Prevalence and management of hypertension in Turner syndrome: data from the International Turner Syndrome (I-TS) registry.

Introduction: Cardiovascular disease is the commonest cause of death in Turner syndrome (TS) for which, arterial hypertension has a direct influence and is a key modifiable risk factor.

Objective: To investigate the prevalence and patterns of hypertension diagnosis and management in adult patients with TS who are registered in a large international multicentre database (TS-HTN study).

Methods: Retrospective multi-centre observational study of patients aged ≥18 years, included in the I-TS (International-TS) registry (2020-2022) utilising registry and participating centre collected data.

Glucocorticoid treatment and new-onset hyperglycaemia and diabetes in people living with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

Introduction: In people living with chronic obstructive pulmonary disease (COPD), we aimed to estimate: (1) the prevalence of glucocorticoid-induced hyperglycaemia (GIH); (2) whether the prevalence of GIH varies by age, baseline diabetes status, treatment duration, ascertainment of glycaemia, definition of hyperglycaemia, study design and year of publication; and (3) the relative risk (RR) of new-onset hyperglycaemia in exposed vs non-exposed to systemic glucocorticoids.

Methods: We searched electronic databases until 9 November 2023 for randomised controlled trials and observational studies including adults diagnosed with COPD, with or without diabetes at baseline, using systemic glucocorticoids equivalent to prednisolone ≥5 mg/day for ≥3 days if exposed. Hyperglycaemia was defined as a blood glucose above a study-specific cut-off.

New Approaches to the Treatment of Hypercortisolism.

This review explores the evolving landscape of treatments for hypercortisolism, highlighting both established and emerging therapies. Although surgery remains the cornerstone of management, medical therapies play a crucial and expanding role, especially in cases of persistent, recurrent, or severe hypercortisolism. We discuss the effectiveness and limitations of steroidogenesis inhibitors, pituitary-directed drugs, glucocorticoid receptor antagonists, and experimental drugs targeting novel molecular pathways that have been implicated in the pathogenesis of hypercortisolism.

Dissociation between liver fat content and fasting metabolic markers of selective hepatic insulin resistance in humans.

Objective: Fasting hyperglycemia and hypertriglyceridemia are characteristic of insulin resistance (IR) and rodent work has suggested this may be due to selective hepatic IR, defined by increased hepatic gluconeogenesis and de novo lipogenesis (DNL), but this has not been shown in humans.

Design: Cross-sectional study in men and women across a range of adiposity.

Methods: Medication-free participants (n = 177) were classified as normoinsulinemic (NI) or hyperinsulinemic (HI) and as having low (LF) or high (HF) liver fat content measured by magnetic resonance spectroscopy.

Glycated haemoglobin is a major predictor of disease severity in patients with NAFLD.

Objectives: Currently, non-invasive scoring systems to stage the severity of non-alcoholic fatty liver disease (NAFLD) do not consider markers of glucose control (glycated haemoglobin, HbA1c); this study aimed to define the relationship between HbA1c and NAFLD severity in patients with and without type 2 diabetes.

Research Design And Methods: Data were obtained from 857 patients with liver biopsy staged NAFLD. Generalized-linear models and binomial regression analysis were used to define the relationships between histological NAFLD severity, age, HbA1c, and BMI.

Recruitment, Retention, and Training of Citizen Scientists in Translational Medicine Research: A Citizen Science Initiative on Non-Alcoholic Fatty Liver Disease.

Citizen science is a participatory science approach in which members of the public (citizens) collaborate with scientists and professional researchers and become involved in research and innovation activities, resulting in the co-creation of scientific knowledge and innovation. Citizen science has been widely applied in research, particularly in the social sciences, environmental sciences, information and communication technologies, and public health. However, the application of this approach in clinical sciences, particularly in translational medicine research, is still nascent.

Service evaluation suggests variation in clinical care provision in adults with congenital adrenal hyperplasia in the UK and Ireland.

Background: Congenital adrenal hyperplasia (CAH) encompasses a rare group of autosomal recessive disorders, characterised by enzymatic defects in steroidogenesis. Heterogeneity in management practices has been observed internationally. The International Congenital Adrenal Hyperplasia registry (I-CAH, https://sdmregistries.

Alterations in plasma protein N-glycosylation after caloric restriction and bariatric surgery.

Background: Protein glycosylation is an enzymatic process known to reflect an individual's physiologic state and changes thereof. The impact of metabolic interventions on plasma protein N-glycosylation has only been sparsely investigated.

Objective: To examine alterations in plasma protein N-glycosylation following changes in caloric intake and bariatric surgery.

Bardet-Biedl syndrome: A focus on genetics, mechanisms and metabolic dysfunction.

Bardet-Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis.

Translating the potential of the urine steroid metabolome to stage NAFLD (TrUSt-NAFLD): study protocol for a multicentre, prospective validation study.

Introduction: Non-alcoholic fatty liver disease (NAFLD) affects approximately one in four individuals and its prevalence continues to rise. The advanced stages of NAFLD with significant liver fibrosis are associated with adverse morbidity and mortality outcomes. Currently, liver biopsy remains the 'gold-standard' approach to stage NAFLD severity.

A novel model for predicting diabetes remission after bariatric surgery based on the measurement of C-peptide and creatinine in serum: A pilot study.

Background And Aims: Bariatric surgery is effective for treating type 2 diabetes (T2D) in patients with obesity, although a significant proportion of these patients do not achieve diabetes remission after the surgery even after significant weight loss and metabolic improvement. C-peptide is a valuable marker of beta cell function and insulin secretion, but renal function must be considered when interpreting measurements in patients with T2D. The study aims to investigate the association of serum levels of C-peptide adjusted for creatinine with diabetes remission and glycemic target achievement after bariatric surgery in patients with obesity and T2D.

Profiling the genome and proteome of metabolic dysfunction-associated steatotic liver disease identifies potential therapeutic targets.

Background & Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 25% of the population and currently has no effective treatments. Plasma proteins with causal evidence may represent promising drug targets. We aimed to identify plasma proteins in the causal pathway of MASLD and explore their interaction with obesity.

Multivariable Model to Predict an ACTH Stimulation Test to Diagnose Adrenal Insufficiency Using Previous Test Results.

Context: The adrenocorticotropin hormone stimulation test (AST) is used to diagnose adrenal insufficiency, and is often repeated in patients when monitoring recovery of the hypothalamo-pituitary-adrenal axis.

Objective: To develop and validate a prediction model that uses previous AST results with new baseline cortisol to predict the result of a new AST.

Methods: This was a retrospective, longitudinal cohort study in patients who had undergone at least 2 ASTs, using polynomial regression with backwards variable selection, at a Tertiary UK adult endocrinology center.

Identification of a human blood biomarker of pharmacological 11β-hydroxysteroid dehydrogenase 1 inhibition.

Background And Purpose: 11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) catalyses the oxoreduction of cortisone to cortisol, amplifying levels of active glucocorticoids. It is a pharmaceutical target in metabolic disease and cognitive impairments. 11β-HSD1 also converts some 7oxo-steroids to their 7β-hydroxy forms.

Long-term health consequences of congenital adrenal hyperplasia.

Congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency accounts for 95% of all CAH cases and is one of the most common inborn metabolic conditions. The introduction of life-saving glucocorticoid replacement therapy 70 years ago has changed the perception of CAH from a paediatric disorder into a lifelong, chronic condition affecting patients of all age groups. Alongside health problems that can develop during the time of paediatric care, there is an emerging body of evidence suggesting an increased risk of developing co-morbidities during adult life in patients with CAH.

Assessing treatment adherence is crucial to determine adequacy of mineralocorticoid therapy.

Background: There is no consensus strategy for mineralocorticoid (MC) therapy titration in patients with primary adrenal insufficiency (PAI). We aim to measure serum fludrocortisone (sFC) and urine fludrocortisone (uFC) levels and to determine their utility, alongside clinical/biochemical variables and treatment adherence to guide MC replacement dose titration.

Methods: Multi-centre, observational, cross-sectional study on 41 patients with PAI on MC replacement therapy.

A low-energy total diet replacement program demonstrates a favorable safety profile and improves liver disease severity in nonalcoholic steatohepatitis.

Objective: Low-energy diets are used to treat obesity and diabetes, but there are fears that they may worsen liver disease in patients with nonalcoholic steatohepatitis (NASH) and significant-to-advanced fibrosis.

Methods: In this 24-week single-arm trial, 16 adults with NASH, fibrosis, and obesity received one-to-one remote dietetic support to follow a low-energy (880 kcal/d) total diet replacement program for 12 weeks and stepped food reintroduction for another 12 weeks. Liver disease severity was blindly evaluated (magnetic resonance imaging proton density fat fraction [MRI-PDFF], iron-corrected T1 [cT1], liver stiffness on magnetic resonance elastography [MRE], and liver stiffness on vibration-controlled transient elastography [VCTE]).

Tissue Glucocorticoid Metabolism in Adrenal Insufficiency: A Prospective Study of Dual-release Hydrocortisone Therapy.

Background: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI because of the nonphysiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy.

"A morning cortisol is the most effective clinical predictor of short synacthen test outcome": A tertiary care centre experience.

Objective: Increasing referrals to Endocrinology with nonspecific symptoms of suspected adrenal insufficiency (AI) has increased use of the short-synacthen test (SST). Prevailing resource and safety concerns emphasise importance of patient selection criterion to optimise SST use. This study aimed to (1) document the adverse event profile of the SST (2) identify any pretest predictors of SST outcome.

Timing of energy intake and the therapeutic potential of intermittent fasting and time-restricted eating in NAFLD.

Non-alcoholic fatty liver disease (NAFLD) represents a major public health concern and is associated with a substantial global burden of liver-related and cardiovascular-related morbidity and mortality. High total energy intake coupled with unhealthy consumption of ultra-processed foods and saturated fats have long been regarded as major dietary drivers of NAFLD. However, there is an accumulating body of evidence demonstrating that the timing of energy intake across a the day is also an important determinant of individual risk for NAFLD and associated metabolic conditions.

Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden.

Long-term cardiometabolic morbidity in young adults with classic 21-hydroxylase deficiency congenital adrenal hyperplasia.

Purpose: To study the current practice for assessing comorbidity in adults with 21-hydroxylase CAH and to assess the prevalence of comorbidity in these adults.

Methods: A structured questionnaire was sent to 46 expert centres managing adults with CAH. Information collected included current therapy and surveillance practice with a particular focus on osteoporosis/osteopaenia, hyperlipidaemia, type 2 diabetes/hyperinsulinaemia, hypertension, CV disease, obesity.