJE-16-0467","DOI":"10.1530\/EJE-16-0467"},{"key":"85168","doi-asserted-by":"crossref","unstructured":"Fassnacht M, Tsagarakis S, Terzolo M, et al. European society of endocrinology clinical practice guidelines on the management of adrenal incidentalomas, in collaboration with the European network for the study of adrenal tumors. Eur J Endocrinol. 2023;189(1):G1-G42. https:\/\/doi.org\/10.1093\/ejendo\/lvad066","DOI":"10.1093\/ejendo\/lvad066"},{"key":"85169","doi-asserted-by":"crossref","unstructured":"Zeiger MA, Thompson GB, Duh QY, et al. American association of clinical endocrinologists and American association of endocrine surgeons medical guidelines for the management of adrenal incidentalomas: Executive summary of recommendations. Endocr Pract. 2009;15(5):450-3. https:\/\/pubmed.ncbi.nlm.nih.gov\/19632968 https:\/\/doi.org\/10.4158\/EP.15.5.450","DOI":"10.4158\/EP.15.5.450"},{"key":"85170","doi-asserted-by":"crossref","unstructured":"Lee JM, Kim MK, Ko SH, et al. Clinical guidelines for the management of adrenal incidentaloma. Endocrinol Metab (Seoul). 2017;32(2):200-18. https:\/\/pubmed.ncbi.nlm.nih.gov\/28685511 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5503865 https:\/\/doi.org\/10.3803\/EnM.2017.32.2.200","DOI":"10.3803\/EnM.2017.32.2.200"},{"key":"85171","doi-asserted-by":"crossref","unstructured":"Pelsma ICM, Fassnacht M, Tsagarakis S, et al. Comorbidities in mild autonomous cortisol secretion and the effect of treatment: Systematic review and meta-analysis. Eur J Endocrinol. 2023;189(4):S88-S101. https:\/\/pubmed.ncbi.nlm.nih.gov\/37801655 https:\/\/doi.org\/10.1093\/ejendo\/lvad134","DOI":"10.1093\/ejendo\/lvad134"},{"key":"85172","doi-asserted-by":"crossref","unstructured":"Adamska A, Ulychnyi V, Siewko K, et al. Cardiovascular risk factors in mild adrenal autonomous cortisol secretion in a Caucasian population. Endocr Connect. 2022;11(9):e220074. https:\/\/pubmed.ncbi.nlm.nih.gov\/35900803 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC9422244 https:\/\/doi.org\/10.1530\/EC-22-0074","DOI":"10.1530\/endoabs.81.EP18"},{"key":"85173","doi-asserted-by":"crossref","unstructured":"Araujo-Castro M, Reincke M, Lamas C. Epidemiology and management of hypertension and diabetes mellitus in patients with mild autonomous cortisol secretion: A review. Biomedicines. 2023;11(12):3115. https:\/\/pubmed.ncbi.nlm.nih.gov\/38137336 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC10740610 https:\/\/doi.org\/10.3390\/biomedicines11123115","DOI":"10.3390\/biomedicines11123115"},{"key":"85174","doi-asserted-by":"crossref","unstructured":"Iacobone M, Citton M, Viel G, et al. Adrenalectomy may improve cardiovascular and metabolic impairment and ameliorate quality of life in patients with adrenal incidentalomas and subclinical Cushing's syndrome. Surgery. 2012;152(6):991-7. https:\/\/pubmed.ncbi.nlm.nih.gov\/23158173 https:\/\/doi.org\/10.1016\/j.surg.2012.08.054","DOI":"10.1016\/j.surg.2012.08.054"},{"key":"85175","doi-asserted-by":"crossref","unstructured":"Koh JM, Song K, Kwak MK, et al. Adrenalectomy improves body weight, glucose, and blood pressure control in patients with mild autonomous cortisol secretion: Results of a randomized controlled trial by the Co-work of Adrenal Research (COAR) study. Ann Surg. 2024;279(6):945-52. https:\/\/pubmed.ncbi.nlm.nih.gov\/38126763 https:\/\/doi.org\/10.1097\/SLA.0000000000006183","DOI":"10.1097\/SLA.0000000000006183"},{"key":"85176","doi-asserted-by":"crossref","unstructured":"Terzolo M, Pia A, Al\u00ec A, et al. Adrenal incidentaloma: A new cause of the metabolic syndrome? J Clin Endocrinol Metab. 2002;87(3):998-1003. https:\/\/pubmed.ncbi.nlm.nih.gov\/11889151 https:\/\/doi.org\/10.1210\/jcem.87.3.8277","DOI":"10.1210\/jc.87.3.998"},{"key":"85177","doi-asserted-by":"crossref","unstructured":"Favero V, Cremaschi A, Parazzoli C, et al. Pathophysiology of mild hypercortisolism: From the bench to the bedside. Int J Mol Sci. 2022;23(2):673. https:\/\/pubmed.ncbi.nlm.nih.gov\/35054858 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8775422 https:\/\/doi.org\/10.3390\/ijms23020673","DOI":"10.3390\/ijms23020673"},{"key":"85178","doi-asserted-by":"crossref","unstructured":"Terzolo M, Stigliano A, Chiodini I, et al. AME position statement on adrenal incidentaloma. Eur J Endocrinol. 2011;164(6):851-70. https:\/\/pubmed.ncbi.nlm.nih.gov\/21471169 https:\/\/doi.org\/10.1530\/EJE-10-1147","DOI":"10.1530\/EJE-10-1147"},{"key":"85179","doi-asserted-by":"crossref","unstructured":"Androulakis II, Kaltsas GA, Kollias GE, et al. Patients with apparently nonfunctioning adrenal incidentalomas may be at increased cardiovascular risk due to excessive cortisol secretion. J Clin Endocrinol Metab. 2014;99(8):2754-62. https:\/\/doi.org\/10.1210\/jc.2013-4064","DOI":"10.1210\/jc.2013-4064"},{"key":"85180","doi-asserted-by":"crossref","unstructured":"Park SH, Kim MJ, Kim JH, et al. Differentiation of adrenal adenoma and nonadenoma in unenhanced CT: New optimal threshold value and the usefulness of size criteria for differentiation. Korean J Radiol. 2007;8(4):328-35. https:\/\/pubmed.ncbi.nlm.nih.gov\/17673844 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2627166 https:\/\/doi.org\/10.3348\/kjr.2007.8.4.328","DOI":"10.3348\/kjr.2007.8.4.328"},{"key":"85181","doi-asserted-by":"crossref","unstructured":"Hamrahian AH, Ioachimescu AG, Remer EM, et al. Clinical utility of noncontrast computed tomography attenuation value (Hounsfield units) to differentiate adrenal adenomas\/hyperplasias from nonadenomas: Cleveland Clinic experience. J Clin Endocrinol Metab. 2005;90(2):871-7. https:\/\/pubmed.ncbi.nlm.nih.gov\/15572420 https:\/\/doi.org\/10.1210\/jc.2004-1627","DOI":"10.1210\/jc.2004-1627"},{"key":"85182","doi-asserted-by":"crossref","unstructured":"Bancos I, Prete A. Approach to the patient with adrenal incidentaloma. J Clin Endocrinol Metab. 2021;106(11):3331-53. https:\/\/pubmed.ncbi.nlm.nih.gov\/34260734 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC8530736 https:\/\/doi.org\/10.1210\/clinem\/dgab512","DOI":"10.1210\/clinem\/dgab512"},{"key":"85183","doi-asserted-by":"crossref","unstructured":"Stavropoulos K, Imprialos KP, Katsiki N, et al. Primary aldosteronism in patients with adrenal incidentaloma: Is screening appropriate for everyone? 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Aberrant cortisol responses to physiological stimuli in patients presenting with bilateral adrenal incidentalomas. Endocrine. 2011;40(3):437-44. https:\/\/pubmed.ncbi.nlm.nih.gov\/21598069 https:\/\/doi.org\/10.1007\/s12020-011-9490-1","DOI":"10.1007\/s12020-011-9490-1"},{"key":"85189","doi-asserted-by":"crossref","unstructured":"Di Dalmazi G, Vicennati V, Garelli S, et al. Cardiovascular events and mortality in patients with adrenal incidentalomas that are either non-secreting or associated with intermediate phenotype or subclinical Cushing's syndrome: A 15-year retrospective study. Lancet Diabetes Endocrinol. 2014;2(5):396-405. https:\/\/pubmed.ncbi.nlm.nih.gov\/24795253 https:\/\/doi.org\/10.1016\/S2213-8587(13)70211-0","DOI":"10.1016\/S2213-8587(13)70211-0"},{"key":"85190","doi-asserted-by":"crossref","unstructured":"Chiodini I, Morelli V, Salcuni AS, et al. Beneficial metabolic effects of prompt surgical treatment in patients with an adrenal incidentaloma causing biochemical hypercortisolism. J Clin Endocrinol Metab. 2010;95(6):2736-45. https:\/\/pubmed.ncbi.nlm.nih.gov\/20375210 https:\/\/doi.org\/10.1210\/jc.2009-2387","DOI":"10.1210\/jc.2009-2387"},{"key":"85191","doi-asserted-by":"crossref","unstructured":"Barzon L, Sonino N, Fallo F, et al. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol. 2003;149(4):273-85. https:\/\/pubmed.ncbi.nlm.nih.gov\/14514341 https:\/\/doi.org\/10.1530\/eje.0.1490273","DOI":"10.1530\/eje.0.1490273"},{"key":"85192","doi-asserted-by":"crossref","unstructured":"Giovanelli L, Aresta C, Favero V, et al. Hidden hypercortisolism: A too frequently neglected clinical condition. J Endocrinol Invest. 2021;44(8):1581-96. https:\/\/pubmed.ncbi.nlm.nih.gov\/33394454 https:\/\/doi.org\/10.1007\/s40618-020-01484-2","DOI":"10.1007\/s40618-020-01484-2"},{"key":"85193","doi-asserted-by":"crossref","unstructured":"Hardy RS, Zhou H, Seibel MJ, et al. Glucocorticoids and bone: Consequences of endogenous and exogenous excess and replacement therapy. Endocr Rev. 2018;39(5):519-48. https:\/\/pubmed.ncbi.nlm.nih.gov\/29905835 https:\/\/doi.org\/10.1210\/er.2018-00097","DOI":"10.1210\/er.2018-00097"},{"key":"85194","doi-asserted-by":"crossref","unstructured":"Morelli V, Eller-Vainicher C, Salcuni AS, et al. Risk of new vertebral fractures in patients with adrenal incidentaloma with and without subclinical hypercortisolism: A multicenter longitudinal study. 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Front Endocrinol (Lausanne). 2024;15:1399311. https:\/\/pubmed.ncbi.nlm.nih.gov\/39086899 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11288901 https:\/\/doi.org\/10.3389\/fendo.2024.1399311","DOI":"10.3389\/fendo.2024.1399311"},{"key":"85199","doi-asserted-by":"crossref","unstructured":"Cho YY, Suh S, Joung JY, et al. Clinical characteristics and follow-up of Korean patients with adrenal incidentalomas. Korean J Intern Med. 2013;28(5):557-64. https:\/\/pubmed.ncbi.nlm.nih.gov\/24009451 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3759761 https:\/\/doi.org\/10.3904\/kjim.2013.28.5.557","DOI":"10.3904\/kjim.2013.28.5.557"},{"key":"85200","doi-asserted-by":"crossref","unstructured":"Liu M, Zhao W, Zhang W, et al. Comparable cognitive impairment was detected in MACS and CS and alleviated after remission of hypercortisolism in MACS. Front Endocrinol (Lausanne). 2024;15:1373101. https:\/\/pubmed.ncbi.nlm.nih.gov\/39145316 https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC11322108 https:\/\/doi.org\/10.3389\/fendo.2024.1373101","DOI":"10.3389\/fendo.2024.1373101"},{"key":"85201","doi-asserted-by":"crossref","unstructured":"Luk Y, Tsang VHM, Lo C, Lee R, Cheung YT, Wong KK, et al. Prevalence of mild autonomous cortisol secretion in adrenal incidentalomas and the significance of subcentimeter adrenal nodules: A single-center cohort study. 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