Diagnosis and Management of Cushing's Disease: A Survey of Endocrinologists from the Middle East and North Africa

Abstract

Background Cushing's disease is the most prevalent cause of endogenous Cushing's syndrome. This study aimed to scope the current clinical practice pattern in managing Cushing's disease by endocrinologists in the Middle Eastern and North African (MENA) region.

Methods A questionnaire dealing with diagnosis, treatment, and follow-up of patients with Cushing's disease was adopted and sent electronically to a convenience sample of endocrinologists from the MENA region.

Results Out of 125 responses received, 88 were eligible for inclusion in the analysis. Most respondents selected the overnight dexamethasone suppression test (ONDST) and 24-hour urinary-free cortisol (UFC) as the best screening tests, 58 (66.7%) and 50 (57.5%) respectively, followed by midnight serum cortisol and midnight salivary cortisol. Measurement of serum adrenocorticotropic hormone (ACTH; 86.2%) and classic high-dose dexamethasone suppression test (40.2%) were selected for localization of the primary lesion. The primary choice of treatment was transsphenoidal pituitary surgery (98.8%). For the recurrence of Cushing's disease, medical therapy was the preferred modality followed by repeated pituitary surgery or bilateral adrenalectomy. In case of treatment failure following the first pituitary surgery and ketoconazole treatment, 36.9% selected pasireotide, while 32.1% chose bilateral adrenalectomy.

Conclusion ONDST and UFC are the two most common tests used to screen an index case with features of hypercortisolism. Pituitary surgery is the primary choice of treatment in Cushing's disease. However, medical treatment by ketoconazole is preferred for recurrent cases. Bilateral adrenalectomy is followed by pasireotide may be chosen in case of treatment failure after pituitary surgery and ketoconazole.

Keywords

clinical practice - Cushing's disease - diagnosis - management - MENA region

Authors' Contributions

All authors contributed to the conceptualization, design of the study, and the process of data collection; S.A.B., M.A.E., and K.M.A.D., were actively involved in interpretation of data and drafted the manuscript for all authors to critique and make relevant corrections. All the authors have read and agreed to final version of this manuscript.

Compliance with Ethical Principles

The study was conducted following the principles of the Declaration of Helsinki. The Institutional Review Board approved the study at Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates. All participants provided informed consent before they could proceed to the survey questions.

Financial Support and Sponsorship

None.

Publication History

Article published online:
05 August 2022

• References

• 1 Pivonello R, De Martino MC, De Leo M, Lombardi G, Colao A. Cushing's syndrome. Endocrinol Metab Clin North Am 2008; 37 (01) 135-149 , ix ix.  
• 2 Nieman LK, Biller BM, Findling JW. et al. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2008; 93 (05) 1526-1540
• 3 Biller BM, Grossman AB, Stewart PM. et al. Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement. J Clin Endocrinol Metab 2008; 93 (07) 2454-2462
• 4 Juszczak A, Morris D, Grossman A. Cushing's syndrome. In: Feingold KR, Anawalt B, Boyce A. et al, eds. Endotext [Internet]. South Dartmouth, MA: MDText.com, Inc.; 2000
• 5 Malek M, Esfehanian F, Amouzegar A. et al. A survey of clinical practice patterns in diagnosis and management of Cushing's disease in Iran. Med J Islam Repub Iran 2016; 30: 334
• 6 Beshyah SA, Sherif IH, Chentli F. et al. Management of prolactinomas: a survey of physicians from the Middle East and North Africa. Pituitary 2017; 20 (02) 231-240
• 7 Beshyah SA, Khalil AB, Sherif IH. et al. Clinical practice patterns in management of Graves' disease in the Middle East and North Africa. Endocr Pract 2017; 23 (03) 299-308
• 8 Ahmad MM, Buhairy B, Al Mousawi F. et al. Physicians' perceptions and practices in management of acromegaly in the MENA region. Hormones (Athens) 2018; 17 (03) 373-381
• 9 Beshyah SA, Al-Saleh Y, El-Hajj Fuleihan G. Management of osteoporosis in the Middle East and North Africa: a survey of physicians' perceptions and practices. Arch Osteoporos 2019; 14 (01) 60
• 10 Beshyah SA, Sherif IH, Mustafa HE, Saadi HF. Patterns of clinical management of hypothyroidism in adults: An electronic survey of physicians from the Middle East and Africa. J Diab Endo Practice 2021; 4: 75-82
• 11 Dorn LD, Lucke JF, Loucks TL, Berga SL. Salivary cortisol reflects serum cortisol: analysis of circadian profiles. Ann Clin Biochem 2007; 44 (pt. 3): 281-284
• 12 Poll EM, Kreitschmann-Andermahr I, Langejuergen Y. et al. Saliva collection method affects predictability of serum cortisol. Clin Chim Acta 2007; 382 (1-2): 15-19
• 13 Smith RE, Maguire JA, Stein-Oakley AN. et al. Localization of 11 beta-hydroxysteroid dehydrogenase type II in human epithelial tissues. J Clin Endocrinol Metab 1996; 81 (09) 3244-3248
• 14 Badrick E, Kirschbaum C, Kumari M. The relationship between smoking status and cortisol secretion. J Clin Endocrinol Metab 2007; 92 (03) 819-824
• 15 Atkinson AB, Kennedy A, Wiggam MI, McCance DR, Sheridan B. Long-term remission rates after pituitary surgery for Cushing's disease: the need for long-term surveillance. Clin Endocrinol (Oxf) 2005; 63 (05) 549-559
• 16 Hammer GD, Tyrrell JB, Lamborn KR. et al. Transsphenoidal microsurgery for Cushing's disease: initial outcome and long-term results. J Clin Endocrinol Metab 2004; 89 (12) 6348-6357
• 17 Mancini T, Porcelli T, Giustina A. Treatment of Cushing disease: overview and recent findings. Ther Clin Risk Manag 2010; 6: 505-516
• 18 Chow JT, Thompson GB, Grant CS, Farley DR, Richards ML, Young Jr WF. Bilateral laparoscopic adrenalectomy for corticotrophin-dependent Cushing's syndrome: a review of the Mayo Clinic experience. Clin Endocrinol (Oxf) 2008; 68 (04) 513-519
• 19 Engelhardt D, Weber MM. Therapy of Cushing's syndrome with steroid biosynthesis inhibitors. J Steroid Biochem Mol Biol 1994; 49 (4-6): 261-267
• 20 Stricker BH, Blok AP, Bronkhorst FB, Van Parys GE, Desmet VJ. Ketoconazole-associated hepatic injury. A clinicopathological study of 55 cases. J Hepatol 1986; 3 (03) 399-406
• 21 de Bruin C, Pereira AM, Feelders RA. et al. Coexpression of dopamine and somatostatin receptor subtypes in corticotroph adenomas. J Clin Endocrinol Metab 2009; 94 (04) 1118-1124
• 22 Tateno T, Kato M, Tani Y, Oyama K, Yamada S, Hirata Y. Differential expression of somatostatin and dopamine receptor subtype genes in adrenocorticotropin (ACTH)-secreting pituitary tumors and silent corticotroph adenomas. Endocr J 2009; 56 (04) 579-584
• 23 Batista DL, Zhang X, Gejman R. et al. The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas. J Clin Endocrinol Metab 2006; 91 (11) 4482-4488
• 24 Saveanu A, Jaquet P. Somatostatin-dopamine ligands in the treatment of pituitary adenomas. Rev Endocr Metab Disord 2009; 10 (02) 83-90
• 25 Hofland LJ, van der Hoek J, Feelders R. et al. The multi-ligand somatostatin analogue SOM230 inhibits ACTH secretion by cultured human corticotroph adenomas via somatostatin receptor type 5. Eur J Endocrinol 2005; 152 (04) 645-654
• 26 Durán-Prado M, Gahete MD, Martínez-Fuentes AJ. et al. Identification and characterization of two novel truncated but functional isoforms of the somatostatin receptor subtype 5 differentially present in pituitary tumors. J Clin Endocrinol Metab 2009; 94 (07) 2634-2643
• 27 Stalla GK, Brockmeier SJ, Renner U. et al. Octreotide exerts different effects in vivo and in vitro in Cushing's disease. Eur J Endocrinol 1994; 130 (02) 125-131
• 28 Lamberts SW, Uitterlinden P, Klijn JM. The effect of the long-acting somatostatin analogue SMS 201-995 on ACTH secretion in Nelson's syndrome and Cushing's disease. Acta Endocrinol (Copenh) 1989; 120 (06) 760-766
• 29 Mazziotti G, Floriani I, Bonadonna S, Torri V, Chanson P, Giustina A. Effects of somatostatin analogs on glucose homeostasis: a meta-analysis of acromegaly studies. J Clin Endocrinol Metab 2009; 94 (05) 1500-1508