The Hormonal Status Comparison of Unilateral and Bilateral Adrenal Adenomas: Are They the Same?

Burak Özbaş; Asena Gökçay Canpolat; Cansu Özbaş; Demet Çorapçıoğlu; Mustafa Şahin

doi:10.58600/eurjther665

Authors

Burak Özbaş Department of Endocrinology and Metabolic Diseases, Dr Abdurrahman Yurtaslan Oncology Research and Training Hospital https://orcid.org/0000-0001-9850-0481
Asena Gökçay Canpolat Department of Endocrinology and Metabolism, Ankara University, School of Medicine, Ankara, Turkey https://orcid.org/0000-0003-1186-2960
Cansu Özbaş Department of Public Health, Gazi University, School of Medicine, Ankara, Turkey https://orcid.org/0000-0001-7349-8063
Demet Çorapçıoğlu Department of Endocrinology and Metabolism, Ankara University, School of Medicine https://orcid.org/0000-0003-0940-9147
Mustafa Şahin Department of Endocrinology and Metabolism, Ankara University, School of Medicine https://orcid.org/0000-0002-4718-0083

DOI:

https://doi.org/10.58600/eurjther665

Keywords:

Autonomous Cortisol Secretion, Bilateral adrenal adenomas, Dehydroepiandrosterone Sulfate

Abstract

Objective: It is not yet clear whether unilateral/bilateral adenomas are different in terms of both functionality and etiology. We investigated whether there were differences in hormonal profiles and evaluate the cortisol secretion profiles of unilateral and bilateral adenomas.

Methods: Hormonal secretory profiles and clinical features of patients with adenomas were collected. Detailed evaluation was made in terms of hypercortisolemia.

Results: Of the 184 patients examined, 140 had unilateral and 44 had bilateral adenomas. 73% of the patients were female and the mean body mass index was 34±8.1kg/m2. The mean age was 57.1±9.8 years. The average size of the adrenal masses was 23.3±10.5mm. While 83% of the evaluated adenomas were nonfunctional, ACS was found in 11% (n:20), hyperaldosteronism in 4% (n:8), and pheochromocytoma (PCC) in 2% (n:3) of the patients. The prevalence of ACS in bilateral/unilateral adenomas was 20.5%/7.9%, respectively. While serum adrenocorticotropic hormone level (25.6±16.6vs19.3±15µg/dL), urinary free cortisol level (162.3±108.3vs243.3±234.2µg/day), and low-dose-dexamethasone-suppression-test results (1.6±1.9vs1.73±1.7µg/dL) were not statistically different, the only difference between unilateral and bilateral adenomas was in serum DHEA-S level (141.4±85vs77.7±73.8 µg/dL, p:0.003).

Conclusion: Although there is no significant difference between the two groups in terms of clinical findings, it is clear that ACS is more prevalent in bilateral adenomas than unilateral. Because of the negative effects of long-term hypercortisolism, precise management of ACS is noteworthy. The evaluation of ACS should be done more carefully in bilateral adenomas considering that ACS is more in bilateral adenomas than unilateral. According to our findings, we also suggest that DHEA-S may be an indicator for ACS.

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References

Cho YY, Suh S, Joung JY, Jeong H, Je D, Yoo H, et al (2013) Clinical characteristics and follow-up of Korean patients with adrenal incidentalomas. Korean J Intern Med. 28(5): 557-64. https://doi.org/10.3904/kjim.2013.28.5.557

Minnaar EM, Human KE, Henneman D, Nio CY, Bisschop PH, Nieveen van Dijkum EJM (2013) An adrenal incidentaloma: how often is it detected and what are the consequences? ISRN Radiol. 2013: 871959. https://doi.org/10.5402/2013/871959

Barzon L, Scaroni C, Sonino N, Fallo F, Gregianin M, Macri C, et al (1998) Incidentally discovered adrenal tumors: endocrine and scintigraphic correlates. J Clin Endocrinol Metab. 83(1): 55-62. https://doi.org/10.1210/jcem.83.1.4501

Petrova J, Jarocka I, Wahrenberg H, Falhammar (2015) Clinical Outcomes in Adrenal Incidentaloma: Experience From One Center. Endocr Pract. 21(8): 870-7. https://doi.org/10.4158/EP15618.OR

Yener S, Yilmaz H, Demir T, Secil M, Comlekci A (2015) DHEAS for the prediction of subclinical Cushing’s syndrome: perplexing or advantageous? Endocrine. 48(2): 669-76. https://doi.org/10.1007/s12020-014-0387-7

. Majnik J, Patocs A, Balogh K, Toth M, Georgics P, Szappanos A, et al (2006) Overrepresentation of the N363S variant of the glucocorticoid receptor gene in patients with bilateral adrenal incidentalomas. J Clin Endocrinol Metab. 91(7): 2796-9. https://doi.org/10.1210/jc.2006-0066

Angeli A, Osella G, Ali A, Terzolo M (1997) Adrenal incidentaloma: an overview of clinical and epidemiological data from the National Italian Study Group. Horm Res. 47(4-6): 279-83. https://doi.org/10.1159/000185477

Bourdeau I, El Ghoyareb N, Gagnon N, Lacroix (2018) MANAGEMENT OF ENDOCRINE DISEASE: Differential diagnosis, investigation and therapy of bilateral adrenal incidentalomas. Eur J Endocrinol. 179(2): R57-R67. https://doi.org/10.1530/EJE-18-0296

Kasperlik-Załuska AA, Rosłonowska E, Słowinska-Srzednicka J, Migdalska B, Jeske W, MakowskaA, et al (1997) Incidentally discovered adrenal mass (incidentaloma): Investigation and management of 208 patients. Clin Endocrinol (Oxf). 46(1): 29-37. https://doi.org/10.1046/j.1365-2265.1997.d01-1751.x

Reincke M, Nieke J, Krestin GP, Saeger W, Allolio B, Winkelmann W (1992) Preclinical Cushing's syndrome in adrenal "incidentalomas": comparison with adrenal Cushing's syndrome. J Clin Endocrinol Metab. 75(3): 826-32. ttps://doi.org/10.1210/jcem.75.3.1517373

Charbonnel B, Chatal JF, Ozonne P (1981) Does the corticoadrenal adenoma with ‘pre-Cushing’s syndrome’ exist? J Nucl Med. 22(12): 1059-61. PMID: 6273512

Fassnacht M, Arlt W, Bancos I, Dralle H, Newell-Price J, Sahdev A, et al (2016) 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. 175(2): G1–G34. https://doi.org/10.1530/EJE-16-0467

Chiodini I, Morelli V, Masserini B, Salcuni AS, Eller-Vainicher C, Viti R, et al (2009) 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. 94(9): 3207–14. https://doi.org/10.1210/jc.2009-0468

Khan U (2019) Nonfunctioning and Subclinical Cortisol Secreting Adrenal Incidentalomas and their Association with Metabolic Syndrome: A Systematic Review. Indian J Endocrinol Metab. 23(3): 332–346. https://doi.org/10.4103/ijem.IJEM_52_19

Toniato A, Merante-Boschin I, Opocher G, Pelizzo MR, Schiavi F, Ballotta E (2009) Surgical versus conservative management for subclinical Cushing syndrome in adrenal incidentalomas: a prospective randomized study. Ann Surg. 249(3): 388-91. https://doi.org/10.1097/SLA.0b013e31819a47d2

Bancos I, Alahdab F, Crowley RK, Chortis V, Delivanis DA, Erickson D, et al (2016) 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. 175(6): R283–R295. https://doi.org/10.1530/EJE-16-0465

Chiodini I, Albani A, Ambrogio AG, Campo M, De Martino MC, Marcelli G, et al (2017) Six controversial issues on subclinical Cushing’s syndrome. Endocrine. 56(2): 262–66. https://doi.org/10.1007/s12020-016-1017-3

Paschou SA, Kandaraki E, Dimitropoulou F, Goulis DG, Vryonidou A (2016) Subclinical Cushing's syndrome in patients with bilateral compared to unilateral adrenal incidentalomas: a systematic review and meta-analysis. Endocrine. 51(2): 225-35. https://doi.org/10.1007/s12020-015-0776-6

Patócs A, Tóth M, Barta C, Sasvári-Székely M, Varga I, Szücs N, et al (2002) Hormonal evaluation and mutation screening for steroid 21-hydroxylase deficiency in patients with unilateral and bilateral adrenal incidentalomas. Eur J Endocrinol. 147(3): 349–355. https://doi.org/10.1530/eje.0.1470349

Di Dalmazi G (2016) The landscape of bilateral adrenal incidentalomas associated with subclinical hypercortisolism. Endocrine. 53(3): 621–3. https://doi.org/10.1007/s12020-016-1004-8

Di Dalmazi G, Pasquali R, Beuschlein F, Reincke M (2015) Subclinical hypercortisolism: a state, a syndrome, or a disease? Eur J Endocrinol. 173(4): M61-71. https://doi.org/10.1530/EJE-15-0272

Nieman LK, Biller BMK, Findling JW, Newell-Price J, Savage MO, Stewart PM, et al (2008) The diagnosis of Cushing’s syndrome: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 93: 1526–1540. https://doi.org/10.1210/jc.2008-0125

Dennedy MC, Annamalai AK, Prankerd-Smith O, Freeman N, Vengopal K, Graggaber J, et al (2017) Low DHEAS: A sensitive and specific test for the detection of subclinical hypercortisolism in adrenal incidentalomas. J Clin Endocrinol Metab. 102(3): 786–792. https://doi.org/10.1210/jc.2016-2718

Labrie F, Luu-The V, Martel C, Chernomoretz A, Calvo E, Morissette J, et al (2006) Dehydroepiandrosterone (DHEA) is an anabolic steroid like dihydrotestosterone (DHT), the most potent natural androgen, and tetrahydrogestrinone (THG). J Steroid Biochem Mol Biol. 100(1-3): 52–8. https://doi.org/10.1016/j.jsbmb.2006.03.006

Zeiger MA, Thompson GB, Duh QY, Hamrahian AH, Angelos P, Elaraj D, et al (2009) The American Association of Clinical Endocrinologists and American Association of Endocrine Surgeons medical guidelines for the management of adrenal incidentalomas. Endocr Pr. 15(Suppl 1): 1–20. https://doi.org/10.4158/EP.15.5.450

Vassilatou E, Vryonidou A, Michalopoulou S, Manolis J, Caratzas J, Phenekos C, et al (2009) Hormonal activity of adrenal incidentalomas: Results from a long-term follow-up study. Clin Endocrinol (Oxf). 70(5): 674–679. https://doi.org/10.1111/j.1365-2265.2008.03492.x

Young Jr WF, du Plessis H, Thompson GB, Grant CS, Farley DR, Richards ML, et al (2008) The clinical conundrum of corticotropin-independent autonomous cortisol secretion in patients with bilateral adrenal masses. World J Surg. 32(5): 856–62. https://doi.org/10.1007/s00268-007-9332-8

Perogamvros I, Vassiliadi DA, Karapanou O, Botoula E, Tzanela M, Tsagarakis S (2015) Biochemical and clinical benefits of unilateral adrenalectomy in patients with subclinical hypercortisolism and bilateral adrenal incidentalomas. Eur J Endocrinol. 173(6): 719–25. https://doi.org/10.1530/EJE-15-0566

Vassilatou E, Vryonidou A, Ionnidis D, Paschou SA, Panagou M, Tzavara I (2014) Bilateral adrenal incidentalomas differ from unilateral adrenal incidentalomas in subclinical cortisol hypersecretion but not in potential clinical implications. Eur J Endocrinol. 171(1): 37–45. https://doi.org/10.1530/EJE-13-0848

Androulakis II, Kaltsas GA, Markou A, Tseniklidi E, Kafritsa P, Pappa T, et al (2011) The functional status of incidentally discovered bilateral adrenal lesions. Clin Endocrinol (Oxf). 75(1): 44–49. https://doi.org/10.1111/j.1365-2265.2011.04013.x

Terzolo M, Pia A, Ali A, Osella G, Reimondo G, Bovio S, et al (2002) Adrenal incidentaloma: A new cause of the metabolic syndrome? J Clin Endocrinol Metab. 87(3): 998–1003. https://doi.org/10.1210/jcem.87.3.8277

Terzolo M, Bovio S, Pia A, Conton PA, Reimondo G, Dall'Asta C, et al (2005) Midnight serum cortisol as a marker of increased cardiovascular risk in patients with a clinically inapparent adrenal adenoma. Eur J Endocrinol. 153(2): 307–315. https://doi.org/10.1530/eje.1.01959

Tadjine M, Lampron A, Ouadi L, Horvath A, Stratakis CA, Bourdeau I (2008) Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease (PPNAD). Clin Endocrinol. 69(3): 367–73. https://doi.org/10.1111/j.1365-2265.2008.03273.x

Ritzel K, Beuschlein F, Mickisch A, Osswald A, Schneider HJ, Schopohl J, Reincke M (2013) Clinical review: Outcome of bilateral adrenalectomy in Cushing’s syndrome: A systematic review. J Clin Endocrinol. Metab. 98: 3939–3948. https://doi.org/10.1210/jc.2013-1470

Dunnick NR (1990) Hanson Lecture Adrenal imaging: Current status. AJR Am J Roentgenol. 154(5): 927–936. https://doi.org/10.2214/ajr.154.5.2108567

Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, et al (2014) Adrenocortical carcinoma. Endocr Rev. 35(2): 282-326. https://doi.org/10.1210/er.2013-1029

Corwin MT, Chalfant JS, Loehfelm TW, Fananapazir G, Lamba R, Mayo-Smith WW (2018) Incidentally Detected Bilateral Adrenal Nodules in Patients Without Cancer: Is Further Workup Necessary? AJR Am J Roentgenol. 210(4): 780–784. https://doi.org/10.2214/AJR.17.18543

Audenet FA, Me´jean A, l Chartier-Kastler E, Roupret M (2013) Adrenal tumours are more predominant in females regardless of their histological subtype: a review. World J Urol 31, 1037–1043. https://doi.org/10.1007/s00345-012-1011-1