Therapeutic Advances in Endocrinology and Metabolism最新文献

Background: Race/ethnicity and low English proficiency healthcare disparities are well established in the United States. We sought to determine if there are race/ethnicity differences in anti-obesity medication (AOM) prescription rates among youth with severe obesity treated in a pediatric weight management clinic and if, among youth from non-primary English speaking families, there are differences in prescriptions between those using interpreters during visits versus not.

Methods: We reviewed electronic health records of 2- to 18-year-olds with severe obesity seen from 2012 to 2021. Race/ethnicity was self-report, and AOMs included topiramate, stimulants (e.g. phentermine, lisdexamfetamine), naltrexone (±bupropion), glucagon-like peptide-1 agonists, and orlistat. We used general linear regression models with log-link to compare incidence rate ratios (IRRs) within the first 1 and 3 years of being followed, controlling for age, percent of the 95th BMI percentile (%BMIp95), number of obesity-related comorbidities (e.g. insulin resistance, hypertension), median household income, and interpreter use. We repeated similar analyses among youth from non-primary English speaking families, comparing those using interpreters versus not.

Results: 1,725 youth (mean age 11.5 years; %BMIp95 142%; 53% non-Hispanic White, 20% Hispanic/Latino, 16% non-Hispanic black; 6% used interpreters) were seen, of which 15% were prescribed AOMs within 1 year. The IRR for prescriptions was lower among Hispanic/Latino compared to non-Hispanic White youth at one (IRR 0.70; CI: 0.49-1.00; p = 0.047) but not 3 years. No other statistically significant differences by race/ethnicity were found. Among non-primary English speaking families, the IRR for prescriptions was higher at 1 year (IRR 2.49; CI: 1.32-4.70; p = 0.005) in those using interpreters versus not.

Conclusions: Among youth seen in a pediatric weight management clinic, AOM prescription incidence rates were lower in Hispanics/Latinos compared to non-Hispanic Whites. Interpreter use was associated with higher prescription incidence rates among non-primary English speakers. Interventions to achieve equity in AOM prescriptions may help mitigate disparities in pediatric obesity.

Background: Cardiac autonomic neuropathy (CAN) is a diabetes-related complication with increasing prevalence and remains challenging to detect in clinical settings. Machine learning (ML) approaches have the potential to predict CAN using clinical data. In this study, we aimed to develop and evaluate the performance of an ML model to predict early CAN occurrence in patients with diabetes.

Methods: We used the diabetes complications screening research initiative data set containing 200 CAN-related tests on more than 2000 participants with type 2 diabetes in Australia. Data were collected on peripheral nerve functions, Ewing's tests, blood biochemistry, demographics, and medical history. The ML model was validated using 10-fold cross-validation, of which 90% were used in training the model and the remaining 10% was used in evaluating the performance of the model. Predictive accuracy was assessed by area under the receiver operating curve, and sensitivity, specificity, positive predictive value, and negative predictive value.

Results: Of the 237 patients included, 105 were diagnosed with an early stage of CAN while the remaining 132 were healthy. The ML model showed outstanding performance for CAN prediction with receiver operating characteristic curve of 0.962 [95% confidence interval (CI) = 0.939-0.984], 87.34% accuracy, and 87.12% sensitivity. There was a significant and positive association between the ML model and CAN occurrence (p < 0.001).

Conclusion: Our ML model has the potential to detect CAN at an early stage using Ewing's tests. This model might be useful for healthcare providers for predicting the occurrence of CAN in patients with diabetes, monitoring the progression, and providing timely intervention.

Background: Masculinising hormone therapy with testosterone is used to align an individual's physical characteristics with their gender identity. Standard testosterone doses and formulations recommended for hypogonadal cisgender men are typically administered, although there are currently limited data evaluating the use of 1% testosterone gel in gender-affirming hormone therapy regimens.

Objectives: The objective of the study was to assess the prescription patterns and serum total testosterone concentrations achieved with 1% testosterone gel in trans and gender diverse individuals.

Materials and methods: A retrospective cross-sectional analysis was undertaken of trans individuals at a primary and secondary care clinic in Melbourne, Australia. Sixty-seven individuals treated with 1% testosterone gel were included. Primary outcomes were testosterone dose and serum total testosterone concentration achieved.

Results: Median age was 25 (22-30) years and median duration of testosterone therapy was 12 (7-40) months. Thirty-five (52%) individuals had a nonbinary gender identity. Initial median testosterone dose was 25 mg (12.5-31.3) daily. Fifty-two (78%) individuals commenced doses <50 mg daily, the recommended starting dose for hypogonadal cisgender men. Median total testosterone concentration achieved was 11.9 nmol/l (7.3-18.6). Polycythaemia (haematocrit >0.5) was documented in eight of 138 (6%) laboratory results in six individuals.

Discussion and conclusions: One percent testosterone gel achieves serum total testosterone concentrations in the cisgender male reference range. A high proportion of individuals had a nonbinary gender identity and most individuals commenced a lower dose than that typically administered to hypogonadal cisgender men, potentially related to slow or 'partial' masculinisation goals.

Cushing's syndrome (CS) is an endocrine disease characterized by excessive adrenocortical steroid production. One of the mainstay pharmacological treatments for CS are steroidogenesis enzyme inhibitors, including the antifungal agent ketoconazole along with metyrapone, mitotane, and aminoglutethimide. Recently, osilodrostat was added to this drug class and approved by the US Food and Drug Administration (FDA) for the treatment of Cushing's Disease. Steroidogenesis enzyme inhibitors inhibit various enzymes along the cortisol biosynthetic pathway and may be used preoperatively to lower cortisol levels and reduce surgical risk associated with tumor resection or postoperatively when surgery and/or radiation therapies are not curative. Because their selectivities for steroidogenic enzymes vary, they may even be administered in combination to achieve relatively rapid control of severe hypercortisolemia. Unfortunately, all currently available inhibitors are accompanied by serious adverse side effects that limit dosing and often result in treatment failures. Although more commonly known as a general anesthetic induction agent, etomidate is another member of the steroidogenesis enzyme inhibitor drug class. It suppresses cortisol production primarily by inhibiting 11β-hydroxylase and is the only inhibitor that may be given parenterally. However, the sedative-hypnotic actions of etomidate limit its use as an acute management option for CS. Thus, some have recommended that it be used only in intensive care settings. In this review, we discuss the initial development of etomidate as an anesthetic agent, its subsequent development as a treatment for CS, and the recent advances in dosing and drug development that dissociate sedative-hypnotic and adrenostatic drug actions to facilitate CS treatment in non-critical care settings.

Introduction: Currently, only glucocorticoids have proved to impact adverse outcomes in COVID-19. However, their risk/benefit balance remains inconclusive and populations' characteristics should be considered.

Objective: The objective was to evaluate the real-life use of glucocorticoids in patients with severe COVID-19 hospitalized in a third-level referral center and to determine the type, accumulated doses, and the in-hospital outcomes related with their use.

Methods: We evaluated a retrospective cohort of 737 patients with criteria for severe COVID-19 and a positive polymerase chain reaction (PCR) test for SARS-CoV-2. We extracted data for epidemiological analysis, medical history, and medications, as well as baseline laboratory tests. Data were analyzed using SPSS 21.0 and nonparametric tests, medians, and interquartile ranges (IQR). A p < 0.05 was considered significant.

Results: A total of 65.3% were men, with a median age of 59 years (IQR 46-70) and a median of 10 days of hospital stay (IQR 6-16), more than 40% had diabetes, hypertension, and/or obesity, and 0.8% used steroids chronically. At the time of the study, 54.0% had been discharged due to improvement and 40.8% died. The most common treatment used was dexamethasone 6 mg/day/10 days (46.6%). Patients with a complete dexamethasone scheme [as proposed by the Randomized Evaluation of COVID-19 Therapy (RECOVERY) study] had a lower mortality risk [hazard ratio (HR) 0.441, 95% confidence interval (CI) 0.232-0.840] in comparison with patients with lower doses (HR 1.803, 95% CI 1.080-3.012). Patients with methylprednisolone or several steroids tended to have higher cumulative doses (equivalent to >675 mg of prednisolone).

Conclusion: The use of steroids in severe COVID-19 reduces mortality only at the dose proposed in the RECOVERY study in the younger population. No benefit of the use of steroids was observed in patients with older age or higher number of comorbidities.

Background: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare autosomal-recessive genetic disorders characterized by metabolic deficiencies in which the body is unable to convert long-chain fatty acids into energy. To date, however, there is limited understanding of the patient experience of LC-FAOD.

Methods: The symptoms, observable signs, and quality of life (QoL) impacts associated with LC-FAOD were explored via a focus group (n = 8) and semi-structured interviews (n = 6) with patients and caregivers of patients with LC-FAOD, and interviews (n = 4) with expert clinicians. Data were analyzed via thematic analysis and summarized in a conceptual model.

Results: Participants reported a wide range of signs and symptoms associated with LC-FAOD, broadly categorized as musculoskeletal, endocrine/nutritional/metabolic, neurological, gastrointestinal/digestive, sensory, cardiovascular, respiratory, urological, and constitutional. LC-FAOD were reported to have a significant impact on various aspects of patients' lives including physical functioning, participation in daily activities, emotional/psychological wellbeing, and social functioning. Lifestyle modifications (such as diet and exercise restrictions) were necessary because of the condition. Symptoms were typically episodic in presentation often arising or exacerbated during catabolic conditions such as prolonged exercise, fasting, physiological stress, and illness/infection. Symptoms were also commonly reported to lead to emergency room visits, hospitalization, and clinical complications.

Conclusion: LC-FAOD have a considerable impact on patients' lives. There is a high degree of concordance in the signs, symptoms, and impacts of LC-FAOD reported by patients, caregivers, and clinicians; however, there were many symptoms and impacts that were only reported by patients and caregivers, thus demonstrating that insights from patient/caregiver experience data are integral for informing medical product development and facilitating patient-centered care.

Background: Insulin resistance (IR) is common in women with polycystic ovary syndrome (PCOS). Metabolic syndrome (MS) involves IR, arterial hypertension, dyslipidemia, and visceral fat accumulation. Therefore, fatness indices and blood lipid ratios can be considered as screening markers for MS. Our study aimed to evaluate the predictive potential of selected indirect metabolic risk parameters to identify MS in PCOS.

Methods: This cross-sectional study involved 596 women aged 18-40 years, including 404 PCOS patients diagnosed according to the Rotterdam criteria and 192 eumenorrheic controls (CON). Anthropometric and blood pressure measurements were taken, and blood samples were collected to assess glucose metabolism, lipid parameters, and selected hormone levels. Body mass index (BMI), waist-to-height ratio (WHtR), homeostasis model assessment for insulin resistance index (HOMA-IR), visceral adiposity index (VAI), lipid accumulation product (LAP), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides-to-HDL cholesterol ratio (TG/HDL-C) were calculated. MS was assessed using the International Diabetes Federation (IDF) and the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) criteria.

Results: MS prevalence was significantly higher in PCOS versus CON. Patients with both MS and PCOS had more unfavorable anthropometric, hormonal, and metabolic profiles versus those with neither MS nor PCOS and versus CON with MS. LAP, TG/HDL-C, VAI, and WHtR were the best markers and strongest indicators of MS in PCOS, and their cut-off values could be useful for early MS detection. MS risk in PCOS increased with elevated levels of these markers and was the highest when TG/HDL-C was used.

Conclusions: LAP, TG/HDL-C, VAI, and WHtR are representative markers for MS assessment in PCOS. Their predictive power makes them excellent screening tools for internists and enables acquiring accurate diagnoses using fewer MS markers.

Clinical manifestations and the need for treatment varies according to age in males with hypogonadism. Early foetal-onset hypogonadism results in disorders of sex development (DSD) presenting with undervirilised genitalia whereas hypogonadism established later in foetal life presents with micropenis, cryptorchidism and/or micro-orchidism. After the period of neonatal activation of the gonadal axis has waned, the diagnosis of hypogonadism is challenging because androgen deficiency is not apparent until the age of puberty. Then, the differential diagnosis between constitutional delay of puberty and central hypogonadism may be difficult. During infancy and childhood, treatment is usually sought because of micropenis and/or cryptorchidism, whereas lack of pubertal development and relative short stature are the main complaints in teenagers. Testosterone therapy has been the standard, although off-label, in the vast majority of cases. However, more recently alternative therapies have been tested: aromatase inhibitors to induce the hypothalamic-pituitary-testicular axis in boys with constitutional delay of puberty and replacement with GnRH or gonadotrophins in those with central hypogonadism. Furthermore, follicle-stimulating hormone (FSH) priming prior to hCG or luteinizing hormone (LH) treatment seems effective to induce an enhanced testicular enlargement. Although the rationale for gonadotrophin or GnRH treatment is based on mimicking normal physiology, long-term results are still needed to assess their impact on adult fertility.