scholarly journals Factors associated with recurrence after endoscopic transphenoidal surgery for Cushing’s disease

Author(s):  
Y Meng ◽  
S Suppiah ◽  
L Gonen ◽  
G Klironomos ◽  
F Gentili ◽  
...  

Introduction: Surgical removal is the standard treatment for Cushing’s disease. Although endoscopic transsphenoidal surgical (ETS) approach has grown in popularity, its efficacy has not yet been established. Furthermore, achieving long-term remission remains challenging. Methods: We conducted a retrospective chart review of 39 consecutive patients who underwent ETS for Cushing’s disease at our institution between 2005 and 2014. Univariate analysis using Pearson’s χ2 test was carried out on variables of patient demographics, radiology, pathology, biochemical markers versus recurrence. Results: The mean age was 40, with 82% females. Average length of follow-up was 44.8 months. Based on serum cortisol level, 28 patients (71%) achieved mid to long-term remission after ETS. Of them, 25 experienced an immediate remission, and 3 achieved a delayed remission as long as 4 months postoperatively. MRI findings of (1) microadenomas or no detectable abnormality, (2) adjacency to the cavernous sinus wall were associated with significantly higher recurrence rate (p<0.05). Histologically, MIB-1 >5% was not a significant variable (p=0.55). Conclusion: We found ETS resection to be an effective and safe procedure for majority of the ACTH-secreting adenomas, with remission rates >70%. Additionally, patients with microadenomas, negative preoperative MR, and cavernous sinus adjacency were less likely to achieve remission.

Author(s):  
O. Cohen-Inbar

For patient with a recurrent or residual acromegaly or Cushing’s disease (CD) after resection, Gamma knife radiosurgery (GKRS) is often used. Hypopituitarism is the most common adverse effect after GKRS treatment. The paucity of studies with long-term follow up has hampered understanding of the latent risks of hypopituitarism in patients with a Acromegaly or CD. We report the long-term risks of hypopituitarism for patients treated with GKRS for Acromegaly or CD. Methods: From a prospectively created, IRB approved database, we identified all patients with a Acromegaly or CD treated with GKRS at the University of Virginia from 1989 to 2008. Only patients with a minimum endocrine follow up of 60 months were included. The median follow-up is 159.5 months (60.1-278). Thorough radiological and endocrine assessments were performed immediately before GKRS and at regular follow-up intervals. New onset of hypopituitarism was defined as pituitary hormone deficits after GKRS requiring corresponding hormone replacement. Results: 60 patients with either Acromegaly or CD were included. Median tumor volume at time of GKRS was 1.3 cm3 (0.3-13.4), median margin dose was 25 Gy (6-30). GKRS induced new pituitary deficiency occurred in 58.3% (n=35) of patients. Growth Hormone deficiency was most common (28.3%, n=17). The actuarial overall rates of hypopituitarism at 3, 5, and 10 years were 10%, 21.7%, and 53.3%, respectively. The median time to hypopituitarism was 61 months after GKRS (range, 12-160). Cavernous sinus invasion of the tumor was found to correlate with the occurrence of a new or progressive hypopituitarism after GKRS (p=0.018). Conclusions: Delayed hypopituitarism increases as a function of time after radiosurgery. Hormone axes appear to vary in terms of radiosensitivity. Patients with adenoma in the cavernous sinus are more prone to develop loss of pituitary function after GKRS.


2003 ◽  
pp. 195-200 ◽  
Author(s):  
S Cannavo ◽  
B Almoto ◽  
C Dall'Asta ◽  
S Corsello ◽  
RM Lovicu ◽  
...  

OBJECTIVE: Since Cushing's disease due to large pituitary tumors is rare, we evaluated biochemical characteristics at entry and the results of first surgical approach and of adjuvant therapeutic strategies during a long-term follow-up period. DESIGN: We studied 26 patients (nine male, 17 female; 42.5+/-12.7 years, mean+/-s.e.) with ACTH-secreting pituitary macroadenoma (tumor diameter: 11-40 mm). METHODS: At entry, plasma ACTH, serum cortisol and 24-h urinary free cortisol (UFC) levels were measured in all patients, a high-dose dexamethasone (dexa) suppression test was evaluated in 22 cases and a corticotrophin releasing hormone (CRH) test in 20 cases. Patients were re-evaluated after operation and, when not cured, they underwent second surgery, radiotherapy and/or ketoconazole treatment. The follow-up period was 78+/-10 months. RESULTS: Before surgery, dexa decreased ACTH (>50% of baseline) in only 14/22 patients. The CRH-stimulated ACTH/cortisol response was normal in six patients, impaired in six patients and exaggerated in eight patients. After operation eight patients were cured, nine had normalized cortisol levels and nine were not cured. Pre-surgery, mean ACTH values were significantly higher in the not cured patients than in those normalized (P<0.05) and cured (P<0.01); the ACTH response to CRH was impaired in only six patients of the not cured group. The tumour diameter was significantly less in cured patients (P<0.02) and in normalized patients (P<0.05) than in the not cured ones. Magnetic resonance imaging (MRI) showed invasion of the cavernous sinus in 2/9 normalized, and in 6/9 not cured patients. After surgery, ACTH, cortisol and UFC were significantly lower than at entry in cured and in normalized patients, but not in not cured patients. In the cured group, the disease recurred in one patient who was unsuccessfully treated with ketoconazole. In the normalized group, a relapse occurred in eight patients: radiotherapy and ketoconazole induced cortisol normalization in one case, hypoadrenalism in one case and were ineffective in another one, while five patients were lost at follow-up. In the not cured group, eight patients underwent second surgery, radiotherapy and/or ketoconazole, while one patient was lost at follow-up. These therapies induced cortisol normalization in two patients and hypoadrenalism in one. CONCLUSIONS: (i) A sub-set of patients with ACTH-secreting pituitary macroadenoma showed low sensitivity to high doses of dexamethasone and to CRH, (ii) pituitary surgery cured Cushing's disease in a minority of patients, (iii) high baseline ACTH levels, impaired ACTH response to CRH, increased tumor size or invasion of the cavernous sinus were unfavourable prognostic factors for surgical therapy, and (iv) second surgery, radiotherapy and/or ketaconazole cured or normalized hypercortisolism in half of the patients with recurrence or not cured.


2021 ◽  
Vol 12 ◽  
Author(s):  
Wentai Zhang ◽  
Mengke Sun ◽  
Yanghua Fan ◽  
He Wang ◽  
Ming Feng ◽  
...  

BackgroundThere are no established accurate models that use machine learning (ML) methods to preoperatively predict immediate remission after transsphenoidal surgery (TSS) in patients diagnosed with histology-positive Cushing’s disease (CD).PurposeOur current study aims to devise and assess an ML-based model to preoperatively predict immediate remission after TSS in patients with CD.MethodsA total of 1,045 participants with CD who received TSS at Peking Union Medical College Hospital in a 20-year period (between February 2000 and September 2019) were enrolled in the present study. In total nine ML classifiers were applied to construct models for the preoperative prediction of immediate remission with preoperative factors. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the performance of the models. The performance of each ML-based model was evaluated in terms of AUC.ResultsThe overall immediate remission rate was 73.3% (766/1045). First operation (p&lt;0.001), cavernous sinus invasion on preoperative MRI(p&lt;0.001), tumour size (p&lt;0.001), preoperative ACTH (p=0.008), and disease duration (p=0.010) were significantly related to immediate remission on logistic univariate analysis. The AUCs of the models ranged between 0.664 and 0.743. The highest AUC, i.e., the best performance, was 0.743, which was achieved by stacking ensemble method with four factors: first operation, cavernous sinus invasion on preoperative MRI, tumour size and preoperative ACTH.ConclusionWe developed a readily available ML-based model for the preoperative prediction of immediate remission in patients with CD.


2014 ◽  
Author(s):  
Andrea Osswald ◽  
Eva Plomer ◽  
Christina Dimopoulou ◽  
Monika Milian ◽  
Rainer Blaser ◽  
...  

2014 ◽  
Author(s):  
Paloma Moreno Moreno ◽  
Julia Silva Fernandez ◽  
Maria Rosa Alhambra Exposito ◽  
Maria angeles Galvez Moreno

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Gabriel Zada

Cushing’s Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing’s Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing’s Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing’s Disease are discussed.


2011 ◽  
Vol 96 (12) ◽  
pp. 3768-3774 ◽  
Author(s):  
Ferdinand Roelfsema ◽  
Daniel M. Keenan ◽  
Johannes D. Veldhuis

Background: The relationship between circulating ACTH levels and cortisol secretion in Cushing's disease is not precisely known. Hypothesis: Chronic ACTH hyperstimulation leads to decreased adrenal potency and is restored after normalization of ACTH secretion. Subjects: Subjects included 20 patients with Cushing's disease, eight patients in long-term remission, and 36 healthy controls. Outcomes: ACTH and cortisol secretion rates and analytical dose-response estimates of endogenous ACTH efficacy (maximal cortisol secretion), dynamic ACTH potency, and adrenal sensitivity (slope term) from 24-h ACTH-cortisol profiles were evaluated. Results: Both basal and pulsatile secretion of ACTH and cortisol were increased in patients with active disease but normal in cured patients. ACTH, but not cortisol pulse frequency, was amplified in patients and restored after successful surgical treatment. ACTH EC50, an inverse measure of potency, was higher during pulse onset in Cushing's disease (59 ± 7.4 ng/liter) than in controls (20 ± 3.7 ng/liter) (P &lt; 0.0001) and remitted patients after surgery [15 ± 3.2 ng/liter, P value not significant (NS) vs. controls] and during pulse recovery phases [128 ± 18 (P &lt;0.0001), 70 ± 8.4, and 67 ± 17 ng/liter (NS vs. controls), respectively]. Efficacy was increased in active disease and normalized after surgical treatment [patients, 38 ± 8.3 nmol/liter · min, vs. controls, 21 ± 2.3 nmol/liter · min (P &lt;0.0001), and cured patients, 15 ± 3.2 nmol/liter · min (NS vs. controls)]. Sensitivity to endogenous ACTH did not differ among the three groups. Conclusion: The adrenal gland in Cushing's disease exhibits decreased responsiveness to submaximal ACTH drive and amplified efficacy, with unchanged sensitivity. These target-gland abnormalities are reversible in long-term remission after pituitary surgery.


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