Impact of Growth Hormone on Adult Bone Quality in Turner Syndrome: A HR-pQCT Study.

Women with Turner syndrome (TS) are known to be at risk of osteoporosis. While childhood growth hormone (GH) treatment is common in TS, the impact of this therapy on bone health has been poorly understood. The objective of this study was to determine the influence of childhood GH treatment on adult bone quality in women with TS. 28 women aged 17-45 with confirmed TS (12 GH-treated) agreed to participate in this cross-sectional study. Dual X-ray absorptiometry (DXA) of lumbar spine, hip, and radius and high-resolution peripheral quantitative computed tomography (HR-pQCT) scans of the radius and tibia were used to determine standard morphological and micro-architectural parameters of bone health. Finite element (FE) analysis and polar moment of inertia (pMOI) were used to estimate bone strength. GH-treated subjects were +7.4 cm taller (95% CI 2.5-12.3 cm, p = 0.005). DXA-determined areal BMD of hip, spine, and radius was similar between treatment groups. Both tibial and radial total bone areas were greater among GH-treated subjects (+20.4 and +21.2% respectively, p < 0.05), while other micro-architectural results were not different between groups. pMOI was significantly greater among GH-treated subjects (radius +35.0%, tibia +34.0%, p < 0.05). Childhood GH treatment compared to no treatment in TS was associated with an increased height, larger bones, and greater pMOI, while no significant difference in DXA-derived BMD, HR-pQCT micro-architectural parameters, or FE-estimated bone strength was detected. The higher pMOI and greater bone size may confer benefit for fracture reduction in these GH-treated patients.

Quality of referral of short children to the paediatric endocrinologist and impact of a fax communication system.

BACKGROUND/OBJECTIVES: In 2001, a chart review of children referred to the authors' endocrine clinic because of short stature revealed that many were referred with insufficient baseline data, had normal height velocity and were within genetic target height. Therefore, a two-way fax communication system was implemented between referring physicians and the authors' service before the first visit. Aspects that were assessed included whether this system increased the information accompanying the patient at referral, resulted in children with nonpathological shortness not being seen in the clinic, and was used differently by paediatricians and general practitioners. STUDY DESIGN: Between January and December 2006, 138 referrals for short stature, diagnosed with familial short stature, constitutional delay or idiopathic short stature, were audited (69 with and 69 without previous fax communication). Data collected included source of referral, clinical information provided, available growth measurements, and results from laboratory and imaging studies. RESULTS: Fax communication resulted in growth curves being provided more often (95.6% of cases versus 40.5% of cases without fax communication [P<0.001]) and more investigations being performed by the referring physician (median [range]: six [zero to 13] investigations versus one [zero to 11]; P<0.001), as well as a diagnosis of nonpathological short stature being given to 31 children based on the growth curve, laboratory and imaging results, without the children being seen in the endocrine clinic. Fax communication was also used more frequently by paediatricians (84%) than by general practitioners (15%). CONCLUSION: The fax communication system resulted in a more complete evaluation of referred patients by their physicians and reduced the number of unnecessary visits to the authors' specialty clinic while promoting medical education.

HISTORIQUE ET OBJECTIFS: En 2001, un examen des dossiers d'enfants aiguillés vers la clinique d'endocrinologie des auteurs en raison de leur petite taille a révélé que bon nombre des aiguillages ne s'accompagnaient pas de données de base suffisantes et que les patients aiguillés présentaient une croissance normale et une taille qui respectait leur cible génétique. C'est pourquoi un système de communication bidirectionnelle par télécopieur a été mis sur pied entre les médecins traitants et le service d'endocrinologie avant le premier rendez-vous. Les auteurs ont évalué si le système permettait d'avoir plus d'information au sujet du patient lors de l'aiguillage, s'il évitait que les patients dont la petite taille n'était pas d'origine pathologique soient vus à la clinique et s'il était utilisé de manière différente par les pédiatres et les omnipraticiens. MÉTHODOLOGIE: De janvier à décembre 2006, les auteurs ont évalué 138 aiguillages en raison d'une petite taille, diagnostiquée comme une petite taille familiale, un retard constitutionnel ou une petite taille idiopathique (69 avec et 69 sans communication antérieure par télécopieur). Les données colligées incluaient la source de l'aiguillage, l'information clinique fournie, les mesures de croissance transmises et les résultats des études de laboratoire et d'imagerie. RÉSULTATS: La communication par télécopieur a permis d'obtenir plus souvent les courbes de croissance (95,6 % des cas plutôt que 40,5 % [P<0,001]) et de faire faire plus d'examens par le médecin traitant (médiane [plage] : six [zéro à 13] examens au lieu d'un [zéro à 11]; P<0,001), ainsi que de poser un diagnostic de petite taille non pathologique chez 38 enfants d'après la courbe de croissance et les résultats de laboratoire et d'imagerie, sans qu'ils soient vus à la clinique d'endocrinologie. Par ailleurs, la communication par télécopieur était plus utilisée par les pédiatres (84 %) que par les omnipraticiens (15 %). CONCLUSION: Le système de communication par télécopieur a donné lieu à une évaluation plus complète des patients aiguillés par leur médecin et réduit le nombre de rendez-vous inutiles à la clinique spécialisée des auteurs, tout en favorisant la formation médicale.

Improving Research on Racial Disparities in Access to Medications to Treat Opioid Use Disorders.

OBJECTIVES: The aims of the study are to review the current research on the association between access to medications for opioid use disorders (MOUD) and race, to identify gaps in research methods, and to propose new approaches to end racialized disparities in access to MOUD. METHODS: We conducted a literature review of English language peer-reviewed published literature from 2010 to 2021 to identify research studies examining the association between race and use of, or access to, MOUD. RESULTS: We reviewed 21 studies related to access to MOUD for Black and White populations. Of the 21 studies, 16 found that Black individuals had lower use of, or access to, MOUD than White individuals, 2 found the opposite among patients in specialty addiction treatment, 1 found that the difference changed over time, and 2 found that distance to opioid treatment programs was shorter for Black residents than for White residents. CONCLUSIONS: To improve future research, we recommend that researchers (1) be clearer on how race is conceptualized and interpreted; (2) explicitly evaluate the intersection of race and other factors that may influence access such as income, insurance status, and geography; (3) use measures of perceived racism, unconscious bias, and self-identified race; (4) collect narratives to better understand why race is associated with lower MOUD access and identify solutions; and (5) evaluate the effect of policies, programs, and clinical training on reducing racial disparities. A multitude of studies find that Black individuals have lower access to MOUD. Researchers must now identify effective solutions for reducing these disparities.

Regulation of Metabolism by an Ensemble of Different Ion Channel Types: Excitation-Secretion Coupling Mechanisms of Adipokinetic Hormone Producing Cells in Drosophila.

Adipokinetic Hormone (AKH) is the primary insect hormone that mobilizes stored energy and is functional equivalent to mammalian glucagon. While most studies have focused on exploring the functional roles of AKH, relatively little is known about how AKH secretion is regulated. We assessed the AKH cell transcriptome and mined the data set for specific insight into the identities of different ion channels expressed in this cell lineage. We found reliable expression of multiple ion channel genes with multiple members for each ionic species. Specifically, we found significant signals for 39 of the either known or suspected ion channel genes within the Drosophila genome. We next performed a targeted RNAi screen aimed to identify the functional contribution of these different ion channels that may participate in excitation-secretion coupling in AKH producing cells (APCs). We assessed starvation survival, because changes in AKH signaling have previously been shown to impact starvation sensitivity. Genetic knockdown of three genes (Ca-Beta, Sur, and sei), in AKH producing cells caused highly significant changes (P < 0.001) in both male and female lifespan, and knockdown of six other genes (Shaw, cac, Ih, NaCP60E, stj, and TASK6) caused significant changes (P < 0.05) in only female lifespan. Specifically, the genetic knockdown of Ca-Beta and Sur led to increases in starvation lifespan, whereas the knockdown of sei decreased starvation survivorship. Focusing on these three strongest candidates from the behavioral screen, we assessed other AKH-dependent phenotypes. The AKH hormone is required for starvation-induced hyperactivity, and we found that these three ion channel gene knockdowns changed activity profiles and further suggest a modulatory role of these channels in AKH release. We eliminated the possibility that these genetic elements caused AKH cell lethality, and using independent methods, we verified expression of these genes in AKH cells. Collectively, these results suggest a model of AKH-cell excitability and establish an experimental framework for evaluating intrinsic mechanisms of AKH release.

How are States Measuring It?: National Survey Findings on State Access Monitoring Efforts for Fee-for-Service Medicaid Enrollees.

For many years, barriers to access have been a significant concern in the Medicaid program. In November 2015, the Centers for Medicare & Medicaid Services issued a Final Rule that requires states to submit access monitoring plans every three years beginning in October 2016. State access monitoring plans must focus on five categories of service and three domains for measuring and monitoring access to care. This article presents findings from the first national survey that examines what states were doing to measure access to fee-for-service Medicaid care prior to the Final Rule. Our findings show states generally collected some type of access to care measure, relied on a multitude of data sources to assess access, and most commonly used these measures to assess adequacy of access. Data from this survey provide a basis for understanding how close states are to complying with the new federal regulation's access monitoring requirements.

Satisfaction with Financial Incentives for Chronic Disease Prevention.

ObjectiveWe examined Medicaid enrollees' experiences and satisfaction with financial incentives-based chronic disease prevention programs in 10 states. MethodsThis cross-site study of the Medicaid Incentives for Prevention of Chronic Diseases model used a mixed-methods approach to assess Medicaid enrollees' experiences and satisfaction with the incentive programs. We conducted 31 in-person focus groups with 212 program participants, followed by a mail survey in English and Spanish (N = 2274). We used both the qualitative focus group data and the quantitative survey data to examine participant satisfaction with the incentives, along with differences by program and incentive characteristics. ResultsOverall, focus group and survey findings aligned, with participants reporting satisfaction with program incentives. Participants felt that the incentives helped them make positive changes to improve their health. Nevertheless, satisfaction varied considerably depending on characteristics of the program, such as the form and magnitude of the incentive, health focus of the program, and program delivery method. ConclusionsProgram and incentive characteristics play key roles in participants' satisfaction and experience with incentive-based, chronic disease prevention programs. Further research is required to examine the optimal design of incentive programs to support sustained behavior change.

Elevated urinary CRELD2 is associated with endoplasmic reticulum stress-mediated kidney disease.

ER stress has emerged as a signaling platform underlying the pathogenesis of various kidney diseases. Thus, there is an urgent need to develop ER stress biomarkers in the incipient stages of ER stress-mediated kidney disease, when a kidney biopsy is not yet clinically indicated, for early therapeutic intervention. Cysteine-rich with EGF-like domains 2 (CRELD2) is a newly identified protein that is induced and secreted under ER stress. For the first time to our knowledge, we demonstrate that CRELD2 can serve as a sensitive urinary biomarker for detecting ER stress in podocytes or renal tubular cells in murine models of podocyte ER stress-induced nephrotic syndrome and tunicamycin- or ischemia-reperfusion-induced acute kidney injury (AKI), respectively. Most importantly, urinary CRELD2 elevation occurs in patients with autosomal dominant tubulointerstitial kidney disease caused by UMOD mutations, a prototypical tubular ER stress disease. In addition, in pediatric patients undergoing cardiac surgery, detectable urine levels of CRELD2 within postoperative 6 hours strongly associate with severe AKI after surgery. In conclusion, our study has identified CRELD2 as a potentially novel urinary ER stress biomarker with potential utility in early diagnosis, risk stratification, treatment response monitoring, and directing of ER-targeted therapies in selected patient subgroups in the emerging era of precision nephrology.

Current concepts surrounding bone health and osteoporosis in Turner syndrome.

Although Turner syndrome is the most common chromosomal disorder in women, a great deal remains to be understood in terms of optimal patient care, particularly as it relates to bone health. These women are known to be at risk for osteoporosis and fracture later in life as a result of a multitude of risk factors. While estrogen replacement and childhood growth hormone treatment are now considered standard of care, little is known of the role of further interventions to prevent and treat osteoporosis in these women. This review aims to highlight the specifics of bone health in Turner syndrome. We explore the bone diagnostic modalities and therapeutic interventions available and their role in the coming years of bone health management in this unique population.

Effect of oxandrolone and timing of oral ethinylestradiol initiation on pubertal progression, height velocity and bone maturation in the UK Turner study.

BACKGROUND: A UK study showed final height in Turner syndrome (TS) girls receiving growth hormone is affected by age at pubertal induction and oxandrolone (Ox). Using data from that study, we analysed the effect of timing of oral ethinylestradiol (EE2) and Ox on height velocity (HV), bone maturation and pubertal progression, and compared growth response in EE2-treated versus spontaneous puberty. METHODS: Analysis of HV, bone age and pubertal stage in 92 TS girls (7-13 years) randomised to Ox (0.05 mg/kg/day; max: 2.5 mg/day) or placebo from 9 years, and EE2 (year 1: 2 µg/day; year 2: 4 µg/day; year 3: 6/8/10 µg/day×4 months) or placebo at 12 years with EE2 at 14 years. Girls enrolled at >12.25 years received EE2 at 14 years ('late group'). RESULTS: Fifty-six girls were randomised to EE2 at 12 years (n=28, 11 Ox) or 14 years (n=28, 13 Ox); there were 19 girls in the late group (9 Ox) and 17 girls with spontaneous puberty (10 Ox). Girls receiving EE2 at 12 versus 14 years had faster bone maturation, but neither group showed acceleration. Ox increased HV without altering bone maturation or pubertal progression. Girls with spontaneous puberty had greater pubertal growth (mean PHV 8.5 cm/year; p<0.001) and height gain (p<0.001) than EE2-treated girls despite similar mean enrolment height SD and dysmorphology scores. CONCLUSION: Pubertal induction with EE2 does not replicate the acceleration observed in unaffected girls or TS girls with spontaneous puberty.

Effect of oxandrolone and timing of pubertal induction on final height in Turner's syndrome: randomised, double blind, placebo controlled trial.

OBJECTIVE: To examine the effect of oxandrolone and the timing of pubertal induction on final height in girls with Turner's syndrome receiving a standard dose of growth hormone. DESIGN: Randomised, double blind, placebo controlled trial. Setting 36 paediatric endocrinology departments in UK hospitals. PARTICIPANTS: Girls with Turner's syndrome aged 7-13 years at recruitment, receiving recombinant growth hormone therapy (10 mg/m(2)/week). INTERVENTIONS: Participants were randomised to oxandrolone (0.05 mg/kg/day, maximum 2.5 mg/day) or placebo from 9 years of age. Those with evidence of ovarian failure at 12 years were further randomised to oral ethinylestradiol (year 1, 2 µg daily; year 2, 4 µg daily; year 3, 4 months each of 6, 8, and 10 µg daily) or placebo; participants who received placebo and those recruited after the age of 12.25 years started ethinylestradiol at age 14. MAIN OUTCOME MEASURE: Final height. Results 106 participants were recruited, of whom 14 withdrew and 82/92 reached final height. Both oxandrolone and late pubertal induction increased final height: by 4.6 (95% confidence interval 1.9 to 7.2) cm (P = 0.001, n = 82) for oxandrolone and 3.8 (0.0 to 7.5) cm (P = 0.05, n = 48) for late pubertal induction with ethinylestradiol. In the 48 children who were randomised twice, the effects on final height (compared with placebo and early induction of puberty) of oxandrolone alone, late induction alone, and oxandrolone plus late induction were similar, averaging 7.1 (3.4 to 10.8) cm (P < 0.001). No cases of virilisation were reported. CONCLUSION: Oxandrolone had a positive effect on final height in girls with Turner's syndrome treated with growth hormone, as did late pubertal induction with ethinylestradiol at age 14 years. However, these effects were not additive, so using both had no advantage. Oxandrolone could, therefore, be offered as an alternative to late pubertal induction for increasing final height in Turner's syndrome. Trial registration Current Controlled Trials ISRCTN50343149.

Hypoechoic thyroid nodules on ultrasound 4 years after prenatal exposure to radioiodine: resolution with thyroxine therapy.

UNLABELLED: We describe an infant inadvertently exposed to radioiodine at 17 weeks gestation. His mother had received 400 MBq of (131)I for hyperthyroidism (total T4 178 nmol/L, thyroid stimulating hormone (TSH) <0.1 mU/L, 4-h (131)I uptake 16%). Following cordocentesis at 27 weeks (free T4 12.7 pmol/L, TSH 35.4 mU/L) intra-amniotic thyroxine was withheld and a male infant was born at 39 weeks gestation, birthweight 3520 g. Cord TSH was low (0.1 mU/L), total T4 151 nmol/L on day 4, the mother having received no medication during pregnancy. Postnatal follow-up showed mild TSH elevation (11.0-19.4 mU/L) but normal free T4 (9-12.7 pmol/L) during the first 2 years of life following which the child was discharged still untreated. On recall at 4.3 years, TSH elevation persisted (15.4 mU/L) and ultrasound showed several hypoechoic thyroid nodules within the left lobe that disappeared after thyroxine treatment. CONCLUSION: In the event of inadvertent exposure to radioiodine in utero, the infant should receive thyroxine therapy from birth in order to protect the thyroid gland from TSH over-stimulation, however mild.