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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Approach to the Patient with Subclinical Cushing’s Syndrome

Author(s): Miomira Ivović, Ljiljana V. Marina*, Antoan S. Šojat, Milina Tančić-Gajić, Zorana Arizanović, Aleksandra Kendereški and Svetlana Vujović

Volume 26, Issue 43, 2020

Page: [5584 - 5590] Pages: 7

DOI: 10.2174/1381612826666200813134328

Price: $65

Open Access Journals Promotions 2
Abstract

A growing number of patients with adrenal incidentalomas and subclinical Cushing’s syndrome (SCS) led to an increasing number of different guidelines, and diagnostic and treatment recommendations. Excess cortisol secretion in patients with SCS is associated with several comorbidities, such as hypertension, dyslipidemia, type 2 diabetes mellitus, and obesity, which in the long-term increase mortality of these patients. Subtle cortisol secretion affects bone health, quality of life and causes depression, but due to the unapparent clinical features, patients with SCS are often at risk between over and under treatment. This narrative review aimed to summarize the latest recommendations on the approach to the patient with subclinical Cushing’s syndrome.

Keywords: Subclinical Cushing's syndrome, adrenal incidentaloma, possible autonomous cortisol secretion, mild autonomous cortisol secretion, mild autonomous cortisol excess, adrenal tumor, non-functional adrenal incidentaloma.

[1]
Bovio S, Cataldi A, Reimondo G, et al. Prevalence of adrenal incidentaloma in a contemporary computerized tomography series. J Endocrinol Invest 2006; 29(4): 298-302.
[http://dx.doi.org/10.1007/BF03344099] [PMID: 16699294]
[2]
Barzon L, Sonino N, Fallo F, Palu G, Boscaro M. Prevalence and natural history of adrenal incidentalomas. Eur J Endocrinol 2003; 149(4): 273-85.
[http://dx.doi.org/10.1530/eje.0.1490273] [PMID: 14514341]
[3]
Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev 2004; 25(2): 309-40.
[http://dx.doi.org/10.1210/er.2002-0031] [PMID: 15082524]
[4]
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.
[http://dx.doi.org/10.1530/EJE-16-0467] [PMID: 27390021]
[5]
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.
[http://dx.doi.org/10.1016/S2213-8587(13)70211-0] [PMID: 24795253]
[6]
Debono M, Bradburn M, Bull M, Harrison B, Ross RJ, Newell-Price J. Cortisol as a marker for increased mortality in patients with incidental adrenocortical adenomas. J Clin Endocrinol Metab 2014; 99(12): 4462-70.
[http://dx.doi.org/10.1210/jc.2014-3007] [PMID: 25238207]
[7]
Morelli V, Reimondo G, Giordano R, et al. Long-term follow-up in adrenal incidentalomas: an Italian multicenter study. J Clin Endocrinol Metab 2014; 99(3): 827-34.
[http://dx.doi.org/10.1210/jc.2013-3527] [PMID: 24423350]
[8]
Patrova J, Kjellman M, Wahrenberg H, Falhammar H. Increased mortality in patients with adrenal incidentalomas and autonomous cortisol secretion: a 13-year retrospective study from one center. Endocrine 2017; 58(2): 267-75.
[http://dx.doi.org/10.1007/s12020-017-1400-8] [PMID: 28887710]
[9]
Bancos I, Alahdab F, Crowley RK, et al. THERAPY OF ENDOCRINE DISEASE: Improvement of cardiovascular risk factors after adrenalectomy in patients with adrenal tumors and subclinical Cushing’s syndrome: a systematic review and meta-analysis. Eur J Endocrinol 2016; 175(6): R283-95.
[http://dx.doi.org/10.1530/EJE-16-0465] [PMID: 27450696]
[10]
Marina L, Ivovic M, Tancic-Gajic M, et al. The need for depression screening in patients with adrenal incidentalomas and (possible) autonomous cortisol secretion - the role of integrated care. Endocr Abstr 2018; 56: GP41.
[11]
Fassnacht M, Allolio B. Clinical management of adrenocortical carcinoma. Best Pract Res Clin Endocrinol Metab 2009; 23(2): 273-89.
[http://dx.doi.org/10.1016/j.beem.2008.10.008] [PMID: 19500769]
[12]
Nieman LK, Biller BMK, Findling JW, et al. The diagnosis of Cushing’s syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93(5): 1526-40.
[http://dx.doi.org/10.1210/jc.2008-0125] [PMID: 18334580]
[13]
Anagnostis P, Karagiannis A, Tziomalos K, Kakafika AI, Athyros VG, Mikhailidis DP. Adrenal incidentaloma: a diagnostic challenge. Hormones (Athens) 2009; 8(3): 163-84.
[http://dx.doi.org/10.14310/horm.2002.1233] [PMID: 19671516]
[14]
Shekelle PG, Ortiz E, Rhodes S, et al. Validity of the Agency for Healthcare Research and Quality clinical practice guidelines: how quickly do guidelines become outdated? JAMA 2001; 286(12): 1461-7.
[http://dx.doi.org/10.1001/jama.286.12.1461] [PMID: 11572738]
[15]
Yanase T, Oki Y, Katabami T, et al. New diagnostic criteria of adrenal subclinical Cushing’s syndrome: opinion from the Japan Endocrine Society. Endocr J 2018; 65(4): 383-93.
[http://dx.doi.org/10.1507/endocrj.EJ17-0456] [PMID: 29576599]
[16]
Di Dalmazi G, Pasquali R, Beuschlein F, Reincke M. Subclinical hypercortisolism: a state, a syndrome, or a disease? Eur J Endocrinol 2015; 173(4): M61-71.
[http://dx.doi.org/10.1530/EJE-15-0272] [PMID: 26282599]
[17]
Morelli V, Palmieri S, Lania A, et al. Cardiovascular events in patients with mild autonomous cortisol secretion: analysis with artificial neural networks. Eur J Endocrinol 2017; 177(1): 73-83.
[http://dx.doi.org/10.1530/EJE-17-0047] [PMID: 28468767]
[18]
Mihailidou AS, Loan Le TY, Mardini M, Funder JW. Glucocorticoids activate cardiac mineralocorticoid receptors during experimental myocardial infarction. Hypertension 2009; 54(6): 1306-12.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.136242] [PMID: 19841288]
[19]
Rizzoni D, Porteri E, De Ciuceis C, et al. Hypertrophic remodeling of subcutaneous small resistance arteries in patients with Cushing’s syndrome. J Clin Endocrinol Metab 2009; 94(12): 5010-8.
[http://dx.doi.org/10.1210/jc.2009-1588] [PMID: 19864447]
[20]
Lupoli R, Ambrosino P, Tortora A, Barba L, Lupoli GA, Di Minno MN. Markers of atherosclerosis in patients with Cushing’s syndrome: a meta-analysis of literature studies. Ann Med 2017; 49(3): 206-16.
[http://dx.doi.org/10.1080/07853890.2016.1252055] [PMID: 27763781]
[21]
Świątkowska-Stodulska R, Sworczak K. Disorders of hemostasis in overt and subclinical hypercortisolism. Exp Clin Endocrinol Diabetes 2013; 121(10): 588-94.
[http://dx.doi.org/10.1055/s-0033-1355385] [PMID: 24277483]
[22]
Ivović M, Marina LV, Vujović S, et al. Nondiabetic patients with either subclinical Cushing’s or nonfunctional adrenal incidentalomas have lower insulin sensitivity than healthy controls: clinical implications. Metabolism 2013; 62(6): 786-92.
[http://dx.doi.org/10.1016/j.metabol.2012.12.006] [PMID: 23332445]
[23]
Elhassan YS, Alahdab F, Prete A, et al. Natural History of Adrenal Incidentalomas With and Without Mild Autonomous Cortisol Excess: A Systematic Review and Meta-analysis. Ann Intern Med 2019; 171(2): 107-16.
[http://dx.doi.org/10.7326/M18-3630] [PMID: 31234202]
[24]
Marina LV, Ivović M, Tančić-Gajić M, et al. Luteinizing hormone and insulin resistance in menopausal patients with adrenal incidentalomas: The cause-effect relationship? Clin Endocrinol (Oxf) 2018; 88(4): 541-8.
[http://dx.doi.org/10.1111/cen.13541] [PMID: 29288564]
[25]
Vassilatou E, Vryonidou A, Ioannidis D, Paschou SA, Panagou M, Tzavara I. Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in subclinical cortisol hypersecretion but not in potential clinical implications. Eur J Endocrinol 2014; 171(1): 37-45.
[http://dx.doi.org/10.1530/EJE-13-0848] [PMID: 24743396]
[26]
Masserini B, Morelli V, Palmieri S, et al. Lipid abnormalities in patients with adrenal incidentalomas: role of subclinical hypercortisolism and impaired glucose metabolism. J Endocrinol Invest 2015; 38(6): 623-8.
[http://dx.doi.org/10.1007/s40618-014-0232-0] [PMID: 25608646]
[27]
Giordano R, Marinazzo E, Berardelli R, et al. Long-term morphological, hormonal, and clinical follow-up in a single unit on 118 patients with adrenal incidentalomas. Eur J Endocrinol 2010; 162(4): 779-85.
[http://dx.doi.org/10.1530/EJE-09-0957] [PMID: 20103607]
[28]
Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E. Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Ann Surg 2009; 249(3): 388-91.
[http://dx.doi.org/10.1097/SLA.0b013e31819a47d2] [PMID: 19247023]
[29]
Akaza I, Yoshimoto T, Iwashima F, et al. Clinical outcome of subclinical Cushing’s syndrome after surgical and conservative treatment. Hypertens Res 2011; 34(10): 1111-5.
[http://dx.doi.org/10.1038/hr.2011.90] [PMID: 21775997]
[30]
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.
[http://dx.doi.org/10.1016/j.surg.2012.08.054] [PMID: 23158173]
[31]
Lopez D, Luque-Fernandez MA, Steele A, Adler GK, Turchin A, Vaidya A. ‘Nonfunctional’ adrenal Tumors and the risk for incident diabetes and cardiovascular outcomes: A cohort study. Ann Intern Med 2016; 165(8): 533-42.
[http://dx.doi.org/10.7326/M16-0547] [PMID: 27479926]
[32]
Delivanis DA, Iñiguez-Ariza NM, Zeb MH, et al. Impact of hypercortisolism on skeletal muscle mass and adipose tissue mass in patients with adrenal adenomas. Clin Endocrinol (Oxf) 2018; 88(2): 209-16.
[http://dx.doi.org/10.1111/cen.13512] [PMID: 29115003]
[33]
Chiodini I, Viti R, Coletti F, et al. Eugonadal male patients with adrenal incidentalomas and subclinical hypercortisolism have increased rate of vertebral fractures. Clin Endocrinol (Oxf) 2009; 70(2): 208-13.
[http://dx.doi.org/10.1111/j.1365-2265.2008.03310.x] [PMID: 18547342]
[34]
Chiodini I, Guglielmi G, Battista C, et al. Spinal volumetric bone mineral density and vertebral fractures in female patients with adrenal incidentalomas: the effects of subclinical hypercortisolism and gonadal status. J Clin Endocrinol Metab 2004; 89(5): 2237-41.
[http://dx.doi.org/10.1210/jc.2003-031413] [PMID: 15126547]
[35]
Athimulam S, Delivanis D, Thomas M, et al. The impact of mild autonomous cortisol secretion on bone turnover markers. J Clin Endocrinol Metab 2020; 105(5): 1469-77.
[http://dx.doi.org/10.1210/clinem/dgaa120] [PMID: 32154561]
[36]
Chiodini I, Morelli V, Masserini B, et al. Bone mineral density, prevalence of vertebral fractures, and bone quality in patients with adrenal incidentalomas with and without subclinical hypercortisolism: an Italian multicenter study. J Clin Endocrinol Metab 2009; 94(9): 3207-14.
[http://dx.doi.org/10.1210/jc.2009-0468] [PMID: 19549741]
[37]
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. J Bone Miner Res 2011; 26(8): 1816-21.
[http://dx.doi.org/10.1002/jbmr.398] [PMID: 21472775]
[38]
Sonino N, Fava GA, Belluardo P, Girelli ME, Boscaro M. Course of depression in Cushing’s syndrome: response to treatment and comparison with Graves’ disease. Horm Res 1993; 39(5-6): 202-6.
[http://dx.doi.org/10.1159/000182736] [PMID: 8314204]
[39]
Sonino N, Guidi J, Fava GA. Psychological aspects of endocrine disease. J R Coll Physicians Edinb 2015; 45(1): 55-9.
[http://dx.doi.org/10.4997/JRCPE.2015.113] [PMID: 25874833]
[40]
Webb SM, Badia X, Barahona MJ, et al. Evaluation of health-related quality of life in patients with Cushing’s syndrome with a new questionnaire. Eur J Endocrinol 2008; 158(5): 623-30.
[http://dx.doi.org/10.1530/EJE-07-0762] [PMID: 18426820]
[41]
Kastelan D, Dzubur F, Dusek T, et al. Health-related quality of life and fatigue in patients with adrenal incidentaloma. Endocrine 2011; 40(1): 84-9.
[http://dx.doi.org/10.1007/s12020-011-9456-3] [PMID: 21442381]
[42]
Zavatta G, Di Dalmazi G. Recent Advances on Subclinical Hypercortisolism. Endocrinol Metab Clin North Am 2018; 47(2): 375-83.
[http://dx.doi.org/10.1016/j.ecl.2018.01.003] [PMID: 29754638]
[43]
Salcuni AS, Morelli V, Eller Vainicher C, et al. Adrenalectomy reduces the risk of vertebral fractures in patients with monolateral adrenal incidentalomas and subclinical hypercortisolism. Eur J Endocrinol 2016; 174(3): 261-9.
[http://dx.doi.org/10.1530/EJE-15-0977] [PMID: 26630908]
[44]
Petramala L, Cavallaro G, Galassi M, et al. Clinical Benefits of Unilateral Adrenalectomy in Patients with Subclinical Hypercortisolism Due to Adrenal Incidentaloma: Results from a Single Center. High Blood Press Cardiovasc Prev 2017; 24(1): 69-75.
[http://dx.doi.org/10.1007/s40292-017-0182-7] [PMID: 28138953]
[45]
Perogamvros I, Vassiliadi DA, Karapanou O, Botoula E, Tzanela M, Tsagarakis S. Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas. Eur J Endocrinol 2015; 173(6): 719-25.
[http://dx.doi.org/10.1530/EJE-15-0566] [PMID: 26330465]
[46]
Grossman A, Johannsson G, Quinkler M, Zelissen P. Therapy of endocrine disease: Perspectives on the management of adrenal insufficiency: clinical insights from across Europe. Eur J Endocrinol 2013; 169(6): R165-75.
[http://dx.doi.org/10.1530/EJE-13-0450] [PMID: 24031090]
[47]
Plat L, Leproult R, L’Hermite-Baleriaux M, et al. Metabolic effects of short-term elevations of plasma cortisol are more pronounced in the evening than in the morning. J Clin Endocrinol Metab 1999; 84(9): 3082-92.
[http://dx.doi.org/10.1210/jc.84.9.3082] [PMID: 10487669]
[48]
Young WF Jr, du Plessis H, Thompson GB, et al. The clinical conundrum of corticotropin-independent autonomous cortisol secretion in patients with bilateral adrenal masses. World J Surg 2008; 32(5): 856-62.
[http://dx.doi.org/10.1007/s00268-007-9332-8] [PMID: 18074172]
[49]
Ueland GÅ, Methlie P, Jøssang DE, et al. Adrenal Venous Sampling for Assessment of Autonomous Cortisol Secretion. J Clin Endocrinol Metab 2018; 103(12): 4553-60.
[http://dx.doi.org/10.1210/jc.2018-01198] [PMID: 30137397]
[50]
Onozawa S, Murata S, Tajima H, et al. Evaluation of right adrenal vein cannulation by computed tomography angiography in 140 consecutive patients undergoing adrenal venous sampling. Eur J Endocrinol 2014; 170(4): 601-8.
[http://dx.doi.org/10.1530/EJE-13-0741] [PMID: 24459237]
[51]
Katabami T, Ishii S, Obi R, Asai S, Tanaka Y. Contralateral adrenal suppression on adrenocortical scintigraphy provides good evidence showing subclinical cortisol overproduction from unilateral adenomas. Endocr J 2016; 63(12): 1123-32.
[http://dx.doi.org/10.1507/endocrj.EJ16-0281] [PMID: 27616151]
[52]
Debillon E, Velayoudom-Cephise FL, Salenave S, et al. Unilateral Adrenalectomy as a First-Line Treatment of Cushing’s Syndrome in Patients With Primary Bilateral Macronodular Adrenal Hyperplasia. J Clin Endocrinol Metab 2015; 100(12): 4417-24.
[http://dx.doi.org/10.1210/jc.2015-2662] [PMID: 26451908]
[53]
Lamas C, Alfaro JJ, Lucas T, Lecumberri B, Barceló B, Estrada J. Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases. Eur J Endocrinol 2002; 146(2): 237-40.
[http://dx.doi.org/10.1530/eje.0.1460237] [PMID: 11834434]
[54]
Iacobone M, Albiger N, Scaroni C, et al. The role of unilateral adrenalectomy in ACTH-independent macronodular adrenal hyperplasia (AIMAH). World J Surg 2008; 32(5): 882-9.
[http://dx.doi.org/10.1007/s00268-007-9408-5] [PMID: 18214589]
[55]
Osswald A, Quinkler M, Di Dalmazi G, et al. Long-Term Outcome of Primary Bilateral Macronodular Adrenocortical Hyperplasia After Unilateral Adrenalectomy. J Clin Endocrinol Metab 2019; 104(7): 2985-93.
[http://dx.doi.org/10.1210/jc.2018-02204] [PMID: 30844071]
[56]
Gupta PK, Natarajan B, Pallati PK, Gupta H, Sainath J, Fitzgibbons RJ Jr. Outcomes after laparoscopic adrenalectomy. Surg Endosc 2011; 25(3): 784-94.
[http://dx.doi.org/10.1007/s00464-010-1256-y] [PMID: 20717696]
[57]
Di Dalmazi G, Berr CM, Fassnacht M, Beuschlein F, Reincke M. Adrenal function after adrenalectomy for subclinical hypercortisolism and Cushing’s syndrome: a systematic review of the literature. J Clin Endocrinol Metab 2014; 99(8): 2637-45.
[http://dx.doi.org/10.1210/jc.2014-1401] [PMID: 24878052]
[58]
Hurtado MD, Cortes T, Natt N, Young WF Jr, Bancos I. Extensive clinical experience: Hypothalamic-pituitary-adrenal axis recovery after adrenalectomy for corticotropin-independent cortisol excess. Clin Endocrinol (Oxf) 2018; 89(6): 721-33.
[http://dx.doi.org/10.1111/cen.13803] [PMID: 29968420]
[59]
Delivanis DA, Athimulam S, Bancos I. Modern Management of Mild Autonomous Cortisol Secretion. Clin Pharmacol Ther 2019; 106(6): 1209-21.
[http://dx.doi.org/10.1002/cpt.1551] [PMID: 31206616]
[60]
Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and treatment of primary adrenal insufficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2016; 101(2): 364-89.
[http://dx.doi.org/10.1210/jc.2015-1710] [PMID: 26760044]
[61]
Braun LT, Reincke M. What is the role of medical therapy in adrenal-dependent Cushing’s syndrome? Best Pract Res Clin Endocrinol Metab 2020; 34(3)101376
[http://dx.doi.org/10.1016/j.beem.2020.101376] [PMID: 32063487]
[62]
Valassi E, Franz H, Brue T, et al. ERCUSYN Study Group Preoperative medical treatment in Cushing’s syndrome: frequency of use and its impact on postoperative assessment: data from ERCUSYN. Eur J Endocrinol 2018; 178(4): 399-409.
[http://dx.doi.org/10.1530/EJE-17-0997] [PMID: 29440375]
[63]
Broersen LHA, Jha M, Biermasz NR, Pereira AM, Dekkers OM. Effectiveness of medical treatment for Cushing’s syndrome: a systematic review and meta-analysis. Pituitary 2018; 21(6): 631-41.
[http://dx.doi.org/10.1007/s11102-018-0897-z] [PMID: 29855779]
[64]
Debono M, Harrison RF, Chadarevian R, Gueroult C, Abitbol JL, Newell-Price J. Resetting the Abnormal Circadian Cortisol Rhythm in Adrenal Incidentaloma Patients With Mild Autonomous Cortisol Secretion. J Clin Endocrinol Metab 2017; 102(9): 3461-9.
[http://dx.doi.org/10.1210/jc.2017-00823] [PMID: 28911138]
[65]
Debono M, Chadarevian R, Eastell R, Ross RJ, Newell-Price J. Mifepristone reduces insulin resistance in patient volunteers with adrenal incidentalomas that secrete low levels of cortisol: a pilot study. PLoS One 2013; 8(4)e60984
[http://dx.doi.org/10.1371/journal.pone.0060984] [PMID: 23577182]
[66]
Rao JU, Engelke UFH, Sweep FCGJ, et al. Genotype-specific differences in the tumor metabolite profile of pheochromocytoma and paraganglioma using untargeted and targeted metabolomics. J Clin Endocrinol Metab 2015; 100(2): E214-22.
[http://dx.doi.org/10.1210/jc.2014-2138] [PMID: 25459911]
[67]
Drogan D, Dunn WB, Lin W, et al. Untargeted metabolic profiling identifies altered serum metabolites of type 2 diabetes mellitus in a prospective, nested case control study. Clin Chem 2015; 61(3): 487-97.
[http://dx.doi.org/10.1373/clinchem.2014.228965] [PMID: 25524438]
[68]
Kotłowska A. Application of chemometric techniques in search of clinically applicable biomarkers of disease. Drug Dev Res 2014; 75(5): 283-90.
[http://dx.doi.org/10.1002/ddr.21213] [PMID: 25160068]
[69]
Di Dalmazi G, Fanelli F, Zavatta G, et al. The Steroid Profile of Adrenal Incidentalomas: Subtyping Subjects With High Cardiovascular Risk. J Clin Endocrinol Metab 2019; 104(11): 5519-28.
[http://dx.doi.org/10.1210/jc.2019-00365] [PMID: 31381072]
[70]
Arlt W, Biehl M, Taylor AE, et al. Urine steroid metabolomics as a biomarker tool for detecting malignancy in adrenal tumors. J Clin Endocrinol Metab 2011; 96(12): 3775-84.
[http://dx.doi.org/10.1210/jc.2011-1565] [PMID: 21917861]
[71]
Kerkhofs TMA, Kerstens MN, Kema IP, Willems TP, Haak HR. Diagnostic Value of Urinary Steroid Profiling in the Evaluation of Adrenal Tumors. Horm Cancer 2015; 6(4): 168-75.
[http://dx.doi.org/10.1007/s12672-015-0224-3] [PMID: 25985881]
[72]
Gatti R, Antonelli G, Prearo M, Spinella P, Cappellin E, De Palo EF. Cortisol assays and diagnostic laboratory procedures in human biological fluids. Clin Biochem 2009; 42(12): 1205-17.
[http://dx.doi.org/10.1016/j.clinbiochem.2009.04.011] [PMID: 19414006]
[73]
Kotłowska A, Puzyn T, Sworczak K, Stepnowski P, Szefer P. Metabolomic biomarkers in urine of cushing’s syndrome patients. Int J Mol Sci 2017; 18(2): 294.
[http://dx.doi.org/10.3390/ijms18020294] [PMID: 28146078]
[74]
Kotłowska A, Maliński E, Sworczak K, Kumirska J, Stepnowski P. The urinary steroid profile in patients diagnosed with adrenal incidentaloma. Clin Biochem 2009; 42(6): 448-54.
[http://dx.doi.org/10.1016/j.clinbiochem.2008.12.027] [PMID: 19297679]
[75]
Di Dalmazi G, Quinkler M, Deutschbein T, et al. Cortisol-related metabolic alterations assessed by mass spectrometry assay in patients with Cushing’s syndrome. Eur J Endocrinol 2017; 177(2): 227-37.
[http://dx.doi.org/10.1530/EJE-17-0109] [PMID: 28566446]

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