Endocrine Health and Health Care Disparities in the Pediatric and Sexual and Gender Minority Populations: An Endocrine Society Scientific Statement.

Endocrine care of pediatric and adult patients continues to be plagued by health and health care disparities that are perpetuated by the basic structures of our health systems and research modalities, as well as policies that impact access to care and social determinants of health. This scientific statement expands the Society's 2012 statement by focusing on endocrine disease disparities in the pediatric population and sexual and gender minority populations. These include pediatric and adult lesbian, gay, bisexual, transgender, queer, intersex, and asexual (LGBTQIA) persons. The writing group focused on highly prevalent conditions-growth disorders, puberty, metabolic bone disease, type 1 (T1D) and type 2 (T2D) diabetes mellitus, prediabetes, and obesity. Several important findings emerged. Compared with females and non-White children, non-Hispanic White males are more likely to come to medical attention for short stature. Racially and ethnically diverse populations and males are underrepresented in studies of pubertal development and attainment of peak bone mass, with current norms based on European populations. Like adults, racial and ethnic minority youth suffer a higher burden of disease from obesity, T1D and T2D, and have less access to diabetes treatment technologies and bariatric surgery. LGBTQIA youth and adults also face discrimination and multiple barriers to endocrine care due to pathologizing sexual orientation and gender identity, lack of culturally competent care providers, and policies. Multilevel interventions to address these disparities are required. Inclusion of racial, ethnic, and LGBTQIA populations in longitudinal life course studies is needed to assess growth, puberty, and attainment of peak bone mass. Growth and development charts may need to be adapted to non-European populations. In addition, extension of these studies will be required to understand the clinical and physiologic consequences of interventions to address abnormal development in these populations. Health policies should be recrafted to remove barriers in care for children with obesity and/or diabetes and for LGBTQIA children and adults to facilitate comprehensive access to care, therapeutics, and technological advances. Public health interventions encompassing collection of accurate demographic and social needs data, including the intersection of social determinants of health with health outcomes, and enactment of population health level interventions will be essential tools.

Examining Inhibitory Affective Processing Within the Rostral Anterior Cingulate Cortex Among Abstinent Cannabis-Using Adolescents and Young Adults.

Cannabis use has been associated with deficits in self-regulation, including inhibitory control. Cannabis users have previously exhibited both structural and functional deficits in the rostral anterior cingulate cortex (rACC), a region involved in self-regulation of emotional response and inhibitory control. The present study aimed to examine whether abstinent cannabis users demonstrated abnormal functional activation and connectivity of the bilateral rACC during an emotional inhibitory processing task, and whether gender moderated these relationships. Cannabis-using (N = 34) and non-using (N = 32) participants ages 16-25 underwent at least 2-weeks of monitored substance use abstinence (excluding tobacco) and fMRI scanning while completing a Go/No-go task using fearful and calm emotional faces as non-targets. Multiple linear regression and ANCOVA were used to determine if cannabis group status was related to rACC activation and context-dependent functional connectivity, and whether gender moderated these relationships. Results showed decreased bilateral rACC activation in cannabis users during fearful response inhibition, although groups did not show any context-dependent connectivity differences between the left or right rACC during calm or fearful inhibition. Gender findings revealed that cannabis-using females compared to males did show aberrant connectivity between the right rACC and right cerebellum. These results are consistent with literature demonstrating aberrant structural and functional rACC findings and suggest that chronic cannabis use may disrupt typical rACC development-even after abstinence-potentially conferring risk for later development of mood disorders. Marginal gender-specific connectivity findings bolster continued findings regarding female vulnerability to effects of cannabis on cognition and affect. Findings should be assessed in longitudinal studies to determine causality and timing effects.

Disrupted Resting State Attentional Network Connectivity in Adolescent and Young Adult Cannabis Users following Two-Weeks of Monitored Abstinence.

BACKGROUND: Numerous neuropsychological studies have shown that cannabis use during adolescence and young adulthood led to deficits in sustained and selective attention. However, few studies have examined functional connectivity in attentional networks among young cannabis users, nor have characterized relationships with cannabis use patterns following abstinence. METHODS: Differences in resting state functional connectivity (RSFC) within the dorsal (DAN) and ventral (VAN) attention networks were examined in 36 adolescent and young adult cannabis users and 39 non-substance using controls following two weeks of monitored abstinence. Observed connectivity differences were then correlated with past-year and lifetime cannabis use, length of abstinence, age of regular use onset, and Cannabis Use Disorder symptoms (CUD). RESULTS: After controlling for alcohol and nicotine use, cannabis users had lower RSFC within the DAN network, specifically between right inferior parietal sulcus and right anterior insula, as well as white matter, relative to controls. This region was associated with more severe cannabis use measures, including increased lifetime cannabis use, shorter length of abstinence, and more severe CUD symptoms. CONCLUSIONS: Findings demonstrate that regular cannabis use by adolescents and young adults is associated with subtle differences in resting state connectivity within the DAN, even after two weeks of monitored abstinence. Notably, more severe cannabis use markers (greater lifetime use, CUD symptoms, and shorter abstinence) were linked with this reduced connectivity. Thus, findings support public policy aimed at reducing and delaying cannabis use and treatments to assist with sustained abstinence. Future longitudinal studies are needed to investigate causation.

Eradicating Racism: An Endocrine Society Policy Perspective.

The Endocrine Society recognizes racism as a root cause of the health disparities that affect racial/ethnic minority communities in the United States and throughout the world. In this policy perspective, we review the sources and impact of racism on endocrine health disparities and propose interventions aimed at promoting an equitable, diverse, and just healthcare system. Racism in the healthcare system perpetuates health disparities through unequal access and quality of health services, inadequate representation of health professionals from racial/ethnic minority groups, and the propagation of the erroneous belief that socially constructed racial/ethnic groups constitute genetically and biologically distinct populations. Unequal care, particularly for common endocrine diseases such as diabetes, obesity, osteoporosis, and thyroid disease, results in high morbidity and mortality for individuals from racial/ethnic minority groups, leading to a high socioeconomic burden on minority communities and all members of our society. As health professionals, researchers, educators, and leaders, we have a responsibility to take action to eradicate racism from the healthcare system. Achieving this goal would result in high-quality health care services that are accessible to all, diverse workforces that are representative of the communities we serve, inclusive and equitable workplaces and educational settings that foster collaborative teamwork, and research systems that ensure that scientific advancements benefit all members of our society. The Endocrine Society will continue to prioritize and invest resources in a multifaceted approach to eradicate racism, focused on educating and engaging current and future health professionals, teachers, researchers, policy makers, and leaders.

Toward the Development of a Culturally Humble Intervention to Improve Glycemic Control and Quality of Life among Adolescents with Type-1 Diabetes and Their Families.

Type-1 Diabetes (T1D) is a prevalent and costly disorder associated with substantial morbidity that differentially impacts low-income and/or minority adolescents and their families. The primary study objective was to develop a guiding model to inform culturally humble interventions for Mid-southern youth with T1D presenting with multiple correlates of suboptimal glycemic control and their families. In order to develop a clinic specific guiding model, conceptualizations of health, the need/type of intervention thought to be most helpful, the optimal structure, and strategies to improve the cultural/regional fit was ascertained from (A) youth with T1D (n = 13) and caregivers (n = 11) via qualitative interviews and, (B) pediatric endocrinologists and nurse practitioners (n = 6), and (C) nurses, diabetes educators, dietitians, and social workers (n = 9) via focus groups. Qualitative themes were synthesized to guide the treatment development model whereby Quality of Life and Glycemic Control would be directly enhanced by interventions to promote Coping, Support, Education, and Improved Psychosocial Functioning and indirectly through improved Adherence and T1D Autonomy delivered in a culturally humble way that affirms youths' T1D identify. These finding suggest that existing evidence-based treatments may provide a great fit for low-income, and/or minority youth with T1D and their families living in the mid-south, provided these interventions are delivered in culturally humble manner.

Evidence Limitations in Determining Sexually Dimorphic Outcomes in Pediatric Post-Traumatic Hypopituitarism and the Path Forward.

Neuroendocrine dysfunction can occur as a consequence of traumatic brain injury (TBI), and disruptions to the hypothalamic-pituitary axis can be especially consequential to children. The purpose of our review is to summarize current literature relevant to studying sex differences in pediatric post-traumatic hypopituitarism (PTHP). Our understanding of incidence, time course, and impact is constrained by studies which are primarily small, are disadvantaged by significant methodological challenges, and have investigated limited temporal windows. Because hormonal changes underpin the basis of growth and development, the timing of injury and PTHP testing with respect to pubertal stage gains particular importance. Reciprocal relationships among neuroendocrine function, TBI, adverse childhood events, and physiological, psychological and cognitive sequelae are underconsidered influencers of sexually dimorphic outcomes. In light of the tremendous heterogeneity in this body of literature, we conclude with the common path upon which we must collectively arrive in order to make progress in understanding PTHP.

Binge and Cannabis Co-Use Episodes in Relation to White Matter Integrity in Emerging Adults.

Background: Growing evidence suggests that cannabis and alcohol (and especially binge alcohol drinking) use independently alters neural structure and functioning, particularly during sensitive developmental time periods (e.g., emerging adulthood). However, few studies have investigated the effects of same-day use of these two substances. Here, white matter (WM) integrity was investigated in relation to binge alcohol drinking, cannabis, and same-day binge and cannabis co-use in adolescents and emerging adults. Methods: FreeSurfer's TRACULA was used to assess WM in emerging adults (n=75; 16-26 years old). Timeline Followback calculated past month cannabis use, binge episodes, and same-day cannabis and binge drinking co-use. Multiple regressions investigated WM by past month cannabis, binge, and co-use. Results: Results revealed co-use episodes were related to lower fractional anisotropy (FA), an overall measure of neuronal integrity, in three tracts (left inferior longitudinal fasciculus [ILF], p=0.02; right anterior thalamic radiation [ATR], p=0.01; and left cingulum cingulate gyrus [CCG], p=0.01); and lower axial diffusivity in left ILF (p=0.03). Cannabis use was significantly related to greater FA in left ILF (p=0.005), left ATR (p=0.02), right ATR (p=0.05), left CCG (p=0.006), right CCG (p=0.03), and right superior longitudinal fasciculus parietal (p=0.03). Binge episodes related to greater FA in right ATR (p=0.03). Conclusions: These findings suggest that co-use was associated with lower WM integrity across frontolimbic tracts. In addition, greater FA was related to greater cannabis use across several tracts and binge alcohol use in one tract. Co-users also appeared to be more severe substance users. Future research should investigate the potential independent and interactive effects of these substances on pre-clinical and clinical levels.

Intrinsic Frontolimbic Connectivity and Mood Symptoms in Young Adult Cannabis Users.

Objective: The endocannbinoid system and cannabis exposure has been implicated in emotional processing. The current study examined whether regular cannabis users demonstrated abnormal intrinsic (a.k.a. resting state) frontolimbic connectivity compared to non-users. A secondary aim examined the relationship between cannabis group connectivity differences and self-reported mood and affect symptoms. Method: Participants included 79 cannabis-using and 80 non-using control emerging adults (ages of 18-30), balanced for gender, reading ability, and age. Standard multiple regressions were used to predict if cannabis group status was associated with frontolimbic connectivity after controlling for site, past month alcohol and nicotine use, and days of abstinence from cannabis. Results: After controlling for research site, past month alcohol and nicotine use, and days of abstinence from cannabis, cannabis users demonstrated significantly greater connectivity between left rACC and the following: right rACC (p = 0.001; corrected p = 0.05; f 2 = 0.55), left amygdala (p = 0.03; corrected p = 0.47; f 2 = 0.17), and left insula (p = 0.03; corrected p = 0.47; f 2 = 0.16). Among cannabis users, greater bilateral rACC connectivity was significantly associated with greater subthreshold depressive symptoms (p = 0.02). Conclusions: Cannabis using young adults demonstrated greater connectivity within frontolimbic regions compared to controls. In cannabis users, greater bilateral rACC intrinsic connectivity was associated with greater levels of subthreshold depression symptoms. Current findings suggest that regular cannabis use during adolescence is associated with abnormal frontolimbic connectivity, especially in cognitive control and emotion regulation regions.

Gender Moderates Chronic Nicotine Cigarette Effects on Verbal Memory in Young Adults.

Background: Rates of nicotine use remain a prominent public health concern, especially among young adults. Previous findings have demonstrated that chronic exposure to nicotine during adolescence may be linked to various neurocognitive deficits. Nicotine differentially affects the brain by gender. Objectives: The present study investigated the effects of gender and chronic nicotine use on cognition in the developing brain. Methods: From 2008 to 2011, 57 young adult (ages 18-25) participants were recruited as part of a larger cross-sectional neuroimaging study and divided into 21 nicotine users (12 female) and 36 non-using controls (17 female). Participants completed various questionnaires, drug use interview, neuropsychological battery, and MRI scan in a university setting. A series of multiple regressions was conducted with nicotine group and gender*nicotine group interaction as predictors. Results: After controlling for gender, nicotine group status alone was not associated with neuropsychological performance. A gender x nicotine interaction was significantly associated with performance on trial 1, short delay free recall, and long delay free recall of the CVLT-II. Female smokers demonstrated better performance on trial 1 and short and long delay free recall than female controls. Male smokers performed more poorly than male controls on short and long delay free recall. Conclusions: These preliminary findings suggest that cognitive effects of chronic nicotine use are moderated by gender. Further research is needed to determine causality, and identify underlying brain structures and function that may be responsible for differences in verbal memory.

Nicotine Effects on White Matter Microstructure in Young Adults.

OBJECTIVE: Nicotine use is widely prevalent among youth, and is associated with white matter microstructural changes as measured by diffusion tensor imaging (DTI). In adults, nicotine use is generally associated with lower fractional anisotropy (FA), but in adolescents/young adults (≤30 years), microstructure appears healthier, indicated by higher FA. This cross-sectional study examined associations between nicotine use and white matter microstructure using fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) in young adults. METHODS: Fifty-three participants (18 nicotine users [10 female]/35 controls [17 female]) ages 18-25 underwent MRI scan, neuropsychological battery, toxicology screening, and drug use interview. Nicotine group associations with FA and MD were examined in various white matter tracts. In significant tracts, AD and RD were measured. Exploratory correlations were conducted between significant tracts and verbal memory and sustained attention/working memory performance. RESULTS: Nicotine users exhibited significantly lower FA than controls in the left anterior thalamic radiation, left inferior longitudinal fasciculus, left superior longitudinal fasciculus-temporal, and left uncinate fasciculus. In these tracts, AD and RD did not differ, nor did MD differ in any tract. White matter quality was positively correlated with sustained attention/working memory performance. CONCLUSIONS: Cigarette smoking may disrupt white matter microstructure. These results are consistent with adult studies, but inconsistent with adolescent/young adult studies, likely due to methodological and sample age differences. Further studies should examine longitudinal effects of nicotine use on white matter microstructure in a larger sample.

Validity, Reliability, and Measurement Invariance of the Diabetes Stress Questionnaire-Short Form.

OBJECTIVE: The purpose of this study was to develop a short form of the Diabetes Stress Questionnaire (DSQ) with adequate psychometric properties (i.e., internal consistency, convergent, criterion, discriminant validity, construct validity, and measurement invariance). METHODS: In total, 181 youth with type 1 diabetes (T1D) completed the 65-item DSQ, and archival data were obtained from 142 youth with T1D to serve as an independent cross-validation sample. Twenty-four items were chosen to retain the original eight scales of the DSQ and to maximize internal consistency and correlations to full subscales. Confirmatory factor analyses were used to evaluate the proposed factor structure of the Diabetes Stress Questionnaire-Short Form (DSQ-SF) and to assess invariance of the DSQ-SF across sex, race, grade level, glycemic control, illness duration, and annual income categories. RESULTS: The 24-item DSQ-SF was found to have good internal consistency, factor structure and fit, correlated highly to the full scale (r = .98), and was invariant across sex, race, grade level (<9th grade or >9th grade), glycemic control, illness duration, and annual income. CONCLUSIONS: The DSQ-SF appears to be a psychometrically robust measure of diabetes-specific stress in youth with T1D. Present findings suggest that the DSQ-SF has the potential to be a useful, quick, cost-effective, and comprehensive screening tool for identifying youth with T1D who may benefit from T1D-specific stress reduction interventions as a way to improve health behaviors, psychosocial well-being, and glycemic control.

Psychological Flexibility Among Youth with Type 1 Diabetes: Relating Patterns of Acceptance, Adherence, and Stress to Adaptation.

Psychological flexibility, a complex concept encompassing both acceptance and action related factors, has been identified as a target for intervention for diabetes management. Research suggests acceptance, self-management, and stress, all factors that influence psychological flexibility, have an impact on adaptation to type 1 diabetes (T1D) by youth independently. However, yet to be explored is individually varying patterns of these variables and how they may relate to diabetes adaptation outcomes. The present study aimed to establish individual variations of patterns of these factors to derive profiles of psychological flexibility, and examine their relations to the adaptation outcomes of glycemic control and health-related quality of life. Youth (N = 162, aged 12-17 years) with T1D completed the Acceptance and Action Diabetes Questionnaire, Diabetes Stress Questionnaire, Self-Care Inventory, and Pediatric Quality of Life-Diabetes Module. Hemoglobin A1c values were abstracted from medical records. Latent profile analysis yielded three profiles: High Acceptance & Adherence/Low Stress, Low Acceptance/Moderate Adherence & Stress, and Low Acceptance & Adherence/High Stress. The High Acceptance & Adherence/Low Stress group displayed significantly higher health-related quality of life and lower HbA1c compared to other groups. Fluid psychological variables, such as acceptance and diabetes stress, and adherence behaviors may be salient targets to increase psychological flexibility for individual psychosocial interventions aimed at improving adaptation to type 1 diabetes in youth.

Patterns of Family Functioning and Diabetes-Specific Conflict in Relation to Glycemic Control and Health-Related Quality of Life Among Youth With Type 1 Diabetes.

Objectives: General and diabetes-specific family functioning may be associated with youth's adaptation to type 1 diabetes (T1D); however, empirically derived patterns of family functioning and diabetes-specific conflict among youth have not been explored in relation to T1D adaptation. Methods: Youth (N = 161, aged 12­18) with T1D and caregivers completed measures of family functioning and diabetes-specific conflict that served as indicators in latent profile analyses. Differences in glycemic control (measured by hemoglobin A1cs [HbA1c] and health-related quality of life [HRQoL]) were compared across profiles. Results: Four profiles that varied by levels of family functioning, diabetes-specific conflict, and congruence between youth and caregiver perspectives emerged and related to T1D adaptation differently. Greater agreement between caregiver and youth and lower diabetes-specific conflict was associated with lower HbA1c and greater HRQoL. Conclusions: Person-centered approaches are useful to quantify how many individuals fit into a particular pattern and determine how specific family dynamics may function together differently in relation to T1D adaptation for various subgroups of the population.

Gestational Vitamin 25(OH)D Status as a Risk Factor for Receptive Language Development: A 24-Month, Longitudinal, Observational Study.

Emerging data suggest that vitamin D status during childhood and adolescence can affect neurocognitive development. The purpose of this study was to investigate whether gestational 25(OH)D status is associated with early childhood cognitive and receptive language development. The Conditions Affecting Neurocognitive Development and Learning in Early Childhood Study (CANDLE) study enrolled 1503 mother-child dyads during the second trimester of healthy singleton pregnancies from Shelby County TN. Among 1020 participants of the total CANDLE cohort for whom 25(OH)D levels were available, mean gestational 25(OH)D level during the second trimester was 22.3 ng/mL (range 5.9-68.4), with 41.7% of values <20 ng/dL. Cognitive and language scaled scores increased in a stair-step manner as gestational 25(OH)D levels in the second trimester rose from <20 ng/dL, through 20-29.99 ng/dL, to ≥30 ng/dL. When controlling for socioeconomic status, race, use of tobacco products, gestational age of the child at birth, and age at the 2-year assessment, the gestational 25(OH)D was positively related to receptive language development (p < 0.017), but not cognitive or expressive language.

Assessing measurement invariance of the diabetes stress questionnaire in youth with type 1 diabetes.

OBJECTIVE: To evaluate the factor structure and measurement invariance of the Diabetes Stress Questionnaire (DSQ), a measure of diabetes-specific stress, across sex, age (<9th grade vs. ≥9th grade), and glycemic control (optimal vs. suboptimal). METHODS: Data from 318 adolescent participants were pooled from four archival data sets and the ongoing Predicting Resiliency in Youth with Type 1 Diabetes study in which the DSQ was completed. Confirmatory factor and measurement invariance analyses were conducted to confirm the proposed factor structure and measurement invariance across sex, age, and glycemic control. RESULTS: The DSQ factor structure was found to have an acceptable fit, which was invariant across sex, age, and glycemic control. CONCLUSIONS: When using the DSQ, differences in diabetes-related stress with respect to sex, age, or glycemic control can be considered meaningful. This study supports the DSQ as an evidence-based and well-established assessment of perceived diabetes stress in youth with type 1 diabetes.