Navigating Complexities: Vitamin D, Skin Pigmentation, and Race.

Vitamin D plays a critical role in many physiological functions, including calcium metabolism and musculoskeletal health. This commentary aims to explore the intricate relationships among skin complexion, race, and 25-hydroxyvitamin D (25[OH]D) levels, focusing on challenges the Endocrine Society encountered during clinical practice guideline development. Given that increased melanin content reduces 25(OH)D production in the skin in response to UV light, the guideline development panel addressed the potential role for 25(OH)D screening in individuals with dark skin complexion. The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants' skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations. Lessons learned from the guideline development process emphasize the necessity of clarity when incorporating race and ethnicity into clinical guidelines. Such clarity is an essential step toward improving health outcomes and ensuring equitable healthcare practices.

The Long-Term Effect of COVID-19 Infection on Body Composition.

BACKGROUND: The effect of COVID-19 infection versus the indirect effect of the pandemic on body composition remains unclear. This study investigates the long-term changes in body composition in COVID-19 survivors compared to a contemporary control group. METHOD: This is a prospective study involving adults who underwent a pre-pandemic whole-body DXA scan (DXA#1) between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including their medical and COVID-19 history. Inflammation markers and fasting lipids were measured. For those participants who experienced a COVID-19 infection between the two DXAs, DXA#2 was acquired at least one year after COVID-19 infection. RESULTS: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n = 80) of the participants experienced a COVID-19 infection between their two DXA scans (COVID-19+ group), and the other half had never had COVID-19. COVID-19-negative participants displayed an increase in annualized trunk fat (g) [922.5 vs. 159.7; p = 0.01], total fat (g) [1564.3 vs. 199.9; p = 0.2], and LBM (g) [974.9 vs. -64.5; p = 0.0002] when compared to the COVID-19+ group. However, among the COVID-19+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p > 0.05). CONCLUSION: During the pandemic, both the COVID-19 survivors and the COVID-19-negative group exhibited increases in weight, total fat, and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19 survivors displayed a decline in lean body mass over the same period, regardless of PASC symptoms.

Perioperative Evaluation and Management of Children with Osteoporosis and Low Bone Mineral Density.

As medical and surgical treatment options for children with osteoporosis expand, multidisciplinary strategies for bone health optimization become more important. Each patient's bone mineral density and fracture history should be interpreted in context. Off-label bisphosphonate use is a standard pharmacologic intervention for children with osteoporosis for optimal bone accrual. It is possible to continue this therapy perioperatively under certain circumstances. The rare side effects (osteonecrosis of the jaw and atypical femur fractures) seem less common in children. Physical therapy, vitamin D supplementation, and other interventions are also important tools for optimal bone health perioperatively and for satisfactory surgical outcomes.

Evolutionary conservation of putative suicidality-related risk genes that produce diminished motivation corrected by clozapine, lithium and antidepressants.

Background: Genome wide association studies (GWAS) and candidate gene analyses have identified genetic variants and genes that may increase the risk for suicidal thoughts and behaviors (STBs). Important unresolved issues surround these tentative risk variants such as the characteristics of the associated genes and how they might elicit STBs. Methods: Putative suicidality-related risk genes (PSRGs) were identified by comprehensive literature search and were characterized with respect to evolutionary conservation, participation in gene interaction networks and associated phenotypes. Evolutionary conservation was established with database searches and BLASTP queries, whereas gene-gene interactions were ascertained with GeneMANIA. We then examined whether mutations in risk-gene counterparts in C. elegans produced a diminished motivation phenotype previously connected to suicide risk factors. Results and conclusions: From the analysis, 105 risk-gene candidates were identified and found to be: 1) highly conserved during evolution, 2) enriched for essential genes, 3) involved in significant gene-gene interactions, and 4) associated with psychiatric disorders, metabolic disturbances and asthma/allergy. Evaluation of 17 mutant strains with loss-of-function/deletion mutations in PSRG orthologs revealed that 11 mutants showed significant evidence of diminished motivation that manifested as immobility in a foraging assay. Immobility was corrected in some or all of the mutants with clozapine, lithium and tricyclic antidepressant drugs. In addition, 5-HT2 receptor and muscarinic receptor antagonists restored goal-directed behavior in most or all of the mutants. These studies increase confidence in the validity of the PSRGs and provide initial clues about possible mechanisms that mediate STBs.

Invited Mini Review Metabolic Bone Disease of Prematurity: Overview and Practice Recommendations.

Metabolic bone disease of prematurity (MBDP) is defined by undermineralization of the preterm infant skeleton arising from inadequate prenatal and postnatal calcium (Ca) and phosphate (PO4) accretion. Severe MBDP can be associated with rickets and fractures. Despite advances in neonatal nutrition, MBDP remains prevalent in premature infants due to inadequate mineral accretion ex-utero. There also remain significant knowledge gaps regarding best practices for monitoring and treatment of MBDP among neonatologists and pediatric endocrinologists. Preventing and treating MBDP can prevent serious consequences including rickets or pathologic fractures. Postnatal monitoring to facilitate early recognition of MBDP is best done by first-tier laboratory screening by measuring serum calcium, phosphorus, and alkaline phosphatase to identify infants at risk. If these labs are abnormal, further studies including assessing parathyroid hormone and/or tubular resorption of phosphate can help differentiate between Ca and PO4 deficiency as primary etiologies to guide appropriate treatment with mineral supplements. Additional research into optimal mineral supplementation for the prevention and treatment of MBDP is needed to improve long-term bone health outcomes and provide a fuller evidence base for future treatment guidelines.

Global Health Disparities in Childhood Rickets.

Nutritional rickets is a global health problem reflecting both historical and contemporary health disparities arising from racial, ethnic, environmental, and geopolitical circumstances. It primarily affects marginalized populations and can contribute to long-term morbidity. Deficits in bone health in childhood may also contribute to osteomalacia/osteoporosis. Solutions require a global public health approach.

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.

Transition of young adults with metabolic bone diseases to adult care.

As more accurate diagnostic tools and targeted therapies become increasingly available for pediatric metabolic bone diseases, affected children have a better prognosis and significantly longer lifespan. With this potential for fulfilling lives as adults comes the need for dedicated transition and intentional care of these patients as adults. Much work has gone into improving the transitions of medically fragile children into adulthood, encompassing endocrinologic conditions like type 1 diabetes mellitus and congenital adrenal hyperplasia. However, there are gaps in the literature regarding similar guidance concerning metabolic bone conditions. This article intends to provide a brief review of research and guidelines for transitions of care more generally, followed by a more detailed treatment of bone disorders specifically. Considerations for such transitions include final adult height, fertility, fetal risk, heritability, and access to appropriately identified specialists. A nutrient-dense diet, optimal mobility, and adequate vitamin D stores are protective factors for these conditions. Primary bone disorders include hypophosphatasia, X-linked hypophosphatemic rickets, and osteogenesis imperfecta. Metabolic bone disease can also develop secondarily as a sequela of such diverse exposures as hypogonadism, a history of eating disorder, and cancer treatment. This article synthesizes research by experts of these specific disorders to describe what is known in this field of transition medicine for metabolic bone diseases as well as unanswered questions. The long-term objective is to develop and implement strategies for successful transitions for all patients affected by these various conditions.

Cushing syndrome as a failed cardiac screen in a patient with McCune-Albright syndrome: a case report.

BACKGROUND: McCune-Albright syndrome is a complex disorder encompassing multiple endocrinopathies. These manifestations are secondary to a mutation in the stimulatory G-protein alpha subunit. Cushing syndrome is due to autonomous secretory function of the adrenal gland and is present in 7.1% of patients with McCune-Albright syndrome. Cardiac newborn screenings assist in the identification of critical congenital heart disease. These screenings have become part of routine postnatal care nationwide. CASE REPORT: A 6-week-old Caucasian male presented to a cardiologist at the University of Tennessee Health Science Center with left ventricular hypertrophy and poor feeding after a failed cardiac newborn screen. He had been previously seen at 2 weeks by a cardiologist on follow-up for abnormal critical congenital heart disease screening. Electrocardiogram and echocardiographic studies identified hypertrophic cardiomyopathy. Other examination findings revealed multiple characteristic café-au-lait lesions along with hypotonia and rounded facies. Given his cardiac disease, he was admitted to the hospital, where an evaluation was done for Cushing syndrome, showing elevated cortisol by immunoassay of 38 µg/dL (1.7-14.0 µg/dL, Vitros 5600) after a dexamethasone suppression test and urinary cortisol elevated to 35 µg/dL/24 hours (reference range 3-9 µg/dL/24 hours) (Esoterix; Calabasas, CA). He was started on metyrapone therapy to block synthesis of cortisol. His cortisol improved and was suppressed less than 2 µg/dL. His hypertension and clinical features of Cushing syndrome improved. CONCLUSIONS: This case demonstrates a unique presentation of Cushing syndrome in a young infant. This is the first case to our knowledge showing significant left ventricular hypertrophy resulting from Cushing syndrome identified following a failure on a critical congenital heart disease screen. It highlights the importance of considering of McCune-Albright syndrome in patients with Cushing syndrome, especially if other clinical features are present. Medical therapy can be used to treat Cushing syndrome and can result in improvement in the cardiovascular pathology.

Treatment Practices and Confidence in the Management of Pediatric Metabolic Bone Disorders.

INTRODUCTION: Pediatric metabolic bone and mineral disorders encompass a wide variety of disorders that can be challenging to diagnose and treat because of inadequate physician training about optimal management. METHODS: As practice variation and confidence levels may impact clinical outcome, we sought to assess physician confidence in managing pediatric metabolic bone and mineral disorders and the spectrum of treatment practices among members of the Pediatric Endocrine Society (PES) and the Canadian Pediatric Endocrine Group (CPEG). Questionnaires were distributed via e-mail to all members of the PES and CPEG and 244 were completed. Responses were summarized using descriptive statistics, and proportions were compared using χ2 or Fisher's exact tests, as appropriate. RESULTS: Variations were observed among the respondents' confidence in the management of bone disorders and in the criteria used to initiate/discontinue intravenous bisphosphonates or prescribe burosumab therapy. Respondents felt confident with the management of 4 out of 20 pediatric bone conditions (confidence was defined as >90% of respondents reporting feeling "somewhat confident" or "very confident"). Physicians working in a bone clinic were more confident in prescribing burosumab for the treatment of X-linked hypophosphatemic rickets compared to those not working in a bone clinic (65% vs. 47%, p = 0.03). Most respondents (52%) reported having received inadequate training in pediatric metabolic bone and mineral disorders. DISCUSSION/CONCLUSION: Dedicated training, knowledge acquisition, and education resources are needed to increase confidence and standardize the use of bone-targeted therapies.

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.

Clinical Characteristics and Predictors of Mortality in Minority Patients Hospitalized with COVID-19 Infection.

OBJECTIVES: To identify the early mortality predictors in minority patients hospitalized with coronavirus disease 2019 (COVID-19). DESIGN: Demographics, presenting characteristics, admission laboratory data, ICU admission, and mortality data were collected from 200 consecutively hospitalized patients with COVID-19. RESULTS: The mean (SD) age was 58.9 (15.1) years, 121(60.5%) were men, 143 (71.5%) were African Americans, and 33 (16.5%) were Latino. Common presenting symptoms were cough 130 (65.0%), shortness of breath 129 (64.5%), and fever 121 (60.5%). One or more comorbid illness occurred in 171 (85.5%) and common comorbidities were hypertension (130 (65.2%)), diabetes (100 (50.0%)) and chronic kidney disease (60 (30.0%)). Of the 200 patients, 71 (35.5%) were treated in the ICU, 47 (24.2%) received mechanical ventilation, 45 (22.5%) died, and 155(77.5%) patients discharged home alive. The non-survivors were significantly older and had elevated markers of inflammation, coagulation, and acute organ damage on presentation. Age ≥ 65 years (odds ratio (OR), 3.78; 95% CI, 1.74-8.22; P = .001), lactate dehydrogenase level > 400 IU/L (OR, 9.1; 95% CI, 2.97-28.1; p < 0.001), C-reactive protein > 20 mg/dl (OR, 5.56; 95%CI, 1.84-16.8; p < 0.001), ferritin > 2000 ng/ml (OR, 5.42; 95%CI, 1.63-17.9; p = 0.006), creatinine kinase > 1000 iu/l (OR, 3.57; 95% CI, 1.23 10.3; p = 0.019), procalcitonin > 2.5 ng/ml (OR, 4.21; 95% CI, 1.47-12.0; p = 0.007), D-dimer level > 3.0 µg/ml (OR,10.9; 95% CI, 3.33-36.2; p = < 0.001), creatinine > 2 mg/dl (OR, 4.5; 95% CI, 1.29-15.8; P = 0.018) at admission were associated independently with increases risk of in-hospital mortality. CONCLUSION: Patients of advanced age that present with elevated biomarkers of inflammation, coagulation, and end-organ damage were at higher risk of mortality.

Three Healthy Eating Patterns and Cardiovascular Disease Risk Markers in 9 to 18 Year Olds With Body Mass Index >95%: A Randomized Trial.

Approximately 20% of American 9 to 18 year olds are obese, and most carry their excess adiposity, with its associated increased risk for cardiovascular disease, into adulthood. We studied cardiovascular disease risk markers changes associated with 3 healthy eating patterns (HEPs) in 96 9 to 18 year olds with a body mass index >95% in a Midwestern health system 1-year randomized trial. All HEPs were associated with similar statistically significant (P < .05 to <.001) cardiovascular disease risk marker improvements in weight, systolic and diastolic blood pressure, total cholesterol, low-density lipoprotein, and myeloperoxidase. Time required was the only identified significant (P < .001) deterrent from enrolling in study. These HEPs had characteristics common to most HEPs: encouraging whole foods, fruits and vegetables, whole grains, beans other legumes, and limiting added salt, saturated fatty acids, added sugars, red meat, processed meats, and other processed foods. Further research on initiatives to ease the time burden, and increase implementation of established healthy eating principles is needed.

A pilot study of a low glycemic load diet in patients with stage I-III colorectal cancer.

BACKGROUND: Consumption of a diet with high glycemic indices has been associated with inferior cancer-specific outcomes in patients with early-stage colorectal cancer, but there is limited prospective evidence that alterations in dietary habits improves cancer outcomes. This study aimed to determine the feasibility and acceptability of following a low glycemic load (GL) diet in patients with stage I-III colorectal cancer. METHODS: Patients with stage I-III colorectal cancer, who completed definitive therapy, and consumed an average daily GL >150 participated in a 12-week tailored face-to-face dietary intervention with a target GL. This study followed a 2-stage design, with 4 planned cohorts, each with an assigned GL target and dietary intervention intensity. The primary endpoint of feasibility was determined by participant compliance, defined as an individual following the assigned GL ≥75% of the time. Compliance was determined using 24-hour telephone recalls. A cohort was deemed feasible if at least 67% of participants were compliant. Secondary endpoints included acceptability of the diet, nutritional support resources necessary to follow the diet, and evaluation of the effect of the diet on physical measures and correlative laboratories. RESULTS: Only cohort 1 was required as the primary endpoint of feasibility was met (stringent GL target, low intensity dietary support). The majority of participants experienced a decrease in body mass index (BMI) and waist circumference, 29% experiencing meaningful weight loss (≥5%). The dietitian spent an average of 6.97 hours (SD 2.18) face-to-face time and 1.58 hours (SD 0.68) by phone with each participant. Significant decreases were seen in total cholesterol, very-low-density lipoprotein (VLDL) and triglycerides (all P<0.05). All participants liked the foods and were satisfied with the diet. All participants felt the in-person meetings were helpful, and 62% did not feel a virtual meeting (e.g., Skype, etc.) could replace in-person meetings. CONCLUSIONS: Patients with stage I-III colorectal cancer can follow a low GL diet with a 12-week in-person dietary intervention. Significant changes in physical and laboratory measures suggest relevant biologic effects of the dietary intervention. This study establishes feasibility, and warrants a larger scale prospective intervention trial to evaluate the impact of a low GL diet on cancer outcomes.