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BACKGROUND: We recently identified 35 women with polycystic ovarian syndrome (PCOS) who exhibited features of micronodular adrenocortical hyperplasia. Steroid hormone analysis can be more accurate using state-of-the-art ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS). We hypothesized that UPC2-MS/MS may be used to better define hormonally this distinct subgroup of patients with PCOS. METHODS: Plasma from PCOS patients (n = 35) and healthy volunteers (HVs, n = 19) who all received dexamethasone testing was analyzed. Samples were grouped per dexamethasone responses and followed by UPC2-MS/MS analysis. When insufficient, samples were pooled from patients with similar responses to allow quantification over the low end of the assay. RESULTS: The C11-oxy C19 (11ß-hydroxyandrostenedione, 11keto-androstenedione, 11ß-hydroxytestosterone, 11keto-testosterone):C19 (androstenedione, testosterone) steroid ratio was decreased by 1.75-fold in PCOS patients compared to HVs. Downstream steroid metabolites 11ß-hydroxyandrosterone and 11keto-androsterone were also measurable. The C11-oxy C21 steroids, 11-hydroxyprogesterone and 11keto-dihydroprogesterone levels, were 1.2- and 1.7-fold higher in PCOS patients compared to HVs, respectively. CONCLUSIONS: We hypothesized that UPC2-MS/MS may accurately quantify steroids, in vivo, and identify novel metabolites in a subgroup of patients with PCOS and adrenal abnormalities. Indeed, it appears that adrenal C11-oxy steroids have the potential of being used diagnostically to identify younger women and adolescents with PCOS who also have some evidence of micronodular adrenocortical hyperplasia. IMPACT: Adrenal C11-oxy steroids may be clinically important in identifying young patients with PCOS and adrenal abnormalities. The steroids presented in our manuscript have not yet been considered in the clinical setting so far, and we believe that this study could represent a first focused step towards the characterization of a distinct subgroup of women with PCOS who may in fact be treated differently than the average patient with PCOS. This paper can change the understanding of PCOS as one disorder: it is in fact a heterogeneous condition. In addition, for the subgroup of patients with PCOS associated with adrenocortical dysfunction, our paper provides novel hormonal markers that can be used diagnostically. Finally, the paper also adds to the basic pathophysiological understanding of adrenocortical-ovarian interactions in steroidogenesis of young women and adolescent girls with PCOS.
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Córtex Suprarrenal/metabolismo , Cromatografia Líquida , Hiperandrogenismo/sangue , Síndrome do Ovário Policístico/sangue , Esteroides/sangue , Espectrometria de Massas em Tandem , Adolescente , Córtex Suprarrenal/fisiopatologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hiperandrogenismo/diagnóstico , Hiperandrogenismo/fisiopatologia , Síndrome do Ovário Policístico/diagnóstico , Síndrome do Ovário Policístico/fisiopatologia , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been widely used in adults with Type 2 diabetes (T2D) and obesity. We sought to evaluate the experience of pediatric endocrinology providers with GLP-1RA and factors that guide them on whether and how to prescribe these medications. METHODS: We surveyed the members of the Pediatric Endocrine Society regarding the use of GLP-1RA in their practice. RESULTS: The respondents (n = 102) were predominantly from academic centers (84%) and 75%reported using GLP-1RA in pediatric patients, mostly to treat T2D and obesity. Patient tolerance for the medication was reported to be the driving factor determining the duration of treatment. Gastrointestinal side effects were observed more commonly than local reactions or elevation of pancreatic enzymes. Lack of clinical experience was reported to be a major barrier for prescribing GLP-1RA, particularly among those with more than 5 years of clinical experience. Finally, liraglutide was used more often (93%) than other GLP-1RA. CONCLUSIONS: The use of GLP-1RA has increased in pediatric patients. Recent Food and Drug Administration approval of liraglutide for pediatric obesity will likely further increase its prescription rate. Providers should be vigilant about side effects and adjust the doses of GLP-1RA accordingly. More efforts should be made by professional societies to educate pediatric endocrinology providers about the proper use of GLP-1RA and enhance their confidence in prescribing these medications.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Peptídeo 1 Semelhante ao Glucagon/agonistas , Hipoglicemiantes/uso terapêutico , Obesidade Infantil/complicações , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Criança , Diabetes Mellitus Tipo 2/complicações , Humanos , Hipoglicemiantes/farmacologia , Inquéritos e Questionários , Adulto JovemRESUMO
AIM: Our aim was to explore the relationship of Low-Density Lipoprotein Cholesterol (LDL-C) with subclinical cardiovascular disease (CVD) in youth with T1D and T2D. We hypothesized the association of LDL-C with elevated arterial stiffness (AS) would be partially accounted by the co-occurrence of other CVD factors. METHOD: We included 1376 youth with T1D and 157 with T2D from the SEARCH study. CVD risk factors including LDL-C, waist to height ratio (WHtR), mean arterial pressure (MAP), HbA1c, albumin to creatinine ratio (ACR), and insulin sensitivity (IS) score were measured at both visits. At follow up, elevated carotid-femoral AS was defined as levels above 6.8 m/s. Multivariable logistic regression evaluated the odds of elevated AS as a function of the average CVD risk factors. RESULTS: At follow up, age was 18.0 ± 4.1 and 21.6 ± 3.5 years and duration of diabetes was 7.8 ± 1.9 and 7.7 ± 1.9 years in T1D and T2D, respectively. Elevated AS was found in 8.4% of T1D and 49.0% of T2D participants. Each SD increase in LDL-C was associated with 1.28 increased odds (95% CI 1.05-1.54, P = .013) of elevated AS in youth with T1D. The association was similar but not statistically significant in T2D. WHtR, IS, and MAP were associated with elevated AS in both groups. Adjustment for WHtR or IS attenuated to non-significance the relationship between LDL-C and AS in T1D. CONCLUSIONS: Obesity and insulin resistance attenuate the association of high LDL-C with AS suggesting they partially account for the adverse effects of LDL-C on cardiovascular health in youth with T1D.
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LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Rigidez Vascular/fisiologia , Adolescente , Adulto , Fatores Etários , Idade de Início , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/epidemiologia , Angiopatias Diabéticas/etiologia , Angiopatias Diabéticas/fisiopatologia , Hemoglobinas Glicadas/análise , Fatores de Risco de Doenças Cardíacas , Humanos , Resistência à Insulina , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Patients with type 1 diabetes (T1DM) typically have normal or even elevated plasma high density lipoprotein (HDL) cholesterol concentrations; however, HDL protein composition can be altered without a change in cholesterol content. Alteration of the HDL proteome can result in dysfunctional HDL particles with reduced ability to protect against cardiovascular disease (CVD). The objective of this study was to compare the HDL proteomes of youth with T1DM and healthy controls (HC) and to evaluate the influence of glycemic control on HDL protein composition. METHODS: This was a cross-sectional case-control study. Blood samples were obtained from patients with T1DM and HC. HDL was isolated from plasma by size-exclusion chromatography and further purified using a lipid binding resin. The HDL proteome was analyzed by mass spectrometry using label-free SWATH peptide quantification. RESULTS: Samples from 26 patients with T1DM and 13 HC were analyzed and 78 HDL-bound proteins were measured. Youth with T1DM had significantly increased amounts of complement factor H related protein 2 (FHR2; adjusted P < 0.05), compared to HC. When patients were analyzed based on glucose control, several trends emerged. Some proteins were altered in T1DM and not influenced by glycemic control (e.g. FHR2) while others were partially or completely corrected with optimal glucose control (e.g. alpha-1-beta glycoprotein, A1BG). In a subgroup of poorly controlled T1DM patients, inter alpha trypsin inhibitor 4 (ITIH4) was dramatically elevated (P < 0.0001) and this was partially reversed in patients with optimal glucose control. Some proteins including complement component C3 (CO3) and albumin (ALB) were significantly different only in T1DM patients with optimal glucose control, suggesting a possible effect of exogenous insulin. CONCLUSIONS: Youth with T1DM have proteomic alterations of their HDL compared to HC, despite similar concentration of HDL cholesterol. The influence of these compositional changes on HDL function are not yet known. Future efforts should focus on investigating the role of these HDL associated proteins in regard to HDL function and their role in CVD risk in patients with T1DM. Trial registration NCT02275091.
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Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Lipoproteínas HDL/sangue , Proteômica/métodos , Adolescente , Fatores Etários , Animais , Biomarcadores/sangue , Glicemia/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Criança , HDL-Colesterol/sangue , Cromatografia Líquida , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Macrófagos/metabolismo , Masculino , Camundongos , Espectrometria de Massas em Tandem , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Patients with type 1 diabetes (T1DM) have increased mortality from cardiovascular disease (CVD). Risk factors for CVD include an elevation of LDL (LDLp) and small HDL (sHDLp) particles, and a decrease in reverse cholesterol transport i.e. HDL-cholesterol efflux capacity (CEC). Our objective was to compare lipoprotein particles and CEC between T1DM and healthy controls (HC) and to explore the associations between NMR lipid particles and cholesterol efflux. METHODS: 78 patients with T1DM and 59 HC underwent fasting lipoprotein profile testing by NMR and measurements of CEC by cell-based method. The associations between NMR lipid particles with CEC were analyzed using multivariable linear regression models. RESULTS: Youth with T1DM had higher total LDLp 724 [(563-985) vs 622 (476-794) nmol/L (P = 0.011)] (Maahs et al. in Circulation 130(17):1532-58, 2014; Shah et al. in Pediatr Diabetes 16(5):367-74, 2015), sHDLp [11.20 (5.7-15.3) vs 7.0 (3.2-13.1) µmol/L (P = 0.021)], and lower medium HDLp [11.20 (8.5-14.5) vs 12.3 (9-19.4), (P = 0.049)] and lower CEC (0.98 ± 0.11% vs 1.05 ± 0.15%, P = 0.003) compared to HC. Moreover, CEC correlated with sHDLp (ß = - 0.28, P = 0.045) and large HDLp (ß = 0.46, P < 0.001) independent of age, sex, ethnicity, BMIz, HbA1c, hsCRP and total HDLp in the diabetic cohort. CONCLUSIONS: Youth with T1DM demonstrated a more atherogenic profile including higher sHDL and LDLp and lower CEC. Future efforts should focus on considering adding lipoprotein particles and CEC in CVD risk stratification of youth with T1DM. Trial registration Clinical Trials Registration Number NCT02275091.
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HDL-Colesterol/sangue , LDL-Colesterol/sangue , Diabetes Mellitus Tipo 1/sangue , Adolescente , Fatores Etários , Biomarcadores/sangue , Estudos de Casos e Controles , Criança , Estudos Transversais , Diabetes Mellitus Tipo 1/diagnóstico , Feminino , Humanos , Espectroscopia de Ressonância Magnética , Masculino , Prognóstico , Adulto JovemRESUMO
Excess adiposity is common in youth with type 1 diabetes, yet little is known about the sociodemographic factors that predict longitudinal trajectories of body fat. We analyzed data from 363 females and 379 males with type 1 diabetes over ~9 years of follow-up (mean baseline age 12.8 ± 2.3 years in females, 13.2 ± 2.4 years in males). Estimated body fat percentage (eBFP) was calculated with validated sex- and race/ethnicity-specific equations. Group-based modeling identified three eBFP trajectories for each sex. All female trajectories showed gradual increases, while male trajectories showed gradual decreases (<5% in eBFP) that plateaued around 7 years of diabetes duration. Female trajectories showed differences in baseline eBFP: Group F1 (38.0%), mean eBFP 27.8 ± 3.0%: Group F2 (47.9%), mean eBFP 33.9 ± 3.0%: and Group F3 (14.1%), mean eBFP 41.7 ± 4.1%. Male trajectories also showed differences in baseline eBFP: Group M1 (57.2%), mean eBFP 22.0 ± 3.0%: Group M2 (30.9%), mean eBFP 33.9 ± 3.0%: and Group M3 (12.9%), mean eBFP 36.1 ± 3.7%. In multinomial models, adjusted for clinical factors (eg, insulin regimen, insulin dose, and hemoglobin A1c), females who reported a single-parent household (adjusted odds ratio [aOR] = 3.34, 95% confidence interval [CI]: 1.49, 7.47), parental education of less than a college degree (aOR = 3.79, 95% CI: 1.60, 9.60), and a lack of private health insurance (aOR = 3.74, 95% CI: 1.45, 9.60), and a household income of less than $75 000 per year (aOR = 3.13, 95% CI: 1.27, 7.70) were approximately three to four times more likely to be in the highest eBFP trajectory group relative to the lowest eBFP trajectory group. Males who reported a household income of <$75 000/year were almost twice as likely to be in the Group M3 than the Group M1 in the unadjusted model only (aOR = 1.79, 95% CI: 0.91, 4.01 vs unadjusted OR: 2.48, 95% CI: 1.22, 5.06). Lower socioeconomic status may be associated with excess body fat throughout adolescence in type 1 diabetes, particularly among females.
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Adiposidade , Diabetes Mellitus Tipo 1/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Idade de Início , Criança , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Estudos Longitudinais , Masculino , Obesidade Infantil/complicações , Classe Social , Fatores Socioeconômicos , Estados Unidos/epidemiologiaRESUMO
PURPOSE OF REVIEW: Patients with type 1 diabetes have increased risk for cardiovascular disease. The purpose of this review is to examine the following: i) current evidence for subclinical cardiovascular disease (CVD) in children with type 1 diabetes (T1DM) ii) known modifiable risk factors for CVD and their relationship to subclinical CVD in this population iii) studies that have addressed these risk factors in order to improve CVD outcomes in children with T1DM RECENT FINDINGS: Subclinical CVD presents in children as increased carotid intima-media thickness, increased arterial stiffness, and endothelial and myocardial dysfunction. Modifiable risk factors for CVD include hyperglycemia, hyperlipidemia, obesity, hypertension, depression, and autonomic dysfunction. Very few randomized controlled studies have been done in children with T1DM to examine how modification of these risk factors can affect their CVD. Children with T1DM have subclinical CVD and multiple modifiable risk factors for CVD. More research is needed to define how modification of these factors affects the progression of CVD.
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Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 1/complicações , Doenças Cardiovasculares/etiologia , Espessura Intima-Media Carotídea , Criança , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Fatores de RiscoRESUMO
OBJECTIVE: To assess skeletal maturity by measuring bone age (BA) in children with Cushing syndrome (CS) before and 1-year after transsphenoidal surgery or adrenalectomy, and to correlate BA with hormone levels and other measurements. STUDY DESIGN: This case series conducted at the National Institutes of Health Clinical Center included 93 children with Cushing disease (CD) (43 females; mean age, 12.3 ± 2.9 years) and 31 children with adrenocorticotropic hormone-independent CS (AICS) (22 females, mean age 10.3 ± 4.5 years). BA was obtained before surgery and at follow-up. Outcome measures were comparison of BA in CD vs AICS and analysis of the effects of hypercortisolism, insulin excess, body mass index, and androgen excess on BA. RESULTS: Twenty-six of the 124 children (21.0%) had advanced BA, compared with the expected general population prevalence of 2.5% (P < .0001). Only 4 of 124 (3.2%) had delayed BA. The majority of children (76%) had normal BA. The average BA z-score was similar in the children with CD and those with AICS (0.6 ± 1.4 vs 0.5 ± 1.8; P = .8865). Body mass index SDS and normalized values of dehydroepiandrosterone, dehydroepiandrosterone sulfate, androsteonedione, estradiol, and testosterone were all significantly higher in the children with advanced BA vs those with normal or delayed BA. Fifty-nine children who remained in remission from CD had follow-up BA 1.2 ± 0.3 years after transsphenoidal surgery, demonstrating decreased BA z-score (1.0 ± 1.6 vs 0.3 ± 1.4; P < .0001). CONCLUSION: Contrary to common belief, endogenous CS in children appears to be associated with normal or even advanced skeletal maturation. When present, BA advancement in CS is related to obesity, insulin resistance, and elevated adrenal androgen levels and aromatization. This finding may have significant implications for treatment decisions and final height predictions in these children.
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Hormônio Adrenocorticotrópico/fisiologia , Determinação da Idade pelo Esqueleto , Desenvolvimento Ósseo , Síndrome de Cushing/fisiopatologia , Síndrome de Cushing/cirurgia , Hormônios Esteroides Gonadais/fisiologia , Obesidade/fisiopatologia , Criança , Síndrome de Cushing/complicações , Feminino , Humanos , Masculino , Obesidade/complicações , Estudos Retrospectivos , Fatores de TempoRESUMO
INTRODUCTION: Gonadotropin releasing hormone analogs (GnRHas) are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. METHODS: The Drugs and Therapeutics Subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the USA. The survey consisted of four main subsections: (1) description of clinical practice; (2) self-assessment of knowledge base of pediatric and adult GnRHa formulations; (3) current practice for treating central precocious puberty (CPP); and (4) utilization of healthcare resources. RESULTS: There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the 3-month preparation, and the histrelin implant (Supprelin®) (88%, 96%, and 91%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) (65%) and 6-month subcutaneous leuprolide (Fensolvi®) (45%). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44%), but in practice, respondents reported a higher percentage of patients treated with the 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (64%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. CONCLUSIONS: The survey indicated there is more familiarity with older, shorter acting GnRHas, which are prescribed in greater numbers than newer, longer acting formulations. There is lack of consensus on the need for central nervous system (CNS) imaging in girls presenting with CPP between 6 and 8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability, there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.
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PURPOSE OF REVIEW: The aim of this review is to describe the clinical, biochemical, radiographic, histological, and functional characteristics of large-cell calcifying Sertoli cell tumors of the testes (LCCSCTs). We describe the two main syndromes associated with these tumors: Peutz-Jeghers syndrome (PJS) caused mainly by mutations in the STK11 (aka LKB1) gene, which encodes a serine-threonine kinase, and Carney complex (CNC), which is most often caused by PRKAR1A mutations, the gene encoding regulatory subunit type 1 of protein kinase A. RECENT FINDINGS: Relatively few patients have been reported in the literature with LCCSCTs. In children they often present as prepubertal and/or peripubertal gynecomastia. Although these tumors are very rare, they occur with higher frequency among patients with PJS and CNC. Orchiectomy was often performed in the past; however, these tumors are overwhelmingly benign and, unless there are significant hormonal changes or pain and/or mass effects, there is no need for surgery. Tumors that lead to hyperestrogenemia may be treated efficiently with aromatase inhibitors; any change in appearance should prompt evaluation for malignancy. SUMMARY: The detection of LCCSCTs may point to an underlying genetic multiple neoplasia syndrome such as PJS or CNC. Surgery is rarely indicated and aromatase inhibitors constitute an effective treatment for those cases that are associated with gynecomastia and/or advanced skeletal age.
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Complexo de Carney/diagnóstico , Síndrome de Peutz-Jeghers/diagnóstico , Tumor de Células de Sertoli/diagnóstico , Neoplasias Testiculares/diagnóstico , Testículo/patologia , Adolescente , Inibidores da Aromatase/uso terapêutico , Complexo de Carney/tratamento farmacológico , Complexo de Carney/patologia , Criança , Pré-Escolar , Ginecomastia/etiologia , Humanos , Masculino , Síndrome de Peutz-Jeghers/complicações , Síndrome de Peutz-Jeghers/tratamento farmacológico , Síndrome de Peutz-Jeghers/patologia , Tumor de Células de Sertoli/complicações , Tumor de Células de Sertoli/tratamento farmacológico , Tumor de Células de Sertoli/patologia , Neoplasias Testiculares/complicações , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Adulto JovemRESUMO
CONTEXT: Pediatric obesity is a serious health problem in the United States. While lifestyle modification therapy with dietary changes and increased physical activity are integral for the prevention and treatment of mild to moderate obesity in youth, only a modest effect on sustained weight reduction is observed in children and young adults with severe obesity. This underscores the need for additional evidence-based interventions for children and adolescents with severe obesity, including pharmacotherapy, before considering invasive procedures such as bariatric surgery. EVIDENCE ACQUISITION: This publication focuses on recent advances in pharmacotherapy of obesity with an emphasis on medications approved for common and rarer monogenic forms of pediatric obesity. EVIDENCE SYNTHESIS: We review medications currently available in the United States, both those approved for weight reduction in children and "off-label" medications that have a broad safety margin. CONCLUSION: It is intended that this review will provide guidance for practicing clinicians and will encourage future exploration for successful pharmacotherapy and other interventions for obesity in youth.
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Fármacos Antiobesidade , Cirurgia Bariátrica , Obesidade Mórbida , Obesidade Infantil , Adolescente , Fármacos Antiobesidade/uso terapêutico , Criança , Humanos , Obesidade Infantil/tratamento farmacológico , Estados Unidos , Redução de PesoRESUMO
BACKGROUND: Youth with type 1 diabetes (T1D) have normal or elevated High-Density Lipoprotein Cholesterol (HDL-C), however, the function of HDL, partly mediated by the HDL proteome, may be impaired. Metformin can be used as an adjunct therapy in youth with T1D, but its effects on the HDL proteome are unknown. OBJECTIVE: To determine the effect of metformin on the HDL proteome. SUBJECTS: Youth (12-20 years old) with T1D who had a BMI > 90th percentile, HbA1c > 8.0% and Tanner stage 5. METHODS: Double-blinded, placebo-controlled randomized sub-study. We examined the effects of metformin (n = 25) or placebo (n = 10) after 6 months on HDL proteome. Changes in HDL proteins were measured by data-independent acquisition (DIA) mass spectrometry and compared between treatment groups. As a secondary outcome, associations between proteins of interest and the most studied function of HDL, the cholesterol efflux capacity (CEC), was examined. RESULTS: The relative abundance of 84 HDL-associated proteins were measured. Two proteins were significantly affected by metformin treatment, peptidoglycan recognition protein 2 (PGRP2; +23.4%, p = .0058) and alpha-2-macroglobulin (A2MG; +29.8%, p = .049). Metformin did not significantly affect CEC. Changes in affected HDL proteins did not correlate with CEC. CONCLUSIONS: Despite having little effect on HDL-C, metformin increased PGRP2 and A2MG protein on HDL in youth with T1D, but had no significant effect on CEC. Further studies are needed to understand the impact of PGRP2 and A2MG on other HDL functions.
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Diabetes Mellitus Tipo 1 , Metformina , Adolescente , Criança , HDL-Colesterol , Diabetes Mellitus Tipo 1/tratamento farmacológico , Método Duplo-Cego , Humanos , Lipoproteínas HDL/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Proteoma , Adulto JovemRESUMO
PURPOSE: Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown. METHODS: We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n = 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups. RESULTS: First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband, P = 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%, P = 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband's condition with a monogenic etiology (de novo mutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband, P = 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands, P = 0.01). CONCLUSION: Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.
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Suppression of menstruation and/or ovarian function in adolescent girls may be desired for a variety of reasons. Numerous medical options exist. The choice of the appropriate modality for an individual patient depends on several factors based on differences in the efficacy of achieving menstrual suppression as well as in their side effect profiles. Adolescence is also a period of bone mass accrual in girls, and several of these modalities may negatively influence peak bone mass. This review focuses on the efficacy of achieving menstrual suppression and the effect on bone health of the various options through an overview of the current literature and also highlights areas in need of further research.
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Densidade Óssea/efeitos dos fármacos , Anticoncepcionais Orais Combinados/administração & dosagem , Menstruação/efeitos dos fármacos , Adolescente , Feminino , HumanosRESUMO
Background: Coronavirus-19 (COVID-19) is a disease caused by the SARS-CoV-2 virus, the seventh coronavirus identified as causing disease in humans. The SARS-CoV-2 virus has multiple potential pathophysiologic interconnections with endocrine systems, potentially causing disturbances in glucose metabolism, hypothalamic and pituitary function, adrenal function and mineral metabolism. A growing body of data is revealing both the effects of underlying endocrine disorders on COVID-19 disease outcome and the effects of the SARS-CoV-2 virus on endocrine systems. However, comprehensive assessment of the relationship to endocrine disorders in children has been lacking. Content: In this review, we present the effects of SARS-CoV-2 infection on endocrine systems and review the current literature on complications of COVID-19 disease in underlying paediatric endocrine disorders. We provide recommendations on management of endocrinopathies related to SARS-CoV-2 infection in this population. Summary and outlook: With the surge in COVID-19 cases worldwide, it is important for paediatric endocrinologists to be aware of the interaction of SARS-CoV-2 with the endocrine system and management considerations for patients with underlying disorders who develop COVID-19 disease. While children and adults share some risk factors that influence risk of complications in SARS-CoV-2 infection, it is becoming clear that responses in the paediatric population are distinct and outcomes from adult studies cannot be extrapolated. Evidence emerging from paediatric studies provides some guidance but highlights the need for more research in this area.
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COVID-19/complicações , Doenças do Sistema Endócrino/complicações , Criança , Gerenciamento Clínico , HumanosRESUMO
AIMS: To determine whether sleep blood pressure (BP) is associated with increased cardiovascular disease (CVD) risk in youth with type 1 diabetes (T1DM). METHODS: We enrolled youth with T1DM, 12-21â¯years old. Carotid-femoral Pulse Wave Velocity (PWVcf) assessed arterial stiffness, a CVD marker. Sleep systolic and diastolic BP variables were obtained from 24-hour BP Monitoring. Linear regression models analyzed the relationship of each BP variable with PWVcf, adjusted for HbA1c. Correlation of sleep BP with urine microalbumin-to-creatinine ratio (UAC) was examined. RESULTS: Nocturnal hypertension was found in 36% and abnormal dipping in 48% of the 25 participants, aged 17.7⯱â¯2.2â¯years old. Sleep systolic BP [betaâ¯=â¯0.039, 95% Confidence Interval (CI; 0.006-0.073)], diastolic BP [betaâ¯=â¯0.058, 95% CI (0.003-0.114)], Mean Arterial Pressure (MAP) [betaâ¯=â¯0.075, 95% CI (0.018-0.131)] and MAP index [betaâ¯=â¯3.547, 95% CI (0.867-6.227)] were significantly associated with PWVcf. Sleep diastolic BP, load, MAP correlated with UAC. CONCLUSIONS: Blood pressure alterations during sleep are common in youth with T1DM and they are associated with arterial stiffness and UAC. Larger studies are needed to confirm our results and examine whether interventions that target sleep and night-time BP could decrease CVD risk.
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Pressão Sanguínea , Diabetes Mellitus Tipo 1 , Hipertensão , Sono , Rigidez Vascular , Adolescente , Albuminúria , Monitorização Ambulatorial da Pressão Arterial , Criança , Ritmo Circadiano , Creatinina/urina , Diabetes Mellitus Tipo 1/complicações , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Análise de Onda de Pulso , Adulto JovemRESUMO
AIMS: Increased adiposity is a risk factor for suboptimal diabetes control and cardiovascular disease (CVD) complications. Our goal was to identify modifiable behavioral characteristics of overweight and obese pediatric patients with type 1 diabetes mellitus (T1DM) who achieve optimal glycemic control and to evaluate their CVD risk compared to lean patients. Our hypothesis was that optimally controlled obese and overweight participants require more total daily insulin and are at higher CVD risk compared to optimally controlled lean participants. METHODS: We analyzed a cohort of 9263 participants with T1DM aged <21â¯years in the T1D Exchange Registry. Optimal diabetes control was defined as HbA1câ¯≤â¯7.5% (58â¯mmol/mol). We compared factors that influence glycemic control in lean, overweight and obese participants with optimal vs. suboptimal control, using logistic regression. RESULTS: Age, race, overweight status, continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) use were important variables influencing glycemic control. In the optimally controlled cohort, 27% of participants were overweight or obese versus 30% in the suboptimally controlled cohort (Pâ¯<â¯0.001). Overweight and obese participants with optimal control were not significantly different from lean participants in terms of CSII use, total daily insulin dosage per kg of bodyweight, glucose checks per day, boluses with bedtime snack, use of CGM, but had higher LDL cholesterol and triglycerides, and lower HDL cholesterol (Pâ¯<â¯0.05). CONCLUSIONS: There were no differences in modifiable behavioral characteristics between the obese, overweight and lean optimally controlled participants. However, predictors of cardiovascular disease were higher in the overweight and obese group.
Assuntos
Diabetes Mellitus Tipo 1/epidemiologia , Controle Glicêmico/estatística & dados numéricos , Sobrepeso/epidemiologia , Obesidade Infantil/epidemiologia , Adolescente , Glicemia/metabolismo , Automonitorização da Glicemia , Criança , Pré-Escolar , Estudos de Coortes , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Hemoglobinas Glicadas/metabolismo , Controle Glicêmico/normas , Humanos , Lactente , Recém-Nascido , Insulina/administração & dosagem , Sistemas de Infusão de Insulina , Masculino , Sobrepeso/sangue , Sobrepeso/complicações , Obesidade Infantil/sangue , Obesidade Infantil/complicações , Sistema de Registros/estatística & dados numéricos , Estados Unidos/epidemiologia , Adulto JovemRESUMO
Adrenal insufficiency (AI) remains a significant cause of morbidity and mortality in children with 1 in 200 episodes of adrenal crisis resulting in death. The goal of this working group of the Pediatric Endocrine Society Drug and Therapeutics Committee was to raise awareness on the importance of early recognition of AI, to advocate for the availability of hydrocortisone sodium succinate (HSS) on emergency medical service (EMS) ambulances or allow EMS personnel to administer patient's HSS home supply to avoid delay in administration of life-saving stress dosing, and to provide guidance on the emergency management of children in adrenal crisis. Currently, hydrocortisone, or an equivalent synthetic glucocorticoid, is not available on most ambulances for emergency stress dose administration by EMS personnel to a child in adrenal crisis. At the same time, many States have regulations preventing the use of patient's home HSS supply to be used to treat acute adrenal crisis. In children with known AI, parents and care providers must be made familiar with the administration of maintenance and stress dose glucocorticoid therapy to prevent adrenal crises. Patients with known AI and their families should be provided an Adrenal Insufficiency Action Plan, including stress hydrocortisone dose (both oral and intramuscular/intravenous) to be provided immediately to EMS providers and triage personnel in urgent care and emergency departments. Advocacy efforts to increase the availability of stress dose HSS during EMS transport care and add HSS to weight-based dosing tapes are highly encouraged.
Assuntos
Insuficiência Adrenal/tratamento farmacológico , Tratamento de Emergência , Glucocorticoides/administração & dosagem , Insuficiência Adrenal/diagnóstico , Insuficiência Adrenal/etiologia , Criança , Glucocorticoides/uso terapêutico , Humanos , Hidrocortisona/análogos & derivados , Hidrocortisona/uso terapêutico , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Pediatric endocrine practices had to rapidly transition to telemedicine care at the onset of the novel coronavirus disease 2019 (COVID-19) pandemic. For many, it was an abrupt introduction to providing virtual healthcare, with concerns related to quality of patient care, patient privacy, productivity, and compensation, as workflows had to change. SUMMARY: The review summarizes the common adaptations for telemedicine during the pandemic with respect to the practice of pediatric endocrinology and discusses the benefits and potential barriers to telemedicine. Key Messages: With adjustments to practice, telemedicine has allowed providers to deliver care to their patients during the COVID-19 pandemic. The broader implementation of telemedicine in pediatric endocrinology practice has the potential for expanding patient access. Research assessing the impact of telemedicine on patient care outcomes in those with pediatric endocrinology conditions will be necessary to justify its continued use beyond the COVID-19 pandemic.