Relacorilant or surgery improved hemostatic markers in Cushing syndrome.

PURPOSE: Glucocorticoid-mediated hypercoagulability can persist in patients with endogenous Cushing syndrome (CS) after curative surgery and may transiently worsen early postoperatively. These studies aimed to characterize coagulation markers at baseline in patients with CS and the impact of relacorilant or remission post-surgery in an open-label, phase 2 study (NCT02804750) and a retrospective, longitudinal, surgical cohort study. METHODS: In the relacorilant study, 34 patients received relacorilant (100-200 mg/day for up to 12 weeks or 250-400 mg/day for up to 16 weeks) and had postbaseline data. Coagulation markers were assessed before and during treatment. In the surgical study, conducted at "Federico II" University of Naples, Italy, coagulation markers were assessed in 30 patients before surgery and after biochemical remission. RESULTS: In the relacorilant study, significant mean changes from baseline to last observed visit were reported in factor VIII (- 18.9%, P = 0.022), activated partial thromboplastin time (aPTT) (+ 1.5 s, P = 0.046), and platelet count (- 68.8*109/L, P < 0.0001), whereas von Willebrand factor was unchanged. In the surgical study, the mean time to hemostasis assessment was 6.2 months. Significant mean changes from baseline to hemostasis assessment were reported in factor VIII (- 24.2%, P = 0.044), von Willebrand factor (- 20.6%, P = 0.018), and aPTT (+ 2.0 s, P = 0.031), whereas platelet count was unchanged. CONCLUSIONS: Several coagulation markers improved in patients with CS after 3-4 months of relacorilant treatment and within an average of 6 months after surgery. Relacorilant's positive effects on coagulation markers support further investigation of its use preoperatively in patients with CS or in patients who are not eligible for surgery. CLINICAL TRIAL REGISTRATION NUMBER: NCT0280475 (registration date: 15 June 2016).

Corticotropin hormone assay interference: A case series.

Measuring the plasma corticotropin (ACTH) concentration is an important step in determining the underlying cause in patients with hypercortisolemia. Interfering substances in immunoassays can lead to erroneous results impacting clinical management. We describe a case series of 12 patients, the majority of whom were being investigated for possible Cushing's syndrome and in whom inconsistencies between the clinical picture and biochemical testing raised concerns of assay interference. ACTH assay interference resulted in falsely elevated ACTH concentrations using the Siemens Immulite assay and consequently led to additional unnecessary testing. Communication between physician and laboratory as well as appropriate investigation (including sample dilution, use of blocking antibodies and testing on an alternate platform) resulted in assay interference identification. Recognition of biochemical results which are clinically discrepant remains an essential step in patient assessment.

Long-term metabolic risk for the metabolically healthy overweight/obese phenotype.

BACKGROUND/OBJECTIVES: The clinical relevance of the metabolically healthy overweight/obese (MHO) phenotype is controversial and the relationships between weight change and the development of cardiometabolic risk factors is unknown. Therefore, we aim to: (1) Assess the long-term risk of developing one or more components of the metabolic syndrome in MHO adults compared with metabolically healthy normal weight (MHNW); (2) Evaluate risk of a composite of death, cardiovascular disease (CVD), and risk of developing type 2 diabetes between adults defined according to baseline body mass index and metabolic health. SUBJECTS/METHODS: Retrospective cohort study of adults 18-65 years of age seen at our institution between 1998 and 2000 who lived in Olmsted County. Metabolically healthy was defined as the absence of all components of the metabolic syndrome (except for waist circumference). Main outcome was the development of metabolic risk factors. The secondary outcome was a composite of mortality, CVD and heart failure. RESULTS: Of the 18 070 individuals with complete data at baseline, 1805 (10%) were MHO (mean age 38±11 years) and 3047 were MHNW (mean age 35±11 years). After a median follow-up of 15 years, interquartile range 10-17, 80% of MHO vs 68% of MHNW developed at least one cardiometabolic risk factor (P<0.001). In multivariate analysis, MHO individuals who gained ⩾10% of their body weight were more likely to have developed metabolic complications compared to MHO individuals that did not gain weight (P=0.001 for 10-15%, P<0.001 for >15% weight gain). The risk for the secondary composite end point was similar between MHO and MHNW, number of events 218/1805 vs 217/3048 for MHO and MHNW, respectively, (hazard ratio: 1.16, 95% confidence interval: 0.96-1.40). CONCLUSIONS: MHO are more likely to develop metabolic complications than MHNW, especially if they gain weight.

Long-term outcomes in patients with multiple endocrine neoplasia type 1 and pancreaticoduodenal neuroendocrine tumours.

BACKGROUND: In patients with multiple endocrine neoplasia type 1 (MEN-1), pancreaticoduodenal (PD) neuroendocrine tumours (NETs) are associated with early mortality, yet the best treatment strategy remains uncertain. AIM: To assess patient important outcomes (mortality and metastasis) of PD-NETs and predictors of outcomes in patients with MEN-1. METHODS: Retrospective cohort of patients with MEN-1 who attended the Mayo Clinic, Rochester, MN from 1997 to 2014. RESULTS: We identified 287 patients with MEN-1; 199 (69%) patients had 217 PD-NETs. Among those with a PD-NETs, 129 (65%) had surgery of which 90 (70%) had their primary surgery performed at Mayo Clinic. The median postoperative follow-up was 8 years during which 13 (14%) patients died. The mean (±standard deviation) age of death was 51 (±9) years. Tumour size, metastasis at surgery or tumour type were not predictive of mortality, but for every year older at surgery, the odds of metastasis increased by 6%. Surgery was not performed in 70 (35%) patients. Among those who were observed/medically managed without known metastatic disease, mean tumour growth was 0·02 cm/year (range, -0·13-0·4 cm/year). Four patients (7%) died at a median age of 77 (range, 51-89) years. CONCLUSION: PD-NETs are common in patients with MEN-1 and are associated with early mortality even after surgical intervention. Active surveillance is a viable option in nonaggressive PD-NETs, although definitive factors identifying such patients are lacking. Therefore, counselling regarding risks and benefits of current treatment options remains integral to the care of patients with MEN-1.

Management of parenteral nutrition associated hyperglycaemia: a comparison of subcutaneous and intravenous insulin regimen.

PN is associated with significant hyperglycaemia, which may be detrimental to clinical outcome. There are few data on the management of this phenomenon outside of intensive care units. In our unit, we studied the efficacy of protocol-based intravenous insulin delivery as compared to subcutaneous insulin prescribed individually outside of the critical care setting. In a retrospective review over a two-year period, we compared patients with PN-associated hyperglycaemia who had received both modes of insulin therapy. A total of 122 who developed PN-associated hyperglycaemia were identified. Those on the intravenous insulin regimen were within glycaemic target for more time than those on the subcutaneous regimen (62% Vs 43%, p = 0.008). We therefore conclude that outside of the critical care setting, intravenous insulin delivers better glycaemic control and should therefore be considered optimum therapy for patients with PN-associated hyperglycaemia.

Intra-operative quality assessment of coronary artery bypass grafts.

Early coronary artery bypass graft (CABG) failure is a troubling complication that may result in a wide range of problems, including refractory angina, myocardial infarction, low cardiac output, arrhythmia, and fatal heart failure. Early graft failures are related to poor quality and size of the distal native vascular bed, coagulation abnormalities, or technical problems involving the graft conduits and anastomoses. Unfortunately, graft failure is difficult to detect during surgery by visual assessment, palpation, or conventional monitoring. We evaluated the accuracy and utility of a transit-time, ultrasonic flow measurement system for measurement of CABGs. There were no differences between transit-time measurements and volumetric-time collected samples in an in vitro circuit over a range of flows from 10 to 100ml/min (Bland and Altman Plot, 1.96 SD). Two hundred and ninety-eight CABGs were examined in 125 patients. Graft flow rate was proportional to the target vessel diameter. Nine technical errors were detected and corrected. Flow waveform morphology provided valuable information related to the quality of the anastamosis, which led to the immediate correction of technical problems at the time of surgery.