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      Natural history of nonfunctioning adrenal incidentalomas: a 10-year longitudinal follow-up study

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          Abstract

          Most data on the natural history of nonfunctioning adrenal incidentalomas (NFAI) are provided by follow-ups up to 5 years. We conducted a 10.5 (9.1–11.9)-year prospective follow-up study of NFAI in 67 participants (20 (29.9%) males, 47 (70.1%) females) of mean age 57.9 (52.3–63.9) years and BMI 27.42 (24.07–30.56) kg/m 2). We also evaluated the associations between baseline BMI and changes of NFAIs’ characteristics at follow-up. Progression to mild autonomous cortisol excess (MACE) was observed in 15 (22 %) patients, with 14 of them having post overnight dexamethasone suppression test (ODST) cortisol between 50 and138 nmol/L and only one > 138 nmol/L. The progression rate was significantly higher in overweight and obese than in normal-weight subjects. Patients that developed MACE had a significantly higher baseline mean cortisol after 1 mg ODST. Tumor enlargement ≥10 mm occurred in 8.9% of patients. In comparison with reports of shorter observational periods, we observed a higher growth rate ≥ 10 mm and higher progression rate from NFAI to MACE, particularly in overweight and obese subjects. All tumors had persistent radiological characteristics typical for adrenal adenoma. We concluded that the duration of the follow-up period is an important factor in characterizing the natural history of NFAI. Higher baseline BMI and higher baseline cortisol after ODST might predict the long-term likelihood of progression in hormonal activity. The magnitudes of observed progressions in growth or hormonal activity were clinically insignificant. Our long-term follow-up, therefore, clearly supports the general view that a long-term monitoring of patients with NFAI is not necessary.

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          European guidance for the diagnosis and management of osteoporosis in postmenopausal women

          Summary Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk from fractures due to osteoporosis. Introduction The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2013. This manuscript updates these in a European setting. Methods Systematic reviews were updated. Results The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk; general and pharmacological management of osteoporosis; monitoring of treatment; assessment of fracture risk; case-finding strategies; investigation of patients; health economics of treatment. The update includes new information on the evaluation of bone microstructure evaluation in facture risk assessment, the role of FRAX® and Fracture Liaison Services in secondary fracture prevention, long-term effects on fracture risk of dietary intakes, and increased fracture risk on stopping drug treatment. Conclusions A platform is provided on which specific guidelines can be developed for national use.
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            Management of adrenal incidentalomas: European Society of Endocrinology Clinical Practice Guideline in collaboration with the European Network for the Study of Adrenal Tumors.

            : By definition, an adrenal incidentaloma is an asymptomatic adrenal mass detected on imaging not performed for suspected adrenal disease. In most cases, adrenal incidentalomas are nonfunctioning adrenocortical adenomas, but may also represent conditions requiring therapeutic intervention (e.g. adrenocortical carcinoma, pheochromocytoma, hormone-producing adenoma or metastasis). The purpose of this guideline is to provide clinicians with best possible evidence-based recommendations for clinical management of patients with adrenal incidentalomas based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. We predefined four main clinical questions crucial for the management of adrenal incidentaloma patients, addressing these four with systematic literature searches: (A) How to assess risk of malignancy?; (B) How to define and manage low-level autonomous cortisol secretion, formerly called 'subclinical' Cushing's syndrome?; (C) Who should have surgical treatment and how should it be performed?; (D) What follow-up is indicated if the adrenal incidentaloma is not surgically removed? SELECTED RECOMMENDATIONS: (i) At the time of initial detection of an adrenal mass establishing whether the mass is benign or malignant is an important aim to avoid cumbersome and expensive follow-up imaging in those with benign disease. (ii) To exclude cortisol excess, a 1mg overnight dexamethasone suppression test should be performed (applying a cut-off value of serum cortisol ≤50nmol/L (1.8µg/dL)). (iii) For patients without clinical signs of overt Cushing's syndrome but serum cortisol levels post 1mg dexamethasone >138nmol/L (>5µg/dL), we propose the term 'autonomous cortisol secretion'. (iv) All patients with '(possible) autonomous cortisol' secretion should be screened for hypertension and type 2 diabetes mellitus, to ensure these are appropriately treated. (v) Surgical treatment should be considered in an individualized approach in patients with 'autonomous cortisol secretion' who also have comorbidities that are potentially related to cortisol excess. (vi) In principle, the appropriateness of surgical intervention should be guided by the likelihood of malignancy, the presence and degree of hormone excess, age, general health and patient preference. (vii) Surgery is not usually indicated in patients with an asymptomatic, nonfunctioning unilateral adrenal mass and obvious benign features on imaging studies. We provide guidance on which surgical approach should be considered for adrenal masses with radiological findings suspicious of malignancy. Furthermore, we offer recommendations for the follow-up of patients with adrenal incidentaloma who do not undergo adrenal surgery, for those with bilateral incidentalomas, for patients with extra-adrenal malignancy and adrenal masses and for young and elderly patients with adrenal incidentalomas.
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              A survey on adrenal incidentaloma in Italy. Study Group on Adrenal Tumors of the Italian Society of Endocrinology.

              The aim of this study was to perform a national survey on occasionally discovered adrenal masses [adrenal incidentalomas (AI)] under the auspices of the Italian Society of Endocrinology. This multicentric and retrospective evaluation of patients with AI includes 1096 cases collected in 26 centers between 1980 and 1995. Relevant information was obtained by means of a specifically tailored questionnaire. Of the 1096 forms received, 1004 were retained for final analysis. Patients were 420 males and 584 females, aged between 15-86 yr (median, 58 yr). Mass size (computed tomography measurement) ranged from 0.5-25 cm (median, 3.0 cm). Hormonal work-up demonstrated that 85% of the masses were nonhypersecretory, 9.2% were defined as subclinical Cushing's syndrome, 4.2% were pheochromocytomas, and 1.6% were aldosteronomas. Adrenalectomy was performed in 380 patients with removal of 198 cortical adenomas (52%), 47 cortical carcinomas (12%), 42 pheochromocytomas (11%), and other less frequent tumor types. Patients with carcinoma were significantly younger than patients with adenoma (median, 46; range, 17-84; vs. 57, 16-83 yr; P = 0.05). Adenomas were significantly smaller than carcinomas (3.5, 1-15 vs. 7.5, 2.6-25 cm; P < 0.001), and a cut-off at 4.0 cm had the highest sensitivity (93%) in differentiating between benign and malignant tumors. Hormonal work-up of patients with subclinical Cushing's syndrome showed low baseline ACTH in 79%, cortisol unsuppressibility after 1 mg dexamethasone in 73%, above normal urinary free cortisol in 75%, disturbed cortisol rhythm in 43%, and blunted ACTH response to CRH in 55%. Only 43% of patients with pheochromocytoma were hypertensive, and 86% showed elevated urinary catecholamines. All patients with aldosteronoma were hypertensive and had suppressed upright PRA. These results indicate that mass size is the most reliable variable in separating benign from malignant AI. Adrenalectomy should be recommended for AI greater than 4.0 cm because of the increased risk of malignancy, especially in young patients. Endocrine evaluation should be performed in all patients to identify silent states of hormone excess.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                19 May 2021
                01 June 2021
                : 10
                : 6
                : 637-645
                Affiliations
                [1 ]Faculty of Medicine , University of Ljubljana, Ljubljana, Slovenia
                [2 ]University Rehabilitation Institute Republic of Slovenia , Ljubljana, Slovenia
                [3 ]Department of Endocrinology , Diabetes and Metabolic Disease, University Medical Center Ljubljana, Ljubljana, Slovenia
                [4 ]Clinical Institute of Radiology , University Medical Center Ljubljana, Ljubljana, Slovenia
                [5 ]Faculty of Medicine , Institute of Biochemistry, Pharmacogenetics Laboratory, University of Ljubljana, Ljubljana, Slovenia
                Author notes
                Correspondence should be addressed to M Jensterle: mojcajensterle@ 123456yahoo.com
                Article
                EC-21-0196
                10.1530/EC-21-0196
                8240720
                34010150
                d5c666e1-c106-46f9-bed0-749490c6fe4f
                © The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 21 April 2021
                : 19 May 2021
                Categories
                Research

                adrenal incidentaloma,body mass index,benign nonfunctioning adrenal incidentaloma,mild autonomous cortisol excess,longitudinal studies

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