Accuracy of Laboratory Tests for the Diagnosis of Cushing Syndrome.

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.

MRI texture analysis in acromegaly and its role in predicting response to somatostatin receptor ligands.

PURPOSE: Given the paucity of reliable predictors of tumor recurrence, progression, or response to somatostatin receptor ligand (SRL) therapy in acromegaly, we attempted to determine whether preoperative MR image texture was predictive of these clinical outcomes. We also determined whether image texture could differentiate somatotroph adenomas from non-functioning pituitary adenomas (NFPAs). METHODS: We performed a retrospective study of patients with acromegaly due to a macroadenoma who underwent transsphenoidal surgery at our institution between 2007 and 2015. Clinical data were extracted from electronic medical records. MRI texture analysis was performed on preoperative non-enhanced T1-weighted images using ImageJ (NIH). Logistic and Cox models were used to determine if image texture parameters predicted outcomes. RESULTS: Eighty-nine patients had texture parameters measured, which were compared to that of NFPAs, while 64 of these patients had follow-up and were included in the remainder of analyses. Minimum pixel intensity, skewness, and kurtosis were significantly different in somatotroph adenomas versus NFPAs (area under the receiver operating characteristic curve, 0.7771, for kurtosis). Furthermore, those with a maximum pixel intensity above the median had an increased odds of IGF-I normalization on SRL therapy (OR 5.96, 95% CI 1.33-26.66), which persisted after adjusting for several potential predictors of response. Image texture did not predict tumor recurrence or progression. CONCLUSION: Our data suggest that MRI texture analysis can distinguish NFPAs from somatotroph macroadenomas with good diagnostic accuracy and can predict normalization of IGF-I with SRL therapy.

Acute Management of Diabetic Ketoacidosis in Adults at 3 Teaching Hospitals in Canada: A Multicentre, Retrospective Cohort Study.

OBJECTIVES: Diabetic ketoacidosis (DKA) is a common acute complication of diabetes mellitus and is associated with significant morbidity and mortality. There is currently a paucity of data concerning the Canadian experience with DKA. We aimed to characterize the acute management and course of DKA at several Canadian hospitals. METHODS: We performed a retrospective cohort study of patients admitted to 3 teaching hospitals in Edmonton, Canada. We extracted clinical and laboratory data from the medical charts of patients admitted to general internal medicine wards or intensive care units with moderate or severe DKA. RESULTS: We included 103 admissions (84 patients) in our study. The majority (68.9%) had type 1 diabetes and presented with severe DKA (60.2%). In the first 24 h, the median (interquartile range) intravenous fluid received was 7.0 (5.5 to 8.8) litres; 23.3% received a priming insulin bolus, 24.3% received bicarbonate and 91.3% received potassium. Hypoglycemia was relatively rare (5.8%), but hypokalemia was common (41.7%). The median time to anion gap ≤12 mmol/L was 8.8 (6.0 to 12.3) h. In 27.1% of cases, intravenous insulin was stopped prior to subcutaneous insulin administration, with a median of 95 (30 to 310) min elapsing before subcutaneous insulin was given. DKA-related mortality was 2.9%. CONCLUSIONS: The acute management of DKA was generally aligned with clinical guidelines. Areas for improvement include preventing hypokalemia by proactively increasing potassium repletion, reducing initial insulin boluses, administering subcutaneous insulin before stopping intravenous insulin and administering sodium bicarbonate judiciously. Protocols and preprinted order sets may be helpful, especially in smaller centres.

MRI texture analysis as a predictor of tumor recurrence or progression in patients with clinically non-functioning pituitary adenomas.

BACKGROUND: There are limited predictors of prognosis in patients with clinically non-functioning pituitary adenomas (NFPAs). We hypothesized that MRI texture analysis may predict tumor recurrence or progression in patients with NFPAs undergoing transsphenoidal pituitary surgery (TSS). OBJECTIVE: To characterize texture parameters on preoperative MRI examinations in patients with NFPAs in relation to prognosis. METHODS: Retrospective study of patients with NFPAs who underwent TSS at our institution between 2009 and 2010. Clinical, radiological and histopathological data were extracted from electronic medical records. MRI texture analysis was performed on coronal T1-weighted non-enhanced MR images using ImageJ (NIH). MRI texture parameters were used to predict tumor recurrence or progression. Both logistic regression and Cox proportional hazard analyses were conducted to adjust for potential confounders. RESULTS: Data on 78 patients were analyzed. On both crude and multivariable-adjusted analyses, mean, median, mode, minimum and maximum pixel intensity were associated with the risk of pituitary tumor recurrence or progression after TSS. Patients whose tumor mean pixel intensity was above the median for the population had a hazard ratio of 0.44 (95% CI: 0.21-0.94, P = 0.034) for recurrence or progression in comparison with tumors below the median. CONCLUSIONS: Our data suggest that MRI texture analysis can predict the risk of tumor recurrence or progression in patients with NFPAs.

Blood pressure lowering efficacy of alpha blockers for primary hypertension.

BACKGROUND: Alpha blockers are occasionally prescribed for hypertension so it is important to determine and compare their effects on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAE). OBJECTIVES: To quantify the dose-related systolic and/or diastolic BP lowering efficacy of alpha blockers versus placebo in the treatment of primary hypertension. SEARCH METHODS: For the updated review, we searched CENTRAL (The Cochrane Library 2012, Issue 4), MEDLINE (1946 to May 2012), EMBASE (1980 to May 2012) and reference lists of articles. SELECTION CRITERIA: Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of fixed-dose monotherapy with an alpha blocker compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was collected from the trials. MAIN RESULTS: Only 10 trials evaluated the dose-related trough BP lowering efficacy of 4 different alpha blockers in 1175 participants with a baseline BP of 155/101 mm Hg. The data do not suggest that any one alpha blocker is better or worse at lowering BP. The best but unsatisfactory estimate of the trough BP lowering efficacy for alpha blockers is -8/-5 mmHg. AUTHORS' CONCLUSIONS: Based on the limited number of published RCTs, the BP lowering effect of alpha blockers is modest; the estimate of the magnitude of trough BP lowering of -8/-5 mmHg is likely an overestimate. There are no clinically meaningful BP lowering differences between different alpha blockers. The review did not provide a good estimate of the incidence of harms associated with alpha blockers because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.

Blood pressure lowering efficacy of alpha blockers for primary hypertension.

BACKGROUND: Alpha blockers are occasionally prescribed for hypertension so it is important to determine and compare their effects on blood pressure (BP), heart rate and withdrawals due to adverse effects (WDAE). OBJECTIVES: To quantify the dose-related systolic and/or diastolic BP lowering efficacy of alpha blockers versus placebo in the treatment of primary hypertension. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library 2009, Issue 1), MEDLINE (1950 to April 2009), EMBASE (1980 to April 2009) and reference lists of articles. SELECTION CRITERIA: Double-blind, randomized, controlled trials evaluating the BP lowering efficacy of fixed-dose monotherapy with an alpha blocker compared with placebo for a duration of 3 to 12 weeks in patients with primary hypertension. DATA COLLECTION AND ANALYSIS: Two authors independently assessed the risk of bias and extracted data. Study authors were contacted for additional information. WDAE information was collected from the trials. MAIN RESULTS: Only 10 trials evaluated the dose-related trough BP lowering efficacy of 4 different alpha blockers in 1175 participants with a baseline BP of 155/101 mm Hg. The data do not suggest that any one alpha blocker is better or worse at lowering BP. The best but unsatisfactory estimate of the trough BP lowering efficacy for alpha blockers is -8/-5 mmHg. AUTHORS' CONCLUSIONS: Based on the limited number of published RCTs, the BP lowering effect of alpha blockers is modest; the estimate of the magnitude of trough BP lowering of -8/-5 mmHg is likely an overestimate. There are no clinically meaningful BP lowering differences between different alpha blockers. The review did not provide a good estimate of the incidence of harms associated with alpha blockers because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.