Commonly used tests to diagnose CS appear highly accurate in referral practices with samples enriched with patients with CS. Their performance in usual clinical practice remains unclear.

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Graves' ophthalmopathy (GO) is characterized by expanded volume of the orbital tissues associated with elevated serum levels of TSH receptor (TSHR) autoantibodies. Because previous studies have demonstrated evidence of adipogenesis within the GO orbit, we sought to determine whether M22, a human monoclonal antibody directed against TSHR, enhances adipogenesis in orbital fibroblasts from patients with GO and, if so, to identify signaling mechanisms involved. GO orbital fibroblast cultures (n=10) were treated for 10 days with bovine TSH (1 or 10·0 U/l) or M22 (1 or 10 ng/ml) in serum-free adipocyte differentiation medium. Some cultures also received a phosphoinositide 3-kinase (PI3K) inhibitor or an inhibitor of cAMP production. In other experiments, confluent cultures (n=8) were treated for between 1 and 30 min with TSH (0·1–10·0 U/l) or M22 (0·1–100 ng/ml) with measurement of cAMP production or levels of phosphorylated AKT (pAKT). We found levels of adiponectin, leptin, and TSHR mRNA to be increased in GO cultures treated for 10 days with either M22 (2·6 mean fold ±0·7; P=0·03) or TSH (13·2±5·8-fold, P=0·048). In other studies, M22 and TSH stimulated cAMP production and pAKT levels in GO cells. Inhibition of PI3K activity during 10 days in culture decreased the levels of M22-stimulated mRNA encoding adiponectin (67±12%; P=0·021), as well as adiponectin and CCAAT/enhancer-binding protein α protein levels. In conclusion, M22 is a pro-adipogenic factor in GO orbital preadipocytes. This antibody appears to act via the PI3K signaling cascade, suggesting that inhibition of PI3K signaling may represent a potential novel therapeutic approach in GO.

Primary Hyperparathyroidism is asymptomatic in most patients (PHPT). We report a case of PHPT in a young male patient. He presented with severe pancreatitis due to hypercalcemia and multiple bone lesions resulting in pathological fractures. The patients recovered rapidly after parathyroidectomy.

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Pregnancy is a challenging physiological process that involves maternal adaptations to the increasing energetics demands imposed by the growing conceptus. Failure to adapt to these requirements may result in serious health complications for the mother and the baby. The mitochondria are biosynthetic and energy-producing organelles supporting the augmented energetic demands of pregnancy. Evidence suggests that placental mitochondria display a dynamic phenotype through gestation. At early stages of pregnancy placental mitochondria are mainly responsible for the generation of metabolic intermediates and reactive oxygen species (ROS), while at later stages of gestation, the placental mitochondria exhibit high rates of oxygen consumption. This review describes the metabolic fingerprint of the placental mitochondria at different stages of pregnancy and summarises key signs of mitochondrial dysfunction in pathological pregnancy conditions, including preeclampsia, gestational diabetes and intrauterine growth restriction (IUGR). So far, the effects of placental-driven metabolic changes governing the metabolic adaptations occurring in different maternal tissues in both, healthy and pathological pregnancies, remain to be uncovered. Understanding the function and molecular aspects of the adaptations occurring in placental and maternal tissue’s mitochondria will unveil potential targets for further therapeutic exploration that could address pregnancy-related disorders. Targeting mitochondrial metabolism is an emerging approach for regulating mitochondrial bioenergetics. This review will also describe the potential therapeutic use of compounds with a recognised effect on mitochondria, for the management of preeclampsia.

Background While gender disparities in surgery are documented worldwide, it is unclear to what extent women consider surgery as a career before embarking on their medical school journey. This study aimed to report the percentage of pre-medical women in Pakistan who intend to eventually specialize in surgery and assess the factors motivating and deterring this decision. Methods An online survey was conducted among female pre-medical (high school) students across Pakistan. Multivariable logistic regression was performed to determine motivating and deterring factors associated with the intention to pursue surgery. Results Out of 1219 female high-school students, 764 (62.7) intended to join medical school. Among these 764, only 9.8% reported an exclusive intent to pursue surgery, while just 20.3% reported considering other specialties in addition to surgery. Significant motivators to pursue surgery exclusively were the intellectual satisfaction of pursuing surgery (adjusted odds ratio: 2.302), having opportunities to travel internationally for work (2.300) and use cuttingedge technology (2.203), interest in the specialty of surgery (2.031), the social prestige of becoming a surgeon (1.910), and considering one's personality well-suited to surgery (1.888). Major deterrents included the lack of interest in surgery (adjusted odds ratio: 3.812), surgical education and training being too difficult (2.440) and lengthy (1.404), and the risk of aggressive behavior from patients (2.239). Conclusion Even before entering medical school, most female pre-medical students have already decided against considering a future surgical career. Deterrents likely stem from women being pressured to conform to deep-seated societal expectations to dedicate their time and energy to domestic responsibilities.