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.

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.

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.

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.

Newborn Screening Protocols and Positive Predictive Value for Congenital Adrenal Hyperplasia Vary across the United States.

Newborn screening for congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency is mandated throughout the US. Filter paper blood specimens are assayed for 17-hydroxyprogesterone (17OHP). Prematurity, low birth weight, or critical illness cause falsely elevated results. The purpose of this report is to highlight differences in protocols among US state laboratories. We circulated a survey to state laboratory directors requesting qualitative and quantitative information about individual screening programs. Qualitative and quantitative information provided by 17 state programs were available for analysis. Disease prevalence ranged from 1:9941 to 1:28,661 live births. Four state laboratories mandated a second screen regardless of the initial screening results; most others did so for infants in intensive care units. All but one program utilized birthweight cut-points, but cutoffs varied widely: 17OHP values of 25 to 75 ng/mL for birthweights >2250-2500 g. The positive predictive values for normal birthweight infants varied from 0.7% to 50%, with the highest predictive values based in two of the states with a mandatory second screen. Data were unavailable for negative predictive values. These data imply differences in sensitivity and specificity in CAH screening in the US. Standardization of newborn screening protocols could improve the positive predictive value.

How Peer Conflict Profiles and Socio-Demographic Factors Influence Type 1 Diabetes Adaptation.

OBJECTIVE: This study aimed to (a) validate the factor structure for a measure of peer conflict in youth with type 1 diabetes (T1D); (b) determine empirical patterns of peer conflict in terms of context (friend vs. nonfriend) and content (diabetes-specific vs. general) within a broader context of socio-demographic factors; and (c) examine how these patterns and socio-demographic factors relate to adolescents' T1D adherence, quality of life, and glycemic control (HbA1c). METHODS: Youth with T1D (N = 178), ages 12-18, reported demographic variables, illness duration, adherence, quality of life, and peer conflict. HbA1c was extracted from medical records. Confirmatory factor analysis validated a factor structure for the Diabetes Peer Conflict Scale (DPCS) and latent profile analysis (LPA) determined profiles of peer conflict. RESULTS: A four-factor structure emerged for the DPCS: general friend conflict, general nonfriend conflict, T1D friend conflict, and T1D nonfriend conflict. Using these factors as indicators in LPA, four profiles were confirmed: (a) Low Overall Conflict (LOC) and (b) Moderate Overall Conflict (MOC), (c) a Nonfriend Conflict (NFC), and (d) a Friend Conflict (FC) profile. Differences were not identified between diabetes specific versus general conflict. Socio-demographic variables did not predict class membership. The LOC profile reported the highest quality of life and best glycemic control, whereas the FC profile reported the lowest adherence behaviors. Conclusions: Peer conflict uniquely contributes to diabetes adaptation above and beyond socio-demographic and illness factors.

Low prevalence of organic pathology in a predominantly black population with premature adrenarche: need to stratify definitions and screening protocols.

BACKGROUND: Premature adrenarche has been described as clinical and biochemical hyperandrogenism before the age of 8 years in girls and 9 years in boys and absence of signs of true puberty. Adrenal pathology such as adrenal tumors or non-classical congenital adrenal hyperplasia (NCCAH) and exogenous androgen exposure need to be excluded prior to diagnosing (idiopathic) premature adrenarche. Premature adrenarche is more common among black girls compared to white girls and other racial groups. Adrenal pathology such as NCCAH is less common as a cause for premature adrenarche compared with idiopathic premature adrenarche. The evaluation guidelines for premature adrenarche however are not individualized based on racial/ethnic differences. Few studies have been done to evaluate a largely black population with premature adrenarche to assess the incidence of adrenal pathology. METHODS: This cross-sectional retrospective study evaluated characteristics of prepubertal patients seen in an endocrine clinic for premature adrenarche. RESULTS: Two hundred and seventy three subjects had signs of early adrenarche. Three subjects were found to have CAH (2 with NCCAH and 1 with late diagnosis classical CAH). None were black. Exogenous androgen exposure was etiology in 4 additional subjects. These 7 patients were excluded from further analysis. The remaining subjects had idiopathic PA (n = 266); 76.7% were females. The mean age at initial visit was 6.42 +/- 1.97 years (with no racial difference) although black subjects were reported symptom onset at a significantly younger age compared to non-Hispanic white patients. CONCLUSIONS: Our study showed organic pathology was very uncommon in a predominantly black population with premature adrenarche. Patient factors that influence the probability of an underlying organic pathology including race/ ethnicity should be considered to individualize evaluation.

Living with an invisible illness: a qualitative study exploring the lived experiences of female children with congenital adrenal hyperplasia.

PURPOSE: Many chronic illnesses are self-evident. However, disorders like congenital adrenal hyperplasia (CAH) are invisible to the naked eye and unnoticeable to others. Therefore, invisible illness is often a shared, misconstrued experience for children with CAH, their caregivers, and the medical community. This experience, along with its lack of awareness and added stigma, may impact overall quality of life (QOL) of such individuals. To facilitate our understanding of QOL of children with CAH, we must first explore their subjective experiences. This study aimed to capture their lived experiences and provide recommendations to support children with CAH. METHODS: We conducted semi-structured interviews with 20 female children with CAH between 7 and 18 years and their caregivers. Interviews were transcribed verbatim, checked for accuracy, and independently coded by the first and second author. Content analysis was used to organize data so that codes could be condensed into categories and themes. Differences around code, category, and theme description were reconciled. RESULTS: Participants' experiences were described in five themes: (1) Making sense of the situation; (2) Emotional and psychological impact of an invisible illness; (3) Normalcy; (4) Disclosure of diagnosis; and (5) Improving the care of children with CAH CONCLUSION: Exploring children's views about living with an invisible illness illuminated individual aspects contributing to our in-depth understanding of experiences of children with CAH. Ongoing education and awareness of CAH is necessary to help mitigate the stigma associated with living with CAH.

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.

Intracranial pathologies associated with central diabetes insipidus in infants.

Background Idiopathic central diabetes insipidus (CDI) has been associated with intracranial pathologies that do not involve the structural pituitary gland or hypothalamus. The objective was to study the association between non-structural hypothalamic/pituitary intracranial pathologies (NSHPIP) with CDI and to review etiologies that may be contributory to the development of CDI. Methods A retrospective query of our intra-institutional database from 2006 to 2015. Children admitted diagnosed with diabetes insipidus (DI) (ICD-9 253.5) between the ages of 0-1 year were included. Patient charts were reviewed to include those who have a documented diagnosis of CDI, hypernatremia (>145 mmol/L), high serum osmolality (>300 mOsm/kg), low urine osmolality (<300 mOsm/kg), and brain imaging reports. Diagnoses of nephrogenic DI were excluded. Results Twenty-three infant patients were diagnosed with CDI. Eleven subjects (48%) had NSHPIP. Of those, 18% had cerebral infarction, 27% had intracranial injury and hemorrhage due to traumatic brain injury, 18% had isolated intraventricular hemorrhage, and 27% had meningitis. Hospital prevalence for NSHPIP, age 0-1 year, ranged from 0.05% to 0.3%. Conclusions Rates of NSHPIP in those with CDI are higher than expected hospital rates (p<0.001), suggesting a possible association between CDI and NSHPIP.

Delayed Puberty.

Delayed puberty is defined as the absence of physical signs of puberty 2 to 2.5 standard deviations above the mean age and affects approximately 2% of adolescents. Causes of delayed puberty are broadly divided into two categories: hypergonadotropic hypogonadism and hypogonadotropic hypogonadism. One exception to this classification system is constitutional delay of growth and puberty, the most common cause of delayed puberty. For the general pediatrician, knowledge of the different causes and initial steps to evaluation is crucial when a patient with delayed puberty presents. [Pediatr Ann. 2018;47(1):e16-e22.].