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The Journal of Clinical Endocrinology... Oct 2019This mini-review offers an update on the rare autoimmune polyendocrinopathy (AP) syndrome with a synopsis of recent developments.
CONTEXT
This mini-review offers an update on the rare autoimmune polyendocrinopathy (AP) syndrome with a synopsis of recent developments.
DESIGN AND RESULTS
Systematic search for studies related to pathogenesis, immunogenetics, screening, diagnosis, clinical spectrum, and epidemiology of AP. AP (orphan code ORPHA 282196) is defined as the autoimmune-induced failure of at least two glands. AP is divided into the rare juvenile type I and the adult types II to IV. The prevalence is 1:100,000 and 1:20,000 for types I and types II to IV, respectively. Whereas type I (ORPHA 3453) is a monogenetic syndrome with an autosomal recessive transmission related to mutations in the autoimmune regulator (AIRE) gene, types II to IV are genetically complex multifactorial syndromes that are strongly associated with certain alleles of HLA genes within the major histocompatibility complex located on chromosome 6, as well as the cytotoxic T lymphocyte antigen 4 and the protein tyrosine phosphatase nonreceptor type 22 genes. Addison disease is the major endocrine component of type II (ORPHA 3143), whereas the coexistence of type 1 diabetes and autoimmune thyroid disease is characteristic for type III (ORPHA 227982). Genetic screening for the AIRE gene is useful in patients with suspected type I, whereas serological screening (i.e., diabetes/adrenal antibodies) is required in patients with monoglandular autoimmunity and suspected AP. If positive, functional endocrine testing of the antibody-positive patients as well as serological screening of their first-degree relatives is recommended.
CONCLUSION
Timely diagnosis, genetic counseling, and optimal long-term management of AP is best offered in specialized centers.
Topics: Adult; Autoimmunity; Child; Comorbidity; Genetic Counseling; Genetic Testing; Humans; Long-Term Care; Polyendocrinopathies, Autoimmune; Prevalence
PubMed: 31127843
DOI: 10.1210/jc.2019-00602 -
Frontiers in Endocrinology 2022In recent years, vitamin D has become the protagonist in many studies. From cardiology to oncology the spotlight was on this vitamin. While in the past it was considered... (Review)
Review
In recent years, vitamin D has become the protagonist in many studies. From cardiology to oncology the spotlight was on this vitamin. While in the past it was considered for its important role in phospho-calcium metabolism and skeletal disorders; today by studying it better, thousands of scenarios and facets have opened up on this vitamin which is actually a hormone in all respects. There are authoritative studies that demonstrate its activity and on: carcinogenesis, inflammation, autoimmunity and endocrinopathies. Its role has been studied in type 1 and type 2 diabetes mellitus, in Hashimoto or Graves' thyroiditis and even in adrenal gland diseases. In fact, there are several studies that demonstrate the possible correlations between vitamin D and: Addison's disease, Cushing disease, hyperaldosteronism or adrenocortical tumors. Moreover, this fascinating hormone and adrenal gland even seem to be deeply connected by common genetic pathways. This review aimed to analyze the works that have tried to study the possible influence of vitamin D on adrenal diseases. In this review we analyze the works that have tried to study the possible influence of vita-min D on adrenal disease.
Topics: Humans; Vitamin D; Diabetes Mellitus, Type 2; Adrenal Glands; Hyperaldosteronism; Vitamins; Hormones
PubMed: 36313775
DOI: 10.3389/fendo.2022.1001065 -
JMIR MHealth and UHealth Mar 2022Engagement is essential for the effectiveness of digital behavior change interventions. Existing systematic reviews examining hypertension self-management interventions... (Review)
Review
BACKGROUND
Engagement is essential for the effectiveness of digital behavior change interventions. Existing systematic reviews examining hypertension self-management interventions via mobile apps have primarily focused on intervention efficacy and app usability. Engagement in the prevention or management of hypertension is largely unknown.
OBJECTIVE
This systematic review explores the definition and role of engagement in hypertension-focused mobile health (mHealth) interventions, as well as how determinants of engagement (ie, tailoring and interactivity) have been implemented.
METHODS
A systematic review of mobile app interventions for hypertension self-management targeting adults, published from 2013 to 2020, was conducted. A total of 21 studies were included in this systematic review.
RESULTS
The engagement was defined or operationalized as a microlevel concept, operationalized as interaction with the interventions (ie, frequency of engagement, time or duration of engagement with the program, and intensity of engagement). For all 3 studies that tested the relationship, increased engagement was associated with better biomedical outcomes (eg, blood pressure change). Interactivity was limited in digital behavior change interventions, as only 7 studies provided 2-way communication between users and a health care professional, and 9 studies provided 1-way communication in possible critical conditions; that is, when abnormal blood pressure values were recorded, users or health care professionals were notified. The tailoring of interventions varied at different aspects, from the tailoring of intervention content (including goals, patient education, advice and feedback from health professionals, reminders, and motivational messages) to the tailoring of intervention dose and communication mode. Tailoring was carried out in a number of ways, considering patient characteristics such as goals, preferences, disease characteristics (eg, hypertension stage and medication list), disease self-management experience levels, medication adherence rate, and values and beliefs.
CONCLUSIONS
Available studies support the importance of engagement in intervention effectiveness as well as the essential roles of patient factors in tailoring, interactivity, and engagement. A patient-centered engagement framework for hypertension self-management using mHealth technology is proposed here, with the intent of facilitating intervention design and disease self-management using mHealth technology.
Topics: Adult; Biomedical Technology; Humans; Hypertension; Mobile Applications; Self-Management; Telemedicine
PubMed: 35234655
DOI: 10.2196/29415 -
Endocrine Practice : Official Journal... Feb 2021Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 or programmed death 1 and its ligand (programmed death ligand 1) have been approved for... (Review)
Review
OBJECTIVE
Immune checkpoint inhibitors (ICIs) targeting cytotoxic T-lymphocyte antigen 4 or programmed death 1 and its ligand (programmed death ligand 1) have been approved for the treatment of a variety of cancers. However, ICI therapy is associated with a risk of immune-related adverse events. In this study, we reviewed reported cases of adrenalitis and primary adrenal insufficiency (PAI)-rare but lethal endocrine immune-related adverse events-in patients who underwent ICI therapy.
METHODS
We searched multiple databases (PubMed, Web of Science, Cochrane, and Scopus) up to February 2020 for case reports on adrenalitis and PAI caused by ICIs.
RESULTS
We identified 15 case reports on ICI-induced adrenalitis and PAI and reviewed their clinical presentation, characteristics, immunologic and imaging features, and treatment. We also developed a screening strategy for PAI in patients treated with ICIs.
CONCLUSION
Given the morbidity and mortality associated with acute adrenal crisis, physicians-especially endocrinologists and oncologists-should be aware of this particular risk. PAI caused by autoimmune adrenalitis predominantly occurs in patients treated with programmed death 1 inhibitor monotherapy. PAI often coexists with other endocrinopathies and requires mineralocorticoid as well as glucocorticoid replacement. Even after withdrawal of ICIs, PAI can persist and requires lifelong replacement therapy.
Topics: Addison Disease; Adrenal Insufficiency; Antineoplastic Agents, Immunological; Humans; Immune Checkpoint Inhibitors; Neoplasms
PubMed: 33554872
DOI: 10.1016/j.eprac.2020.09.016 -
Advances in Nutrition (Bethesda, Md.) Jan 2023Results from observational studies suggest that children and adolescents consuming ready-to-eat cereals (RTECs) have a healthier BMI and lower odds of overweight and... (Review)
Review
The Impact of Ready-to-Eat Cereal Intake on Body Weight and Body Composition in Children and Adolescents: A Systematic Review of Observational Studies and Controlled Trials.
Results from observational studies suggest that children and adolescents consuming ready-to-eat cereals (RTECs) have a healthier BMI and lower odds of overweight and obesity than consumers of other breakfasts or breakfast skippers. However, randomized controlled trials in children and adolescents are few and have been inconsistent in demonstrating a causal relationship between RTEC intake and body weight or body composition. The objective of this study was to evaluate the effect of RTEC intake on body weight and body composition outcomes in children and adolescents. Prospective cohort, cross-sectional and controlled trials in children or adolescents were included. Retrospective studies and studies in subjects with disease, other than obesity, type-2 diabetes (T2D), metabolic syndrome, or prediabetes, were excluded. A search in PubMed and CENTRAL databases yielded 25 relevant studies, which were qualitatively analyzed. Fourteen of the 20 observational studies demonstrated that children and adolescents consuming RTEC have a lower BMI, lower prevalence and odds of overweight/obesity and more favorable indicators of abdominal obesity than nonconsumers or less frequent consumers. Controlled trials were few and only one reported a loss of 0.9 kg in overweight/obese children with RTEC consumption when accompanied by nutrition education. The risk of bias was low for most studies, but six had some concerns or high risk. The results were similar with presweetened and nonpresweetened RTEC. No studies reported a positive association of RTEC intake with body weight or body composition. Although controlled trials do not show a direct effect of RTEC consumption on body weight or body composition, the preponderance of observational data supports the inclusion of RTEC as part of a healthy dietary pattern for children and adolescents. Evidence also suggests similar benefits on body weight and body composition regardless of the sugar content. Additional trials are needed to determine the causality between RTEC intake and body weight and body composition outcomes. PROSPERO REGISTRATION: CRD42022311805.
Topics: Child; Humans; Adolescent; Overweight; Edible Grain; Energy Intake; Body Mass Index; Cross-Sectional Studies; Prospective Studies; Retrospective Studies; Pediatric Obesity; Body Weight; Body Composition; Randomized Controlled Trials as Topic
PubMed: 36811587
DOI: 10.1016/j.advnut.2022.11.003 -
Applied Neuropsychology. Adult 2023Addison's disease (AD) entails a chronic insufficient production of gluco- and mineralocorticoids. Fatigue and decreased quality of life are frequently reported...
Addison's disease (AD) entails a chronic insufficient production of gluco- and mineralocorticoids. Fatigue and decreased quality of life are frequently reported symptoms, but little is known about its effects on cognition. This study aims to explore the existence of cognitive impairment in patients with AD and the influence of treatment regimens. We conducted a systematic review. Inclusion criteria were met by 10 articles, most of them ranked as intermediate quality. Three studies analyzed the relationship between AD and cognitive impairment; one explored the effect of delaying treatment showing no effect on cognitive performance, and another one studied the effect of fludrocortisone treatment. Episodic memory was the most frequent cognitive domain impaired across studies, in comparison to healthy controls. Two papers investigated the relationship between impaired sleep quality and poor cognitive performance. Two studies related cognitive impairments with hypocortisolism-derived brain neuroglycopenia. Two studies investigated the effect of DHEA substitution. In conclusion, patients exhibit a moderately reduced performance in verbal learning. The pathophysiology of this impairment is likely multifactorial. Future studies should include larger sample sizes, the use of comprehensive and multi-domain neuropsychological and behavioral protocols, and neuroimaging.
PubMed: 35767730
DOI: 10.1080/23279095.2022.2090256 -
Clinical Immunology (Orlando, Fla.) Mar 2024Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of...
BACKGROUND
Adrenal hemorrhage (AH) can occur in patients with antiphospholipid Syndrome (APS). We aimed to characterize the clinical manifestations, treatments, and outcomes of patients presenting with APS-associated AH (APS-AH) through a retrospective cohort and a systematic literature review (SLR).
METHODS
We performed a mixed-source approach combining a multicenter cohort with an SLR of patients with incident APS-AH. We included patients from Mayo Clinic and published cases with persistent positivity for antiphospholipid antibodies and presenting with AH, demonstrated by imaging or biopsy. We extracted demographics, clinical characteristics, laboratory findings, treatment strategies, and outcomes (primary adrenal insufficiency and mortality). We used Kaplan-Meier and Cox models for survival analysis.
RESULTS
We included 256 patients in total, 61 (24%) from Mayo Clinic and 195 (76%) from the SLR. The mean age was 46.8 (SD 15.2) years, and 45% were female. 69% of patients had bilateral adrenal involvement and 64% presented adrenal insufficiency. The most common symptoms at presentation were abdominal pain in 79%, and nausea and vomiting 46%. Hyponatremia (77%) was the most common electrolyte abnormality. Factors associated with primary adrenal insufficiency were bilateral adrenal involvement at initial imaging (OR 3.73, CI; 95%, 1.47-9.46) and anticardiolipin IgG positivity (OR 3.80, CI; 95%, 1.30-11.09). The survival rate at five years was 82%. History of stroke was associated with 3.6-fold increase in mortality (HR 3.62, 95% CI; 1.33-9.85).
CONCLUSION
AH is a severe manifestation of APS with increased mortality. Most patients developed permanent primary adrenal insufficiency, particularly those positive for anticardiolipin IgG and bilateral adrenal involvement.
Topics: Female; Humans; Male; Middle Aged; Addison Disease; Antiphospholipid Syndrome; Hemorrhage; Immunoglobulin G; Multicenter Studies as Topic; Retrospective Studies; Adult
PubMed: 38244823
DOI: 10.1016/j.clim.2024.109906 -
Journal of Clinical Medicine Sep 2020The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the... (Review)
Review
The ongoing coronavirus disease 2019 (COVID-19) pandemic has resulted in efforts to identify therapies to ameliorate adverse clinical outcomes. The recognition of the key role for increased inflammation in COVID-19 has led to a proliferation of clinical trials targeting inflammation. The purpose of this review is to characterize the current state of immunotherapy trials in COVID-19, and focuses on associated cardiotoxicities, given the importance of pharmacovigilance. The search terms related to COVID-19 were queried in ClinicalTrials.gov. A total of 1621 trials were identified and screened for interventional trials directed at inflammation. Trials ( = 226) were fully assessed for the use of a repurposed drug, identifying a total of 141 therapeutic trials using a repurposed drug to target inflammation in COVID-19 infection. Building on the results of the Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial demonstrating the benefit of low dose dexamethasone in COVID-19, repurposed drugs targeting inflammation are promising. Repurposed drugs directed at inflammation in COVID-19 primarily have been drawn from cancer therapies and immunomodulatory therapies, specifically targeted anti-inflammatory, anti-complement, and anti-rejection agents. The proposed mechanisms for many cytokine-directed and anti-rejection drugs are focused on evidence of efficacy in cytokine release syndromes in humans or animal models. Anti-complement-based therapies have the potential to decrease both inflammation and microvascular thrombosis. Cancer therapies are hypothesized to decrease vascular permeability and inflammation. Few publications to date describe using these drugs in COVID-19. Early COVID-19 intervention trials have re-emphasized the subtle, but important cardiotoxic sequelae of potential therapies on outcomes. The volume of trials targeting the COVID-19 hyper-inflammatory phase continues to grow rapidly with the evaluation of repurposed drugs and late-stage investigational agents. Leveraging known clinical safety profiles and pharmacodynamics allows swift investigation in clinical trials for a novel indication. Physicians should remain vigilant for cardiotoxicity, often not fully appreciated in small trials or in short time frames.
PubMed: 32932930
DOI: 10.3390/jcm9092935 -
Pituitary Feb 2024Isolated adrenocorticotropic hormone deficiency (IAD) is considered to be a rare disease. Due to the nonspecific clinical presentation, precise data on the prevalence... (Review)
Review
Isolated adrenocorticotropic hormone deficiency (IAD) is considered to be a rare disease. Due to the nonspecific clinical presentation, precise data on the prevalence and incidence are lacking. In this systematic review, we aimed to analyse the clinical characteristics, association with autoimmune diseases, and management of acquired idiopathic IAD cases. A structured search was conducted after developing a search strategy combining terms for acquired (idiopathic) IAD. Articles describing an adult case with a diagnosis of ACTH deficiency using dynamic testing, no deficiency of other pituitary axes, and MRI of the brain/pituitary protocolled as normal, were included. Exclusion criteria were cases describing congenital IAD, cases with another aetiology for IAD, and articles where full text was not available. In total 42 articles were included, consisting of 85 cases of acquired idiopathic IAD. Distribution by sex was approximately equal (F:M; 47:38). Lethargy was the most common presenting symptom (38%), followed by weight loss (25%), anorexia (22%), and myalgia/arthralgia (12%). Eight cases (9.5%) presented with an Addison crisis. 31% of cases had an autoimmune disease at diagnosis of which Hashimoto hypothyroidism was the most frequent. Data about follow-up was scarce; dynamic testing was repeated in 4 cases of which 2 showed recovery of the adrenal axis. We report the largest case series of acquired idiopathic IAD to date. Our systematic review highlights the lack of a clear definition and diagnostic work-up. Based on the findings in this review a proposition is made for a flowchart to diagnose acquired idiopathic IAD.
Topics: Adult; Humans; Endocrine System Diseases; Adrenal Insufficiency; Adrenocorticotropic Hormone; Hypoglycemia; Genetic Diseases, Inborn
PubMed: 38151529
DOI: 10.1007/s11102-023-01366-9 -
Rheumatology and Therapy Sep 2019In 2016, SB4 (Benepali) became the first etanercept (ETN) biosimilar to obtain marketing authorisation in Europe. Despite robust analytical and clinical comparisons,... (Review)
Review
INTRODUCTION
In 2016, SB4 (Benepali) became the first etanercept (ETN) biosimilar to obtain marketing authorisation in Europe. Despite robust analytical and clinical comparisons, outstanding questions remain on SB4 use in routine practice.
METHODS
A systematic search for publications on real-world evidence of SB4 effectiveness, safety and drug survival was undertaken using search terms (SB4 OR Benepali OR biosimilar etanercept OR innovator etanercept) in the BIOSIS Toxicology, BIOSIS Previews, Embase and MEDLINE databases up to 17 January 2019.
RESULTS
Of 959 articles identified, eight journal articles, two journal letters and 23 congress abstracts were selected on criteria of original real-world evidence with a clinical focus. As expected with real-world evidence, quality scoring showed that the evidence had high external validity but lower internal validity. A total of 13,552 patients were described across nine European countries and all approved SB4 indications: 2499 were ETN-naïve and 11,053 switched from reference ETN to SB4 (switchers). Switch acceptance rates (a combination of clinicians offering and patients accepting initiation on SB4) ranged between 51.6% and 99.0%; patient support programmes positively contributed to acceptance. Disease activity was generally similar pre- and post-switch (typically 3-month timeframe). Retention rates across studies were at least 75% (up to 12 months follow-up). No new safety signals were identified. Differences in discontinuation rates versus historic controls reported in some studies may have been influenced by differences in treatment practices, lack of clinician confidence and nocebo effects.
CONCLUSION
Nearly 2500 ETN-naïve patients have been initiated on SB4 and outcomes are similar to those patients receiving reference ETN. Overall this systematic review of real-world evidence provides additional reassurance that SB4 is as effective and safe as reference ETN in both switched and naïve patients.
FUNDING
Biogen International GmbH.
PubMed: 31385263
DOI: 10.1007/s40744-019-00169-4