European Endocrinology最新文献

Therapeutic advances have revolutionised cancer treatment over the last two decades, but despite improved survival and outcomes, adverse effects to anticancer therapy such as dyselectrolytaemias do occur and need to be managed appropriately. This review explores essential aspects of sodium homeostasis in cancer with a focus on alterations arising from anticancer medications. Sodium and water balance are tightly regulated by close interplay of stimuli arising from hypothalamic osmoreceptors, arterial and atrial baroreceptors and the renal juxtaglomerular apparatus. This delicate balance can be disrupted by cancer itself, as well as the medications used to treat it. Some of the conventional chemotherapeutics, such as alkylating agents and platinum-based drugs, can cause hyponatraemia and, on rare occasions, hypernatraemia. Other conventional agents such as vinca alkaloids, as well as newer targeted cancer therapies including small molecule inhibitors and monoclonal antibodies, can cause hyponatraemia, usually as a result of inappropriate antidiuretic hormone secretion. Hyponatraemia can also sometimes occur secondarily to drug-induced hypocortisolism or salt-wasting syndromes. Another atypical but distinct mechanism for hyponatraemia is via pituitary dysfunction induced by immune checkpoint inhibitors. Hypernatraemia is uncommon and occasionally ensues as a result of drug-induced nephrogenic diabetes insipidus. Identification of the aetiology and appropriate management of these conditions, in addition to averting treatment-related problems, can be lifesaving in critical situations.

Background and aims: The impact of altered cholesterol metabolism on post-prandial lipids in Indians with hypothyroidism is not known. This study evaluated the impact of overt primary hypothyroidism (OPH) and subclinical hypothyroidism (ScH) on post-prandial lipids after a standardised, carbohydrate-rich, mixed meal.

Methods: Endocrinology outpatients were screened for possible inclusion into the study. Patients >18 years of age with hypothyroidism who were not taking levothyroxine and who did not present with any comorbidities underwent biochemical evaluation following a carbohydrate-rich, mixed meal. Assessments included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, lipoprotein-A (Lp-A), apolipoprotein-A1 (apo-A1), apolipoprotein-B (apo-B), insulin and fasting glucose. Assessments were carried out 1 hour, 2 hours and 4 hours after the meal. Patients were compared against healthy matched controls recruited from healthcare professionals in the hospital (asymptomatic and apparently healthy nursing staff, reception staff and ward staff).

Results: Data from 194 patients (161 with ScH and 33 with OPH) and 40 euthyroid controls were analysed. Anthropometry, body mass index, glycaemia and insulin resistance were comparable among patients with OPH and ScH, and controls. LDL-C and Lp-A were significantly higher in those with OPH, compared with ScH and controls, at baseline, 1 hour, 2 hours and 4 hours after mixed meal consumption (all p<0.05). There was progressive and similar decline in post-prandial TC, LDL-C and Lp-A in all three groups. Triglycerides were similar among the OPH, ScH and control groups, both in fasting and post-prandial state, with a progressive and similar increase in post-prandial triglycerides in all three groups.

Conclusion: This study demonstrated that severity of hypothyroidism had no impact on post-prandial TC, LDL-C and Lp-A. In addition, hypothyroidism had no impact on post-prandial triglycerides. Therefore, we conclude that lipid profile can be reliably estimated in a non-fasting state in individuals with ScH and OPH.

Takotsubo cardiomyopathy (TCMP) is a cardiac disorder, often seen in post-menopausal women, that resembles an acute coronary syndrome in its clinical presentation. The aetiopathogenesis of TCMP may have an endocrine basis, and hence we believe the term 'takotsubo endocrinopathy' may be more appropriate. In this review, we describe the various endocrine disorders that may lead to TCMP. We also describe the pathogenetic mechanism by which these endocrine disorders may lead to TCMP. Cardiomyopathy associated with pheochromocytoma closely resembles TCMP and we have suggested that it must be ruled out in all patients presenting with TCMP. The role of oestrogen deficiency in the pathogenesis of TCMP is examined in this article. The importance of the involvement of an endocrinologist in the management of TCMP is emphasised.

Cardiorenal syndrome (CRS) in people with type 2 diabetes mellitus (T2DM) illustrates the bidirectional link between the heart and the kidneys, with acute or chronic dysfunction of one organ adversely impacting the function of the other. Of the five subtypes identified, type 1 and 2 CRS occur because of the adverse impact of cardiac conditions on the kidneys. Type 3 and 4 occur when renal conditions affect the heart, and in type 5, systemic conditions impact the heart and kidneys concurrently. The cardiovascular and renoprotective benefits evidenced with sodium-glucose cotransporter-2 (SGLT2) inhibitors make them a potential choice in the management of CRS. Cardiovascular protection is mediated by a reduction in cardiac workload, blood pressure, and body weight; with improvement in lipid profile, uric acid levels, and adaptive ketogenesis process. Renoprotection is facilitated by reduction in albuminuria and hypoxic stress, and restoration of tubuloglomerular feedback. The favourable effect on cardiovascular complications and death, as well as renal complications and progression to end-stage kidney disease, has been confirmed in clinical trials. Guidelines endorse first-line use of SGLT2 inhibitors after metformin in patients with T2DM with high cardiovascular risk, chronic kidney disease or both. Since most trials with SGLT2 inhibitors excluded subjects with acute illness, patients with CRS subtypes 1 and 3 have not been studied adequately, making SGLT2 initiation in clinical practice challenging. Ongoing trials may provide evidence for SGLT2 inhibitor use in CRS. This review aims to enhance understanding of CRS and provide guidance for judicious use of SGLT2 inhibitors in T2DM.

Background: The prevalence of obesity is increasing rapidly in India and so are its associated comorbidities. Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, is commonly associated with obesity. However, limited data are available on its prevalence and clinical indicators among morbidly obese Indian women. The aim of our study was to find the prevalence of NAFLD in morbidly obese Indian women and study the clinically measurable obesity indicators that would best predict NAFLD.

Methods: This was a cross-sectional study, conducted in the Department of Endocrinology, Diabetes and Metabolism, Christian Medical College, Vellore. Women were enrolled who were diagnosed to have NAFLD on sonography. Anthropometric variables, such as body mass index, waist circumference, hip circumference, waist-hip ratio and waist-height ratio were measured and compared between the two groups. SPSS Statistics 21.0 software was used for analysing the data.

Results: One hundred and six consecutive, morbidly obese women were recruited in this study. Nearly three-quarters (73.6%) of the 106 morbidly obese participants were found to have NAFLD. We found waist circumference, body mass index and waist-height ratio to be most useful in distinguishing between patients with and without NAFLD, and found waist-height ratio was the best screening tool for diagnosing NAFLD.

Conclusion: NAFLD is present in a large proportion of morbidly obese women. Waist-height ratio could be used a surrogate screening tool to detect NAFLD in resource-constrained settings.

Hydroxychloroquine has been used in rheumatology for decades. This review highlights the mechanistic, clinical and safety data with regards to hydroxychloroquine use in novel coronavirus disease (COVID-19) in people with or without metabolic syndrome. PubMed and Medline were searched for articles published from January 1970 to March 2020 using the terms 'COVID-19', 'corona-virus 2019', 'hydroxychloroquine', 'hypertension', 'diabetes', 'cardiac disease', 'retina' and 'kidney disease'. Hypertension, diabetes and cardiovascular disease are the three most common comorbidities in people with COVID-19, meaning that such people have greater morbidity and mortality. Mechanistically, hydroxychloroquine inhibits SARS-CoV-2 virus uptake into cells by inhibiting angiotensin-converting enzyme 2 glycosylation. This inhibits lysosome activation and the associated cytokine storm, thus reducing the risk of acute respiratory distress syndrome and multiple organ dysfunction syndrome, which is the primary cause of death. Small, in-human studies have shown hydroxychloroquine to improve outcomes in COVID-19, either alone or in combination with azathioprine and other antiviral medications. Retina safety is not an issue with short term use of hydroxychloroquine in COVID-19. Dose reduction is warranted when glomerular filtration rate is <50 mL/min. Cardiac monitoring is warranted in people with established cardiac disease, and cardiac rhythm should be closely monitored when hydroxychloroquine is used with azithromycin, lopinavir, ritonavir or remdesivir. Anti-diabetes medication doses may need to be reduced during treatment with hydroxychloroquine. While we await data from large, in-human trials, short-term use of hydroxychloroquine in COVID-19 is justified, as this molecule has stood the test of time with regards to use in humans for other indications.

Introduction: There is a paucity of data analysing the reasons for primary non-adherence following first prescription of insulin among patients with uncontrolled type 2 diabetes mellitus (T2DM) in India. To address this, and to attempt to understand these reasons, an exploratory study was undertaken to assess the prevalence of primary non-adherence with insulin and barriers to insulin initiation in these patients.

Methods: Study participants were randomly selected from patients with T2DM who visited the diabetes clinic of a tertiary care teaching public hospital in Rishikesh, Uttarakhand, India, and were prescribed insulin for the first time in last 2-year period. All participants were evaluated for history of primary non-adherence, and those who were non-adherent were subsequently interviewed face-to-face using a modified, validated semi-structured questionnaire to identify the reasons for primary non-adherence. A focused group discussion was also conducted with eight physicians to elicit their views about reasons for primary non-adherence with insulin.

Results: A total of 225 patients were identified and interviewed; of these, 105 were identified with a history of primary non-adherence and underwent a subsequent face-to-face interview. There was a high prevalence of primary non-adherence with insulin among the participants of this study. The main reasons for non-adherence were low self-efficacy, doubt about clinical benefits of insulin, fear of hypoglycaemia, needle phobia, unaffordability of insulin and blood glucose monitoring device, strong faith in alternative medicines and mythical ideologies, and fears of insulin being addictive and that it may cause rapid aging.

Conclusion: With the high prevalence of primary non-adherence, and the multitude of reasons for this, it is clear that we need to eliminate these barriers to treatment. Thus, provision of dedicated diabetes educators in each diabetes clinic and availability of cost-effective insulin and blood glucose monitoring devices for the underprivileged population are key to achieve this.

Over half of people with diabetes mellitus develop diabetic polyneuropathy (DPN), which is a major cause of reduced quality of life due to disabling neuropathic pain, sensory loss, gait instability, fall-related injury, and foot ulceration and amputation. The latter represents a major health and economic burden, with lower limb amputation rates related to diabetes increasing in the UK. There is a need for early diagnosis of DPN so that early management strategies may be instigated, such as achieving tight glucose control and management of cardiovascular risk factors, in an attempt to slow its progression. To this end, a one-stop microvascular assessment involving a combined eye, foot and renal screening clinic has proven feasible in the UK. Unfortunately, there are currently no approved disease-modifying therapies for DPN. Some disease-modifying agents have demonstrated efficacy, but further large trials using appropriate clinical endpoints are required before these treatments can be routinely recommended. There has been emerging evidence highlighting a reduction in vitamin D levels in cases of painful DPN and the potential for vitamin D supplementation in deficient individuals to improve neuropathic pain; however, this needs to be proved in randomised clinical trials. The use of established agents for neuropathic pain in DPN is limited by poor efficacy and adverse effects, but patient stratification using methods such as pain phenotyping are being tested to determine whether this improves the outcomes of such agents in clinical studies. In addition, innovative approaches such as the topical 8% capsaicin patch, new methods of electrical stimulation and novel therapeutic targets such as NaV1.7 offer promise for the future. This article aims to discuss the challenges of diagnosing and managing DPN and to review current and emerging lifestyle interventions and therapeutic options.

Cancer immunotherapy and targeted therapy, though less toxic than conventional chemotherapy, can increase the risk of thyroid dysfunction. Immune checkpoint inhibitors render the cancer cells susceptible to immune destruction, but also predispose to autoimmune disorders like primary hypothyroidism as well as central hypothyroidism secondary to hypophysitis. Tyrosine kinase inhibitors act by blocking vascular endothelial growth factor receptors and their downstream targets. Disruption of the vascular supply from the inhibition of endothelial proliferation damages not only cancer cells but also organs with high vascularity like the thyroid. Interferon-α, interleukin-2 and thalidomide analogues can cause thyroid dysfunction by immune modulation. Alemtuzumab, a monoclonal antibody directed against the cell surface glycoprotein CD52 causes Graves' disease during immune reconstitution. Metaiodobenzylguanidine, combined with 131-iodine, administered as a radiotherapeutic agent for tumours derived from neural crest cells, can cause primary hypothyroidism. Bexarotene can produce transient central hypothyroidism by altering the feedback effect of thyroid hormone on the pituitary gland. Thyroid dysfunction can be managed in the usual manner without a requirement for dose reduction or discontinuation of the implicated agent. This review aims to highlight the effect of various anticancer agents on thyroid function. Early recognition and appropriate management of thyroid disorders during cancer therapy will help to improve treatment outcomes.