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Endocrinology, Diabetes & Metabolism... Apr 2024A previously healthy 17-year-old female presented to the emergency department with complaints of vomiting, shortness of breath, and tachycardia. She was found to have an...
SUMMARY
A previously healthy 17-year-old female presented to the emergency department with complaints of vomiting, shortness of breath, and tachycardia. She was found to have an elevated blood glucose and was admitted for presumed new onset type 1 diabetes mellitus (T1DM). During the admission, she was noted to have frequent episodes of hypoglycemia despite conservative insulin dosing and high urine output with glucosuria, which seemed out of proportion to her glucose levels and fluid status. She also had persistent hyponatremia despite normalization of blood glucose. Further work-up was initiated to investigate alternative or additional diagnoses to explain these atypical findings. Adrenocorticotropic hormone (ACTH) level was elevated, consistent with the diagnosis of Addison's disease, which led to the subsequent diagnosis of autoimmune polyglandular syndrome type II (APS-2). This is one of the first reports in the literature of concurrent diagnosis of T1DM and Addison's disease at initial presentation and demonstrates the importance of not anchoring to one diagnosis.
LEARNING POINTS
This case shows the importance of considering multiple diagnoses and investigating atypical signs and symptoms. This case highlights the importance of a thorough history including review of systems. Hyponatremia and recurrent hypoglycemia in a person with type 1 diabetes should raise suspicion for adrenal insufficiency. This case makes us consider the screening for Addison's disease in a person with new onset type 1 diabetes in addition to autoimmune thyroid disease and celiac disease. People with an autoimmune disease should be monitored for other autoimmune diseases in the future.
PubMed: 38744309
DOI: 10.1530/EDM-23-0106 -
Endocrinologia, Diabetes Y Nutricion Apr 2024
Topics: Humans; Male; Prostatic Neoplasms; Addison Disease; Aged; Carcinoma, Neuroendocrine; Neuroendocrine Tumors
PubMed: 38735680
DOI: 10.1016/j.endien.2024.01.011 -
International Journal of Clinical... May 2024Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar...
A randomised, crossover trial exploring the patient perspective and effectiveness of biosimilar adalimumab transition: IBD reference and biosimilar adalimumab cross over study (iBaSS).
BACKGROUND
Patient satisfaction has been positively associated with adherence which is expected to impact outcomes. Although vital for successful implementation of biosimilar medicines, little is known about the patient perspective of transition.
AIM
The aim of this study was to investigate clinical outcomes and patient experience of transitioning between reference adalimumab and a biosimilar (SB5).
METHOD
iBaSS is a phase IV single-centre, prospective, randomised, single-blind, cross-over study in adult subjects with Crohn's disease. Participants, stable on adalimumab before consent, received 24 weeks of treatment with both reference adalimumab and SB5. The primary outcome was the proportion of patients maintaining baseline clinical status throughout each treatment period, with patients' perspective of disease control and treatment satisfaction assessed as secondary outcomes.
RESULTS
A total of 112 participants, representative of the heterogeneous patient populations encountered in routine clinical practice, were enrolled. A similar proportion of participants maintained baseline clinical status through each treatment period: 81.8% with reference adalimumab and 79.5% with SB5. Patient reported outcomes (IBD-Control questionnaire (SB5: 15.5; reference adalimumab 15) and TSQM), adverse events and therapeutic drug monitoring remained consistent through both treatment periods, although a higher median injection pain VAS score was noted with SB5 (53/100 versus 6/100 with reference adalimumab). The number of switches undertaken in the study did not impact serum drug concentration or immunogenicity.
CONCLUSION
This study, mimicking real world adalimumab transition, demonstrates that patients undertaking brand transition can be expected to have consistent clinical and satisfaction outcomes.
CLINICAL TRIAL REGISTERED WITH EUDRACT
Number 2018-004967-30.
PubMed: 38734866
DOI: 10.1007/s11096-024-01739-5 -
Journal of the American College of... May 2024Nondilated left ventricular cardiomyopathy (NDLVC) has been recently differentiated from dilated cardiomyopathy (DCM). A comprehensive characterization of these 2...
BACKGROUND
Nondilated left ventricular cardiomyopathy (NDLVC) has been recently differentiated from dilated cardiomyopathy (DCM). A comprehensive characterization of these 2 entities using cardiac magnetic resonance (CMR) and genetic testing has never been performed.
OBJECTIVES
This study sought to provide a thorough characterization and assess clinical outcomes in a large multicenter cohort of patients with DCM and NDLVC.
METHODS
A total of 462 patients with DCM (227) or NDLVC (235) with CMR data from 4 different referral centers were retrospectively analyzed. The study endpoint was a composite of sudden cardiac death or major ventricular arrhythmias.
RESULTS
In comparison to DCM, NDLVC had a higher prevalence of pathogenic or likely pathogenic variants of arrhythmogenic genes (40% vs 23%; P < 0.001), higher left ventricular (LV) systolic function (LV ejection fraction: 51% ± 12% vs 36% ± 15%; P < 0.001) and higher prevalence of free-wall late gadolinium enhancement (LGE) (27% vs 14%; P < 0.001). Conversely, DCM showed higher prevalence of pathogenic or likely pathogenic variants of nonarrhythmogenic genes (23% vs 12%; P = 0.002) and septal LGE (45% vs 32%; P = 0.004). Over a median follow-up of 81 months (Q1-Q3: 40-132 months), the study outcome occurred in 98 (21%) patients. LGE with septal location (HR: 1.929; 95% CI: 1.033-3.601; P = 0.039) was independently associated with the risk of sudden cardiac death or major ventricular arrhythmias together with LV dilatation, older age, advanced NYHA functional class, frequent ventricular ectopic activity, and nonsustained ventricular tachycardia.
CONCLUSIONS
In a multicenter cohort of patients with DCM and NDLVC, septal LGE together with LV dilatation, age, advanced disease, and frequent and repetitive ventricular arrhythmias were powerful predictors of major arrhythmic events.
Topics: Humans; Male; Female; Cardiomyopathy, Dilated; Middle Aged; Retrospective Studies; Magnetic Resonance Imaging, Cine; Adult; Aged; Death, Sudden, Cardiac; Follow-Up Studies
PubMed: 38719365
DOI: 10.1016/j.jacc.2024.02.041 -
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICPis) induce autoimmune diseases, including autoimmune polyendocrine syndrome type 2 (APS-2), which is defined as a combination of at... (Review)
Review
BACKGROUND
Immune checkpoint inhibitors (ICPis) induce autoimmune diseases, including autoimmune polyendocrine syndrome type 2 (APS-2), which is defined as a combination of at least two of the following endocrinopathies: autoimmune thyroid disease, type 1 diabetes, and Addison's disease. Cases with the full triad are rare. We present a case of an elderly woman who developed APS-2 with the complete triad shortly after starting anti-programmed cell death 1 (anti-PD1) treatment and review the related literature.
CASE
A 60-year-old woman, without any personal or family history of autoimmune and endocrine diseases, started the immunotherapy of anti-PD1 (camrelizumab) for squamous cell carcinoma of the urethral meatus. She developed primary hypothyroidism with elevated antibodies to thyroid peroxidase and thyroglobulin after 25 weeks of treatment, and developed primary adrenal insufficiency with adrenal crisis and fulminant type 1 diabetes with ketoacidosis after 45 weeks. Therefore, this patient met the diagnosis of APS-2 and was given multiple hormone replacement including glucocorticoid, levothyroxine and insulin therapy. Continuous improvement was achieved through regular monitoring and titration of the dosage.
CONCLUSIONS
Different components of APS-2 may appear at different time points after anti-PD1 administration, and can be acute and life-threatening. A good prognosis can be obtained by appropriate replacement with multiple hormones.
INSIGHTS
With the clinical application of ICPis to APS-2, the complexity of its treatment should be paid enough attention.
Topics: Humans; Female; Polyendocrinopathies, Autoimmune; Middle Aged; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Diabetes Mellitus, Type 1
PubMed: 38707904
DOI: 10.3389/fimmu.2024.1366335 -
Cureus Apr 2024We report a case of a 17-year-old girl who developed toxic epidermal necrolysis (TEN) secondary to preoperative iodine administration before thyroidectomy for Graves'...
We report a case of a 17-year-old girl who developed toxic epidermal necrolysis (TEN) secondary to preoperative iodine administration before thyroidectomy for Graves' disease. Past medical history was significant for COVID-19 and multisystem inflammatory syndrome in Children (MISC-C), with subsequent diagnoses of type 1 diabetes mellitus (T1DM), Addison disease, and Graves' disease. Her Graves disease was initially managed with methimazole. While there are reported cases of Stevens-Johnson syndrome (SJS) and TEN due to methimazole, the patient had discontinued methimazole over one month prior. Therefore, she likely represents the first case of TEN reported secondary to potassium iodide solution in a pediatric patient. Given the rarity of TEN in pediatric patients, our case highlights the challenges in managing complex autoimmune conditions and underscores the importance of careful medication choices in such cases.
PubMed: 38707124
DOI: 10.7759/cureus.57618 -
Obesity Pillars Jun 2024This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and...
BACKGROUND
This joint expert review by the Obesity Medicine Association (OMA) and National Lipid Association (NLA) provides clinicians an overview of the pathophysiologic and clinical considerations regarding obesity, dyslipidemia, and cardiovascular disease (CVD) risk.
METHODS
This joint expert review is based upon scientific evidence, clinical perspectives of the authors, and peer review by the OMA and NLA leadership.
RESULTS
Among individuals with obesity, adipose tissue may store over 50% of the total body free cholesterol. Triglycerides may represent up to 99% of lipid species in adipose tissue. The potential for adipose tissue expansion accounts for the greatest weight variance among most individuals, with percent body fat ranging from less than 5% to over 60%. While population studies suggest a modest increase in blood low-density lipoprotein cholesterol (LDL-C) levels with excess adiposity, the adiposopathic dyslipidemia pattern most often described with an increase in adiposity includes elevated triglycerides, reduced high density lipoprotein cholesterol (HDL-C), increased non-HDL-C, elevated apolipoprotein B, increased LDL particle concentration, and increased small, dense LDL particles.
CONCLUSIONS
Obesity increases CVD risk, at least partially due to promotion of an adiposopathic, atherogenic lipid profile. Obesity also worsens other cardiometabolic risk factors. Among patients with obesity, interventions that reduce body weight and improve CVD outcomes are generally associated with improved lipid levels. Given the modest improvement in blood LDL-C with weight reduction in patients with overweight or obesity, early interventions to treat both excess adiposity and elevated atherogenic cholesterol (LDL-C and/or non-HDL-C) levels represent priorities in reducing the risk of CVD.
PubMed: 38706496
DOI: 10.1016/j.obpill.2024.100108 -
Physiological Reports May 2024Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults.... (Review)
Review
Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults. Myosteatosis and its inflammatory milieu play a larger role in adipose tissue dysfunction, muscle tissue dysfunction, and increased passive muscle stiffness. Combined with the age-related decline of sex hormones and development of anabolic resistance, myosteatosis also contributes to insulin resistance, impaired muscle mechanics, loss of force production from the muscle, and increased risk of chronic disease. Due to its highly inflammatory secretome and the downstream negative effects on muscle metabolism and mechanics, myosteatosis has become an area of interest for aging researchers and clinicians. Thus far, myosteatosis treatments have had limited success, as many lack the potency to completely rescue the metabolic and physical consequences of myosteatosis. Future research is encouraged for the development of reliable assessment methods for myosteatosis, as well as the continued exploration of pharmacological, nutritional, and exercise-related interventions that may lead to the success in attenuating myosteatosis and its clinical consequences within the aging population.
Topics: Humans; Muscle, Skeletal; Aging; Aged; Adipose Tissue
PubMed: 38705872
DOI: 10.14814/phy2.16042 -
American Heart Journal Aug 2024Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein... (Randomized Controlled Trial)
Randomized Controlled Trial
Obicetrapib on top of maximally tolerated lipid-modifying therapies in participants with or at high risk for atherosclerotic cardiovascular disease: rationale and designs of BROADWAY and BROOKLYN.
BACKGROUND
Obicetrapib, a novel, selective cholesteryl ester transfer protein (CETP) inhibitor, reduces low-density lipoprotein cholesterol (LDL-C), LDL particles, apolipoprotein (Apo) B, and lipoprotein(a) [Lp(a)] and increases high-density lipoprotein cholesterol (HDL-C) when added to statins with or without ezetimibe. By substantially reducing LDL-C, obicetrapib has the potential to lower atherogenic lipoproteins in patients with atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) whose LDL-C levels remain high despite treatment with available maximally tolerated lipid-modifying therapies, addressing an unmet medical need in a patient population at high risk for cardiovascular events.
METHODS AND RESULTS
BROADWAY (NCT05142722) and BROOKLYN (NCT05425745) are ongoing placebo-controlled, double-blind, randomized Phase III trials designed to examine the efficacy, safety, and tolerability of obicetrapib as an adjunct to dietary intervention and maximally tolerated lipid-modifying therapies in participants with a history of ASCVD and/or underlying HeFH whose LDL-C is not adequately controlled. The primary efficacy endpoint was the percent change in LDL-C from baseline to day 84. Other endpoints included changes in Apo B, non-HDL-C, HDL-C, Apo A1, Lp(a), and triglycerides in addition to parameters evaluating safety, tolerability, and pharmacokinetics. BROADWAY also included an adjudicated assessment of major adverse cardiovascular events, measurements of glucose homeostasis, and an ambulatory blood pressure monitoring substudy. A total of 2,532 participants were randomized in BROADWAY and 354 in BROOKLYN to receive obicetrapib 10 mg or placebo (2:1) for 365 days with follow-up through 35 days after the last dose. Results from both trials are anticipated in 2024.
CONCLUSION
These trials will provide safety and efficacy data to support the potential use of obicetrapib among patients with ASCVD or HeFH with elevated LDL-C for whom existing therapies are not sufficiently effective or well-tolerated.
Topics: Humans; Atherosclerosis; Anticholesteremic Agents; Double-Blind Method; Cholesterol, LDL; Male; Female; Cholesterol Ester Transfer Proteins; Cholesterol, HDL; Hyperlipoproteinemia Type II; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lipoprotein(a); Middle Aged
PubMed: 38705341
DOI: 10.1016/j.ahj.2024.05.002 -
International Immunopharmacology May 2024This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune...
OBJECTIVE
This study employed Mendelian Randomization (MR) to investigate the causal relationship between genetic susceptibility to vitiligo and the risk of various autoimmune diseases, along with the mediating role of blood metabolites.
METHODS
We performed two-sample MR analyses using aggregated genome-wide association studies (GWAS) data on 486 blood metabolites, vitiligo, and nine autoimmune diseases to investigate blood metabolites' causal effects on the susceptibility of vitiligo and the associations of vitiligo with nine autoimmune comorbidities. We also applied multivariable MR to unravel metabolites by which vitiligo influences the pathogenesis of autoimmune diseases.
RESULTS
Our findings indicate that vitiligo amplified the risk of several autoimmune diseases, including rheumatoid arthritis (OR 1.17; 95 % CI 1.08-1.27), psoriasis (OR 1.10; 95 % CI 1.04-1.17), type 1 diabetes (OR 1.41; 95 % CI 1.23-1.63), pernicious anemia (OR 1.23; 95 % CI 1.12-1.36), autoimmune hypothyroidism (OR 1.19; 95 % CI 1.11-1.26), alopecia areata (OR 1.22; 95 % CI 1.10-1.35), and autoimmune Addison's disease (OR 1.22; 95 % CI 1.12-1.33). Additionally, our analysis identified correlations with vitiligo for 14 known (nine risk, five protective) and seven uncharacterized serum metabolites. After adjusting for genetically predicted levels of histidine and pyruvate, the associations between vitiligo and these diseases were attenuated.
CONCLUSIONS
We substantiated vitiligo's influence on susceptibility to seven autoimmune diseases and conducted a thorough investigation of serum metabolites correlated with vitiligo. Histidine and pyruvate are potential mediators of vitiligo associated with autoimmune diseases.By combining metabolomics with genomics, we provide new perspectives on the etiology of vitiligo and its immune comorbidities.
Topics: Vitiligo; Humans; Mendelian Randomization Analysis; Autoimmune Diseases; Genome-Wide Association Study; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide
PubMed: 38691918
DOI: 10.1016/j.intimp.2024.112132