Clinical Features and Remission Rates in Cushing’s Disease: A
                    Comparison of MRI-Detectable and MRI-Undetectable Pituitary
                    Adenomas

Serhat Uysal; Cem Sulu; Ilkin Muradov; Serdar Sahin; Nurdan Gul; Ozlem Soyluk Selcukbiricik; Ayse Kubat Uzum; Gokcen Unal Kocabas; Banu Sarer Yurekli; Aysa Hacioglu; Zuleyha Karaca; Mehmet Barburoglu; Bora Korkmazer; Osman Kizilkilic; Pinar Kadioglu

doi:10.1055/a-2527-2029

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2025; 57(03): 163-169
DOI: 10.1055/a-2527-2029

Original Article: Endocrine Care

Clinical Features and Remission Rates in Cushing’s Disease: A Comparison of MRI-Detectable and MRI-Undetectable Pituitary Adenomas

Serhat Uysal

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Cem Sulu

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Ilkin Muradov

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Serdar Sahin

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Nurdan Gul

²Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University, Istanbul, Turkey (Ringgold ID: RIN60521)

,

Ozlem Soyluk Selcukbiricik

²Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University, Istanbul, Turkey (Ringgold ID: RIN60521)

,

Ayse Kubat Uzum

²Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University, Istanbul, Turkey (Ringgold ID: RIN60521)

,

Gokcen Unal Kocabas

³Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Ege University, Izmir, Turkey (Ringgold ID: RIN64212)

,

Banu Sarer Yurekli

³Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Ege University, Izmir, Turkey (Ringgold ID: RIN64212)

,

Aysa Hacioglu

⁴Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Erciyes University, Kayseri, Turkey (Ringgold ID: RIN64212)

,

Zuleyha Karaca

⁴Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Erciyes University, Kayseri, Turkey (Ringgold ID: RIN64212)

,

Mehmet Barburoglu

⁵Department of Radiology, Faculty of Medicine, Istanbul University, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Bora Korkmazer

⁵Department of Radiology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Osman Kizilkilic

⁵Department of Radiology, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

,

Pinar Kadioglu

¹Department of Internal Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey (Ringgold ID: RIN64298)

› Author Affiliations

Abstract

We aimed to characterize the clinical features and remission rates of patients with Cushing’s Disease (CD) without magnetic resonance imaging (MRI) detectable pituitary adenoma compared to CD patients with MRI-detectable pituitary adenoma.All patients with adrenocorticotropic hormone (ACTH)-dependent Cushing’s syndrome (CS) without MRI-detectable pituitary adenoma underwent high-dose dexamethasone suppression test, corticotropin-releasing hormone stimulation test, and/or bilateral inferior petrosal sinus sampling (BIPSS). The diagnosis of CD in patients without MRI-detectable adenoma was confirmed when the results of dynamic testing and sampling concordantly indicated ACTH-producing adenoma.These patients were included in MRI-undetectable group. Patients with ACTH-dependent CS had pituitary adenoma≥6 mm and those with pituitary adenoma<6 mm but BIPSS findings indicative of CD were included in MRI-detectable adenoma group. The study included 60 patients without MRI-detectable adenoma and 74 patients with MRI-detectable adenoma. At presentation, patients without MRI-detectable adenoma were older [47 years (30.25–58) vs. 40.5 years (29–49), p=0.036]. Hypertension (65% vs. 47.3%), diabetes mellitus (58.3% vs. 39.2%), and cardiovascular disease (13.3% vs. 2.7%) were more common in patients without MRI-detectable adenoma (p=0.040, p=0.027, p=0.020; respectively). The transsphenoidal surgery as initial treatment was higher in the patients with MRI-detectable adenoma group (97.3% vs. 80%, p=0.001). Third-month remission (60.4% vs. 63.8%, p=0.700) after surgery, and remission rates in the last visit (65.3% vs. 79.7%, p=0.077) were similar between the two groups. Inconclusion, the absence of an MRI-detectable adenoma underscores the necessity for comprehensive management.

Keywords

Cushing’s disease - management - pituitary adenoma - sella imaging - transsphenoidal surgery

Full Text

References

References
1 Mehta GU, Lonser RR, Oldfield EH. The history of pituitary surgery for Cushing disease: historical vignette. J Neurosurg 2012; 116: 261-268
2 Nieman LK. Cushing’s syndrome: update on signs, symptoms and biochemical screening. Eur J Endocrinol 2015; 173: M33-M38
3 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: 1526-1540
4 Ferriere A, Tabarin A. Cushing’s disease. Presse Méd 2021; 50: 104091
5 Gadelha MR, Vieira Neto L. Efficacy of medical treatment in C ushing’s disease: a systematic review. Clin Endocrinol 2014; 80: 1-12
6 Swearingen B, Biller BM, Barker FG. et al. Long-term mortality after transsphenoidal surgery for Cushing disease. Ann Inter Med 1999; 130: 821-824
7 Batista D, Courkoutsakis NA, Oldfield EH. et al. Detection of adrenocorticotropin-secreting pituitary adenomas by magnetic resonance imaging in children and adolescents with cushing disease. J Clin Endocrinol Metab 2005; 90: 5134-5140
8 Grober Y, Grober H, Wintermark M. et al. Comparison of MRI techniques for detecting microadenomas in Cushing’s disease. J Neurosurg 2018; 128: 1051-1057
9 Lonser RR, Nieman L, Oldfield EH. Cushing’s disease: pathobiology, diagnosis, and management. Journal of neurosurgery 2017; 126: 404-417
10 Sabahi M, Shahbazi T, Maroufi SF. et al. MRI–Negative Cushing’s disease: a review on therapeutic management. World Neurosurg 2022; 162: 126-137. e121
11 Jagannathan J, Sheehan JP, Jane JA. Evaluation and management of Cushing syndrome in cases of negative sellar magnetic resonance imaging. Neurosurg Focus 2007; 23: 1-7
12 Chow JT, Thompson GB, Grant CS. et al. Bilateral laparoscopic adrenalectomy for corticotrophin–dependent Cushing’s syndrome: a review of the Mayo Clinic experience. Clin Endocrinol 2008; 68: 513-519
13 Bertagna X, Guignat L. Approach to the Cushing’s disease patient with persistent/recurrent hypercortisolism after pituitary surgery. J Clin Endocrinol Metab 2013; 98: 1307-1318
14 Fleseriu M, Auchus R, Bancos I. et al. Consensus on diagnosis and management of Cushing’s disease: a guideline update. Lancet Diabetes Endocrinol 2021; 9: 847-875
15 Lacroix A, Feelders RA, Stratakis CA. et al. Cushing’s syndrome. Lancet 2015; 386: 913-927
16 Bertagna X, Guignat L, Groussin L. et al. Cushing’s disease. Best Pract Res Clin Endocrinol Metab 2009; 23: 607-623
17 Hayes AR, Grossman AB. The ectopic adrenocorticotropic hormone syndrome: rarely easy, always challenging. Endocrinol Metab Clin 2018; 47: 409-425
18 Oldfield EH, Doppman JL, Nieman LK. et al. Petrosal sinus sampling with and without corticotropin-releasing hormone for the differential diagnosis of Cushing’s syndrome. N Eng J Med 1991; 325: 897-905
19 Wu ZQ, Xu HG. Preanalytical stability of adrenocorticotropic hormone depends on both time to centrifugation and temperature. J Clin Lab Anal 2017; 31: e22081
20 Asa SL, Mete O, Perry A. et al. Overview of the 2022 WHO classification of pituitary tumors. Endocr Pathol 2022; 33: 6-26
21 Ragnarsson O, Olsson DS, Chantzichristos D. et al. The incidence of Cushing’s disease: a nationwide Swedish study. Pituitary 2019; 22: 179-186
22 Valassi E. Clinical presentation and etiology of Cushing’s syndrome: Data from ERCUSYN. J Neuroendocrinol 2022; 34: e13114
23 Tatsi C, Bompou ME, Flippo C. et al. Paediatric patients with Cushing disease and negative pituitary MRI have a higher risk of nonremission after transsphenoidal surgery. Clin Endocrinol 2021; 95: 856-862
24 Sun Y, Sun Q, Fan C. et al. Diagnosis and therapy for Cushing’s disease with negative dynamic MRI finding: a single-centre experience. Clin Endocrinol 2012; 76: 868-876
25 Sharifi G, Amin AA, Sabahi M. et al. MRI-negative Cushing’s disease: management strategy and outcomes in 15 cases utilizing a pure endoscopic endonasal approach. BMC Endocr Disord 2022; 22: 154
26 Akirov A, Shimon I, Fleseriu M. et al. Clinical study and systematic review of pituitary microadenomas vs. macroadenomas in Cushing’s disease: does size matter?. J Clin Med 2022; 11: 1558
27 Machado M, Alcantara A, Pereira A. et al. Negative correlation between tumour size and cortisol/ACTH ratios in patients with Cushing’s disease harbouring microadenomas or macroadenomas. J Endocrinol Investig 2016; 39: 1401-1409
28 Woo YS, Isidori AM, Wat WZ. et al. Clinical and biochemical characteristics of adrenocorticotropin-secreting macroadenomas. J Clin Endocrinol Metab 2005; 90: 4963-4969
29 Newell-Price J, Bertagna X, Grossman AB. et al. Cushing’s syndrome. Lancet 2006; 367: 1605-1617
30 Sharma S, Nieman L, Feelders R. Comorbidities in Cushing’s disease. Pituitary 2015; 18: 188-194
31 Hwang Y-C, Chung JH, Min Y-K. et al. Comparisons between macroadenomas and microadenomas in Cushing’s disease: characteristics of hormone secretion and clinical outcomes. J Korean Med Sci 2009; 24: 46
32 Mathioudakis N, Pendleton C, Quinones-Hinojosa A. et al. ACTH-secreting pituitary adenomas: size does not correlate with hormonal activity. Pituitary 2012; 15: 526-532
33 Bansal P, Lila A, Goroshi M. et al. Duration of post-operative hypocortisolism predicts sustained remission after pituitary surgery for Cushing’s disease. Endocr Connect 2017; 6: 625-636
34 Pouratian N, Prevedello DM, Jagannathan J. et al. Outcomes and management of patients with Cushing’s disease without pathological confirmation of tumor resection after transsphenoidal surgery. J Clin Endocrinol Metab 2007; 92: 3383-3388
35 Cebula H, Baussart B, Villa C. et al. Efficacy of endoscopic endonasal transsphenoidal surgery for Cushing’s disease in 230 patients with positive and negative MRI. Acta Neurochirurg 2017; 159: 1227-1236
36 Cristante J, Lefournier V, Sturm N. et al. Why we should still treat by neurosurgery patients with Cushing disease and a normal or inconclusive pituitary MRI. J Clin Endocrinol Metab 2019; 104: 4101-4113
37 Hofmann BM, Hlavac M, Martinez R. et al. Long-term results after microsurgery for Cushing disease: experience with 426 primary operations over 35 years. J Neurosurg 2008; 108: 9-18
38 Starke RM, Reames DL, Chen C-J. et al. Endoscopic transsphenoidal surgery for cushing disease: techniques, outcomes, and predictors of remission. Neurosurgery 2013; 72: 240-247
39 Jagannathan J, Smith R, DeVroom HL. et al. Outcome of using the histological pseudocapsule as a surgical capsule in Cushing disease. J Neurosurg 2009; 111: 531-539
40 Prevedello DM, Pouratian N, Sherman J. et al. Management of Cushing’s disease: outcome in patients with microadenoma detected on pituitary magnetic resonance imaging. J Neurosurg 2008; 109: 751-759