scholarly journals Prediction of the transsphenoidal endoscopic adenomectomy results in patients with cushing’s disease

2022 ◽  
pp. 152-161
Author(s):  
N. V. Kuritsyna ◽  
U. A. Tsoy ◽  
V. Yu. Cherebillo ◽  
A. A. Paltsev ◽  
A. I. Tsiberkin ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Serum Cortisol Level ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Morning Serum Cortisol ◽  
Transsphenoidal Adenomectomy ◽  
Important Challenge ◽  
One Year

Introduction. Transsphenoidal adenomectomy (TSA) is the method of choice in the treatment of Cushing’s disease (CD), but remission of hypercorticism cannot be achieved in all patients. The search for predictors of CD remission after TSA remains to be an important challenge in the endocrinology today.Aim. To study the preoperative and postoperative data of patients with CD to identify the predictors of hypercorticism remission after TSA.Materials and methods. 101 patients with confirmed CD after TSA were included. One year after operation all patients were examined for the presence of hypercorticism remission and divided into two groups: with CD remission and its absence. In both groups’ preoperative pituitary magnetic resonance imaging (MRI) data, the results of preoperative high dose dexamethasone suppression test (HDDST) and the results of serum cortisol collected in the morning 2–3 days after surgery were compared.Results. One year after TSA, CD remission was confirmed in 63 patients (62.4%), whereas in 38 patients (37.6%) hypercortisolism persisted. Favorable predictors of CD remission were: the adenoma size > 3 mm without the invasive growth according to pituitary MRI (specificity 82.4%, sensitivity 82.8%), serum cortisol suppression ≥ 74% in preoperative HDDST (specificity 81.5%, sensitivity 86.3%), morning serum cortisol level in 2–3 days after surgery ≤ 388 nmol/l (specificity 79.3%, sensitivity 97.4%).Conclusions. Pituitary MRI data, the results of preoperative HDDST and morning serum cortisol in the 2–3 days after surgery can be used as predictors of CD remission.

scholarly journals Prognostic markers of remission of cushing's disease after transsphenoidal endoscopic adenomektomii.

2018 ◽  
Vol 95 (12) ◽  
pp. 1106-1111
Author(s):  
Natalia V. Gussaova ◽  
W. A. Choi ◽  
V. Yu. Cerebillo ◽  
A. A. Paltsev ◽  
A. V. Savello ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Threshold Value ◽  
Optimal Threshold ◽  
Cushing's Disease ◽  
High Dose ◽  
High Dose Dexamethasone ◽  
Free Cortisol ◽  
One Year ◽  
Cortisol Suppression

Aim. To study the role of prognostic oral high-dose dexamethasone suppression test (HDDST) and pituitary MRI in the prognosis of Cushing’s disease (CD). remission after transsphenoidal endoscopic surgery (TSS). Material and methods. 59 patients with Cushing’s disease (9 men, 50 women, mean age 40 years (15-72) underwent TSS were included. Before the TSS HDDST and pituitary MRI were performed in all cases. Postoperative examination was done one year after surgery. Remission criteria were: combination of normal midnight serum cortisol levels, normal 24 hour urine free cortisol (UFC) excretion and serum cortisol suppression less than 50 nmol/l in 1-mg dexamethasone test or secondary adrenal insufficiency (the need for glucocorticoid replacement). The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was calculated by ROC-analysis. Results. One year after surgery CD remission was confirmed in 39 patients, whereas in 20 patients hypercortisolism persisted. The optimal threshold value of serum cortisol suppression in the HDDST for prediction of CD remission after TSS was 72%. Test’s sensitivity and specificity were 82% and 84%, respectively. The probability of wrong prediction was 17% (p=0,0001). In our study, the results of TSS did not correlate with MRI adenoma size.

scholarly journals Morning Serum Cortisol as a Predictor for the HPA Axis Recovery in Cushing’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Q. Cui ◽  
D. Liu ◽  
B. Xiang ◽  
Q. Sun ◽  
L. Fan ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cross Sectional Study ◽  
Cushing's Disease ◽  
Confirmatory Test ◽  
Acth Stimulation ◽  
Cross Sectional ◽  
Postoperative Course ◽  
Morning Serum Cortisol

Background. The suppressed hypothalamic-pituitary-adrenal (HPA) axis after successful surgery for Cushing’s disease (CD) will recover in almost all patients. We aimed to identify the predictive factors for HPA axis recovery in CD patients with postoperative remission. Design and Methods. This observational retrospective cross-sectional study enrolled 69 CD patients with postoperative remission in Huashan Hospital from 2015 to 2019. All subjects had a detailed clinical evaluation. The low-dose ACTH stimulation test (LDT) was conducted as the gold standard for assessing the HPA axis function. Results. Peak cortisol in LDT was found only to be positively correlative with morning serum cortisol (MSC) ( ρ = 0.451 , p < 0.001 ). The MSC was higher ( p < 0.001 ), and the median postoperative course was significantly longer ( p = 0.025 ) in the patients with the recovered HPA axis function compared with unrecovered patients. The AUC value of MSC for predicting the recovery of the HPA axis was 0.701, and the optimal cutoff was 6.25 μg/dl (sensitivity 85.19% and specificity 47.62%). Other useful cutoff values were 10.74 μg/dl (specificity 100%) and 4.18 μg/dl (sensitivity 100%). Besides, combined with the postoperative course, the AUC values were higher than MSC alone (0.935 vs. 0.701, p < 0.001 ). Conclusions. MSC is a viable first-step diagnostic predictor for HPA axis recovery in CD patients with postoperative remission. For the patients with cortisol levels between 4.18 and 10.74 μg/dl, a confirmatory test should be conducted. When the MSC level was 10.74 μg/dl or greater, the replacement therapy could be discontinued.

scholarly journals Tumor shrinkage by metyrapone in Cushing's disease exhibiting glucocorticoid-induced positive feedback

2021 ◽  
Author(s):  
Yasutaka Tsujimoto ◽  
Hiroki Shichi ◽  
Hidenori Fukuoka ◽  
Masaaki Yamamoto ◽  
Itsuko Sato ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Positive Feedback ◽  
Cultured Cells ◽  
Ex Vivo ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
High Dose ◽  
Tumor Shrinkage ◽  
Feedback Systems ◽  
Cross Sectional

Abstract Context Paradoxical increases in serum cortisol in the dexamethasone suppression test (DST) have been rarely observed in Cushing’s disease (CD). Its pathophysiology and prevalence remain unclear. Case description A 62-year-old woman with suspected CD showed paradoxical increases in cortisol after both 1-mg and 8-mg DST (1.95-fold and 2.52-fold, respectively). The initiation of metyrapone paradoxically decreased plasma ACTH levels and suppressed cortisol levels. Moreover, the pituitary tumor considerably shrank during metyrapone treatment. Ex vivo experiments The resected tumor tissue was enzymatically digested, dispersed, and embedded into Matrigel as 3-D cultured cells. ACTH levels in the media were measured. In this tumor culture, ACTH levels increased 1.3-fold after dexamethasone treatment (p &lt;0.01) while control tumor cultures exhibited no increase in ACTH levels, but rather 20–40% suppression (p &lt;0.05). Clinical study A cross-sectional, retrospective, multicenter study that included 92 patients with CD who underwent both low dose- (LD) and high dose- (HD) DST from 2014 to 2020 was performed. Eight cases (8.7 %) showed an increase in serum cortisol after both LDDST and HDDST. Conclusions This is the first report of a patient with GC-driven positive-feedback CD who showed both ACTH suppression and tumor shrinkage by metyrapone. Our cohort study revealed that 8.7% of patients with CD patients possibly possess GC-driven positive feedback systems, thereby suggesting the presence of a new subtype of CD that is different from the majority of CD cases. The mechanisms exhibiting GC positive-feedback in CD and the therapeutic approach for these patients remain to be investigated.

scholarly journals Earlier post-operative hypocortisolemia may predict durable remission from Cushing’s disease

2018 ◽  
Vol 178 (3) ◽  
pp. 255-263 ◽  
Author(s):  
Natasha Ironside ◽  
Gregoire Chatain ◽  
David Asuzu ◽  
Sarah Benzo ◽  
Maya Lodish ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Serum Cortisol Level ◽  
Clinical Prediction ◽  
Patients At Risk ◽  
Level 2 ◽  
Clinical Prediction Tool ◽  
Durable Remission

Context Achievement of hypocortisolemia following transsphenoidal surgery (TSS) for Cushing’s disease (CD) is associated with successful adenoma resection. However, up to one-third of these patients recur. Objective We assessed whether delay in reaching post-operative cortisol nadir may delineate patients at risk of recurrence for CD following TSS. Methods A retrospective review of 257 patients who received 291 TSS procedures for CD at NIH, between 2003 and 2016. Early biochemical remission (serum cortisol nadir <5 μg/dL) was confirmed with endocrinological and clinical follow-up. Recurrence was detected by laboratory testing, clinical stigmata or medication dependence during a median follow-up of 11 months. Results Of the 268 unique admissions, remission was recorded in 241 instances. Recurrence was observed in 9% of these cases with cortisol nadir ≤5 μg/dL and 6% of cases with cortisol nadir ≤2 μg/dL. The timing of hypocortisolemia was critical in detecting late recurrences. Morning POD-1 cortisol <3.3 μg/dL was 100% sensitive in predicting durable remission and morning POD-3 cortisol ≥18.5 μg/dL was 98.6% specific in predicting remote recurrence. AUROC analysis revealed that hypocortisolemia ≤5 µg/dL before 15 h (post-operative) had 95% sensitivity and an NPV of 0.98 for durable remission. Serum cortisol level ≤2 µg/dL, when achieved before 21 h, improved sensitivity to 100%. Conclusions In our cohort, early, profound hypocortisolemia could be used as a clinical prediction tool for durable remission. Achievement of hypocortisolemia ≤2 µg/dL before 21 post-operative hours appeared to accurately predict durable remission in the intermediate term.

Prediction of Recurrence after Transsphenoidal Surgery for Cushing’s Disease: The Use of Machine Learning Algorithms

2019 ◽  
Vol 108 (3) ◽  
pp. 201-210 ◽  
Author(s):  
Yifan Liu ◽  
Xiaohai Liu ◽  
Xinyu Hong ◽  
Penghao Liu ◽  
Xinjie Bao ◽  
...  
Keyword(s):  
Machine Learning ◽  
Cushing’S Disease ◽  
Predictive Models ◽  
Transsphenoidal Surgery ◽  
Characteristic Curve ◽  
Serum Cortisol ◽  
Machine Learning Algorithms ◽  
Cushing's Disease ◽  
Morning Serum Cortisol ◽  
Better Than

Background: There are no reliable predictive models for recurrence after transsphenoidal surgery (TSS) for Cushing’s disease (CD). Objectives: This study aimed to develop machine learning (ML)-based predictive models for CD recurrence after initial TSS and to evaluate their performance. Method: A total of 354 CD patients were included in this retrospective, supervised learning, data mining study. Predictive models for recurrence were developed according to 17 variables using 7 algorithms. Models were evaluated based on the area under the receiver operating characteristic curve (AUC). Results: All patients were followed up for over 12 months (mean ± SD 43.80 ± 35.61). The recurrence rate was 13.0%. Age (p < 0.001), postoperative morning serum cortisol nadir (p = 0.002), and postoperative (p < 0.001) and preoperative (p = 0.04) morning adrenocorticotropin (ACTH) level were significantly related to recurrence. AUCs of the 7 models ranged from 0.608 to 0.781. The best performance (AUC = 0.781, 95% CI 0.706, 0.856) appeared when 8 variables were introduced to the random forest (RF) algorithm, which was much better than that of logistic regression (AUC = 0.684, p = 0.008) and that of using only postoperative morning serum cortisol (AUC = 0.635, p < 0.001). According to the feature selection algorithms, the top 3 predictors were age, postoperative serum cortisol, and postoperative ACTH. Conclusions: Using ML-based models for prediction of the recurrence after initial TSS for CD is feasible, and RF performs best. The performance of most of ML-based models was significantly better than that of some conventional models.

scholarly journals Cavernous sinus sampling in patients with Cushing's disease

2015 ◽  
Vol 38 (2) ◽  
pp. E6 ◽  
Author(s):  
Till Burkhardt ◽  
Jörg Flitsch ◽  
Philine van Leyen ◽  
Nina Sauer ◽  
Jens Aberle ◽  
...  
Keyword(s):  
Cavernous Sinus ◽  
Cushing’S Disease ◽  
Adrenocorticotropic Hormone ◽  
Correct Diagnosis ◽  
Cushing's Disease ◽  
High Dose ◽  
Consecutive Series ◽  
Test Results ◽  
High Dose Dexamethasone ◽  
Invasive Method

OBJECT Correct diagnosis and precise localization of adenomas in patients with Cushing's disease are essential for avoiding unsuccessful transsphenoidal pituitary exploration. In addition to the well-established inferior petrosal sinus sampling, preoperative cavernous sinus sampling (CSS) was introduced as a potentially improved way to predict adenoma lateralization. The authors present their results with CSS in a consecutive series of patients with Cushing's disease. METHODS During 1999–2014, transsphenoidal surgeries were consecutively performed in 510 patients with Cushing's disease. For most patients, suppression of cortisol in high-dose dexamethasone tests and stimulation of adrenocorticotropic hormone and cortisol after administration of corticotropin-releasing hormone were sufficient to prove the diagnosis of adrenocorticotropic hormone–dependent hypercortisolism. Of the 510 patients, 67 (13%) were referred to the department of neuroradiology for CSS according to the technique of Teramoto. The indications for CSS were unclear endocrine test results or negative MRI results. Data for all patients were retrospectively analyzed. RESULTS A central/peripheral gradient was found in 59 patients; lateralization to the left or right side was found in 51. For 8 patients with a central/peripheral gradient, no left/right gradient could be determined. For another 8 patients with equivocal test results, no central/peripheral gradient was found. No severe CSS-associated complications were encountered. Of the 51 patients who underwent transsphenoidal surgery, the predicted lateralization was proven correct for 42 (82%). CONCLUSIONS As MRI techniques have improved, the number of potential candidates for this invasive method has decreased in the past decade. However, because detecting minute adenomas remains problematic, CSS remains a useful diagnostic tool for patients with Cushing's disease.

scholarly journals Five years follow up of patients with Сushing’s disease with and without visualized pituitary adenoma on MRI, who underwent transsphenoidal adenomectomy

2017 ◽  
Vol 63 (5) ◽  
pp. 276-281
Author(s):  
Patimat M. Khandaeva ◽  
Zhanna E. Belaya ◽  
Lyudmila Ya. Rozhinskaya ◽  
Aleksandr V. Vorontsov ◽  
Andrey Yu. Grigoriev ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Cushing’S Disease ◽  
Remission Rate ◽  
Serum Cortisol ◽  
Urinary Free Cortisol ◽  
Cushing's Disease ◽  
Surgery Complications ◽  
Free Cortisol ◽  
Transsphenoidal Adenomectomy

The remission rate of Cushing’s disease in patients after neurosurgery varies from 59 to 94%, while the recurrence rate is 3 to 46%. Aim — to evaluate the five-year outcome in neurosurgery patients with Cushing’s disease (CD), depending on preoperative MRI-based identification of pituitary adenoma. Material and methods. The study included 105 neurosurgery patients with histologically confirmed CD. CD remission was confirmed by the development of adrenal insufficiency and/or normalization of serum cortisol and 24-hour urinary free cortisol (24h UFC) levels, as well as by clinical remission. Results. Pituitary adenoma was not visualized by gadolinium MRI in 35 cases. The size of visualized pituitary adenoma varied from 0.3 to 29 mm. After first neurosurgery, remission was achieved in 87 (82.8%) patients. After second neurosurgery, remission occurred in 12 patients. Radiation therapy was conducted in 24 patients. Six patients had bilateral adrenalectomy. Two patients died during remission: one patient died from stroke two years after neurosurgery, and the other patient died due to surgery complications. During five-year follow-up after neurosurgery, remission continued in 76 (72.8%) patients, including 27 (77%) of 35 patients without MRI-detected adenoma and 49 (70%) of 70 patients with MRI-detected pituitary adenoma, p=0.15. Sixty-six patients developed recurrence, and 14 patients had active hypercortisolism. Conclusion. There was no correlation between the rate of preoperative MRI-based detection of pituitary adenoma and the rate of remission in neurosurgery patients with Cushing’s disease during the five year follow-up. The size of pituitary adenoma was a risk factor for adenoma recurrence.

The corticotropin-releasing factor test in the differential diagnosis of Cushing's syndrome: A comparison with the lysine-vasopressin test

1990 ◽  
Vol 123 (3) ◽  
pp. 331-338 ◽  
Author(s):  
A. Tabarin ◽  
F. San Galli ◽  
S. Dezou ◽  
F. Leprat ◽  
J.-B. Corcuff ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Cushing’S Syndrome ◽  
Cushing’S Disease ◽  
Cushing's Syndrome ◽  
Cushing's Disease ◽  
High Dose ◽  
Ectopic Acth ◽  
Ectopic Acth Secretion ◽  
Etiological Diagnosis ◽  
High Dose Dexamethasone

Abstract. The diagnostic accuracy of the CRH test was compared with that of the LVP test in 28 consecutive patients with ACTH-dependent Cushing's syndrome. A false negative response to CRH was found in 3 of 21 patients with pituitary-dependent Cushing's disease and to LVP in 4. The 7 patients with ectopic ACTH secretion were unresponsive to CRH, whereas 2 did respond to LVP. CRH and high-dose dexamethasone tests combination led to concordant results in 79% of patients. In all cases the etiological diagnosis suggested was correct. LVP and high-dose dexamethasone tests combination led to concordant results in only 71% of patients and the etiological diagnosis suggested was erroneous in one. Individual tolerance to the CRH test was also clearly better than that to the LVP test. It is concluded that the CRH test, alone or in combination with the high-dose dexamethasone test must be preferentially used to the LVP test in the differential diagnosis of ACTH-dependent Cushing's disease.

scholarly journals Long-term remission and recurrence rates in Cushing's disease: predictive factors in a single-centre study

2013 ◽  
Vol 168 (4) ◽  
pp. 639-648 ◽  
Author(s):  
Krystallenia I Alexandraki ◽  
Gregory A Kaltsas ◽  
Andrea M Isidori ◽  
Helen L Storr ◽  
Farhad Afshar ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Serum Cortisol Level ◽  
Single Centre ◽  
Retrospective Case ◽  
Recurrence Rates ◽  
Dexamethasone Resistance ◽  
Remission Criteria

ObjectiveTo investigate the early and late outcomes of patients with Cushing's disease (CD) submitted to a neurosurgical procedure as first-line treatment.DesignIn this single-centre retrospective case notes study, 131 patients with CD with a minimum follow-up period of 6 years (124 operated by transsphenoidal surgery (TSS) and seven by the transcranial approach) were studied. Apparent immediate cure: post-operative 0900 h serum cortisol level <50 nmol/l; remission: cortisol insufficiency or restoration of ‘normal’ cortisol levels with resolution of clinical features; and recurrence: dexamethasone resistance and relapse of hypercortisolaemic features.ResultsIn patients operated by TSS, remission of hypercortisolaemia was found in 72.8% of 103 microadenomas and 42.9% of 21 macroadenomas, with recurrence rates 22.7 and 33.3% respectively with a 15-year mean follow-up (range, 6–29 years). Of 27 patients with microadenomas operated after 1991, with positive imaging and pathology, 93% obtained remission with 12% recurrence. In multivariate analysis, the time needed to achieve recovery of hypothalamo-pituitary–adrenal axis was the only significant predictor of recurrence; all patients who recurred showed recovery within 3 years from surgery: 31.3% of patients had total hypophysectomy with no recurrence; 42% of patients with selective adenomectomy and 26.5% with hemi–hypophysectomy showed recurrence rates of 31 and 13% respectively (χ2=6.275, P=0.03). Strict remission criteria were not superior in terms of the probability of recurrence compared with post-operative normocortisolaemia.ConclusionsLifelong follow-up for patients with CD appears essential, particularly for patients who have shown rapid recovery of their axis. The strict criteria previously used for ‘apparent cure’ do not appear to necessarily predict a lower recurrence rate.

Early post-operative morning serum cortisol measurement as a predictor of remission of Cushing's disease

2017 ◽  
Author(s):  
Nithin Thoppuram ◽  
Nigel Mendoza ◽  
Ramesh Nair ◽  
Emma Hatfield ◽  
Karim Meeran ◽  
...  
Keyword(s):  
Cushing’S Disease ◽  
Serum Cortisol ◽  
Cushing's Disease ◽  
Morning Serum Cortisol
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