TouchREVIEWS in endocrinology最新文献

The prevalence of type 1 diabetes (T1D) is increasing worldwide. T1D reduces life expectancy due to complications including cardiovascular disease. Sodium-glucose co-transporter (SGLT) inhibitors are a new class of drugs developed to treat type 2 diabetes (T2D), and now they can be used as an adjunct to insulin in T1D. In clinical trials, they have been shown to improve glycaemic control and decrease body weight without the risk of increased hypoglycaemia and with a reduction in insulin dose. Four SGLT2 inhibitors have been approved in Europe for the treatment of T2D, while only dapagliflozin and sotagliflozin, a dual SGLT1 and SGLT2 inhibitor approved in 2019, have been approved for the treatment of T1D. Both can be used as an adjunct therapy in combination with insulin in adults with a body mass index (BMI) of ≥27 kg/m², inadequately controlled with insulin. In Europe, dapagliflozin is the only currently available SGLT2 inhibitor indcated as adjunct therapy for patients with T1D. The subgroup of patients with a BMI of ≥27 kg/m² from the DEPICT-1 and -2 trials (Dapagliflozin Evaluation in Patients with Inadequately Controlled Type 1 diabetes) showed similar reduction in hyperglycaemia and body weight but no significant increased risk of diabetic ketoacidosis (DKA) than the overall trial population. The risk of DKA has been shown to increase in patients with T1D treated with adjunct therapy with SGLT2 inhibitors, and studies on sotagliflozin and empagliflozin have suggested a dose response. Thus, it is important to educate patients and doctors how to recognize symptoms of upcoming DKA and mitigate it. An independent DKA education programme has recently been developed to instruct patients with T1D being treated with SGLT inhibitor therapies with and without insulin pumps to prevent, identify and treat DKA. Despite these considerations, clinical trials support the use of SGLT2 inhibitors in the management of T1D. The benefits and potential risks of dapagliflozin as an adjunct therapy to insulin in adults with T1D should be considered in each individual case. Here we discuss the efficacy and safety of dapagliflozin as adjunct therapy in patients with T1D.

Immune checkpoint inhibitors are potent and promising immunotherapeutic agents that are increasingly used for the management of various types of advanced cancers. The widespread approval of this group of drugs simultaneously revealed immune-related adverse events as unique side-effects. Endocrinopathies are one of the most common immune-related adverse events. The precise pathogenic mechanisms for these endocrinopathies are still unclear. Though few of the endocrinopathies are reversible, calling for only symptom control, most are irreversible, requiring multiple long-term hormone replacement therapies. However, in contrast to other organ-specific immune-related adverse events, patients with endocrinopathies can continue their immune checkpoint therapy, provided the hormone replacement therapy is adequate and the symptoms are controlled. Though patients who have developed immune-related adverse events demonstrate superior antitumor activity and overall survival, due to the high morbidity associated with the immune-related adverse events, researchers are trying to uncouple the antitumour activity associated with immune checkpoint inhibitor therapy from the immune-related adverse events, to preserve antitumour activity without adverse events.

The adoption and the maintenance of a proper training routine are critical elements for optimal blood glucose management and overall health improvement in individuals with diabetes. Physical activity reduces cardiovascular risk, contributes to weight loss and improves overall wellbeing. A combination of aerobic and resistance exercise maximizes the benefit of daily training. The risk of exercise-induced complications varies depending on the activity type and the presence of diabetes-related complications. Prescribing a personalized exercise programme may reduce the risk and maximize the benefit of physical activity in patients with diabetes.

Every 20 seconds a limb is amputated somewhere in the world due to diabetes. This is a global health problem that requires a global solution. The International Conference on Medical Image Computing and Computer Assisted Intervention challenge, which concerns the automated detection of diabetic foot ulcers (DFUs) using machine learning techniques, will accelerate the development of innovative healthcare technology to address this unmet medical need. In an effort to improve patient care and reduce the strain on healthcare systems, recent research has focused on the creation of cloud-based detection algorithms. These can be consumed as a service by a mobile app that patients (or a carer, partner or family member) could use themselves at home to monitor their condition and to detect the appearance of a DFU. Collaborative work between Manchester Metropolitan University, Lancashire Teaching Hospitals and the Manchester University NHS Foundation Trust has created a repository of 4,000 DFU images for the purpose of supporting research toward more advanced methods of DFU detection. This paper presents a dataset description and analysis, assessment methods, benchmark algorithms and initial evaluation results. It facilitates the challenge by providing useful insights into state-of-the-art and ongoing research.

Renal tubular acidosis (RTA) is a condition characterized by normal anion gap metabolic acidosis. Type 1 and type 2 RTA are the most common, and are caused by defective secretion of hydrogen ions and impaired absorption of bicarbonate, respectively. Long-standing uncorrected acidosis can lead to metabolic bone disease (MBD). Rickets and osteomalacia remain the commonest manifestations of uncorrected RTA. In addition, there can be a myriad of other skeletal manifestations like fractures, pseudofractures, secondary osteoporosis and even sclerotic bone disease. The postulated mechanism for bone involvement includes acidosis-mediated exaggerated osteoclastic bone resorption. Other contributory factors include abnormal renal handling of phosphate leading to hypophosphataemia in proximal RTA, and impaired vitamin D metabolism and action. In distal RTA, hypercalciuria and secondary hyperparathyroidism may play a key role for bone involvement. Recognizing the disease in its early course is important to prevent permanent sequelae of skeletal involvement. Most of these patients may, in fact, undergo orthopaedic interventions without primary correction of acidosis. We describe five cases who presented with MBD in varied forms. While evaluating the aetiology of MBD, they were diagnosed with RTA. Subsequently, we attempted to analyse the causes of RTA. Although the common causes were ruled out, genetic aetiology could not be ascertained due to resource constraints. RTA remains an important differential diagnosis of MBD. More awareness is required to diagnose the disease early and to treat it adequately. Our case series is an attempt to provide the clinical, biochemical and skeletal spectrum of RTA. In addition, we have attempted to provide algorithms for the approach and evaluation of RTA along with their varied causes.

Progressive hirsutism and moderate to severe male-pattern balding in women requires exclusion of an adrenal or ovarian tumour, especially in the presence of significantly elevated androgen levels. We present the case of a 68-year-old woman who was referred to an endocrinology clinic with insidious onset excessive facial hair growth and loss of scalp hair. Her testosterone levels were significantly elevated at 13 nmol/L (normal range: 0.1-1.4 nmol/L), although dehydroepiandrosterone sulphate and 17-hydroxyprogesterone levels were normal, suggestive of an ovarian source of androgens. Repeated radiologic investigations, including pelvic ultrasound, and abdominal and pelvic computed tomography, could not identify the obvious source of androgens. Based on strong clinical suspicion of an ovarian tumour, she underwent an elective salpingo-oophorectomy, which detected an occult Leydig cell tumour on histopathological analysis. Post-operatively, her hyperandrogenic features significantly improved and testosterone levels normalized.

Non-alcoholic fatty liver disease (NAFLD) is one of most frequent causes of chronic liver disease. Global prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) with advanced fibrosis is increasing day by day. Patients with NAFLD are more susceptible to encounter cardiovascular morbidity and mortality. Apart from lifestyle changes and dietary modifications, no effective pharmacotherapy is available to prevent the progression of NAFLD to NASH and advanced stages of hepatic fibrosis and cirrhosis. Dexamphetamine is the d-isomer of amphetamine, which acts by inhibiting monoamine reuptake and direct stimulation of dopamine and noradrenaline release. Presently, dexamphetamine is indicated for the treatment of attention deficit hyperactivity disorder and narcolepsy, but since its use was found to be associated with weight loss, it is also now used as an off-label drug for the treatment of obesity. Direct or indirect evidence is present in the form case reports, case series and from effects of related drugs to support the potential role of dexamphetamine in NAFLD. There is an urgent need to initiate preclinical and clinical studies involving robust methodology and adequate sample sizes to explore the potential of dexamphetamine in patients with NAFLD. In this review, we will discuss the therapeutic potential of dexamphetamine for the treatment of NAFLD.

Background: The features of polycystic ovary syndrome (PCOS) vary greatly among adolescent girls and adult women. Some of the features of PCOS may overlap with features of normal pubertal development in girls. Methods: This cross-sectional study was conducted among adolescents newly diagnosed with PCOS attending a tertiary hospital in Bangladesh. The relevant clinical, metabolic and hormonal profiles of 175 participants were evaluated. Results: The mean age of the study participants was 16.8 (±1.7) years. Oligomenorrhea was the predominant menstrual irregularity (88%). More than one-quarter of participants (27.4%) had a first-degree relative with PCOS, and 12% had a first-degree relative with type 2 diabetes. More than three-quarters (77.7%) had acanthosis nigricans. The majority (69.1%) were overweight (29.7%) or obese (39.4%), whereas 6.3% were underweight. A total of 65.7% had abdominal obesity. One-fifth (20%) of participants had pre-hypertension, and 3.4% were hypertensive. Around one-quarter (24%) had abnormal glucose tolerance (prediabetes 21.1%, diabetes 2.9%) and the majority (90.9%) had dyslipidaemia. The median Ferriman-Gallwey score was 12, 94.9% of participants had hirsutism and 33.7% had biochemical hyperandrogenism. Metabolic syndrome was present in 42.3% of participants. Higher body mass index and presence of hirsutism were associated with higher risks of metabolic syndrome. Conclusions: The clinical, metabolic and hormonal profiles of Bangladeshi adolescents with PCOS highlight risk factors and the need for clinical vigilance with respect to metabolic disease.

Polycystic ovary syndrome (PCOS) is a heterogeneous syndrome, with long-term sequelae from birth to senescence. The long-term effects of PCOS are attributed to several metabolic aberrations ensuing the syndrome. In a systematic review of literature regarding the cardiovascular risk factors that accompany PCOS, we found that macrovascular function has been assessed by flow-mediated dilatation (FMD), microvascular function by venous occlusion plethysmography (VOP), and arterial structure by ultrasonographic assessment of intima-media thickness (IMT) usually of the carotid artery. Contradictory results have been reported; however, in most studies, endothelial dysfunction, an early marker of atherosclerosis assessed either by haemodynamic methods such as FMD or by biochemical methods such as endothelin-1 levels, was found to be impaired. VOP is a less-studied method, with few indices altered. IMT was found to be altered in most of the included studies, but the population was more heterogeneous. Inflammatory markers, including C-reactive protein, were also found to be altered in most studies. On the other hand, a number of interventions have been shown beneficial for the markers of cardiovascular risk, in the context of insulin-sensitizers. However, other interventions such as oral contraceptive pills or statins did not consistently show a similar beneficial effect. In summary, the early identification and eventual treatment of cardiovascular clinical and biochemical risk factors may be used in clinical practice to prevent potential 'silent' triggers of cardiovascular disease.

Pheochromocytoma (PHEO) is a rare tumour that arises from adreno-medullary chromaffin cells and secretes catecholamines. These hormones are also secreted by paragangliomas, which derive from extra-adrenal cells of the sympathetic paravertebral ganglia. At least one-third of PHEOs are familial. Neurofibromatosis type 1 (NF1), or von Recklinghausen's disease, is diagnosed upon clinical criteria, and the study of PHEO is advised if hypertension is present. The incidence of PHEO in NF1 is 0.1-5.7% and explains hypertension in 20-50% of these patients. Recent advances in the treatment of this condition and preoperative preparation allow us to reduce its high cardiovascular morbimortality. Here we present the case of a 31-year-old female with known NF1 who presented with 5 months' history of non-specific symptoms and an episode of intraoperative hypertensive crisis. The workup detected a left sided PHEO, which was treated surgically. Our case illustrates the high prevalence of hereditary PHEO and how its presentation can go unnoticed. It reinforces the significance of screening for PHEO in patients with NF1.