Quality of Life in Men With Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is a disorder of adrenal steroid biosynthesis, leading to hypocortisolism, hypoaldosteronism, and hyperandrogenism. Impaired quality of life (QoL) has been demonstrated in women with CAH, but data on men with CAH are scarce. We hypothesized that disease severity and poor treatment control are inversely associated with QoL. In this study, 109 men (16-68 years) with 21OHD were included. The WHOQOL-BREF questionnaire was used to measure self-reported QoL domain scores on a 0-100 scale, where higher scores reflect better QoL. QoL domain scores were compared to published data on healthy and chronically ill reference populations from France, Germany, the Netherlands, and the United Kingdom. Differences in QoL scores among groups of disease severity and treatment control were tested within the study population. Overall, the men with CAH in this study appeared to rate their QoL as good. Median domain scores were 78.6 (IQR: 67.9-85.7) for physical health, 79.2 (IQR: 66.7-87.5) for psychological health, 75.0 (IQR: 58.3-83.3) for social relationships, and 81.3 (IQR: 71.9-90.6) for environment. In general, these scores were similar to WHOQOL-BREF domain scores in healthy references and higher compared to chronically ill reference populations. The domain scores did not differ among genotype groups, but patients with undertreatment or increased 17-hydroxyprogestrone concentrations scored higher on several QoL domains (p<0.05). Patients treated with dexamethasone or prednisone scored higher on the physical health, psychological health, and social relationships domains, but not on the environmental domain. In conclusion, QoL domain scores appeared to be comparable to healthy reference populations and higher compared to patients with a chronic illness. QoL was not influenced by genotype, but undertreatment and use of dexamethasone or prednisone were associated with higher QoL

Intelligence, reason of state and the art of governing risk and opportunity in early modern Europe

Drawing upon primary and secondary historical material, this paper explores the role of intelligence in early modern government. It focuses upon developments in seventeenth- and early-eighteenth-century England, a site-specific genealogical moment in the broader history of state power/knowledges. Addressing a tendency in Foucauldian work to neglect pre-eighteenth-century governance, the analysis reveals a set of interrelated processes which gave rise to an innovative technique for anticipating hazard and opportunity for the state. At the intersection of raison d’État, the evolving art of government, widespread routines of secrecy and a post-Westphalia field of European competition and exchange, intelligence was imagined as a fundamental solution to the concurrent problems of ensuring peace and stability while improving state forces. In the administrative offices of the English Secretary of State, an assemblage of complex and interrelated procedures sought to produce and manipulate information in ways which exposed both possible risks to the state and potential opportunities for expansion and gain. As this suggests, the art of intelligence played an important if largely unacknowledged role in the formation and growth of the early modern state. Ensuring strategic advantage over rivals, intelligence also limited the ability of England's neighbours to dominate trade, control the seas and master the colonies, functioning as a constitutive feature of European balance and equilibrium. As the analysis concludes, understanding intelligence as a form of governmental technique – a way of doing something – reveals an entirely novel way of thinking about and investigating its myriad (historical and contemporary) formations

Natural law, state formation and the foundations of social theory

This article proceeds from the claim that the earliest examples of sociological method were linked by a critique of the theories of natural law proposed in the Enlightenment. It illustrates this point by surveying the rise of social theory in the aftermath of the French Revolution and by examining approaches to natural law in key texts in the history of sociology. However, the article claims that natural law remains a blind spot for sociological method, and the original sociological dismissal of natural law as a formal body of normative postulates has prevented the formation of sociology as a comprehensive system of social interpretation. Using a series of historical examples, the article then argues that natural law theory needs in itself to be viewed sociologically, and, throughout modern history, ius-natural thinking has served not only to establish formal norms for evaluating social and political practices, but also to form the positive preconditions for the evolution of contemporary society in its distinctive differentiated form. The article concludes by arguing that a sociological reconstruction of natural law points the way towards a sociological theory of theory, which has typically proved elusive for sociological methodologies

X chromosome gene dosage as a determinant of congenital malformations and of age-related comorbidity risk in patients with Turner syndrome, from childhood to early adulthood

International audienceObjective Turner Syndrome is associated with several phenotypic conditions associated with a higher risk of subsequent comorbidity. We aimed to evaluate the prevalence of congenital malformations and the occurrence of age-related comorbid conditions and to determine whether the frequencies of congenital and acquired conditions depend on X chromosome gene dosage, as a function of karyotype subgroup. Design and methods This national retrospective observational cohort study includes 1501 patients. We evaluated the prevalence of congenital malformations and the cumulative incidence of subsequent specific comorbidities at five-year intervals, from the ages of 10 to 30 years, with stratification by karyotype subgroup: 45,X (n = 549), 45,X/46,isoXq (n = 280), 46,X,r(X)/46,XX (n = 106), 45,X/46,XX (n = 221), presence of Y (n = 87). Results Median age was 9.4 (3.7-13.7) years at first evaluation and 16.8 (11.2-21.4) years at last evaluation. Congenital heart (18.9%) malformations were more frequent in 45,X patients, and congenital renal (17.2%) malformations were more frequent in 45,X, 45,X/46,isoXq and 46,X,r(X)/46,XX patients than in those with 45,X/46,XX mosaicism or a Y chromosome (P < 0.0001). The cumulative incidence of subsequent acquired conditions, such as thyroid disease, hearing loss, overweight/obesity, dyslipidemia and, to a lesser extent, celiac disease, glucose intolerance/type 2 diabetes, hypertension and liver dysfunction increased with age, but less markedly for patients with mosaicism than for those with other karyotypes. Patients with a ring chromosome were more prone to metabolic disorders. Conclusion These data suggest that X gene chromosome dosage, particularly for Xp genes, contributes to the risk of developing comorbidities

Fasting insulin has a stronger association with an adverse cardiometabolic risk profile than insulin resistance: The RISC study

Objective: Fasting insulin concentrations are often used as a surrogate measure of insulin resistance. We investigated the relative contributions of fasting insulin and insulin resistance to cardiometabolic risk and preclinical atherosclerosis. Design and methods: The Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) cohort consists of 1326 European non-diabetic, overall healthy men and women aged 30-60 years. We performed standard oral glucose tolerance tests and hyperinsulinemic euglycemic clamps. As a general measure of cardiovascular risk, we assessed the prevalence of the metabolic syndrome in 1177 participants. Carotid artery intima media thickness (IMT) was measured by ultrasound to assess preclinical atherosclerosis. Results: Fasting insulin was correlated with all elements of the metabolic syndrome. Insulin sensitivity (M/I) was correlated with most elements. The odds ratio for the metabolic syndrome of those in the highest quartile of fasting insulin compared with those in the lower quartiles was 5.4 (95% confidence interval (CI) 2.8-10.3, adjusted for insulin sensitivity) in men and 5.1 (2.6-9.9) in women. The odds ratio for metabolic syndrome of those with insulin sensitivity in the lowest quartile of the cohort compared with those in the higher quartiles was 2.4 (95% CI 1.3-4.7, adjusted for fasting insulin) in men and 1.6 (0.8-3.1) in women. Carotid IMT was only statistically significantly associated with fasting insulin in both men and women. Conclusions: Fasting insulin, a simple and practical measure, may be a stronger and independent contributor to cardiometabolic risk and atherosclerosis in a healthy population than hyperinsulinemic euglycemic clamp-derived insulin sensitivity. © 2009 European Society of Endocrinology