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      The effect of unilateral adrenalectomy on patients with primary bilateral macronodular adrenal hyperplasia

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          Abstract

          Purpose

          To evaluate the long-term effect of unilateral adrenalectomy (uADX) on patients with primary bilateral macronodular adrenal hyperplasia (PBMAH).

          Methods

          We retrospectively reviewed 29 patients (including 11 men and 18 women) with PBMAH and Cushing’s syndrome (CS) between 2005 and 2019 who underwent uADX in our center. Clinical symptoms, serum cortisol (8:00 a.m., 4:00 p.m., and 0:00 a.m.), 24 h urinary free cortisol (UFC), computed tomography (CT) scan of the adrenal gland, and pituitary nuclear magnetic resonance (MR) scan performed before and after operation were analyzed.

          Results

          The median follow-up time was 39 (13–134) months. uADX decreased significantly at 24 h UFC (median: 357.14 vs. 89.50 ug/24 h, P < 0.001) and serum cortisol (8:00 a.m.) (median: 22.88 vs. 12.50 ug/uL, P < 0.001) 1 year after surgery. In total, 17 of 29 patients had normal UFC again 1 year after surgery, while one of them suffered a relapse after 61 months. However, uADX failed to decrease UFC to the normal range in the other patients. Ten of the remaining 12 uncured patients and the relapsed patient finally underwent contralateral adrenalectomy (cADX). The 24 h UFC of the patients who were cured ( n = 17) after uADX was significantly lower than that of the uncured patients ( n = 12) (222.30 vs. 579.10 ug/24 h, P = 0.011).

          Conclusion

          uADX may be an appropriate treatment for patients with mildly elevated cortisol, while contralateral adrenalectomy (cADX) may be required for patients with highly elevated cortisol. The level of 24 h UFC is helpful to predict patients’ prognosis.

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          Most cited references18

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          Cushing's syndrome.

          Chronic exposure to excess glucorticoids results in diverse manifestations of Cushing's syndrome, including debilitating morbidities and increased mortality. Genetic and molecular mechanisms responsible for excess cortisol secretion by primary adrenal lesions and adrenocorticotropic hormone (ACTH) secretion from corticotroph or ectopic tumours have been identified. New biochemical and imaging diagnostic approaches and progress in surgical and radiotherapy techniques have improved the management of patients. The therapeutic goal is to normalise tissue exposure to cortisol to reverse increased morbidity and mortality. Optimum treatment consisting of selective and complete resection of the causative tumour is necessay to allow eventual normalisation of the hypothalamic-pituitary-adrenal axis, maintenance of pituitary function, and avoidance of tumour recurrence. The development of new drugs offers clinicians several choices to treat patients with residual cortisol excess. However, for patients affected by this challenging syndrome, the long-term effects and comorbidities associated with hypercortisolism need ongoing care.
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            Multisystem morbidity and mortality in Cushing's syndrome: a cohort study.

            Cushing's syndrome (CS) is associated with hypercoagulability, insulin resistance, hypertension, bone loss, and immunosuppression. To date, no adequately large cohort study has been performed to assess the multisystem effects of CS.
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              ARMC5 mutations in macronodular adrenal hyperplasia with Cushing's syndrome.

              Corticotropin-independent macronodular adrenal hyperplasia may be an incidental finding or it may be identified during evaluation for Cushing's syndrome. Reports of familial cases and the involvement of both adrenal glands suggest a genetic origin of this condition. We genotyped blood and tumor DNA obtained from 33 patients with corticotropin-independent macronodular adrenal hyperplasia (12 men and 21 women who were 30 to 73 years of age), using single-nucleotide polymorphism arrays, microsatellite markers, and whole-genome and Sanger sequencing. The effects of armadillo repeat containing 5 (ARMC5) inactivation and overexpression were tested in cell-culture models. The most frequent somatic chromosome alteration was loss of heterozygosity at 16p (in 8 of 33 patients for whom data were available [24%]). The most frequent mutation identified by means of whole-genome sequencing was in ARMC5, located at 16p11.2. ARMC5 mutations were detected in tumors obtained from 18 of 33 patients (55%). In all cases, both alleles of ARMC5 carried mutations: one germline and the other somatic. In 4 patients with a germline ARMC5 mutation, different nodules from the affected adrenals harbored different secondary ARMC5 alterations. Transcriptome-based classification of corticotropin-independent macronodular adrenal hyperplasia indicated that ARMC5 mutations influenced gene expression, since all cases with mutations clustered together. ARMC5 inactivation decreased steroidogenesis in vitro, and its overexpression altered cell survival. Some cases of corticotropin-independent macronodular adrenal hyperplasia appear to be genetic, most often with inactivating mutations of ARMC5, a putative tumor-suppressor gene. Genetic testing for this condition, which often has a long and insidious prediagnostic course, might result in earlier identification and better management. (Funded by Agence Nationale de la Recherche and others.).
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                Author and article information

                Contributors
                yuzhongwei789@126.com
                gaojie91@163.com
                sfk10570@rjh.com.cn , jsj_yu_16@sina.com
                Journal
                Hormones (Athens)
                Hormones (Athens)
                Hormones (Athens, Greece)
                Springer International Publishing (Cham )
                1109-3099
                2520-8721
                17 February 2023
                17 February 2023
                2023
                : 22
                : 2
                : 235-242
                Affiliations
                [1 ]GRID grid.16821.3c, ISNI 0000 0004 0368 8293, Department of Urology, , RuiJin Hospital Lu Wan Branch, Shanghai Jiaotong University School of Medicine, ; Shanghai, 200020 China
                [2 ]GRID grid.412540.6, ISNI 0000 0001 2372 7462, Department of Endocrinology, , Putuo Hospital, Shanghai University of Traditional Chinese Medicine, ; Shanghai, 200062 China
                [3 ]GRID grid.412277.5, ISNI 0000 0004 1760 6738, Department of Urology, , Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, ; Shanghai, China
                Article
                428
                10.1007/s42000-023-00428-8
                10209252
                36800160
                afe05a02-72aa-437f-b63e-8c55477dcf2c
                © The Author(s) 2023

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 11 June 2022
                : 9 January 2023
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81572621
                Award ID: 81972494
                Award Recipient :
                Funded by: Science Research Project of Shanghai Municipal Health Commision
                Award ID: 202040018
                Award Recipient :
                Categories
                Original Article
                Custom metadata
                © Hellenic Endocrine Society 2023

                primary bilateral macronodular adrenal hyperplasia (pbmah),cushing’s syndrome,unilateral adrenalectomy,urinary free cortisol

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