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INTRODUCTION: For academic promotion, clinical faculty are expected to excel in clinical care, teaching, and scholarship. Ensuring adequate protected time and resources to engage in scholarly work in the face of competing clinical responsibilities is critical. The authors examined academic leaders' perspectives across affiliate hospitals of a large medical school regarding the definition of clinical full-time effort and academic time, best practices to enable academic success, and barriers to faculty advancement. METHODS: Open-ended, semistructured, individual interviews were conducted with a purposive sample of clinical department and division heads. Interview data were examined to illuminate the range and commonalities in practices and to identify successful approaches. RESULTS: Interviews were conducted with 17 academic leaders across 6 affiliate hospitals. There was considerable variability in clinical full-time effort definition. "Academic time," more accurately characterized as "nonclinical time," was typically 1 day a week for nonshift specialties and mostly used for administrative work or completing clinical documentation. Certain departments were more explicit in designating and protecting time for academic pursuits; some had invested resources in intensive programs for academic advancement with built-in expectations for accountability. The impact of documentation burden was considerable in certain departments. DISCUSSION AND CONCLUSION: Marked variability exists in time allocations for clinical and academic work, as well as in resources for academic success. This supports the potential value of establishing standards for defining and protecting academic time, motivating clinical faculty to engage in academic work, and building accountability expectations. Sharing best practices and setting standards may enhance academic advancement. Strategies to reduce documentation burden may enhance wellness. [ABSTRACT FROM AUTHOR]

The hypothalamic hormone oxytocin (OXT) plays an important role in a range of physiological processes and social-emotional functioning in both sexes. In women, physiological stimuli, such as suckling and parturition, result in pulsatile release of OXT into the peripheral circulation via the posterior pituitary gland. However, data regarding OXT secretory patterns in men during a state of rest are limited. Further, the relationship between secretory dynamics of OXT and emotional measures has never been evaluated. We hypothesized a pulsatile pattern of OXT secretion in men, and explored the relationship between OXT secretory patterns and social-emotional functioning. Methods Deconvolution analysis was performed on serum OXT levels obtained every 5 min over a period of 10 h in 5 healthy normal weight men. Area under the curve (AUC), average OXT values, and pulse characteristics [pulse number, inter-pulse interval, pulse height and mass (area under each pulse)] were calculated. State Adult Attachment Measure (SAAM) assessed types of human attachment. Interpersonal Support Evaluation List (ISEL) assessed perception of social support. Toronto Alexithymia Scale (TAS-20) measured the ability to express and identify one’s own emotions. Results Mean age was 22.8 ± 1.2 years, and BMI was 21.7 ± 0.4 kg/m 2 (mean ± SEM). Assuming a basal secretion of zero and a half life of five to seven minutes, we demonstrated the following: OXT AUC: 5421 ± 1331 pg/ml, mean OXT level: 9.1 pg/ml, mean pulse number: 22 ± 3/10hr, mean pulse height: 1.81 ± 0.48 pg/ml, mean pulse mass: 30.34 ± 10.29 pg/ml and mean inter-pulse interval: 27 ± 4 min. The SAAM Avoidant scale correlated negatively with mean OXT pulse height (r = −0.90, p = 0.04) and pulse mass (r = −0.95, p = 0.01). The ISEL Belonging score correlated positively with OXT AUC (r = 0.89, p = 0.04) and average OXT (r = 0.93, p = 0.02). ISEL Appraisal score also had a positive association with mean OXT pulse height (r = 0.99, p = 0.0006) and pulse mass (r = 0.98, p = 0.003). Finally, ISEL total score had a significant correlation with average OXT values (r = 0.90, p = 0.04). While none of the subjects had a score in the alexithymia range, TAS-20 Difficulty describing feelings score had an inverse correlation with OXT pulse height (r = −0.96, p = 0.01) and pulse mass (r = −0.99, p = 0.001). TAS-20 total score also had an inverse correlation with OXT pulse height (r = −0.94, p = 0.02) and pulse mass (r = −0.96, p = 0.009). Conclusion We demonstrate a pulsatile pattern of peripheral OXT secretion in healthy men at rest. Subjects with lower OXT pulse height and pulse mass had a more avoidant style of attachment, felt less supported, and expressed greater difficulty in describing their feelings. Our findings support the concept that OXT is a key mediator of social-emotional functioning. Future studies to determine causality are warranted. [ABSTRACT FROM AUTHOR]

We describe initial manifestations, approach to diagnosis, and treatment of a patient with congenital disorder of glycosylation type 1b (CDG 1b), previously managed as acetylcarnitine deficiency. A 9-year-old girl initially diagnosed with and treated for acetylcarnitine deficiency at an outside hospital presented with recurrent hypoglycemia, failure to thrive, poor weight gain, and short stature. She had discontinued levocarnitine therapy because of lack of response, and testing with us demonstrated a normal carnitine and acyl carnitine panel and hyperinsulinemic hypoglycemia during a diagnostic fast. Oral diazoxide and hydrochlorothiazide were initiated with resolution of hypoglycemia. She had iron deficiency anemia, but an upper gastrointestinal evaluation was normal. Genetic testing confirmed a diagnosis of CDG 1b caused by deficiency of mannose phosphate isomerase. Oral mannose was started with gradual reduction in and eventual discontinuation of the diazoxide dose. Hypoglycemia in the pediatric age group needs a systematic approach. It is important to raise awareness of CDG 1b, which can present as persistent hyperinsulinemic hypoglycemia. Mannose supplementation can ameliorate clinical symptoms and biochemical abnormalities. [ABSTRACT FROM AUTHOR]

The article describes the case of a child patient with an enlarging mass in the right breast. It discusses the patient's medical history, results of his medical examination, ultrasound examination of the right breast, the evaluation of the child for possible gynecomastia and causes of gynecomastia and final diagnosis.

Anorexia nervosa (AN) is a condition of severe undernutrition associated with adaptive changes in many endocrine axes. These changes include hypogonadotropic hypogonadism, acquired growth hormone resistance with low insulin- like growth factor 1 (IGF-1) levels, hypercortisolemia, altered secretion of adipokines and appetite-regulating hormones, and low bone mineral density (BMD). Bone health is impaired subsequent to a low body mass index, decreased lean mass, and the endocrine changes described above. In addition to low areal BMD, AN is characterized by a decrease in volumetric BMD, changes in bone geometry, and reductions in strength estimates, leading to an increased risk for fracture. Weight restoration is essential for restoration of normal endocrine function; however, hypercortisolemia, high peptide YY levels, and ghrelin dynamics may not completely normalize. In some patients, hypogonadotropic hypogonadism persists despite weight restoration. Weight gain and menstrual recovery are critical for improving bone health in AN; however, residual deficits may persist. Physiologic estrogen replacement using transdermal, but not oral, estrogen increases bone accrual in adolescents with AN, while bisphosphonates improve BMD in adults. Recombinant human IGF-1 and teriparatide have been used in a few studies as bone anabolic therapies. More data are necessary to determine the optimal therapeutic strategies for low BMD in AN. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Low bone mineral density (BMD) is a known consequence of anorexia nervosa (AN) and is particularly concerning during adolescence, a critical time for bone accrual. A comprehensive synthesis of available data regarding impaired bone health, its determinants, and associated management strategies in AN is currently lacking. This systematic review aims to synthesize information from key physiologic and prospective studies and trials, and provide a thorough understanding of impaired bone health in AN and its management. Method Search terms included 'anorexia nervosa' AND 'bone density' for the period 1995-2015, limited to articles in English. Papers were screened manually based on journal impact factor, sample size, age of participants, and inclusion of a control group. When necessary, we included seminal papers published before 1995. Results AN leads to low BMD, impaired bone quality and increased fracture risk. Important determinants are low lean mass, hypogonadism, IGF-1 deficiency, and alterations in other hormones that impact bone health. Weight gain and menses restoration are critical for improving bone outcomes in AN. Physiologic estrogen replacement as the transdermal patch was shown to increase bone accrual in one study in adolescent females with AN; however, residual deficits persist. Bisphosphonates are potentially useful in adults with AN. Discussion To date, evidence suggests that the safest and most effective strategy to improve bone health in AN is normalization of weight with restoration of menses. Pharmacotherapies that show promise include physiologic estradiol replacement (as the transdermal estradiol patch), and in adults, bisphosphonates. Further studies are necessary to determine the best strategies to normalize BMD in AN. [ABSTRACT FROM AUTHOR]

Background: Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with 123I or 99Tc (99mTc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with 99mTc uptake for diagnosis of pediatric hyperthyroidism. Methods: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and 99mTc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. 99mTc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Results: Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ ( p=0.01) with a degree of agreement (kappa) of 0.69. Conclusion: 99mTc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of 99mTc (two and a half times as much as TSI), it is reasonable to reserve 99mTc uptake assessment for hyperthyroidism of unclear etiology and negative TSI. [ABSTRACT FROM AUTHOR]

Background Obesity is associated with a relative deficiency of growth hormone, which is predictive of greater visceral fat and markers of cardiovascular risk. The study's purpose was to use recombinant human growth hormone (rhGH) as a physiologic probe to assess the effects of reversing obesity-related GH deficiency on body composition, cardiovascular risk markers, and insulin resistance. Methods 22 obese girls 13-21 years old were followed for a randomized 6-month trial of rhGH vs. placebo/no treatment. At baseline and 6-months, DXA was performed for body composition, MRI to measure visceral, subcutaneous and total adipose tissue (VAT, SAT and TAT), and fasting blood drawn for IGF-1, inflammatory cardiovascular risk markers [soluble intercellular adhesion molecule (sICAM), high sensitivity CRP], lipids and HbA1C. An oral glucose tolerance test (OGTT) was performed. Twelve girls completed the 6-month visit. Baseline and mean 6-month change were compared between the groups using the Student ttest and the relationship between variables was determined through multiple regression analysis. Results After 6-months, the rhGH group maintained IGF-1 levels, and had decreases in total cholesterol (p = 0.03), sICAM-1 (p = 0.04) and HbA1C (p = 0.03) compared to placebo/no treatment. The rhGH group trended towards greater decreases in LDL and 2-hour OGTT glucose. Glucose tolerance did not worsen with rhGH administration. Conclusions Administering rhGH in small doses is able to stabilize IGF-1 levels in obesity. We have also shown that rhGH administration leads to an improvement in some markers of cardiovacular risk with without adversely affecting glucose tolerance. Trial registration Clinical Trial Registration Number: NCT01169103. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a condition of severe low weight that is associated with low bone mass, impaired bone structure, and reduced bone strength, all of which contribute to increased fracture risk. Adolescents with AN have decreased rates of bone accrual compared with normal-weight controls, raising additional concerns of suboptimal peak bone mass and future bone health in this age group. Changes in lean mass and compartmental fat depots, and hormonal alterations secondary to nutritional factors contribute to impaired bone metabolism in AN. The best strategy to improve bone density is to regain weight and menstrual function. Oral estrogen-progesterone combinations are not effective in increasing bone density in adults or adolescents with AN, and transdermal testosterone replacement is not effective in increasing bone density in adult women with AN. However, physiological estrogen replacement as transdermal estradiol with cyclic progesterone does increase bone accrual rates in adolescents with AN to approximate that in normal-weight controls, leading to a maintenance of bone density Z-scores. A recent study has shown that risedronate increases bone density at the spine and hip in adult women with AN. However, bisphosphonates should be used with great caution in women of reproductive age, given their long half-life and potential for teratogenicity, and should be considered only in patients with low bone density and clinically significant fractures when non-pharmacological therapies for weight gain are ineffective. Further studies are necessary to determine the best therapeutic strategies for low bone density in AN. [ABSTRACT FROM AUTHOR]

The objective of this case report is to present a pharmacologic strategy for treatment of adolescents with anorexia nervosa (AN) and low bone mineral density (BMD). We present a 17.5-year-old girl with a 3-year history of AN and longstanding inability to optimize nutrition and gain weight, and a decrease over time in her already low BMD. A year after treatment with the 17-β estradiol patch (100 mcg twice weekly) with cyclic oral progesterone (2.5 mg medroxyprogesterone acetate daily for days 1-10 of every month), her spine and hip BMD Z-scores improved, and a further decrease was prevented. This novel treatment is a consideration for girls with AN at greatest risk for low BMD. Adolescents with AN are at risk for low BMD, and the most effective treatment is weight and menses restoration, which can be difficult to attain and to sustain. Recent studies have shown promising results with pharmacological therapy for low BMD in AN. This article discusses current concepts related to bone loss in AN, and new pharmacologic considerations for adolescents at greatest risk for low BMD. © 2013 by Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

I Gonadal steroids, including androgens and oestrogens, play a critical part in bone metabolism, and conditions associated with a deficiency of gonadal steroids can reduce BMD in adults and impair bone accrual in adolescents. In addition, other associated hormone alterations, for example, insulin-like growth factor 1 deficiency or high cortisol levels, can further exacerbate the effect of hypogonadism on bone metabolism, as can factors such as calcium and vitamin D deficiency, low body weight and exercise status. This Review discusses the effects of different hypogonadal states on bone metabolism in female adolescents and young adults, with particular emphasis on conditions associated with low energy availability, such as anorexia nervosa and athletic amenorrhoea, in which many factors other than hypogonadism affect bone. In contrast to most hypogonadal conditions, in which replacement of gonadal steroids is sufficient to normalize bone accrual rates and BMD, gonadal steroid replacement may not be sufficient to normalize bone metabolism in these states of energy deficit. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a condition of profound undernutrition associated with alterations in various neuroendocrine axes, many of which contribute to a marked impairment in bone accrual and low bone mineral density. This review focuses on changes in the hypothalamo-pituitary-gonadal axis, the growth hormone insulin-like growth factor-1 axis, and the hypothalamo-pituitary-adrenal axis in AN, as well as alterations in various appetite-regulating hormones. In addition, the review discusses low bone mineral density and altered bone microarchitecture in AN, the pathophysiology underlying impaired bone metabolism, and possible therapeutic strategies to optimize bone health. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN) is a condition of self-imposed starvation associated with multiple endocrine abnormalities that contribute to low bone density in both males and females. Hormonal alterations in AN include a state of acquired growth hormone (GH) resistance with low IGF-1 levels, hypogonadism, relative hypercortisolemia, elevations in levels of ghrelin, peptide YY and adiponectin, and reductions in leptin. Weight gain associated with menstrual recovery leads to stabilization of bone density, whereas persistence of low weight and amenorrhea causes further decreases in bone density. Low bone density in AN is refractory to oral estrogen replacement, although a combination of oral estrogen with rhIGF-1 causes an increase in bone density in adult women with AN. In addition to low bone density, alterations in bone microarchitecture have been reported in AN, with reductions in apparent bone trabecular volume, trabecular thickness and number, and an increase in trabecular separation. AN may also impact stature adversely, particularly when it begins before epiphyseal fusion and is long-standing. [ABSTRACT FROM AUTHOR]

Abstract: Background: Adolescents with anorexia nervosa (AN) have low bone density and low levels of surrogate markers of bone formation. Low bone density is a consequence of hormonal alterations that include hypogonadism and decreases in IGF-1, a bone trophic factor. Although IGF-1 is key to pubertal bone accretion, and effects have been demonstrated in adults, there are no data regarding the effect of recombinant human (rh) IGF-1 administration in adolescents with AN. Objectives: We hypothesized that rhIGF-1 would cause an increase in PINP, a bone formation marker, in girls with AN, without any effect on CTX, a bone resorption marker. Subjects and methods: RhIGF-1 was administered at a dose of 30–40 mcg/k twice daily to 10 consecutive girls with AN 12–18 years old for 7–9 days. Ten age-matched girls with AN were followed without rhIGF-1 for a similar period. IGF-1, PINP and CTX levels were measured. Results: RhIGF-1 administration caused an increase in IGF-1 from day-1 to day-4/5 (p <0.0001) and day-1 to day-8/9 (p <0.0001). Simultaneously, PINP increased from day-1 to day-4/5 (p =0.004) and day-1 to day-8/9 (p =0.004), with a smaller increase from day-4/5 to day-8/9 (p =0.048). CTX levels did not change with rhIGF-1 administration. No changes occurred in IGF-1 or PINP levels in girls not receiving rhIGF-1; however, CTX levels increased significantly (p =0.01). Percent change in PINP was significantly higher (p =0.02) and percent change in CTX was significantly lower (p =0.006) in girls who received rhIGF-1 compared to those who did not receive any intervention. RhIGF-1 was well tolerated without hypoglycemia. Conclusion: Short-term administration of rhIGF-1 causes an increase in a surrogate bone formation markers in girls with AN without significant side effects. [Copyright &y& Elsevier]

Given the recent spate of reports of vitamin D deficiency, there is a need to reexamine our understanding of natural and other sources of vitamin D, as well as mechanisms whereby vitamin D synthesis and intake can he optimized. This state-of-the-art report from the Drug and Therapeutics Committee of the Lawson Wilkins Pediatric Endocrine Society was aimed to perform this task and also reviews recommendations for sun exposure and vitamin D intake and possible caveats associated with these recommendations. [ABSTRACT FROM AUTHOR]

Although body composition, insulin sensitivity, and lipids are markedly altered in overweight adolescents, hormonal associations with these parameters have not been well characterized. Growth hormone (GH) deficiency and hypercortisolemia predispose to abdominal adiposity and insulin resistance, and GH secretion is decreased in obese adults. We hypothesized that low-peak GH on the GH-releasing hormone (GHRH)-arginine stimulation test and high cortisol in overweight adolescents would be associated with higher regional fat, insulin resistance, and lipids. We examined the following parameters in 15 overweight and 15 bone age-matched control 12- to 18-yr-old girls: 1) body composition using dual-energy X-ray absorptiometry and MR [visceral and subcutaneous adipose tissue at L4-L5 and soleus intramyocellular lipid (¹H-MR spectroscopy)], 2) peak GH on the GHRH-arginine stimulation test, 3) mean overnight GH and cortisol, 4) 24-h urinary free cortisol (UFC), 5) fasting lipids, and 6) an oral glucose tolerance test. Stepwise regression was the major tool employed to determine relationships between measured parameters. Log peak GH on the GHRH-arginine test was lower (P = 0.03) and log UFC was higher (P = 0.02) in overweight girls. Log mean cortisol (overnight sampling) was associated positively with subcutaneous adipose tissue and, with body mass index standard deviation score, accounted for 92% of its variability, whereas log peak GH and body mass index standard deviation score accounted for 88% of visceral adipose tissue variability and log peak GH for 34% of the intramyocellular lipid variability. Log mean cortisol was independently associated with log homeostasis model assessment of insulin resistance, LDL, and HDL and explained 49-59% of the variability. Our data indicate that lower peak GH and higher UFC in overweight girls are associated with visceral adiposity, insulin resistance, and lipids. [ABSTRACT FROM AUTHOR]

Anorexia nervosa (AN), an eating disorder characterized by severe undernutrition and associated with hypogonadotropic hypogonadism, causes marked deficits in bone mass accrual when the disorder begins in the teenage years. Although bone mass accrual improves with weight gain and menstrual recovery, residual deficits persist. Women with a history of teenage onset of AN are more likely to be osteopenic than age-matched women without this history, even after many years of weight and menstrual recovery. Non-recovered women with persistent low weight and amenorrhea have continued decreases in bone density, with a high prevalence of both osteopenia and osteoporosis. Unlike anorexia nervosa, normal-weight bulimia is not associated with low bone density, unless there is a past history of low weight or amenorrhea. A second possible skeletal effect of teenage-onset anorexia nervosa is short stature. Duration of illness and time of onset of anorexia nervosa in relation to the pubertal growth spurt are likely important determinants of statural growth. Adolescent boys with anorexia nervosa are more likely than adolescent girls to have short stature, possibly because growth potential persists for two years longer in boys than in girls. Thus, many adolescent girls may have completed growth or be close to growth completion at the time that they develop anorexia nervosa, whereas adolescent boys may still have significant growth potential remaining. This remaining growth potential may be impaired as a consequence of low levels of insulin-like growth factor-I (IGF-I) levels from persistent undernutrition. [ABSTRACT FROM AUTHOR]

Leptin, an adipocytokine that suppresses appetite and may regulate neuroendocrine pathways, is low in undernourished states like anorexia nervosa (AN). Although leptin exhibits pulsatility, secretory characteristics have not been well described in adolescents and in AN, and the contribution of hypoleptinemia to increased growth hormone (GH) and cortisol in AN has not been explored. We hypothesized that hypoleptinemia in AN reflects decreased basal and pulsatile secretion and may predict increased GH and cortisol levels. Sampling for leptin, GH, cortisol, and ghrelin was performed every 30 min (from 2000 to 0800) in 23 AN and 21 controls 12-18 yr old, and data were analyzed using Cluster and deconvolution methods. Estradiol, thyroid hormones, and body composition were measured. AN girls had lower pulsatile and total leptin secretion than controls (P < 0.0001) subsequent to decreased burst mass (P < 0.0001) and basal secretion (P = 0.02). Nutritional markers predicted leptin characteristics. In a regression model including BMI, body fat, and ghrelin, leptin independently predicted GH burst interval and frequency. Valley leptin contributed to 56% of the variability in GH burst interval, and basal leptin and fasting ghrelin contributed to 42% of variability in burst frequency. Pulsatile leptin independently predicted urine free cortisol/creatinine (15% of variability). Valley leptin predicted cortisol half-life (22% of variability). Leptin predicted estradiol and thyroid hormone levels. In conclusion, hypoleptinemia in AN is subsequent to decreased basal and pulsatile secretion and nutritionally regulated. Leptin predicts GH and cortisol parameters and with ghrelin predicts GH burst frequency. Low leptin and high ghrelin may be dual stimuli for high GH concentrations in undernutrition. [ABSTRACT FROM AUTHOR]

Ghrelin is an orexigenic peptide and a growth hormone (GH) secretagogue. Secretory dynamics of ghrelin have not been characterized in adolescents with anorexia nervosa (AN). We hypothesized that, compared with healthy adolescents, girls with AN would have increased ghrelin concentrations measured over 12 h of nocturnal sampling from increased basal and pulsatile secretion, and endogenous ghrelin would independently predict GH and cortisol. We examined ghrelin concentration and secretory dynamics in 22 girls with AN and 18 healthy adolescents 12–18 yr old. Associations between ghrelin, various hormones, and measures of insulin resistance were examined. On Cluster analysis, girls with AN had higher ghrelin concentrations than controls, including total area under the curve (AUC) (P = 0.002), nadir (P = 0.0006), and valley levels (P = 0.002). On deconvolution analysis, secretory burst amplitude (P = 0.03) and burst mass (P = 0.04) were higher in AN, resulting in higher pulsatile (P = 0.05) and total ghrelin secretion (P = 0.03). Fasting ghrelin independently predicted GH burst frequency (r = 0.44, P = 0.005). The nutritional markers body mass index and body fat predicted postglucose and valley ghrelin but not fasting levels. Ghrelin parameters were inversely associated with fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), leptin, and IGF-I. HOMA-IR was the most significant predictor of most ghrelin parameters. Valley ghrelin independently predicted cortisol burst frequency (52% of variability), and ghrelin parameters independently predicted total triiodothyronine and LH levels. Higher ghrelin concentrations in adolescents with AN are a consequence of increased secretory burst mass and amplitude. The most important predictor of ghrelin concentration is insulin resistance, and ghrelin in turn predicts GH and cortisol burst frequency. [ABSTRACT FROM AUTHOR]

Objective. Anorexia nervosa (AN) is an eating disorder that leads to a number of medical sequelae in adult women and has a mortality rate of 5.6% per decade; known complications include effects on hematologic, biochemical, bone density, and body composition parameters. Few data regarding medical and developmental consequences of AN are available for adolescents, in particular for an outpatient community-dwelling population of girls who have this disorder. The prevalence of AN is increasing in adolescents, and it is the third most common chronic disease in adolescent girls. Therefore, it is important to determine the medical effects of this disorder in this young population. Methods. We examined clinical characteristics and performed hematologic, biochemical, hormonal, and bone density evaluations in 60 adolescent girls with AN (mean age: 15.8 ± 1.6 years) and 58 healthy adolescent girls (mean age: 15.2 ± 1.8 years) of comparable maturity. Nutritional and pubertal status; vital signs; a complete blood count; potassium levels; hormonal profiles; bone density at the lumbar and lateral spine; total body, hip, and femoral neck (by dual-energy x-ray absorptiometry) and body composition (by dual-energy x-ray absorptiometry) were determined. Results. All measures of nutritional status such as weight, percentage of ideal body weight, body mass index, lean body mass, fat mass, and percentage of fat mass were significantly lower in girls with AN than in control subjects. Girls with AN had significantly lower heart rates, lower systolic blood pressure, and lower body temperature compared with control subjects. Total red cell and white cell counts were lower in AN than in control subjects. Among girls with AN, 22% were anemic and 22% were leukopenic. None were hypokalemic. Mean age at menarche did not differ between the groups. However, the proportion of girls who had AN and were pre-menarchal was significantly higher compared with healthy control subjects who... [ABSTRACT FROM AUTHOR]

Mullerian inhibiting substance (MIS), also known as anti-Mullerian hormone (AMH), causes Mullerian duct involution during male sexual differentiation and also has a postnatal regulatory role in the gonads. Serum MIS/AMH has a gonad specific pattern of expression and its concentrations are sexually dimorphic in children; hence measurement of serum MIS/AMH helps in the evaluation of children with gonadal disorders. In boys with cryptorchidism (non-palpable gonads), serum MIS/AMH correlates with testicular tissue. A measurable value is predictive of undescended testes while an undetectable value is highly suggestive of anorchia. In minimally virilized phenotypic females, MIS/AMH helps differentiate between gonadal and non-gonadal causes of virilization. In children with intersex conditions, MIS/AMH values assist differential diagnosis: a value above the normal female range is predictive of testicular tissue, while an undetectable value is suggestive of absent testicular tissue. Thus, MIS/AMH is useful for delineating gonadal pathology and facilitates the differential diagnosis and management of children with diverse gonadal disorders. [Copyright &y& Elsevier]

Abstract The prevalence of anorexia nervosa has increased in recent years, and a large proportion of adults as well as adolescents with this disorder have low bone density and, therefore, an increased risk of fractures. Anorexia nervosa often begins during adolescence, when peak bone mass is accumulated, resulting in significant deficits in bone mass accrual. Therefore, it is important to determine bone mineral density in adolescent and adult women who have this disorder, and to improve or at least stabilize bone metabolism in those with low bone mass. To do this, it is necessary to understand the mechanisms underlying low bone density in anorexia nervosa. This article discusses current concepts related to bone loss associated with anorexia nervosa, including how to prevent it. [ABSTRACT FROM AUTHOR]

Objective: Preclinical work suggests that excess glucocorticoids and reduced cortical γ-aminobutyric acid (GABA) may affect sex-dependent differences in brain regions implicated in stress regulation and depressive phenotypes. The authors sought to address a critical gap in knowledge, namely, how stress circuitry is functionally affected by glucocorticoids and GABA in current or remitted major depressive disorder (MDD). Methods: Multimodal imaging data were collected from 130 young adults (ages 18–25), of whom 44 had current MDD, 42 had remitted MDD, and 44 were healthy comparison subjects. GABA+ (γ-aminobutyric acid and macromolecules) was assessed using magnetic resonance spectroscopy, and task-related functional MRI data were collected under acute stress and analyzed using data-driven network modeling. Results: Across modalities, trait-related abnormalities emerged. Relative to healthy comparison subjects, both clinical groups were characterized by lower rostral anterior cingulate cortex (rACC) GABA+ and frontoparietal network amplitude but higher amplitude in salience and stress-related networks. For the remitted MDD group, differences from the healthy comparison group emerged in the context of elevated cortisol levels, whereas the MDD group had lower cortisol levels than the healthy comparison group. In the comparison group, frontoparietal and stress-related network connectivity was positively associated with cortisol level (highlighting putative top-down regulation of stress), but the opposite relationship emerged in the MDD and remitted MDD groups. Finally, rACC GABA+ was associated with stress-induced changes in connectivity between overlapping default mode and salience networks. Conclusions: Lifetime MDD was characterized by reduced rACC GABA+ as well as dysregulated cortisol-related interactions between top-down control (frontoparietal) and threat (task-related) networks. These findings warrant further investigation of the role of GABA in the vulnerability to and treatment of MDD. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Method Results Discussion Avoidant/restrictive food intake disorder (ARFID) is common among populations with nutrition‐related medical conditions. Less is known about the medical comorbidity/complication frequencies in youth with ARFID. We evaluated the medical comorbidities and metabolic/nutritional markers among female and male youth with full/subthreshold ARFID across the weight spectrum compared with healthy controls (HC).In youth with full/subthreshold ARFID (n = 100; 49% female) and HC (n = 58; 78% female), we assessed self‐reported medical comorbidities via clinician interview and explored abnormalities in metabolic (lipid panel and high‐sensitive C‐reactive protein [hs‐CRP]) and nutritional (25[OH] vitamin D, vitamin B12, and folate) markers.Youth with ARFID, compared with HC, were over 10 times as likely to have self‐reported gastrointestinal conditions (37% vs. 3%; OR = 21.2; 95% CI = 6.2–112.1) and over two times as likely to have self‐reported immune‐mediated conditions (42% vs. 24%; OR = 2.3; 95% CI = 1.1–4.9). ARFID, compared with HC, had a four to five times higher frequency of elevated triglycerides (28% vs. 12%; OR = 4.0; 95% CI = 1.7–10.5) and hs‐CRP (17% vs. 4%; OR = 5.0; 95% CI = 1.4–27.0) levels.Self‐reported gastrointestinal and certain immune comorbidities were common in ARFID, suggestive of possible bidirectional risk/maintenance factors. Elevated cardiovascular risk markers in ARFID may be a consequence of limited dietary variety marked by high carbohydrate and sugar intake. [ABSTRACT FROM AUTHOR]

Background: Cognitive‐behavioral therapy for avoidant/restrictive food intake disorder (ARFID; CBT‐AR) theoretically targets three prototypic motivations (sensory sensitivity, lack of interest/low appetite, fear of aversive consequences), aligned with three modularized interventions. As an exploratory investigation, we: (1) evaluated change in candidate mechanisms in relationship to change in ARFID severity, and (2) tested if assignment (vs. not) to a module resulted in larger improvements in the corresponding mechanism. Method: Males and females (N = 42; 10–55 years) participated in an open trial of CBT‐AR. Results: Decreases in scaled scores for each candidate mechanism had medium to large correlations with decreases in ARFID severity—sensory sensitivity: −0.7 decrease (r =.42, p =.01); lack of interest/low appetite: −0.3 decrease (r =.60, p <.0001); and fear of aversive consequences: −1.1 decrease (r =.33, p =.05). Linear mixed models revealed significant weekly improvements for each candidate mechanism across the full sample (ps <.0001). There were significant interactions for the sensory and fear of aversive consequences modules–for each, participants who received the corresponding module had significantly larger decreases in the candidate mechanism than those who did not receive the module. Discussion: Sensory sensitivity and fear of aversive consequences improved more if the CBT‐AR module was received, but lack of interest/low appetite may improve regardless of receipt of the corresponding module. Future research is needed to test target engagement in CBT‐AR with adaptive treatment designs, and to identify valid and sensitive measures of candidate mechanisms. Public Significance: The mechanisms through which components of CBT‐AR work have yet to be elucidated. We conducted an exploratory investigation to test if assignment (vs. not) to a CBT‐AR module resulted in larger improvements in the corresponding prototypic ARFID motivation that the module intended to target. Measures of the sensory sensitivity and the fear of aversive consequences motivations improved more in those who received the corresponding treatment module, whereas the lack of interest/low appetite measure improved regardless of if the corresponding module was received. [ABSTRACT FROM AUTHOR]

Sleeve gastrectomy is the most commonly performed weight loss surgery in adolescents with moderate-to-severe obesity. While studies in adults have reported on the deleterious effects of gastric bypass surgery on bone structure and strength estimates, data are lacking for the impact of sleeve gastrectomy on these measures in adolescents. To evaluate the impact of sleeve gastrectomy on bone outcomes in adolescents and young adults over 12 months using dual energy X-ray absorptiometry (DXA) and high resolution peripheral quantitative computed tomography (HRpQCT). We enrolled 44 youth 14–22 years old with moderate to severe obesity; 22 underwent sleeve gastrectomy and 22 were followed without surgery (16 females and 6 males in each group). At baseline and 12 months, DXA was used to assess areal bone mineral density (aBMD), HRpQCT of the distal radius and tibia was performed to assess bone geometry, microarchitecture and volumetric BMD (vBMD), and finite element analysis to assess strength estimates (stiffness and failure load). These analyses were adjusted for age, sex, race and the bone measure at baseline. Fasting blood samples were assessed for calcium, phosphorus, and 25(OH) vitamin D (25OHD) levels. Over 12-months, the surgical group lost 27.2% of body weight compared to 0.1% in the non-surgical (control) group. Groups did not differ for changes in 25OHD levels (p = 0.186). Compared to controls, the surgical group had reductions in femoral neck and total hip aBMD Z-scores (p ≤ 0.0006). At the distal tibia, compared to controls, the surgical group had reductions in cortical area and thickness and trabecular number, and increases in trabecular area and separation (p ≤ 0.026). At the distal radius, the surgical group had greater reductions in trabecular vBMD, than controls (p = 0.010). The surgical group had an increase in cortical vBMD at both sites (p ≤ 0.040), possibly from a decrease in cortical porosity (p ≤ 0.024). Most, but not all, differences were attenuated after adjusting for 12-month change in BMI. Groups did not differ for changes in strength estimates over time, except that increases in tibial stiffness were lower in the surgical group (p = 0.044) after adjusting for 12-month change in BMI. Over 12 months, weight loss associated with sleeve gastrectomy in adolescents had negative effects on areal BMD and certain HRpQCT parameters. However, bone strength estimates remained stable, possibly because of a simultaneous decrease in cortical porosity and increase in cortical volumetric BMD. Additional research is necessary to determine the relative contribution(s) of weight loss and the metabolic effects of surgery on bone outcomes, and whether the observed effects on bone stabilize or progress over time. • Femoral neck and total hip bone mineral density (BMD) (DXA) decreased after surgery • % Change in trabecular number was lower in the surgical group at the radius/tibia • % Change in trabecular separation was higher in the surgical group at both sites • Cortical volumetric BMD increased after surgery at both sites • Strength estimates did not change following surgery at either site [ABSTRACT FROM AUTHOR]

• Eating Disorders have a multifactorial etiopathogenesis. • Neuroendocrine changes have been detected in acute and recovered ED people. • The state or trait nature of those changes is still debated. • The potential role of neuroendocrine changes in the pathogenesis and maintenance of EDs is illustrated. [ABSTRACT FROM AUTHOR]

Objective: Few studies have focused on brain structure in atypical anorexia nervosa (atypical AN). This study investigates differences in gray matter volume (GMV) between females with anorexia nervosa (AN) and atypical AN, and healthy controls (HC). Method: Structural magnetic resonance imaging data were acquired for 37 AN, 23 atypical AN, and 41 HC female participants. Freesurfer was used to extract GMV, cortical thickness, and surface area for six brain lobes and associated cortical regions of interest (ROI). Primary analyses employed linear mixed‐effects models to compare group differences in lobar GMV, followed by secondary analyses on ROIs within significant lobes. We also explored relationships between cortical gray matter and both body mass index (BMI) and symptom severity. Results: Our primary analyses revealed significant lower GMV in frontal, temporal and parietal areas (FDR <.05) in AN and atypical AN when compared to HC. Lobar GMV comparisons were non‐significant between atypical AN and AN. The parietal lobe exhibited the greatest proportion of affected cortical ROIs in both AN versus HC and atypical AN versus HC. BMI, but not symptom severity, was found to be associated with cortical GMV in the parietal, frontal, temporal, and cingulate lobes. No significant differences were observed in cortical thickness or surface area. Discussion: We observed lower GMV in frontal, temporal, and parietal areas, when compared to HC, but no differences between AN and atypical AN. This indicates potentially overlapping structural phenotypes between these disorders and evidence of brain changes among those who are not below the clinical underweight threshold. Public significance: Despite individuals with atypical anorexia nervosa presenting above the clinical weight threshold, lower cortical gray matter volume was observed in partial, temporal, and frontal cortices, compared to healthy individuals. No significant differences were found in cortical gray matter volume between anorexia nervosa and atypical anorexia nervosa. This underscores the importance of continuing to assess and target weight gain in clinical care, even for those who are presenting above the low‐weight clinical criteria. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. Method: Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21–46 years. Results: Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p <.05). Adjusting for weight, deficits in tibial cortical bone variables persisted (p <.05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high‐resolution peripheral quantitative computed tomography (HR‐pQCT) variables in atypical anorexia nervosa. Discussion: Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR‐pQCT variables are associated with increased fracture risk. Public Significance: Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation. [ABSTRACT FROM AUTHOR]

Summary: To understand whether the bone loss which occurs after vertical sleeve gastrectomy increases the risk of fracture, we used an engineering model to estimate risk in participants before and after surgery. We found that estimated risk decreased 1 year after surgery and remained lower, though had rebounded, at year 2. Purpose: Vertical sleeve gastrectomy (VSG) improves metabolic health in young people with obesity but is accompanied by substantial loss of bone mass and estimated bone strength. We thus estimated fracture risk following VSG using the load-to-strength ratio (LSR), which integrates bone strength estimates with the predicted force of a fall. Methods: Prospective 2-year study of youth ages 13–24 years with obesity undergoing VSG (n = 24) or lifestyle therapy (n = 34). We performed high-resolution peripheral quantitative computed tomography of the distal radius and microfinite element analysis to estimate bone strength and calculated LSR. Results: VSG participants lost 26.4 ± 8.1% weight at year 1 (p < 0.001), which was sustained at year 2, while control participants gained weight at year 2 (4.5 ± 8.3%, p = 0.009). The predicted impact force decreased at years 1 and 2 following VSG (p < 0.001) but increased at year 2 among controls (p = 0.011). Estimated bone strength was unchanged at year 1 but decreased (p < 0.001) at year 2 following VSG, while bone strength did not change in controls. At year 1, the LSR decreased among VSG participants (p < 0.001), implying a lower risk of fracture. At year 2, the LSR was lower than baseline (p < 0.001), but higher compared to year 1 (p = 0.001). LSR did not change in the control group. Conclusions: Short-term estimated fracture risk at the radius following VSG decreases. However, ongoing bone loss despite stable weight between years 1 and 2 leads to a concerning rise in estimated fracture risk. Longer follow-up will be critical to evaluate the trajectory of fracture risk. (ClinicalTrials.gov NCT02557438, registered 9/23/2015). [ABSTRACT FROM AUTHOR]

The Male Athlete Triad is a medical syndrome most common in adolescent and young adult male athletes in sports that emphasize a lean physique, especially endurance and weight-class athletes. The 3 interrelated conditions of the Male Athlete Triad occur on spectrums of energy deficiency/low energy availability (EA), suppression of the hypothalamic--pituitary--gonadal axis, and impaired bone health, ranging from optimal health to clinically relevant outcomes of energy deficiency/low EA with or without disordered eating or eating disorder, functional hypogonadotropic hypogonadism, and osteoporosis or low bone mineral density with or without bone stress injury (BSI). Because of the importance of bone mass acquisition and health concerns in adolescence, screening is recommended during this time period in the at-risk male athlete. Diagnosis of the Male Athlete Triad is best accomplished by a multidisciplinary medical team. Clearance and return-to-play guidelines are recommended to optimize prevention and treatment. Evidence-based risk assessment protocols for the male athlete at risk for the Male Athlete Triad have been shown to be predictive for BSI and impaired bone health and should be encouraged. Improving energetic status through optimal fueling is the mainstay of treatment. A Roundtable on the Male Athlete Triad was convened by the Female and Male Athlete Triad Coalition in conjunction with the 64th Annual Meeting of the American College of Sports Medicine in Denver, Colorado, in May of 2017. In this second article, the latest clinical research to support current models of screening, diagnosis, and management for at-risk male athlete is reviewed with evidence-based recommendations. [ABSTRACT FROM AUTHOR]

Background: Recent research suggests that individuals with eating disorders (EDs) report elevated anhedonia, or loss of pleasure. Although individuals with avoidant/restrictive food intake disorder (ARFID) often express that they do not look forward to eating, it is unclear whether they experience lower pleasure than those without EDs. Thus, identifying whether individuals with ARFID experience anhedonia may yield important insights that inform clinical conceptualization and treatment. Methods: A sample of 71 participants ages 10–23 with full and subthreshold ARFID and 33 healthy controls (HCs) completed the Pica, ARFID, and Rumination Disorder Interview, a diagnostic interview to assess ARFID profile severity (lack of interest in food, sensory sensitivity, fear of aversive consequences) and the Temporal Experience of Pleasure Scale (TEPS), a self-report measure of consummatory and anticipatory pleasure. Statistical analyses were performed using the full TEPS and also the TEPS with food-related items removed. Results: The ARFID group reported significantly lower anticipatory and consummatory pleasure compared to HCs, but these differences were no longer significant after controlling for depression, nor after removing food items from the TEPS. Within the ARFID sample, greater ARFID severity was associated with lower anticipatory pleasure across analyses, and greater endorsement of the lack of interest in food profile was related to lower anticipatory pleasure. ARFID severity was also associated with lower consummatory pleasure using the full TEPS, but this relationship was no longer significant with food items removed. Conclusions: These results provide initial evidence for lower pleasure before potentially pleasurable events in individuals with more severe ARFID, particularly those with the lack of interest phenotype. Our findings also suggest that depression is likely to contribute low pleasure in this population. Future research should seek to further characterize how dimensions of pleasure relate to the maintenance and treatment of ARFID symptoms. Plain English summary: Individuals with eating disorders often report elevated anhedonia, or an inability to experience pleasure. Past research on pleasure in eating disorders has focused primarily on individuals with anorexia nervosa and bulimia nervosa, and it is unclear whether people with other eating disorders also experience lower pleasure than healthy individuals. In the current study, we measured anticipatory pleasure (looking forward to something enjoyable) and consummatory pleasure (enjoying a pleasant stimulus) in a sample with avoidant/restrictive food intake disorder (ARFID) and healthy controls. We also repeated our analyses after removing food-related items from the scale assessing pleasure. The ARFID group scored lower on both dimensions of pleasure than controls, but this difference was primarily due to greater depression symptoms and the presence of food-related items in the pleasure questionnaire. Within the ARFID sample, individuals with more severe ARFID reported less anticipatory pleasure, even after removing questions about enjoyment of food. Lower anticipatory pleasure was especially characteristic of the lack of interest in eating phenotype of ARFID. These results suggest that ARFID severity, lack of interest in eating, and depression contribute to low pleasure in this population. [ABSTRACT FROM AUTHOR]

Objective: To determine mechanisms contributing to impaired bone health in youth 24 months following sleeve gastrectomy (SG). Design: Twenty-four-month longitudinal observational study. Methods: Participants included 23 youth undergoing SG and 30 non-surgical controls (NS) 13-25 years old with moderate-to-severe obesity. Subjects underwent fasting labs for bone turnover markers (N-terminal propeptide of type 1 procollagen, C-telopeptide (CTX)), sex hormones, sex hormone binding globulin (SHBG), and enteric peptides, DXA for areal bone mineral density (aBMD) and body composition, high-resolution peripheral quantitative CT for volumetric BMD (vBMD) at the distal radius and tibia, and microfinite element analysis for strength estimates. Results: Groups did not differ for mean age or BMI z-scores. Over 24 months, compared to NS, SG had greater reductions in BMI z-scores, and spine, hip, and femoral neck aBMD Z-scores (P ≤ .012), greater increases in serum CTX and SHBG (P ≤ .039), and greater decreases in estrone and ghrelin (P ≤ .021). Among females, estrone and free androgen index (FAI) decreased (P ≤ .022) in SG vs NS groups. After controlling for age and sex, decreases in BMI and lean mass were associated with decreases in total hip and femoral neck aBMD Z-scores, and decreases in radial total and trabecular vBMD and failure load, and tibial total and trabecular vBMD. Among females, after controlling for age, decreases in estrone were associated with decreases in spine aBMD Z-scores and radial total and trabecular vBMD, and decrease in FAI with decreases in radial failure load. Conclusion: Reductions in BMI, lean mass, and sex steroids over 24 months post-SG are associated with bone loss and could be targeted for preventative or therapeutic interventions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the response of anorexigenic oxytocin to food intake among adolescents and young adults with avoidant/restrictive food intake disorder (ARFID), a restrictive eating disorder characterized by lack of interest in food or eating, sensory sensitivity to food, and/or fear of aversive consequences of eating, compared with healthy controls (HC). Design: Cross-sectional. Methods: A total of 109 participants (54 with ARFID spectrum and 55 HC) were instructed to eat a ~400-kcal standardized mixed meal. We sampled serum oxytocin at fasting and at 30-, 60-, and 120-min postmeal. We tested the hypothesis that ARFID would show higher mean oxytocin levels across time points compared with HC using a mixed model ANOVA. We then used multivariate regression analysis to identify the impact of clinical characteristics (sex, age, and body mass index [BMI] percentile) on oxytocin levels in individuals with ARFID. Results: Participants with ARFID exhibited greater mean oxytocin levels at all time points compared with HC, and these differences remained significant even after controlling for sex and BMI percentile (P = .004). Clinical variables (sex, age, and BMI percentile) did not show any impact on fasting and postprandial oxytocin levels among individuals with ARFID. Conclusions: Consistently high oxytocin levels might be involved in low appetite and sensory aversions to food, contributing to food avoidance in individuals with ARFID. [ABSTRACT FROM AUTHOR]

Functional hypothalamic amenorrhea (FHA) is associated with low BMD and decreased rates of bone mass accrual, particularly in conditions of severe undernutrition, such as anorexia nervosa. In addition to immediate fracture risk, the finding of impaired bone metabolism in young women raises concerns about reduced peak bone mass, an important determinant of bone health in later life. Appropriate treatment of FHA is, therefore, crucial for restoration of BMD and for bone mass accrual. Vescovi et al. have performed a systematic review of the literature in order to assess therapeutic strategies that aim to reverse bone loss in women with FHA. In this Practice Point commentary, I discuss the extent to which hormonal and nonhormonal therapies have, or have not, been beneficial in optimizing bone health. In addition, I emphasize the importance of weight gain and recovery of reproductive function in the preservation of bone health in women with FHA. [ABSTRACT FROM AUTHOR]

Background: Avoidant/restrictive food intake disorder (ARFID) is a restrictive eating disorder commonly associated with medical complications of undernutrition and low weight. In adolescence, a critical time for bone accrual, the impact of ARFID on bone health is uncertain. We aimed to study bone health in low-weight females with ARFID, as well as the association between peptide YY (PYY), an anorexigenic hormone with a role in regulation of bone metabolism, and bone mineral density (BMD) in these individuals. We hypothesized that BMD would be lower in low-weight females with ARFID than healthy controls (HC), and that PYY levels would be negatively associated with BMD. Methods: We performed a cross-sectional study in 14 adolescent low-weight females with ARFID and 20 HC 10–23 years old. We assessed BMD (total body, total body less head and lumbar spine) using dual x-ray absorptiometry (DXA) and assessed fasting total PYY concentration in blood. Results: Total body BMD Z-scores were significantly lower in ARFID than in HC (− 1.41 ± 0.28 vs. − 0.50 ± 0.25, p = 0.021). Mean PYY levels trended higher in ARFID vs. HC (98.18 ± 13.55 pg/ml vs. 71.40 ± 5.61 pg/ml, p = 0.055). In multivariate analysis within the ARFID group, PYY was negatively associated with lumbar BMD adjusted for age (β = -0.481, p = 0.032). Conclusion: Our findings suggest that female adolescents with low-weight ARFID may have lower BMD than healthy controls and that higher PYY levels may be associated with lower BMD at some, but not all, sites in ARFID. Further research with larger samples will be important to investigate whether high PYY drives bone loss in ARFID. Plain English summary: Avoidant/restrictive food Intake disorder (ARFID) is a condition characterized by lack of interest in eating/food, sensory sensitivity and/or fear of aversive consequences of eating. It is associated with low weight and undernutrition, which can lead to medical complications. Specifically, low weight in patients with ARFID raises concerns of impaired bone health. In this study, we compared bone mineral density (BMD), a measure of bone health, in 14 low-weight females with ARFID and 20 healthy females 10–23 years old. We also examined the association between BMD and peptide YY (PYY), a hormone that induces satiety and inhibits bone formation. A strong negative association between bone health and PYY was previously reported in females with anorexia nervosa. Thus, we hypothesized a similar association in low weight females with ARFID. We found that BMD may be lower in low-weight females with ARFID than in healthy females and that higher PYY levels are associated with lower BMD at some but not all sites. We concluded that bone health may be a concern in low-weight females with ARFID. This finding is important as low BMD raises concerns for increased fracture risk, which in turn could have a detrimental effect on quality of life. [ABSTRACT FROM AUTHOR]

Oxytocin (OXT), an anorexigenic hormone, is also bone anabolic. Further, OXT administration results in increases in lean mass (LM) in adults with sarcopenic obesity. We examine, for the first time, associations of OXT with body composition and bone endpoints in 25 youth 13–25 years old with severe obesity who underwent sleeve gastrectomy (SG) and 27 non-surgical controls (NS). Forty participants were female. Subjects underwent fasting blood tests for serum OXT and DXA for areal bone mineral density (aBMD) and body composition. At baseline, SG vs. NS had higher median body mass index (BMI) but did not differ for age or OXT levels. Over 12 months, SG vs. NS had greater reductions in BMI, LM, and fat mass (FM). OXT decreased in SG vs. NS 12 months post-SG. While baseline OXT predicted a 12-month BMI change in SG, decreases in OXT levels 12 months post-SG were not associated with decreases in weight or BMI. In SG, decreases in OXT were positively associated with decreases in LM but not with decreases in FM or aBMD. Loss of LM, a strong predictor of BMD, after bariatric surgery may reduce functional and muscular capacity. OXT pathways may be targeted to prevent LM loss following SG. [ABSTRACT FROM AUTHOR]

Background: The Pica, ARFID, and Rumination Disorder Interview (PARDI) is a structured interview that can be used to determine diagnosis, presenting characteristics, and severity across three disorders, including avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the psychometric properties of a questionnaire focused specifically on ARFID (PARDI-AR-Q), which has the potential to provide related information with less participant burden. Methods: Adolescents and adults (n = 71, ages 14–40 years) with ARFID (n = 42) and healthy control participants (HC, n = 29) completed the PARDI-AR-Q and other measures. A subset of the ARFID group (n = 27) also completed the PARDI interview. Results: An exploratory factor analysis of proposed subscale items identified three factors corresponding to the ARFID phenotypes of avoidance based on the sensory characteristics of food, lack of interest in eating or food, and concern about aversive consequences of eating. Further analyses supported the internal consistency and convergent validity of the PARDI-AR-Q subscales, and subscale ratings on the questionnaire showed large and significant correlations (all p-values < 0.001; r's ranging from 0.48 to 0.77) with the corresponding subscales on the interview. The ARFID group scored significantly higher than HC on all subscales. Furthermore, 90% of the ARFID group scored positive on the PARDI-AR-Q diagnostic algorithm while 93% of the HC scored negative. Conclusions: Though replication in larger and more diverse samples is needed, findings provide early support for the validity of the PARDI-AR-Q as a self-report measure for possible ARFID in clinical or research settings. Plain English summary: Few measures are available for detecting avoidant/restrictive food intake disorder (ARFID) in clinics or research settings. This makes it difficult for individuals with the disorder to be identified and offered appropriate care. We developed the Pica, ARFID, and Rumination Disorder Interview ARFID Questionnaire (PARDI-AR-Q), a brief self-report measure of possible ARFID, and evaluated how well it worked in the current study. In our preliminary study of 71 adolescents and adults, most individuals with ARFID (90%) scored positive on this measure, whereas most healthy control participants (93%) scored negative. Our findings provide early support for the PARDI-AR-Q as a promising new measure for detecting possible ARFID when a full clinical interview is not possible. [ABSTRACT FROM AUTHOR]

Objective: There is a paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID) to aid identification and classification of cases for both clinical and research purposes. To evaluate the factor structure, construct validity, and criterion validity of the Pica ARFID and Rumination Disorder Interview (PARDI; ARFID module), we administered the PARDI to 129 children and adolescents ages 9–23 years (M = 16.1) with ARFID (n = 84), subclinical ARFID (n = 11), and healthy controls (n = 34). Method: We used exploratory factor analysis to examine the factor structure of the PARDI in children, adolescents, and young adults with an ARFID diagnosis, the Kruskal‐Wallis analysis of variance and Spearman correlations to test the construct validity of the measure, and non‐parametric receiver operating characteristic curves to evaluate the criterion validity of the PARDI. Results: Exploratory factor analysis yielded a 3‐factor structure: (1) concern about aversive consequences of eating, (2) low appetite/low interest in food, and (3) sensory sensitivity. Participants with ARFID demonstrated significantly higher levels of sensory sensitivity, low appetite/low‐food interest, and concern about aversive consequences of eating symptoms relative to control participants. The construct validity for each PARDI subscale was supported and clinical cutoffs for the low appetite/low interest in food (1.1) and sensory sensitivity subscales (0.6) were established. Discussion: These data present evidence for the factor structure and validity of the PARDI diagnostic interview for diagnosing ARFID in children, adolescents, and young adults, supporting the use of this tool to facilitate ARFID clinical assessment and research. Public Significance: Due to the paucity of validated diagnostic interviews for avoidant/restrictive food intake disorder (ARFID), we evaluated the factor structure and validity of the Pica ARFID and Rumination Disorder Interview (ARFID module). Findings suggest that the interview assesses 3 components of ARFID: concern about aversive consequences of eating, low‐appetite, and sensory sensitivity, and that clinical threshold scores on the latter two subscales can be used to advance ARFID assessment. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa is complicated by high bone resorption, low bo ne mineral density (BMD), and increased fracture risk. We investigated whether off-label antiresorptive therapy with denosumab increases BMD in women with anorexia nervosa. Design: Twelve-month, randomized, double-blind, placebo-controlled study. Methods: Thirty ambulatory women with anorexia nervosa and areal BMD (aB MD) T-score <-1.0 at =1 sites were randomized to 12 months of denosumab (60 mg subcutaneously q6 m onths)(n = 20) or placebo (n = 10). Primary end point was postero-anterior (PA) lumbar spine aBMD by dual-e nergy x-ray absorptiometry. Secondary end points included femoral neck aBMD, tibia and radius volumetric BMD and bone microarchitecture by high-resolution peripheral quantitative CT, tibia and radius failure load by fin ite element analysis (FEA), and markers of bone turnover. Results: Baseline mean (±s.d.) age (29 ± 8 (denosumab) vs 29 ± 7 years (placebo)), BMI (19.0 ± 1.7 vs 18.0 ± 2.0 kg/m2), and aBMD (PA spine Z-score -1.6±1.1 vs -1.7±1.4) were similar between groups. PA lumbar spine aBMD increase d in the denosumab vs placebo group over 12 months (P = 0.009). The mean (95% CI) increase in PA lumbar spine aBMD was 5.5 (3.8-7.2)% in the denosumab group and 2.2 (-0.3-4.7)% in the placebo group. The change in femoral neck aBMD was similar between groups. Radial trabecular number incre ased, radial trabecular separation decreased, and tibial cortical porosity decreased in the denosumab vs placebo group (P = 0.006). Serum C-terminal telopeptide of type I collagen and procollagen type I N-terminal propeptide decreas ed in the denosumab vs placebo group (P < 0.0001). Denosumab was well tolerated. Conclusions: Twelve months of antiresorptive therapy with denosumab reduced bone turnover and increased spine aBMD, the skeletal site most severely affected in women with ano rexia nervosa. [ABSTRACT FROM AUTHOR]

Objective: Research comparing psychiatric comorbidities between individuals with avoidant/restrictive food intake disorder (ARFID) and anorexia nervosa (AN) is limited. ARFID often develops in childhood, whereas AN typically develops in adolescence or young adulthood. Understanding how age may impact differential psychological comorbidity profiles is important to inform etiological conceptualization, differential diagnosis, and treatment planning. We aimed to compare the lifetime frequency of psychiatric comorbidities and suicidality between females with ARFID (n = 51) and AN (n = 40), investigating the role of age as a covariate. Method: We used structured interviews to assess the comparative frequency of psychiatric comorbidities/suicidality. Results: When age was omitted from analyses, females with ARFID had a lower frequency of depressive disorders and suicidality compared to AN. Adjusting for age, only suicidality differed between groups. Discussion: This is the first study to compare comorbidities in a similar number of individuals with ARFID and AN, and a structured clinical interview to confer ARFID and comorbidities, covarying for age, and the first to compare suicidality. Although suicidality is at least three times less common in ARFID than AN, observed differences in other psychiatric comorbidities may reflect ARFID's relatively younger age of presentation compared to AN. Public Significance: Our results highlight that, with the exception of suicidality, which was three times less common in ARFID than AN irrespective of age, observed differences in psychiatric comorbidities in clinical practice may reflect ARFID's younger age at clinical presentation compared to AN. [ABSTRACT FROM AUTHOR]

In adults, low-weight restrictive eating disorders, including anorexia nervosa (AN), are marked by chronicity and diagnostic crossover from restricting to binge-eating/purging. Less is known about the naturalistic course of these eating disorders in adolescents, particularly atypical AN (atyp-AN) and avoidant/restrictive food intake disorder (ARFID). To inform nosology of low-weight restrictive eating disorders in adolescents, we examined outcomes including persistence, crossover, and recovery in an 18-month observational study. We assessed 82 women (ages 10–23 years) with low-weight eating disorders including AN (n = 40; 29 restricting, 11 binge-eating/purging), atyp-AN (n = 26; 19 restricting, seven binge-eating/purging), and ARFID (n = 16) at baseline, nine months (9 M; 75% retention), and 18 months (18 M; 73% retention) via semi-structured interviews. First-order Markov modeling was used to determine diagnostic persistence, crossover, and recovery occurring at 9 M or 18 M. Among all diagnoses, the likelihood of remaining stable within a given diagnosis was greater than that of transitioning, with the greatest probability among ARFID (0.84) and AN-R (0.62). Persistence of BP and atypical presentations at follow-up periods was less stable (AN-BP probability 0.40; atyp-AN-R probability 0.48; atyp-AN-BP probability, 0.50). Crossover from binge-eating/purging to restricting occurred 72% of the time; crossover from restricting to binge-eating/purging occurred 23% of the time. The likelihood of stable recovery (e.g., recovery at both 9 M and 18 M) was between 0.00 and 0.36. Across groups, intake diagnosis persisted in about two-thirds, and recovery was infrequent, underscoring the urgent need for innovative treatment approaches to these illnesses. Frequent crossover between AN and atyp-AN supports continuity between typical and atypical presentations, whereas no crossover to ARFID supports its distinction. [ABSTRACT FROM AUTHOR]

Avoidant/restrictive food intake disorder (ARFID) occurs across the weight spectrum, however research addressing the coexistesnce of ARFID with overweight/obesity (OV/OB) is lacking. We aimed to establish co-occurrence of OV/OB and ARFID and to characterize divergent neurobiological features of ARFID by weight. Youth with full/subthreshold ARFID (12 with healthy weight [HW], 11 with OV/OB) underwent fasting brain fMRI scan while viewing food/non-food images (M age = 16.92 years, 65% female, 87% white). We compared groups on BOLD response to high-calorie foods (HCF) (vs. objects) in food cue processing regions of interest. Following fMRI scanning, we evaluated subjective hunger pre- vs. post-meal. We used a mediation model to explore the association between BMI, brain activation, and hunger. Participants with ARFID and OV/OB demonstrated significant hyperactivation in response to HCF (vs. objects) in the orbitofrontal cortex (OFC) and anterior insula compared with HW participants with ARFID. Mediation analysis yielded a significant indirect effect of group (HW vs. OV/OB) on hunger via OFC activation (effect = 18.39, SE = 11.27, 95% CI [−45.09, −3.00]), suggesting that OFC activation mediates differences in hunger between ARFID participants with HW and OV/OB. Compared to youth with ARFID and HW, those with OV/OB demonstrate hyperactivation of brain areas critical for the reward value of food cues. Postprandial changes in subjective hunger depend on BMI and are mediated by OFC activation to food cues. Whether these neurobiological differences contribute to selective hyperphagia in ARFID presenting with OV/OB and represent potential treatment targets is an important area for future investigation. [ABSTRACT FROM AUTHOR]

Objective: Anorexia nervosa (AN) is a serious condition characterized by undernutrition, complicated by endocrine dysregulation, and with few predictors of recovery. Urinary free cortisol (UFC) is a predictor of weight gain, but 24‐h urine samples are challenging to collect. We hypothesized that serum dehydroepiandrosterone sulfate (DHEAS), which like cortisol is regulated by adrenocorticotropic hormone (ACTH), would predict weight gain and increases in fat mass in women with AN. Methods: We prospectively studied 34 women with AN and atypical AN, mean age 27.4 ± 7.7 years (mean ± SD), who received placebo in a 6‐month randomized trial. Baseline DHEAS and 24‐h UFC were measured by liquid chromatography with tandem mass spectrometry. Body composition was assessed at baseline and 6 months by DXA and cross‐sectional abdominal CT at L4. Results: Mean baseline DHEAS level was 173 ± 70 μg/dl (0.7 ± 0.3 times the mean normal range for age) and mean baseline UFC (n = 15) was 20 ± 18 μg/24 h (normal: 0–50 μg/24 h). Higher DHEAS levels predicted weight gain over 6 months (r = 0.61, p <.001). DHEAS levels also predicted increases in fat mass (r = 0.40, p =.03), appendicular lean mass (r = 0.38, p =.04), and abdominal adipose tissue (r = 0.60, p <.001). All associations remained significant after controlling for age, baseline BMI, OCP use, duration of AN, and SSRI/SNRI use. DHEAS levels correlated with UFC (r = 0.61, p =.02). Discussion: In women with AN, higher serum DHEAS predicts weight gain and increases in fat and muscle mass. Additional studies are needed to confirm these findings and further elucidate the association between DHEAS and weight gain. Public Significance: Anorexia nervosa is a severe psychiatric condition, and predictors of weight recovery are needed to improve prognostication and guide therapeutic decision making. While urinary cortisol is a predictor of weight gain, 24‐h urine collections are challenging to obtain. Like cortisol, dehydroepiandrosterone sulfate (DHEAS) is a hormone produced by the adrenal glands. As a readily available blood test, DHEAS holds promise as more practical biomarker of weight gain in anorexia nervosa. [ABSTRACT FROM AUTHOR]

Objective Hyperinsulinaemia is an important determinant of the polycystic ovarian syndrome ( PCOS). In addition to lifestyle measures, therapeutic strategies include the use of oestrogen-progesterone combination pills ( EP), and insulin sensitizers such as metformin, either alone or in combination. Data are limited regarding the impact of metformin alone vs metformin with EP on cardiometabolic risk in overweight adolescents with PCOS. We hypothesized that metformin alone would lead to an improvement in HbA1C and lipid levels in overweight adolescent girls with PCOS compared with meformin with EP. Study design Retrospective clinic-based therapy. Patients and measurements We examined the effects of therapy with metformin alone ( n = 14) vs metformin with EP ( n = 13) on HbA1C and lipid parameters over 10-14 months in 27 overweight girls, drawn from a clinic population of adolescents with PCOS. Results The groups did not differ for age, body mass index ( BMI), HbA1C or baseline lipids. After at least 10 months, the metformin only group compared with the metformin and EP group had a decrease in total cholesterol (−0·605 ± 0·100 vs 0·170 ± 0·348 m m, P = 0·02, nonparametric test) and triglycerides (−0·342 ± 0·184 vs 0·262 ± 0·133 m m, P = 0·02), despite similar changes in BMI (−1·6 ± 0·7 vs 0·6 ± 2·1 kg/m2, P = 0·25) and HbA1C (0·03 ± 0·06 vs 0·03 ± 0·13%, P = 0·99). Differences between groups remained significant after controlling for baseline parameters and for changes in BMI. Conclusion Metformin alone more effectively improves lipid parameters than metformin with EP in adolescent PCOS, as indicated by a decrease in total cholesterol and triglycerides. This effect is not related to BMI changes. [ABSTRACT FROM AUTHOR]

Energy status plays a key role in the health of athletes and exercising individuals. Energy deficiency/low energy availability (EA), referring to a state in which insufficient energy intake and/or excessive exercise energy expenditure has resulted in compensatory metabolic adaptations to conserve fuel, can affect numerous physiological systems in women and men. The Female Athlete Triad, Male Athlete Triad, and Relative Energy Deficiency in Sport (RED-S) models conceptualize the effects of energy deficiency in athletes, and each model has strengths and limitations. For instance, the Female Athlete Triad model depicts relationships between low EA, reproductive, and bone health, underpinning decades of experimental evidence, but may be perceived as limited in scope, while the more recent RED-S model proposes a wider range of potential health effects of low EA, though many model components require more robust scientific justification. This critical review summarizes current evidence regarding the effects of energy deficiency on athlete health by addressing the quality of the underlying science, the strengths and limitations of each model, and highlighting areas where future research is needed to advance the field. With the health and wellness of athletes and exercising individuals as the overarching priority, we conclude with specific steps that will help focus future research on the Female and Male Athlete Triad and RED-S, and encourage all researchers, clinicians, and practitioners to collaborate to support the common goal of promoting the highest quality science and evidence-based medicine in pursuit of the advancement of athletes' health, well-being, and performance. [ABSTRACT FROM AUTHOR]

Objective: Data regarding clinical characteristics in males with AN are limited. We aimed to delineate clinical, biochemical, and hematological features in community‐dwelling adolescent and young adult males with AN. Method: A retrospective chart review of electronic medical records from 2000 to 2016 was conducted for 53 males aged 10–23 years old; AN (n = 36) and healthy controls (n = 17) were similar for Tanner stage. Results: Adolescent and young adult males with AN were diagnosed at a mean age of 15.9 ± 3.0 years. The most prevalent strategy for weight loss (following calorie restriction) was over‐exercising. Labs demonstrated polycythemia, leukopenia, and thrombocytopenia, but no electrolyte abnormalities. Compared with healthy controls of similar Tanner stage, males with AN had lower total testosterone levels. A significant proportion of males with AN had traumatic bone fractures. Discussion: Over‐exercising is a common secondary weight loss strategy in males with AN. Testosterone levels are lower than in controls, but electrolyte abnormalities are rare. With enhanced provider awareness, diagnostic delays may be prevented. [ABSTRACT FROM AUTHOR]