Exp Clin Endocrinol Diabetes 2020; 128(12): 827-834
DOI: 10.1055/a-0998-7884
Article

Unilateral Adrenalectomy for Primary Bilateral Macronodular Adrenal Hyperplasia: Analysis of 71 Cases

Mohammad Sheikh-Ahmad
1   Department of Endocrinology, Bnai Zion Medical Center, Haifa, Istael
,
Gabriel Dickstein
1   Department of Endocrinology, Bnai Zion Medical Center, Haifa, Istael
,
Ibrahim Matter
2   Department of Surgery, Bnai Zion Medical Center, Haifa, Israel
,
Carmela Shechner
1   Department of Endocrinology, Bnai Zion Medical Center, Haifa, Istael
,
Jacob Bejar
3   Department of Pathology, Bnai Zion Medical Center, Haifa, Israel
,
Maria Reut
1   Department of Endocrinology, Bnai Zion Medical Center, Haifa, Istael
,
Gideon Sroka
2   Department of Surgery, Bnai Zion Medical Center, Haifa, Israel
,
Monica Laniado
2   Department of Surgery, Bnai Zion Medical Center, Haifa, Israel
,
Leonard Saiegh
1   Department of Endocrinology, Bnai Zion Medical Center, Haifa, Istael
› Author Affiliations

Abstract

Objective Primary bilateral macronodular adrenal hyperplasia (PBMAH) is characterized by benign bilateral enlarged adrenal masses, causing Cushing’s syndrome (CS). The aim of the current article is to define the role of unilateral adrenalectomy (UA) in treating patients with CS related to PBMAH.

Methods A PubMed database search was conducted to identify articles reporting UA to treat PBMAH. We also report cases of PBMAH from our medical center treated by UA.

Results A total number of 71 cases of PBMAH (62 cases reported in the literature and 9 cases from our center) are presented. Most patients were women (73.2%) and most UA involved the left side (64.3%). In most cases, the resected gland was the larger one. Following UA, 94.4% of cases had remission of hypercortisolism. Recurrence rate of CS was 19.4% and hypoadrenalism occurred in 29.6%. After UA, when the size of the remained adrenal gland was equal or greater than 3.5 cm, CS persisted in 21.4% of cases, and recurrence occurred in 27.3% of cases (after 20±9.2 months). However, when the size of the remained gland was less than 3.5 cm, CS resolved in all cases and recurrence occurred in 21.2% of cases after a long period (65.6±52.1 months). High levels of urinary free cortisol (UFC) were not correlated with post-surgical CS recurrence or persistence.

Conclusions UA leads to beneficial outcomes in patients with CS related to PBMAH, also in cases with pre-surgical elevated UFC or contralateral large gland.



Publication History

Received: 23 March 2019
Received: 08 August 2019

Accepted: 16 August 2019

Article published online:
21 October 2019

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Lacroix A, Bourdeau I. Bilateral adrenal Cushing’s syndrome: Macronodular adrenal hyperplasia and primary pigmented nodular adrenocortical disease. Endocrinol Metab Clin North Am 2005; 34: 441-458
  • 2 Costa MH, Lacroix A. Cushing’s syndrome secondary to ACTH-independent macronodular adrenal hyperplasia. Arq Bras. Endocrinol Metab 2007; 51: 1226-1237
  • 3 Louiset E, Duparc C, Young J. et al. Intraadrenal corticotropin in bilateral macronodular adrenal hyperplasia. N Engl J Med 2013; 369: 2115-2125
  • 4 Iwata M, Oki Y, Okazawa T. et al. A rare case of adrenocorticotropic hormone (ACTH) independent macroadrenal hyperplasia showing ectopic production of ACTH. Intern Med 2012; 51: 2181-2187
  • 5 Christopoulos S, Bourdeau I, Lacroix A. Clinical and subclinical ACTH-independent macronodular adrenal hyperplasia andaberrant hormone receptors. Horm Res 2005; 64: 119-131
  • 6 Miyamura N, Taguchi T, Murata Y. et al. Inherited adrenocorticotropin independent macronodular adrenal hyperplasia with abnormal cortisol secretion by vasopressin and catecholamines: Detection of the aberrant hormone receptors on adrenal gland. Endocrine 2002; 19: 319-326
  • 7 van Aken MO, Pereira AM, van Thiel SW. et al. Irregular and frequent cortisol secretory episodes with preserved diurnal rhythmicity inprimary adrenal Cushing’s syndrome. J Clin Endocrinol Metab 2005; 90: 1570-1577
  • 8 Libé R, Coste J, Guignat L. et al. Aberrant cortisol regulations in bilateral macronodular adrenal hyperplasia: A frequentfinding in a prospective study of 32 patients with overt or subclinical Cushing’s syndrome. Eur J Endocrinol 2010; 163: 129-138
  • 9 Ioachimescu AG, Remer EM, Hamrahian AH. Adrenal incidentalomas: A disease of modern technology offering opportunities for improved patient care. Endocrinol Metab Clin North Am 2015; 44: 335-354
  • 10 Lacroix A, Bourdeau I, Lampron A. et al. Aberrant G protein coupled receptor expression in relation to adrenocortical overfunction. Clin Endocrinol (Oxf) 2010; 73: 1-15
  • 11 Lacroix A, Hamet P, Boutin JM. Leuprolide acetate therapy in luteinizing hormone–dependent Cushing’s syndrome. N Engl J Med 1999; 341: 1577-1581
  • 12 Oki K, Yamane K, Nakanishi S. et al. Improvement of hypercortisolism by β-blocker therapy in subclinical Cushing’s syndrome associated with ACTH-independent macronodular adrenocortical hyperplasia. Endocrine 2009; 36: 372-376
  • 13 Boronat M, Lucas T, Barceló B. et al. Cushing’s syndrome due to autonomous macronodular adrenal hyperplasia: Long-term follow-up after unilateral adrenalectomy. Postgrad Med J 1996; 72: 614-616
  • 14 Doppman JL, Chrousos GP, Papanicolaou DA. et al. Adrenocorticotropin-independent macronodular adrenal hyperplasia: an uncommon cause of primary adrenal hypercortisolism. Radiology 2000; 216: 797-802
  • 15 Lamas C, Alfaro JJ, Lucas T. et al. Is unilateral adrenalectomy an alternative treatment for ACTH-independent macronodular adrenal hyperplasia?: Long-term follow-up of four cases. Eur J Endocrinol 2002; 146: 237-240
  • 16 Ogura M, Kusaka I, Nagasaka S. et al. Unilateral adrenalectomy improves insulin resistance and diabetes mellitus in a patient with ACTH-independent macronodular adrenal hyperplasia. Endocr J. 2003; 50: 715-721
  • 17 Vezzosi D, Cartier D, Régnier C. et al. Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors. Eur J Endocrinol 2007; 156: 21-31
  • 18 Albiger NM, Occhi G, Mariniello B. et al. Food-dependent Cushing’s syndrome: From molecular characterization to therapeutical results. Eur J Endocrinol 2007; 157: 771-778
  • 19 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: 882-889
  • 20 Mazzuco TL, Chaffanjon P, Martinie M. et al. Adrenal Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia: Prediction of the efficacy of beta blockade therapy and interest of unilateral adrenalectomy. Endocr J 2009; 56: 867-877
  • 21 Kobayashi T, Miwa T, Kan K. et al. Usefulness and limitations of unilateral adrenalectomy for ACTH-independent macronodular adrenal hyperplasia in a patient with poor glycemic control. Intern Med 2012; 51: 1709-1713
  • 22 Ito T, Kurita Y, Shinbo H. et al. Successful treatment for adrenocorticotropic hormone-independent macronodularadrenal hyperplasia with laparoscopic adrenalectomy: A case series. J Med Case Rep 2012; 6: 312-317
  • 23 Xu Y, Rui W, Qi Y. et al. The role of unilateral adrenalectomy in corticotropin-independent bilateral adrenocortical hyperplasias. World J Surg 2013; 37: 1626-1632
  • 24 Maghrabi A, Yaqub A, Denning KL. et al. Challenges in the diagnostic work-up and management of patients with subclinical Cushing’s syndrome and bilateral adrenal masses. Endocr Pract 2013; 19: 515-521
  • 25 Albiger NM, Ceccato F, Zilio M. et al. An analysis of different therapeutic options in patients with Cushing’s syndrome due to bilateral macronodular adrenal hyperplasia: A single-centre experience. Clin Endocrinol (Oxf) 2015; 82: 808-815
  • 26 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: 4417-4424
  • 27 Alexandraki KI, Grossman AB. Is urinary free cortisol of value in the diagnosis of Cushing’s syndrome?. Curr Opin Endocrinol Diabetes Obes 2011; 18: 259-263
  • 28 Lumachi F, Zucchetta P, Marzola MC. et al. Usefulness of CT scan, MRI and radiocholesterol scintigraphy for adrenal imaging in Cushing’s syndrome. Nucl Med Commun 2002; 23: 469-473
  • 29 André Lacroix MD. Cushing’s syndrome due to primary bilateral macronodular adrenal hyperplasia. available at http://www.uptodate.com Accessed August 13 2018
  • 30 Morioka M, Ohashi Y, Watanabe H. et al. ACTH-independent macronodular adrenocortical hyperplasia (AIMAH): Report of two cases and the analysis of steroidogenic activity in adrenal nodules. Endocr J 1997; 44: 65-72