CONTEXT Signs and symptoms of Cushing's syndrome (CS) overlap with common diseases, such as the metabolic syndrome, obesity, osteoporosis, and depression. Therefore, it can take years to finally diagnose CS, although early diagnosis is important for prevention of complications. OBJECTIVE The aim of this study was to assess the time span between first symptoms and diagnosis of CS in different populations to identify factors associated with an early diagnosis. DATA SOURCES A systematic literature search via PubMed was performed to identify studies reporting on time to diagnosis in CS. In addition, unpublished data from patients of our tertiary care center and 4 other centers were included. STUDY SELECTION Clinical studies reporting on the time to diagnosis of CS were eligible. Corresponding authors were contacted to obtain additional information relevant to the research question. DATA EXTRACTION Data were extracted from the text of the retrieved articles and from additional information provided by authors contacted successfully. From initially 3326 screened studies 44 were included. DATA SYNTHESIS Mean time to diagnosis for patients with CS was 34 months (ectopic CS: 14 months; adrenal CS: 30 months; and pituitary CS: 38 months; P \textless .001). No difference was found for gender, age (\textless18 and \geq18 years), and year of diagnosis (before and after 2000). Patients with pituitary CS had a longer time to diagnosis in Germany than elsewhere. CONCLUSIONS Time to diagnosis differs for subtypes of CS but not for gender and age. Time to diagnosis remains to be long and requires to be improved.

/pdf/time-to-diagnosis-in-cushing-s-syndrome-a-meta-analysis-1vzsg8a0ac.pdf

Time to Diagnosis in Cushing's Syndrome: A Meta-Analysis Based on 5367 Patients

In patients with Cushing’s disease (CD), prompt diagnosis and treatment are essential for favorable long-term outcomes, although this remains a challenging task. The differential diagnosis of CD is still difficult in some patients, even with an organized stepwise diagnostic approach. Moreover, despite the use of high-resolution magnetic resonance imaging (MRI) combined with advanced fine sequences, some tumors remain invisible. Surgery, using various surgical approaches for safe maximum tumor removal, still remains the first-line treatment for most patients with CD. Persistent or recurrent CD after unsuccessful surgery requires further treatment, including repeat surgery, medical therapy, radiotherapy, or sometimes, bilateral adrenalectomy. These treatments have their own advantages and disadvantages. However, the most important thing is that this complex disease should be managed by a multidisciplinary team with collaborating experts. In addition, a personalized and individual-based approach is paramount to achieve high success rates while minimizing the occurrence of adverse events and improving the patients’ quality of life. Finally, the recent new insights into the pathophysiology of CD at the molecular level are highly anticipated to lead to the introduction of more accurate diagnostic tests and efficacious therapies for this devastating disease in the near future.

Cushing's Disease.

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.

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

Development and validation of an MRI-based radiomic signature for the preoperative prediction of treatment response in patients with invasive functional pituitary adenoma.

Abstract Objective We aimed to perform a systematic review and meta-analysis of all-cause and cause-specific mortality of patients with benign endogenous Cushing syndrome (CS). Methods The protocol was registered in PROSPERO (CRD42017067530). PubMed, EMBASE, CINHAL, Web of Science, and Cochrane Central searches were undertaken from inception to January 2021. Outcomes were the standardized mortality ratio (SMR), proportion, and cause of deaths. The I2 test, subgroup analysis, and meta-regression were used to assess heterogeneity across studies. Results SMR was reported in 14 articles including 3691 patients (13 Cushing disease [CD] and 7 adrenal CS [ACS] cohorts). Overall SMR was 3.0 (95% CI, 2.3-3.9; I2 = 80.5%) for all CS, 2.8 (95% CI, 2.1-3.7; I2 = 81.2%) for CD and 3.3 (95% CI, 0.5-6.6; I2 = 77.9%) for ACS. Proportion of deaths, reported in 87 articles including 19 181 CS patients (53 CD, 24 ACS, and 20 combined CS cohorts), was 0.05 (95% CI, 0.03-0.06) for all CS subtypes with meta-regression analysis revealing no differences between CS subtypes (P = .052). The proportion of deaths was 0.1 (10%) in articles published before 2000 and 0.03 (3%) in 2000 until the last search for CS (P < .001), CD (P < .001), and ACS (P = .01). The causes of death were atherosclerotic diseases and thromboembolism (43.4%), infection (12.7%), malignancy (10.6%), active disease (3.5%), adrenal insufficiency (3.0%), and suicide (2.2%). Despite improved outcomes in recent years, increased mortality from CS persists. The causes of death highlight the need to prevent and manage comorbidities in addition to treating hypercortisolism.

The Effect of Endogenous Cushing Syndrome on All-cause and Cause-specific Mortality

BACKGROUND: The mainstay of treatment for symptomatic or large chronic subdural hematoma (CSDH) is surgery, but controversy still exists regarding the best surgical technique. Three different techniques are commonly used: burr hole craniostomy (BHC), minicraniotomy (MC), and twist drill craniostomy (TDC). OBJECTIVE: To determine which surgical technique for drainage of CSDH offers best results. METHODS: We set up a multicenter prospective randomized trial (Comparison of Chronic Subdural Hematoma Treatment [COMPACT] trial) comparing BHC, MC, and TDC for the surgical treatment of CSDH. The primary end point was reoperation rate, and secondary end points included complication rates and clinical outcome. Patients were considered to have good outcome when they did not undergo reoperation, suffered no surgical or medical complication, and had no related mortality. Clinical outcome was also evaluated by evolution of the Markwalder score and the modified Rankin score. RESULTS: Two-hundred forty-five patients were included in the final analysis: 79 BHC, 84 MC, and 82 TDC. Mean duration of surgery was shorter for TDC than for BHC and MC (P < .001). Reoperation rate was 7.6% for BHC, 13.1% for MC, and 19.5% for TDC (P = .07). This trend toward better results for BHC was not statistically significant in logistic regression analysis. The proportion of patients with good outcome was 78.5% for BHC group, 76.2% for MC, and 69.5% for TDC (P = .4). Evolution of the Markwalder score and modified Rankin score were not significantly different between treatment groups. CONCLUSION: All 3 techniques are effective at treating patients with CSDH with eventual 6-month outcome being similar. Although not reaching statistical significance in our study, BHC offers the lowest recurrence rate combined with manageable complication rate.

Randomized Trial Comparing Burr Hole Craniostomy, Minicraniotomy, and Twist Drill Craniostomy for Treatment of Chronic Subdural Hematoma

Outcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience over 20 Years.

Granulomatous Reaction on a Double-Level Cervical Total Disc Arthroplasty.

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Papers

Randomized Trial Comparing Burr Hole Craniostomy, Minicraniotomy, and Twist Drill Craniostomy for Treatment of Chronic Subdural Hematoma

Outcome of Transsphenoidal Surgery for Cushing Disease: A Single-Center Experience over 20 Years.

Granulomatous Reaction on a Double-Level Cervical Total Disc Arthroplasty.