Using an evidence-based approach, this guideline addresses important clinical issues regarding the evaluation and management of hypopituitarism in adults, including appropriate biochemical assessments, specific therapeutic decisions to decrease the risk of co-morbidities due to hormonal over-replacement or under-replacement, and managing hypopituitarism during pregnancy, pituitary surgery, and other types of surgeries.
Objectives
To determine the 99th percentile upper reference limit for the highly sensitive cardiac troponin T assay (hs-cTnT) in three large independent cohorts.
Background
The presently recommended 14 ng/L cutpoint for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization.
Methods
Data were included from three well characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease and kidney disease (subcohort 1) and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex and race.
Results
The 99th percentile values for the hs-cTnT assay in DHS, ARIC and CHS were 18, 22 and 36 ng/L respectively (subcohort 1) and 14, 21 and 28 ng/L respectively (subcohort 2). These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men aged 65–74 with no cardiovascular disease in our study had cTnT values above the current myocardial infarction threshold.
Conclusions
Use of a uniform 14 ng/L cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay.
Metabolic and inflammatory responses and changes in fatigue were studied in groups of patients undergoing either laparoscopic (n = 14) or open (n = 10) elective cholecystectomy. The mean(s.e.m.) cortisol concentration was significantly (P < 0.001) increased from 342(80) and 424(91) nmol l-1 before operation to 895(46) and 966(53) nmol l-1 after surgery in patients undergoing laparoscopic and open cholecystectomy respectively. There was no difference in cortisol response between the groups. Glucose concentration was increased (P < 0.02) at the end of surgery from mean(s.e.m.) preoperative levels of 5.54(0.15) and 6.16(0.15) mmol l-1 to postoperative values of 7.46(0.29) and 8.46(0.86) mmol l-1 for the laparoscopic and open procedures respectively. The mean glucose concentration during the initial 12 h after surgery was significantly greater (P < 0.02) following open than laparoscopic cholecystectomy. The mean(s.e.m.) albumin concentration fell significantly (P < 0.01) during surgery by an equivalent extent from 38.9(0.77) and 38.5(1.10)g l-1 to 35.2(0.79) and 34.6(0.97) g l-1. The mean (95 per cent confidence interval) interleukin (IL)6 concentration peaked 4 h after surgery at 57.2 (44.6-73.4) pg ml-1 following laparoscopic and 99.3 (72.8-135.4) pg ml-1 after open cholecystectomy. Mean (95 per cent confidence interval) C-reactive protein (CRP) levels at 24 h were 17.0 (12.7-21.2) and 49.0 (25.3-93.6) mg l-1 and at 48 h 28.0 (21.4-35.4) and 70.0 (36.4-133.6) mg l-1 following laparoscopic and open operations. The differences in IL-6 and CRP level between the groups were significant (P < 0.01). Mean(s.e.m.) fatigue scores were significantly (P < 0.05) increased from preoperative values of 2.4(0.24) and 2.6(0.44) to 5.5(0.56) and 6.8(0.51) at 24 h after laparoscopic and open operations. At 48 h the mean(s.e.m.) fatigue score (5.6(0.57)) remained significantly (P < 0.05) raised only after open cholecystectomy. Hand grip strength was significantly (P < 0.05) reduced only after the open procedure, to a mean(s.e.m.) of 88(6) per cent of the preoperative value. These results demonstrate that aspects of the metabolic and acute-phase responses are attenuated following laparoscopic cholecystectomy, consistent with a reduction in tissue trauma.
SummaryElectrocution on poorly designed power poles is increasingly shown to pose a threat for the populations of many large raptors. Here we document that a power line in Sudan continues to cause mortality of Egyptian Vultures Neophron percnopterus, a problem that was first identified in 1984. We suggest that this power line may have caused the death of sufficient Egyptian Vultures to partially explain population declines in the Middle East, from where the electrocuted birds may originate. This report highlights the urgent need to plan and retro-fit power lines in Africa with non-lethal support structures.
Circulating levels and role of IL-6, IL-1ra, TNFsr-II and CRP in patients with heatstroke is not fully known. This study correlated levels of these mediators with outcome in 26 patients. In survivors (n=20), IL-6 concentration declined on cooling, whereas in non-survivors levels continued to increase at 6 h following admission before declining. Admission TNFsr-II concentrations in survivors were significantly lower than non-survivors and levels continued to rise in both groups. IL-1ra levels were markedly elevated in both groups. Changes in cytokine levels were not influenced by renal function. Elevated C-reactive protein levels were observed for both groups and remained so despite cooling, furthermore, there was no correlation with alanine aminotransferase levels. The study demonstrated the elevation of the above mediators and suggested a role in the pathogenesis of heatstroke. Markedly elevated levels or those that remained elevated despite cooling were associated with mortality.
Heatstroke is the most severe form of heat-related disorders that include mild heat intolerance, heat exhaustion and heat stress. The incidence of heat-related disorders is increasing due to several factors that include climate change, co-morbidities and drug usage. Patients with heatstroke present with a core body temperature above 408C, multiorgan dysfunction and central nervous system disorder. The pathogenesis of heatstroke is not fully understood; however, heat-shock proteins, inflammatory cytokines and their modulators have been implicated. The clinical biochemistry laboratory plays an important role in the management of patients with heatstroke. Biochemical findings in patients with heatstroke include elevated urea, creatinine, cardiac and skeletal muscle enzymes, myoglobin and troponin. There is also biochemical evidence of metabolic acidosis, respiratory alkalosis, hepatic injury with elevated enzyme levels as well as abnormal hematological and coagulation indices. This review article aims at increasing awareness of the biochemical changes seen in patients with heatstroke and their possible role in prognosis and in elucidating the pathogenesis of heatstroke.
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