Accuracy of Laboratory Tests for the Diagnosis of Cushing Syndrome

2020 ◽  
Vol 105 (6) ◽  
pp. 2081-2094 ◽  
Author(s):  
Brandon P Galm ◽  
Nidan Qiao ◽  
Anne Klibanski ◽  
Beverly M K Biller ◽  
Nicholas A Tritos

Abstract Context The diagnosis of Cushing syndrome (CS) can be challenging. It remains to be determined which diagnostic tests are the most accurate. Objective To summarize the accuracy of diagnostic tests for CS using contemporary meta-analytic techniques (hierarchical models). Data Sources PubMed, Embase, Scopus, Web of Science, and the Cochrane Database of Systemic Reviews (inception until August 3, 2018). Study Selection Studies performed in adults that determined the accuracy of one or more diagnostic tests: overnight 1-mg dexamethasone suppression test (DST), 2-day low-dose DST (2d DST), 24-hour urinary free cortisol (UFC), late-night salivary cortisol (LNSC), midnight serum cortisol (MSC), and the dexamethasone-suppressed CRH (dex-CRH) and desmopressin (dex-DDAVP) tests. Data Extraction Two authors independently extracted data and performed methodological assessments. Data Synthesis One hundred thirty-nine studies (14 140 participants) were included in the analysis. The respective sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio (95% confidence interval [CI]) estimates include the following: DST 98.6% (96.9%-99.4%), 90.6% (86.4%-93.6%), 10.5 (7.2-15.3), and 0.016 (0.007-0.035); 2d DST 95.3% (91.3%-97.5%), 92.8% (85.7%-96.5%), 13.2 (6.47-27.1), and 0.051 (0.027-0.095); UFC 94.0% (91.6%-95.7%), 93.0% (89.0%-95.5%), 13.3 (8.47-21.0), and 0.065 (0.046-0.092); LNSC 95.8% (93.%-97.2%), 93.4% (90.7%-95.4%), 14.6 (10.3-20.7), and 0.045 (0.030-0.066); MSC 96.1% (93.5%-97.6%), 93.2% (88.1%-96.3%), 14.2 (7.96-25.2), and 0.042 (0.026-0.069); and dex-CRH 98.6% (90.4%-99.8%), 85.9% (67.6%-94.7%), 7.0 (2.80-17.6), and 0.016 (0.002-0.118). A single study evaluated dex-DDAVP. Meta-regression and a novel network meta-analytic approach suggest that DST is the most sensitive while UFC is the least sensitive. Conclusions All of the included diagnostic tests for CS are highly sensitive and specific. It appears that the DST is the most sensitive while the UFC is less sensitive. The specificity of all first-line tests appears comparable.

2016 ◽  
Vol 34 (7) ◽  
pp. 476-484 ◽  
Author(s):  
Charlotte Dewdney ◽  
Margaret MacDougall ◽  
Rachel Blackburn ◽  
Gavin Lloyd ◽  
Alasdair Gray

IntroductionProcedural sedation and analgesia (PSA) is commonplace in the ED. Previous studies have identified capnography as a reliable indicator of PSA-induced respiratory depression. This review investigates the potential effect on patient safety of the use of capnography in addition to standard monitoring for adult patients undergoing PSA in the ED.MethodsMEDLINE, Embase, Scopus, CINAHL and Google Scholar were searched systematically for ED studies using capnography during PSA. Data extraction was performed by two independent authors. Using MedCalc V.13.3.3 and Meta-DiSc V.1.4, data were aggregated under the random-effects model and heterogeneity was assessed using Cochran's Q-test and the I2 statistic.ResultsOf the 737 studies that were screened, 7 studies met the eligibility criteria, representing a total of 662 patients. The aggregate diagnostic accuracy for capnography identifying an adverse event included a diagnostic OR of approximately 6 (OR: 5.87; 95% CI 2.41 to 14.3; p<0.001), sensitivity 0.82 (95% CI 0.76 to 0.87), specificity 0.6 (95% CI 0.55 to 0.64), negative likelihood ratio 0.3 (95% CI 0.12 to 0.75) and positive likelihood ratio 1.89 (95% CI 1.53 to 2.34). There was a lack of statistical evidence for a difference in the proportion of adverse events detected when capnography was used in addition to standard monitoring (48.8% (95% CI 32.85 to 64.92)) compared with chance alone (50%).ConclusionsThere is no firm evidence that capnography provides additional safety compared with standard monitoring alone during PSA in adults in the ED. There is a paucity of published research involving preoxygenated patients who remain on high-flow oxygen throughout PSA. Well-powered randomised controlled trials, employing an accepted adverse event reporting tool in such patients, are required. Until then, we advocate continued compliance with current professional recommendations for the use of capnography during PSA in adults in the ED.


Author(s):  
Deepak Dhamnetiya ◽  
Ravi Prakash Jha ◽  
Shalini Shalini ◽  
Krittika Bhattacharyya

AbstractDiagnostic tests are pivotal in modern medicine due to their applications in statistical decision-making regarding confirming or ruling out the presence of a disease in patients. In this regard, sensitivity and specificity are two most important and widely utilized components that measure the inherent validity of a diagnostic test for dichotomous outcomes against a gold standard test. Other diagnostic indices like positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, accuracy of a diagnostic test, and the effect of prevalence on various diagnostic indices have also been discussed. We have tried to present the performance of a classification model at all classification thresholds by reviewing the receiver operating characteristic (ROC) curve and the depiction of the tradeoff between sensitivity and (1–specificity) across a series of cutoff points when the diagnostic test is on a continuous scale. The area under the ROC (AUROC) and comparison of AUROCs of different tests have also been discussed. Reliability of a test is defined in terms of the repeatability of the test such that the test gives consistent results when repeated more than once on the same individual or material, under the same conditions. In this article, we have presented the calculation of kappa coefficient, which is the simplest way of finding the agreement between two observers by calculating the overall percentage of agreement. When the prevalence of disease in the population is low, prospective study becomes increasingly difficult to handle through the conventional design. Hence, we chose to describe three more designs along with the conventional one and presented the sensitivity and specificity calculations for those designs. We tried to offer some guidance in choosing the best possible design among these four designs, depending on a number of factors. The ultimate aim of this article is to provide the basic conceptual framework and interpretation of various diagnostic test indices, ROC analysis, comparison of diagnostic accuracy of different tests, and the reliability of a test so that the clinicians can use it effectively. Several R packages, as mentioned in this article, can prove handy during quantitative synthesis of clinical data related to diagnostic tests.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A128-A128
Author(s):  
Daniela Salazar ◽  
Cláudia Fernandes Costa ◽  
Joana Oliveira ◽  
Liliana Violante ◽  
Ana Luísa Cunha ◽  
...  

Abstract Background: Cushing syndrome due to ectopic CRH or ACTH secretion can be rarely caused by pheochromocytoma, commonly as part of genetic conditions. Case: A 21 year-old male, previously healthy, with no usual medication, went to the physician assistant for hematuria. The kidney US revealed, besides lithiasis, a highly vascularized mass in the right adrenal gland with 10 cm. In his first evaluation the patient had no complaints or pheochromocitoma/hypercortisolism stigmata, other than hand tremor and slight rounding of the face. Blood pressure was 149/88 mmHg, and heart rate 86 bpm. There was no family history of endocrine disease. He rapidly developed increased appetite, insomnia, and severe myalgias, with filling of supraclavicular fossae, facial plethora, and cervical and truncal acne. Laboratory analysis showed abnormal overnight dexamethasone suppression test (57.4 µg/dL, N &lt; 1.8), elevated ACTH 378 pg/mL (N 9.0–52.0), 24h-urinary free cortisol (UFC) (5334.0 µg/24h, N 4.3–176.0), and late-night salivar cortisol (1.44 µg/dL, N &lt; 0.32), hypokalemia (2.8 mEq/L, N 3.8–5.0), and leukocytosis (22.4*109/L, N 4.0–11.0); DHEA-S 962 µg/dL (N 80–560), 4-androstenedione 380 ng/dL (N 70–360), 17-OH progesterone 4.5 ng/mL (N 0.59–3.44), cromogranine A 6063 ng/mL (N 0–100), and markedly elevated urinary amines (adrenaline 173 nmol/24h, N 0–109; noradrenaline 5033 nmol/24h, N 89–473; normetanephrine 334605 nmol/24h, N 480–2424; metanephrine 15998 nmol/24h, N 264–1729; dopamine 4808 nmol/24h, N 424–2612). Hypercalcemia with hypophosphatemia and supressed PTH level was also detected. 68Ga-DOTANOC PET revealed a mass of the right adrenal gland with overexpression of somatostatin receptors (likely pheochromocytoma), without evidence of other tumor lesions of neuroendocrine origin. Pituitary MRI showed normal pituitary gland. Potassium supplementation, alpha-blockade with phenoxybenzamine, and metyrapone were initiated. Due to severe back pain, a CT scan of the spine was performed detecting compressive osteoporotic fractures in the mid dorsal and low dorsal segments. The patient was submitted to right adrenalectomy. Histology revealed pheochromocytoma with 11.2*9mm, with capsular and vascular invasion, extra-adrenal extension, necrosis, and atypical mitosis, with Ki67 of 9.5% and PASS score of 16. Postoperative analysis showed ACTH 45.6 pg/mL (N 7.2-63,3), late-night salivar cortisol &lt; 0,0544 µg/dL (N &lt; 0,32) and free urinary cortisol 41.4 µg/24h (N 4.3–176.0). Discussion: Ectopic cushing syndrome caused by pheochromocytoma is a rarely described entity. In this young patient, it caused rapid clinical progression of hypercortisolism with important hydroelectrolytic disturbances and compressive vertebral fractures, requiring prompt surgical intervention for clinical remission and improvement.


2017 ◽  
Vol 176 (5) ◽  
pp. 613-624 ◽  
Author(s):  
Elena Valassi ◽  
Holger Franz ◽  
Thierry Brue ◽  
Richard A Feelders ◽  
Romana Netea-Maier ◽  
...  

Objective To evaluate which tests are performed to diagnose hypercortisolism in patients included in the European Registry on Cushing’s syndrome (ERCUSYN), and to examine if their use differs from the current guidelines. Patients and methods We analyzed data on the diagnostic tests performed in 1341 patients with Cushing’s syndrome (CS) who have been entered into the ERCUSYN database between January 1, 2000 and January 31, 2016 from 57 centers in 26 European countries. Sixty-seven percent had pituitary-dependent CS (PIT-CS), 24% had adrenal-dependent CS (ADR-CS), 6% had CS from an ectopic source (ECT-CS) and 3% were classified as having CS from other causes (OTH-CS). Results Of the first-line tests, urinary free cortisol (UFC) test was performed in 78% of patients, overnight 1 mg dexamethasone suppression test (DST) in 60% and late-night salivary cortisol (LSaC) in 25%. Use of LSaC increased in the last five years as compared with previous years (P < 0.01). Use of HDDST was slightly more frequent in the last 5 years as compared with previous years (P < 0.05). Of the additional tests, late-night serum cortisol (LSeC) was measured in 62% and 48-h 2 mg/day low-dose dexamethasone suppression test (LDDST) in 33% of cases. ACTH was performed in 78% of patients. LSeC and overnight 1 mg DST supported the diagnosis of both PIT-CS and ADR-CS more frequently than UFC (P < 0.05). Conclusions Use of diagnostic tests for CS varies across Europe and partly differs from the currently available guidelines. It would seem pertinent that a European consensus be established to determine the best diagnostic approach to CS, taking into account specific inter-country differences with regard to the availability of diagnostic tools.


2020 ◽  
Vol 14 ◽  
pp. 175346662098186
Author(s):  
Li Xu ◽  
Minhan Yi ◽  
Yun Tan ◽  
Zixun Yi ◽  
Yuan Zhang

Background: It is unclear whether microRNAs could be a potential diagnostic biomarker for asthma or not. The objective of this study is to figure out the diagnostic value of microRNAs in asthma. Methods: Literature retrieval, screening of publications, specific data extraction, and quality evaluation were conducted according to the standard criteria. Stata 14.0 software was used to analyze the diagnostic value of microRNA for asthma, including the combined sensitivity (Sen), specificity (Spe), the area under the curve (AUC), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Results: A total of 72 studies, containing 4143 cases and 2188 controls, were included for this comprehensive analysis. None of the included publications were rated low in quality. We summarized that, compared with controls, more than 100 miRNAs were reported differently expressed in asthma, although the expression trends were inconsistent. Besides, there were five studies among these 72 articles that applied the diagnostic evaluation of microRNAs in asthma. We found that the pooled Sen, Spe, and AUC for the combination of miR-185-5p, miR-155, let-7a, miR-21, miR-320a, miR-1246, miR-144-5p, and miR-1165-3p in asthma were 0.87 (95%CI: 0.72–0.95), 0.84 (95%CI: 0.74–0.91), and 0.93 (95%CI: 0.89–0.94) individually, and the PLR, NLR, and DOR were 5.5 (95%CI: 3.1–9.7), 0.15 (95%CI: 0.07–0.36), and 35 (95%CI: 10–127) in asthma, respectively. In terms of subgroup analyses, we found that the Sen for these combination miRNAs from serum was higher than that in plasma, while the Spe in plasma worked better than that in serum. Furthermore, compared with children, the combination of above miRNAs from adults had higher Spe and similar Sen. Conclusions: From our analysis, the combination of miR-185-5p, miR-155, let-7a, miR-21, miR-320a, miR-1246, miR-144-5p, and miR-1165-3p from peripheral blood could potentially act as a diagnostic biomarker for asthma. The reviews of this paper are available via the supplemental material section.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Elizabeth H. G. Turner ◽  
Mc Daniel H. Lang ◽  
Andrea M. Spiker

AbstractWhile septic arthritis can be a straightforward diagnosis, there are many cases when the diagnosis is difficult to make. The aim of this study was to review the last decade’s literature on the diagnosis of septic arthritis of the native joint in adults and summarize that data in an easy to follow algorithm to clarify how the last decade’s data may be applied to the diagnosis of septic arthritis. A search of PubMed and CINAHL databases was performed to identify studies that compared results diagnostic tests for septic arthritis. We cross referenced this search with searches of additional databases (including Cochrane Library and Scopus) to confirm similar search results. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool was used by two independent reviewers to determine study quality and risk of bias. After applying inclusion and exclusion criteria to the initial search, 15 papers total were included for analysis. All 15 papers were of high quality methodology as determined by the QUADAS tool. There were 26 different diagnostics tests used across the 15 papers included for review. Three of those diagnostic tests had specificity and sensitivity greater than 80%. Eight tests had a positive likelihood ratio of ≥10. Three tests had a negative likelihood ratio < 0.1, indicating that they may help to rule out septic arthritis. A flowchart was created to summarize the findings of our review, so that physicians may reference this visual in making the appropriate diagnosis when the commonly held standards of cell count, gram stain, and culture aren’t enough to make the diagnosis.


2021 ◽  
Vol 20 ◽  
pp. 153303382110119
Author(s):  
Wen-Ting Zhang ◽  
Guo-Xun Zhang ◽  
Shuai-Shuai Gao

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Bo Zhang ◽  
Bingjie Zhang ◽  
Zhulin Zhou ◽  
Yutong Guo ◽  
Dan Wang

AbstractObjectiveGlycosylated hemoglobin (HbA1c) has obvious clinical value in the diagnosis of diabetes, but the conclusions on the diagnostic value of diabetic retinopathy (DR) are not consistent. This study aims to comprehensively evaluate the accuracy of glycosylated hemoglobin in the diagnosis of diabetic retinopathy through the meta-analysis of diagnostic tests.MethodsCochrane Library, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), China Wanfang Database, Chinese Biomedical Literature Database (CBM) were searched until November, 2020. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was used to assess the quality of the included studies. The pooled sensitivity, specificity, positive likelihood ratio (+LR), negative likelihood ratio (-LR), diagnostic odds ratio (DOR) and areas under the receiver operating characteristic (ROC) curve were calculated by Stata 15.0 software.ResultsAfter screening, 18 high-quality papers were included. The results of meta-analysis showed that the combined DOR = 18.19 (95% CI: 10.99–30.11), the sensitivity= 0.81 (95% CI): 0.75 ~ 0.87), specificity = 0.81 (95%CI: 0.72 ~ 0.87), +LR = 4.2 (95%CI: 2.95 ~ 6.00), −LR = 0.23 (95%CI: 0.17 ~ 0.31), and the area under the Summary ROC curve was 0.88 (95%CI:  0.85 ~ 0.90).ConclusionThe overall accuracy of HbA1cC forin diagnosing diabetic retinopathy is good. As it is more stable than blood sugar and is not affected by meals, it may be a suitable indicator for diabetic retinopathy.


2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199296
Author(s):  
Juan Wang ◽  
Liu Yang ◽  
Yanjun Diao ◽  
Jiayun Liu ◽  
Jinjie Li ◽  
...  

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.


BMJ Open ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. e038088
Author(s):  
Jacky Tu ◽  
Peter Gowdie ◽  
Julian Cassar ◽  
Simon Craig

BackgroundSeptic arthritis is an uncommon but potentially significant diagnosis to be considered when a child presents to the emergency department (ED) with non-traumatic limp. Our objective was to determine the diagnostic accuracy of clinical findings (history and examination) and investigation results (pathology tests and imaging) for the diagnosis of septic arthritis among children presenting with acute non-traumatic limp to the ED.MethodsSystematic review of the literature published between 1966 and June 2019 on MEDLINE and EMBASE databases. Studies were included if they evaluated children presenting with lower limb complaints and evaluated diagnostic performance of items from history, physical examination, laboratory testing or radiological examination. Data were independently extracted by two authors, and quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool.Results18 studies were identified, and included 2672 children (560 with a final diagnosis of septic arthritis). There was substantial heterogeneity in inclusion criteria, study setting, definitions of specific variables and the gold standard used to confirm septic arthritis. Clinical and investigation findings were reported using varying definitions and cut-offs, and applied to differing study populations. Spectrum bias and poor-to-moderate study design quality limit their applicability to the ED setting.Single studies suggest that the presence of joint tenderness (n=189; positive likelihood ratio 11.4 (95% CI 5.9 to 22.0); negative likelihood ratio 0.2 (95% CI 0.0 to 1.2)) and joint effusion on ultrasound (n=127; positive likelihood ratio 8.4 (95% CI 4.1 to 17.1); negative likelihood ratio 0.2 (95% CI 0.1 to 0.3)) appear to be useful. Two promising clinical risk prediction tools were identified, however, their performance was notably lower when tested in external validation studies.DiscussionDifferentiating children with septic arthritis from non-emergent disorders of non-traumatic limp remains a key diagnostic challenge for emergency physicians. There is a need for prospectively derived and validated ED-based clinical risk prediction tools.


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