Publications by authors named "Madhusmita Misra"

261 Publications

Editorial: Insights in pediatric Endocrinology: 2021.

Front Endocrinol (Lausanne) 2022 25;13:977912. Epub 2022 Jul 25.

Division of Pediatric Endocrinology, Massachusetts General Hospital, Boston, MA, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.977912DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9359621PMC
August 2022

Load-to-strength ratio at the radius is higher in adolescent and young adult females with obesity compared to normal-weight controls.

Bone 2022 Aug 7;164:116515. Epub 2022 Aug 7.

Department of Radiology, Massachusetts General Hospital, Harvard Medical School, United States of America.

Background: Among adolescents with extremity fractures, individuals with obesity have greater representation compared with individuals of normal-weight, despite having higher areal and volumetric bone mineral density (aBMD, vBMD) than their normal-weight counterparts. The relative increase in BMD in individuals with obesity may thus be insufficient to support the greater force generated upon falling. The load-to-strength ratio is a biomechanical approach for assessing the risk of fracture by comparing applied force to bone strength, with higher load-to-strength ratios indicating higher fracture risk.

Objective: To assess the load-to-strength ratio at the distal radius in adolescent and young adult females with severe obesity (OB) compared with normal-weight healthy controls (HC). We hypothesized that OB have a higher load-to-strength ratio compared to HC.

Methods: We examined bone parameters in 65 girls 14-21 years old: 33 OB and 32 HC. We used dual-energy X-ray absorptiometry (DXA) to assess body composition, high resolution peripheral quantitative CT (HR-pQCT) to estimate vBMD, and microfinite element analysis (μFEA) to assess bone strength at the distal radius. To quantify fracture risk, we computed the load-to-strength ratio, where the numerator is defined as the load applied to the outstretched hand during a forward fall and the denominator is the bone strength, as estimated by μFEA.

Results: Although OB had higher total vBMD than HC (368.3 vs. 319.9 mgHA/cm, p = 0.002), load-to-strength ratio at the radius was greater in OB than HC after controlling for age and race (0.66 vs. 0.54, p < 0.0001). In OB, impact force and load-to-strength ratio were associated negatively with % lean mass (r = -0.49; p = 0.003 and r = -0.65; p < 0.0001 respectively) and positively with visceral fat (r = 0.65; p < 0.0001 and r = 0.36; p = 0.04 respectively).

Conclusions: Adolescent and young adult females with obesity have higher load-to-strength ratio at the distal radius due to higher forces applied to bone in a fall combined with incomplete adaptation of bone to increasing body weight. This is differentially affected by lean mass, fat mass, and visceral fat mass.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2022.116515DOI Listing
August 2022

Functional hypothalamic amenorrhea: Impact on bone and neuropsychiatric outcomes.

Front Endocrinol (Lausanne) 2022 22;13:953180. Epub 2022 Jul 22.

Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

Functional hypothalamic amenorrhea is a state of reversible hypogonadism common in adolescents and young women that can be triggered by energy deficit or emotional stress or a combination of these factors. Energy deficit may be a consequence of (i) reduced caloric intake, as seen in patients with eating disorders, such as anorexia nervosa, or (ii) excessive exercise, when caloric intake is insufficient to meet the needs of energy expenditure. In these conditions of energy deficit, suppression of the hypothalamic secretion of gonadotrophin-releasing hormone (with resulting hypoestrogenism) as well as other changes in hypothalamic-pituitary function may occur as an adaptive response to limited energy availability. Many of these adaptive changes, however, are deleterious to reproductive, skeletal, and neuropsychiatric health. Particularly, normoestrogenemia is critical for normal bone accrual during adolescence, and hypoestrogenemia during this time may lead to deficits in peak bone mass acquisition with longstanding effects on skeletal health. The adolescent years are also a time of neurological changes that impact cognitive function, and anxiety and depression present more frequently during this time. Normal estrogen status is essential for optimal cognitive function (particularly verbal memory and executive function) and may impact emotion and mood. Early recognition of women at high risk of developing hypothalamic amenorrhea and its timely management with a multidisciplinary team are crucial to prevent the severe and long-term effects of this condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2022.953180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355702PMC
August 2022

One-Year Self-Reported Appetite Is Similar in Adolescents with Obesity Who Do or Do Not Undergo Sleeve Gastrectomy.

Nutrients 2022 Jul 26;14(15). Epub 2022 Jul 26.

Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit st, Boston, MA 02114, USA.

Background: With the growing prevalence of severe obesity in adolescents, sleeve gastrectomy (SG), a type of metabolic bariatric surgery (MBS), is increasingly being performed at a younger age. Data regarding changes in homeostatic and hedonic appetite following SG are conflicting in adults, with some studies showing no change and others showing a decrease in appetite. Data evaluating the effect of SG on appetite during adolescence, when appetite is more plastic, are currently lacking.

Objective: To evaluate appetite changes one year after SG in adolescents with obesity vs. in non-surgical controls (NS).

Methods: Thirty-nine subjects 13-21 years old with severe obesity were followed for a year; 19 underwent SG, and 20 were followed without surgery. Subjects had fasting blood tests for appetite-regulating hormones and completed a visual analog scale for appetite assessment (VAS).

Results: The SG group had a decrease in body mass index (BMI) at one-year (baseline: 48.2 ± 1.7 kg/m; one-year follow-up: 42.6 ± 1.0 kg/m ( ≤ 0.0001)). No within- or between-group differences were noted in the one-year change in appetite in the SG and NS groups. After SG, fasting ghrelin decreased ( ≤ 0.0001); however, no changes were noted in peptide YY (PYY) levels. Changes in one homeostatic appetite measure following SG were inversely associated with changes in fasting PYY (r = -0.583, = 0.011). Appetite changes were not associated with weight loss or final BMI.

Conclusions: There were no changes in appetite measures one-year after SG from pre-surgery levels in adolescents with obesity, and appetite changes were not associated with changes in BMI. It is important to evaluate the impact of long-term appetite changes, if any, on weight loss after SG.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu14153054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331365PMC
July 2022

Differential comorbidity profiles in avoidant/restrictive food intake disorder and anorexia nervosa: Does age play a role?

Int J Eat Disord 2022 Jul 18. Epub 2022 Jul 18.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eat.23777DOI Listing
July 2022

Elevated Fasting Satiety-Promoting Cholecystokinin (CCK) in Avoidant/Restrictive Food Intake Disorder Compared to Healthy Controls.

J Clin Psychiatry 2022 Jul 11;83(5). Epub 2022 Jul 11.

Department of Medicine, Harvard Medical School, Boston, Massachusetts.

Avoidant/restrictive food intake disorder (ARFID) is characterized by food avoidance or dietary restriction not primarily motivated by body weight/shape concerns. Individuals with ARFID can report early satiation, post-prandial fullness, and high intermeal satiety, but whether these symptoms are related to differences in the biology underlying appetite regulation is unknown. In male and female children and adolescents, we hypothesized that fasting levels of cholecystokinin (CCK), a satiety hormone, would be elevated in participants with ARFID (full or subthreshold) versus healthy controls (HCs). Within the ARFID group, we also explored the relations of CCK with weight status, subjective appetite ratings, and ARFID severity and phenotypes.

A total of 125 participants (83 with full/subthreshold ARFID (per ) and 42 HCs, aged 10.2-23.7 years; 61% female; July 2014-December 2019) underwent fasting blood draws for CCK, completed self-report measures assessing subjective state and trait appetite ratings, and completed a semistructured interview assessing ARFID severity.

Fasting CCK was higher in those with full/subthreshold ARFID versus HCs with a large effect ( = 25.0,  < .001, η = 0.17), controlling for age, sex, and body mass index (BMI) percentile. Within the ARFID group, CCK was not significantly related to BMI percentile, subjective appetite ratings, or ARFID characteristic measures.

CCK may contribute to etiology and/or maintenance of ARFID, as children and adolescents with heterogeneous presentations of avoidant/restrictive eating appear to show elevated fasting levels compared to healthy youth. Further research is needed to understand relations between CCK and appetite, weight, and eating behavior in ARFID.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4088/JCP.21m14111DOI Listing
July 2022

Physiologic Transdermal Estradiol Replacement Mimics Effects of Endogenous Estrogen on Bone Outcomes in Hypoestrogenic Women with Anorexia Nervosa.

Nutrients 2022 Jun 21;14(13). Epub 2022 Jun 21.

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Boston, MA 02114, USA.

Background: While physiologic estrogen replacement results in increases in areal bone mineral density (aBMD) in hypoestrogenic adolescent girls and young adult women with AN, data are lacking regarding its impact on measures of volumetric BMD (vBMD), bone geometry, and structure.

Methods: 23 young women with anorexia nervosa (AN) and 27 normal-weight healthy controls (HC) between 14-25 years old were followed for 12 months. AN participants received transdermal 17β-estradiol (continuously) with 10 days of cyclic oral progesterone (100 mg daily) every month for the study duration (AN-E+). DXA was used to measure aBMD and body composition, high resolution peripheral quantitative CT (HRpQCT) to assess vBMD, bone geometry and structure at the distal radius and tibia, and microfinite element analysis to estimate strength.

Results: Groups did not differ for age. Median baseline BMI z-scores were -1.13 (-1.58, -0.38) in AN-E+ vs. 0.08 (-0.40, 0.84) in HC ( < 0.0001). For most HRpQCT parameters and strength estimates, young women with AN receiving physiologic estrogen replacement demonstrated similar changes over 12 months as did normoestrogenic HC. Additionally, radial cortical tissue mineral density, cortical vBMD, and failure load increased ( = 0.01; = 0.02; = 0.004 respectively) over 12 months in AN-E+ compared to HC.

Conclusions: With physiologic estrogen replacement, bone accrual improved in AN to approximate changes observed in normoestrogenic controls followed without any intervention, with additional benefits observed for cortical tissue mineral density, cortical vBMD, and failure load at the radius in AN vs. controls. Thus, this strategy for estrogen replacement effectively mimics the effects of endogenous estrogen on bone structure and estimated strength.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/nu14132557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268216PMC
June 2022

Dehydroepiandrosterone sulfate levels predict weight gain in women with anorexia nervosa.

Int J Eat Disord 2022 Aug 2;55(8):1100-1107. Epub 2022 Jul 2.

Neuroendocrine Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eat.23767DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9357210PMC
August 2022

Changes in sex steroids and enteric peptides after sleeve gastrectomy in youth in relation to changes in bone parameters.

J Clin Endocrinol Metab 2022 Jun 11. Epub 2022 Jun 11.

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.

Context: Sleeve gastrectomy (SG) improves metabolic endpoints but is associated with impaired bone outcomes.

Objective: To determine mechanisms contributing to impaired bone health in youth following SG.

Design: 12-month longitudinal observational study.

Setting: Multi-disciplinary tertiary care hospital.

Patients: 64 youth 13-25 years old with moderate-to-severe obesity (51 females); 30 underwent SG and 34 were non-surgical controls (NS).

Intervention(s): SG based on a combined decision-making process between treatment team and patient.

Main Outcome Measure(s): Fasting blood for enteric peptides, sex steroids, sclerostin, and bone turnover markers [N-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide (CTX)]; DXA measures of areal bone mineral density (aBMD) and body composition; high resolution peripheral quantitative CT measures of volumetric BMD (vBMD); microfinite element analysis of strength estimates (distal radius and tibia).

Results: SG had greater reductions in BMI z-scores, serum estrone and the free androgen index (FAI) (p≤0.046) and greater increases in sclerostin, P1NP and CTX (p≤0.010) than NS. Fasting ghrelin decreased in SG vs. NS (p<0.0001); fasting PYY did not change. Most changes were driven by female SG participants. Among females (majority of study participants), after controlling for baseline age and race, reductions in aBMD Z-scores were positively associated with changes in BMI, lean mass, estrone, FAI, and ghrelin, and inversely with changes in sclerostin. Decreases in total vBMD of the radius and tibia were associated positively with decreases in BMI. Increases in CTX were associated with decreases in BMI, lean mass, and ghrelin, and increases in sclerostin.

Conclusions: Bone loss after SG in youth is associated with changes in body composition, sex steroids, sclerostin and enteric peptides. These are potential targets for future preventative or therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgac361DOI Listing
June 2022

Eighteen-month Course and Outcome of Adolescent Restrictive Eating Disorders: Persistence, Crossover, and Recovery.

J Clin Child Adolesc Psychol 2022 Apr 27:1-11. Epub 2022 Apr 27.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital.

Objective: 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.

Method: We assessed 82 women (ages 10-23 years) with low-weight eating disorders including AN ( = 40; 29 restricting, 11 binge-eating/purging), atyp-AN ( = 26; 19 restricting, seven binge-eating/purging), and ARFID ( = 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.

Results: 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.

Conclusion: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15374416.2022.2034634DOI Listing
April 2022

The female athlete triad: review of current literature.

Curr Opin Endocrinol Diabetes Obes 2022 02;29(1):44-51

Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

Purpose Of Review: Adolescence and young adulthood are a critical period in the life of women for optimizing long-term bone health. Young athletes lead a demanding lifestyle with increased dietary requirements to meet the robust demands of energy expenditure to maintain a state of energy balance. During a time of fast paced changes and unpredictable societal demands on young athletes, it is important to review the severe consequences of energy deficiency and options for adequate management.

Recent Findings: This review focuses on hormonal adaptations that occur in energy deficient female athletes that lead to menstrual irregularities and impaired bone health, increasing the risk for stress and other fractures. We also describe management strategies to mitigate the consequences of limited energy availability on bone and other outcomes.

Summary: These strategies should help guide the management of young female athletes to prevent irreversible changes to their bone health. Identifying current knowledge should help increase awareness among medical providers, which can then be communicated to the sports community, parents, and athletes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MED.0000000000000690DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702454PMC
February 2022

The Path Towards Progress: A Critical Review to Advance the Science of the Female and Male Athlete Triad and Relative Energy Deficiency in Sport.

Sports Med 2022 Jan 19;52(1):13-23. Epub 2021 Oct 19.

Department of Kinesiology, Pennsylvania State University, University Park, PA, 16802, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40279-021-01568-wDOI Listing
January 2022

Clinical, biochemical, and hematological characteristics of community-dwelling adolescent and young adult males with anorexia nervosa.

Int J Eat Disord 2021 12 7;54(12):2213-2217. Epub 2021 Oct 7.

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/eat.23622DOI Listing
December 2021

Meta-analysis of structural MRI studies in anorexia nervosa and the role of recovery: a systematic review protocol.

Syst Rev 2021 09 13;10(1):247. Epub 2021 Sep 13.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, MA, USA.

Background: Anorexia nervosa (AN) is associated with structural brain abnormalities. Studies have reported less cerebral tissue and more cerebrospinal fluid (CSF) in individuals with AN relative to healthy controls, although findings are variable and inconsistent due to variations in sample size, age, and disease state (e.g., active AN, weight-recovered AN). Further, it remains unclear if structural brain abnormalities observed in AN are a consequence of specific brain pathologies or malnutrition, as very few longitudinal neuroimaging studies in AN have been completed.

Methods: To overcome this issue, this comprehensive meta-analysis will combine region-of-interest (ROI) and voxel-based morphometry (VBM) approaches to understand how regional and global structural brain abnormalities differ among individuals with AN and healthy controls (HCs). Additionally, we aim to understand how clinical characteristics and physiological changes during the course of illness, including acute illness vs. weight recovery, may moderate these structural abnormalities. We will create an online database of studies that have investigated structural brain abnormalities in AN. Data will be reviewed independently by two members of our team using MEDLINE databases, Web of Science, PsycINFO, EMBASE, and CINAHL. We will conduct ROI and VBM meta-analysis using seed-based d mapping in AN and HCs. We will include all studies that include structural neuroimaging of individuals with AN (both acute and weight-recovered) and HCs between January 1997 and 2020.

Discussion: This systematic review will assess the effects of AN compared to HC on brain structure. Futhermore, it will explore the role of acute AN and weight-recovered AN on brain structure. Findings will help researchers and clinicians to better understand the course of illness in AN and the nature of recovery, in terms of weight, malnutrition, and the state of the brain.

Systematic Review Registration: PROSPERO CRD42020180921.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13643-021-01799-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438886PMC
September 2021

A Moving Target: How We Define Avoidant/Restrictive Food Intake Disorder Can Double Its Prevalence.

J Clin Psychiatry 2021 09 7;82(5). Epub 2021 Sep 7.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, Boston, Massachusetts.

The criteria for avoidant/restrictive food intake disorder (ARFID) include ambiguities. Diagnostic criteria that allow for clinical judgment are essential for clinical practice. However, ambiguities can have major implications for treatment access and comparability and generalizability of research studies. The purpose of this study was to determine the degree to which distinct operationalizations of the diagnostic criteria for ARFID contribute to differences in the frequency of individuals who are eligible for the ARFID diagnosis.

Because criteria B, C, and D are rule-outs, we focused on criterion A, identified 19 potential operational definitions, and determined the extent to which these different methods impacted the proportion of individuals who met criteria for ARFID in a sample of children, adolescents, and young adults (n = 80; September 2016-February 2020) enrolled in an avoidant/restrictive eating study.

Within each criterion, the proportion of individuals meeting diagnostic criteria differed significantly across the methodologies (all values < .008). Using the strictest definition of each criterion, 50.0% (n = 40) of participants met criteria for ARFID. In contrast, under the most lenient definition of each criterion, the number nearly doubled, resulting in 97.5% (n = 78) meeting ARFID criteria.

Comparison of diagnostic definitions for ARFID among children, adolescents, and young adults confirmed a broad range of statistically distinct proportions within a single sample. Our findings support the need for additional contextual support and consensus among disciplines on operationalization in both research and clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4088/JCP.20m13831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493963PMC
September 2021

Cognitive-behavioral therapy for adults with avoidant/restrictive food intake disorder.

J Behav Cogn Ther 2021 Mar 3;31(1):47-55. Epub 2021 Mar 3.

Eating Disorders Clinical and Research Program, Massachusetts General Hospital, 2 Longfellow Place, Suite 200, Boston, MA 02114, USA.

There are currently no evidence-based treatments for adults with avoidant/restrictive food intake disorder (ARFID). The purpose of this study was to evaluate the acceptability, feasibility, and proof-of-concept of cognitive-behavioral therapy for ARFID (CBT-AR) for adults. Males and females (ages 18-55 years) were offered 20-30 outpatient sessions of CBT-AR delivered by one of five therapists. Of 18 eligible adults offered CBT-AR, 15 chose to participate and 14 completed treatment. All patients endorsed high ratings of treatment credibility and expected improvement after the first session, and 93% of completers provided high ratings of satisfaction at the conclusion of treatment. Therapists rated the majority (80%) of patients as "much improved" or "very much improved." Based on intent-to-treat analyses, ARFID severity on the Pica, ARFID, and Rumination Disorder Interview (PARDI) showed a large and significant decrease from pre- to post-treatment; and patients incorporated a mean of 18.0 novel foods. The underweight subgroup ( = 4) gained an average of 11.38 pounds, showing a large and significant increase in mean BMI from the underweight to the normal-weight range. At post-treatment, 47% of patients no longer met criteria for ARFID. To our knowledge, this is the first prospective treatment study of ARFID in adults. The findings of this study provide preliminary evidence of feasibility, acceptability, and proof-of-concept of CBT-AR for heterogeneous presentations of ARFID in adults. Randomized controlled trials are needed to confirm these findings. ClinicalTrials.gov Identifier: NCT02963220.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jbct.2020.10.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375627PMC
March 2021

Reductions in rostral anterior cingulate GABA are associated with stress circuitry in females with major depression: a multimodal imaging investigation.

Neuropsychopharmacology 2021 11 6;46(12):2188-2196. Epub 2021 Aug 6.

Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, MA, USA.

The interplay between cortical and limbic regions in stress circuitry calls for a neural systems approach to investigations of acute stress responses in major depressive disorder (MDD). Advances in multimodal imaging allow inferences between regional neurotransmitter function and activation in circuits linked to MDD, which could inform treatment development. The current study investigated the role of the inhibitory neurotransmitter GABA in stress circuitry in females with current and remitted MDD. Multimodal imaging data were analyzed from 49 young female adults across three groups (current MDD, remitted MDD (rMDD), and healthy controls). GABA was assessed at baseline using magnetic resonance spectroscopy, and functional MRI data were collected before, during, and after an acute stressor and analyzed using a network modeling approach. The MDD group showed an overall lower cortisol response than the rMDD group and lower rostral anterior cingulate cortex (ACC) GABA than healthy controls. Across groups, stress decreased activation in the frontoparietal network (FPN) but increased activation in the default mode network (DMN) and a network encompassing the ventromedial prefrontal cortex-striatum-anterior cingulate cortex (vmPFC-Str-ACC). Relative to controls, the MDD and rMDD groups were characterized by decreased FPN and salience network (SN) activation overall. Rostral ACC GABA was positively associated with connectivity between an overlapping limbic network (Temporal-Insula-Amygdala) and two other circuits (FPN and DMN). Collectively, these findings indicate that reduced GABA in females with MDD was associated with connectivity differences within and across key networks implicated in depression. GABAergic treatments for MDD might alleviate stress circuitry abnormalities in females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41386-021-01127-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505659PMC
November 2021

Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Trial.

J Bone Miner Res 2021 11 2;36(11):2116-2126. Epub 2021 Sep 2.

Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA.

Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6 months of rhIGF-1 followed by 6 months of risedronate ("rhIGF-1/Risedronate") (n = 33), 12 months of risedronate ("Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/Risedronate (p = 0.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1/Risedronate than the Risedronate or Placebo groups (p < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/Risedronate than Placebo group (p < 0.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. © 2021 American Society for Bone and Mineral Research (ASBMR).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jbmr.4420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595577PMC
November 2021

Editorial: Management of Bone Disorders in Children.

Front Endocrinol (Lausanne) 2021 5;12:725655. Epub 2021 Jul 5.

Division of Pediatric Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.725655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288073PMC
February 2022

The Male Athlete Triad-A Consensus Statement From the Female and Male Athlete Triad Coalition Part II: Diagnosis, Treatment, and Return-To-Play.

Clin J Sport Med 2021 Jul;31(4):349-366

Department of Family Medicine, University of California, Los Angeles, Los Angeles, California.

Abstract: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/JSM.0000000000000948DOI Listing
July 2021

Ghrelin and PYY in low-weight females with avoidant/restrictive food intake disorder compared to anorexia nervosa and healthy controls.

Psychoneuroendocrinology 2021 07 28;129:105243. Epub 2021 Apr 28.

Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, United States of America; Department of Medicine, Harvard Medical School, Boston, MA, United States of America.

Background: Avoidant/restrictive food intake disorder (ARFID) is characterized by restrictive eating and failure to meet nutritional needs but is distinct from anorexia nervosa (AN) because restriction is not motivated by weight/shape concerns. We examined levels of orexigenic ghrelin and anorexigenic peptide YY (PYY) in young females with ARFID, AN and healthy controls (HC).

Methods: 94 females (22 low-weight ARFID, 40 typical/atypical AN, and 32 HC ages 10-22 years) underwent fasting blood draws for total ghrelin and total PYY. A subset also provided blood 30, 60 and 120 min after a standardized meal.

Results: Females with ARFID ate less than those with AN or HC (ps<0.012); were younger (14.4 ± 3.2 years) than those with AN (18.9 ± 3.1 years) and HC (17.4 ± 3.1 years) (ps<0.003) and at a lower Tanner stage (3.1 ± 1.5) than AN (4.5 ± 1.1;) and HC (4.4 ± 1.1; ps<0.005), but did not differ in BMI percentiles or BMI Z-scores from AN (ps>0.44). Fasting and postprandial ghrelin were lower in ARFID versus AN (ps≤.015), but not HC (ps≥0.62). Fasting and postprandial PYY did not differ between ARFID versus AN or HC (ps≥0.13); ARFID did not demonstrate the sustained high PYY levels post-meal observed in those with AN and HC. Secondary analyses controlling age or Tanner stage and calories consumed showed similar results. Exploratory analyses suggest that the timing of the PYY peak in ARFID is earlier than HC, showing a peak PYY level 30 min post-meal (p = .037).

Conclusions: ARFID and AN appear to have distinct patterns of secretion of gut-derived appetite-regulating hormones that may aid in differential diagnosis and provide new treatment targets.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.psyneuen.2021.105243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8363304PMC
July 2021

Impact of sleeve gastrectomy on bone outcomes in adolescents vs. adults with obesity.

Bone 2021 08 24;149:115975. Epub 2021 Apr 24.

Neuroendocrine Unit, Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America; Pediatric Endocrine Unit, Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.

Background: Sleeve gastrectomy (SG) is the most common metabolic and bariatric surgery (MBS) procedure in adolescents and adults. Only few studies have assessed bone outcomes following SG and it is unknown whether skeletal changes differ by age group. Recent studies have identified marrow adipose tissue (MAT) as a novel biomarker for bone quality with studies in adults showing high MAT in those with visceral adiposity and a reciprocal increase in MAT with bone loss.

Objective: To determine the impact of SG on volumetric BMD (vBMD) and MAT in adolescents and adults with obesity. We hypothesized that SG would lead to a decrease in vBMD and increase in MAT but that these changes would be less pronounced in adolescents compared to adults.

Materials And Methods: The study was IRB-approved and HIPAA-compliant. Written informed consent/assent was obtained. We examined 10 adolescents (mean age 17.8 ± 2.5 years, mean BMI 43.5 ± 5.6 kg/m) and 10 sex, race, and BMI-matched adults (mean age 49.5 ± 13.6 years, mean BMI 43.7 ± 5.9 kg/m), before and 12 months after SG. At baseline and 12 months, subjects underwent quantitative CT of the lumbar spine (L1-L2) to assess trabecular vBMD, single voxel proton MR spectroscopy at 3 T (PRESS pulse sequence without water suppression) at L1-L2 to quantify MAT, and MRI of the abdomen to assess visceral (VAT) and subcutaneous adipose tissue (SAT).

Results: At baseline, adolescents had lower MAT (p = 0.0002) and higher vBMD (p = 0.050) compared to adults. Adolescents and adults lost 27.9 ± 6.5 vs. 25.0 ± 11.2% of body weight (p < 0.0001 for within group change), while there was no significant difference between groups (p = 0.455). There was a significant reduction in vBMD in adults (-3.9 ± 3.9%, p = 0.005) and a trend for a reduction in adolescents (-3.7 ± 7.5%, p = 0.119), with no significant difference between groups (p = 0.944). Lumbar MAT content increased in both adults and adolescents (p ≤ 0.034), while the difference was not significant between groups (p = 0.281). In adolescents and adults, 12-month percent change in weight and BMI was positively associated with % change in MAT (p ≤ 0.042). 12-month percent change in MAT was positively associated with 12-month % change in SAT in adolescents and 12-month percent change in VAT in adults (p ≤ 0.045).

Conclusion: SG in adolescents and adults with severe obesity is associated with a reduction in lumbar vBMD and an increase in lumbar MAT, although the reduction in adolescents did not reach statistical significance, with no significant differences in these endpoints between groups. Our results suggest detrimental effects of bariatric surgery on bone for patients across the life span.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2021.115975DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217278PMC
August 2021

Memory and Executive Function in Adolescent and Young Adult Females with Moderate to Severe Obesity Before and After Weight Loss Surgery.

Obes Surg 2021 07 7;31(7):3372-3378. Epub 2021 Apr 7.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

There is a global increase in the prevalence of severe obesity in females during adolescence, which is a critical period for neurocognitive development. An increasing number of adolescents and young adults are now undergoing weight loss surgery as a treatment strategy for obesity. In addition to metabolic complications, obesity has been linked to neurocognitive comorbidity, and studies exploring cognitive performance in adolescents with severe obesity and the impact of bariatric surgery on cognitive abilities are limited. Verbal memory and executive function were assessed cross-sectionally in 69 females with moderate to severe obesity and 24 females without obesity, 13-24 years old. In an exploratory analysis, cognitive changes were also assessed longitudinally over 12 months in a subset of 35 females with moderate to severe obesity following weight loss surgery (n = 21) or following usual care without surgery (n = 14). In cross-sectional analysis, females with moderate to severe obesity showed lower scores for short-term and long-term recall (verbal memory) and response inhibition and cognitive flexibility (executive function) than the comparison group, when adjusted for age and baseline intelligence. Females with moderate to severe obesity who underwent surgery showed significant weight loss but no improvement in verbal memory and executive function scores over 12 months compared with those who did not have surgery. Females with moderate to severe obesity demonstrate worse performance in tests of verbal memory and executive function than the comparison group without obesity. In addition, exploratory analyses provide no indication that weight loss surgery improves these observed cognitive decrements over a period of 12 months. Further studies are necessary to comprehensively evaluate changes in cognitive function following bariatric surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11695-021-05386-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8725619PMC
July 2021

Neurobiology of Avoidant/Restrictive Food Intake Disorder in Youth with Overweight/Obesity Versus Healthy Weight.

J Clin Child Adolesc Psychol 2021 Mar 26:1-14. Epub 2021 Mar 26.

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School.

: 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/15374416.2021.1894944DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464625PMC
March 2021

Effect of Transdermal Estradiol and Insulin-like Growth Factor-1 on Bone Endpoints of Young Women With Anorexia Nervosa.

J Clin Endocrinol Metab 2021 06;106(7):2021-2035

Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.

Context: Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency.

Objective: To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes.

Design: Double-blind, randomized, placebo-controlled 12-month longitudinal study.

Participants: Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study.

Intervention: Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range.

Main Outcome Measures: Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates.

Results: Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups.

Conclusions: We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgab145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8427708PMC
June 2021

The epidemiology and management patterns of pediatric pituitary tumors in the United States.

Pituitary 2021 Jun 12;24(3):412-419. Epub 2021 Jan 12.

Computational Neuroscience Outcomes Center, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Purpose: Hypothalamic-pituitary axis dysfunction and mass effect symptoms in the pediatric population can indicate a pituitary region tumor. Herein, we evaluate the epidemiology and management of this rare entity.

Methods: Pediatric patients (≤ 21yo) who presented from 2004 to 2017 with a pituitary tumor were evaluated from the U.S. National Cancer Database. The distributions and management patterns of pituitary tumors were assessed by patients' tumor type, age, sex, race/ethnicity, tumor size, and insurance status.

Results: 19.7% of intracranial tumors in the pediatric population originated in the pituitary region. 7653 pediatric patients with pituitary region tumors were identified, 68.2% of whom were female, with the tumors predominantly occurring in early adolescence (46.9%) and late adolescence (34.8%). The majority of pediatric pituitary region tumors were pituitary adenomas (77.9%), followed by craniopharyngiomas (18.1%) and germ cell tumors (1.6%). Girls demonstrated higher proportions of pituitary adenomas across all ages than boys. Asian/Pacific Islander patients were independently more likely to present at younger ages (mean 13.9yrs) and with germ cell tumors than patients of other races/ethnicities. Only 5.5% of patients were uninsured (referent), but they were independently more likely to present at older ages (mean 17.9yrs) and less likely to undergo surgery than patients with private insurance (OR = 1.93, 95% CI = 1.47-2.52, p < 0.001) or Medicaid (OR = 1.51, 95% CI = 1.14-2.00, p = 0.004).

Conclusion: Pituitary region tumors comprise a significant fraction of intracranial pediatric tumors, particularly in adolescent girls. The differential diagnosis of pituitary tumor types differed significantly by patients' age, sex, and race/ethnicity. Uninsured patients were associated with delays in care and less surgical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11102-020-01120-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415131PMC
June 2021

Changes in marrow adipose tissue in relation to changes in bone parameters following estradiol replacement in adolescent and young adult females with functional hypothalamic amenorrhea.

Bone 2021 04 6;145:115841. Epub 2021 Jan 6.

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States; Division of Pediatric Endocrinology, Mass General Hospital for Children and Harvard Medical School, Boston, MA, United States. Electronic address:

Context: Low energy availability causes disruption of hypothalamic gonadotropin-releasing hormone secretion leading to functional hypothalamic amenorrhea (FHA) and hypoestrogenism, which in turn contributes to decreased bone mineral density (BMD) and increased bone marrow adipose tissue (MAT). Transdermal estradiol administration in physiologic doses increases BMD in adolescents and adults with FHA. However, the impact of estrogen replacement on MAT in relation to changes in BMD has not been studied in adolescents and young adults. We hypothesized that physiologic estrogen replacement would lead to decreases in MAT, associated with increases in BMD.

Methods And Materials: We studied 15 adolescent and young adult females with FHA (14-25 years). All participants received a17β- estradiol transdermal patch at a dose of 0.1 mg/day (applied twice weekly) for 12 months. Participants also received cyclic progestin for 10-12 days each month. We quantified MAT (lipid/water ratio) of the fourth lumbar (L4) vertebral body and femoral diaphysis by single proton (1H)-magnetic resonance spectroscopy, and compartmental volumetric BMD of the distal radius and tibia using high-resolution peripheral quantitative computed tomography.

Results: Transdermal estradiol therapy over 12 months resulted in a decrease in MAT at the lumbar (L4) vertebra from 0.92 ± 0.55 at baseline to 0.63 ± 0.29 at 12-months (p = 0.008), and an increase in radial and tibial cortical vBMD (p = 0.006, p = 0.0003). Changes in L4 MAT trended to be inversely associated with changes in radial cortical vBMD (rho = -0.47, p = 0.08).

Conclusion: We show that in adolescent and young adult girls with FHA, MAT decreases following transdermal estrogen therapy and these changes are associated with increased cortical vBMD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2021.115841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8022869PMC
April 2021

Racial differences in lumbar marrow adipose tissue and volumetric bone mineral density in adolescents and young adults with obesity.

Bone Rep 2020 Dec 13;13:100726. Epub 2020 Oct 13.

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States of America.

Background: Areal bone mineral density (BMD) of the lumbar spine by DXA is greater in Black compared to White adolescents. Bone strength is determined not only by BMD but also its microenvironment, and marrow adipose tissue (MAT) has been shown to be an important determinant of skeletal integrity, independent of BMD. Racial differences in volumetric BMD (vBMD) and MAT in adolescents and young adults with obesity are unknown.

Objective: To assess racial differences in lumbar vBMD and MAT in Black and White adolescents and young adults with obesity and to assess body composition determinants of bone parameters. We hypothesized that Blacks will have higher vBMD and lower MAT of the lumbar spine compared to Whites.

Methods: The study group comprised 77 adolescents/young adults, 25 Black and 52 White, (mean age 18.2 ± 2.5 years, range 13 to 24 years) with moderate to severe obesity (mean body mass index (BMI) 46.2 ± 7.3 kg/m, range 35.5 to 69.7 kg/m). Groups were similar in age, BMI, and sex distribution (p > 0.84). Subjects underwent QCT of the lumbar spine (L1-L2) for assessment of vBMD with the use of a calibration phantom and 1H-MRS/MRI for quantification of lumbar MAT content (L1-L2) and abdominal fat and thigh muscle mass. Groups were compared by Student's -test or Wilcoxon test. Correlation analysis was performed to assess associations between bone parameters and body composition.

Results: Black adolescents/young adults with obesity had higher vBMD compared to Whites (p < 0.0001), while there was no significant difference in lumbar MAT (p = 0.64). There were also no significant differences in body composition measures between groups (p ≥ 0.28). An inverse association between MAT and vBMD was observed in Whites (r = -0.47, P = 0.001) but not in Blacks (p = 0.6). There were no significant associations between body composition measures and bone parameters (p > 0.1).

Conclusion: There are racial differences in lumbar vBMD in adolescents and young adults with moderate to severe obesity, with Blacks having higher vBMD than Whites, while there were no differences in MAT content. The known inverse association between BMD and MAT was only observed in Whites but not in Blacks, suggesting possible racial differences in stem cell differentiation into the bone and fat lineages.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bonr.2020.100726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772680PMC
December 2020

Repeatability and reliability of GABA measurements with magnetic resonance spectroscopy in healthy young adults.

Magn Reson Med 2021 05 20;85(5):2359-2369. Epub 2020 Nov 20.

Center for Depression, Anxiety and Stress Research, McLean Hospital, Belmont, Massachusetts, USA.

Purpose: Gamma-aminobutyric acid (GABA) abnormalities have been implicated in a range of neuropsychiatric disorders. Despite substantial interest in probing GABA in vivo, human imaging studies relying on magnetic resonance spectroscopy (MRS) have generally been hindered by technical challenges, including GABA's relatively low concentration and spectral overlap with other metabolites. Although past studies have shown moderate-to-strong test-retest repeatability and reliability of GABA within certain brain regions, many of these studies have been limited by small sample sizes.

Methods: GABA+ (macromolecular-contaminated) test-retest reliability and repeatability were assessed via a Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) MRS sequence in the rostral anterior cingulate cortex (rACC; n = 21) and dorsolateral prefrontal cortex (dlPFC; n = 20) in healthy young adults. Data were collected on a 3T scanner (Siemens Prisma, Siemens Healthcare, Erlangen, Germany) and GABA+ results were reported in reference to both total creatine (GABA+/tCr) and water (GABA+/water).

Results: Results showed strong test-retest repeatability (mean GABA+/tCr coefficient of variation [CV] = 4.6%; mean GABA+/water CV = 4.0%) and reliability (GABA+/tCr intraclass correlation coefficient [ICC] = 0.77; GABA+/water ICC = 0.87) in the dlPFC. The rACC showed acceptable (but comparatively lower) repeatability (mean GABA+/tCr CV = 8.0%; mean GABA+/water CV = 7.5%), yet low-moderate reliability (GABA+/tCr ICC = 0.40; GABA+/water ICC = 0.44).

Conclusion: The present study found excellent GABA+ MRS repeatability and reliability in the dlPFC. The rACC showed inferior results, possibly because of a combination of shimming impedance and measurement error. These data suggest that MEGA-PRESS can be utilized to reliably distinguish participants based on dlPFC GABA+ levels, whereas the mixed results in the rACC merit further investigation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/mrm.28587DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902337PMC
May 2021

Bone Metabolism in Adolescents Undergoing Bariatric Surgery.

J Clin Endocrinol Metab 2021 01;106(2):326-336

Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Purpose: The prevalence of childhood obesity has increased over past decades with a concomitant increase in metabolic and bariatric surgery (MBS). While MBS in adults is associated with bone loss, only a few studies have examined the effect of MBS on the growing skeleton in adolescents.

Methods: This mini-review summarizes available data on the effects of the most commonly performed MBS (sleeve gastrectomy and gastric bypass) on bone in adolescents. A literature review was performed using PubMed for English-language articles.

Results: Dual-energy x-ray absorptiometry (DXA) measures of areal bone mineral density (aBMD) and BMD Z scores decreased following all MBS. Volumetric BMD (vBMD) by quantitative computed tomography (QCT) decreased at the lumbar spine while cortical vBMD of the distal radius and tibia increased over a year following sleeve gastrectomy (total vBMD did not change). Reductions in narrow neck and intertrochanteric cross-sectional area and cortical thickness were observed over this duration, and hip strength estimates were deleteriously impacted. Marrow adipose tissue (MAT) of the lumbar spine increased while MAT of the peripheral skeleton decreased a year following sleeve gastrectomy. The amount of weight loss and reductions in lean and fat mass correlated with bone loss at all sites, and with changes in bone microarchitecture at peripheral sites.

Conclusion: MBS in adolescents is associated with aBMD reductions, and increases in MAT of the axial skeleton, while sleeve gastrectomy is associated with an increase in cortical vBMD and decrease in MAT of the peripheral skeleton. No reductions have been reported in peripheral strength estimates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1210/clinem/dgaa836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823234PMC
January 2021
-->