Depressive and anxiety symptoms, and neural correlates of reward and punishment anticipation in female athletes with amenorrhea.

Objective: Studies in estrogen deficiency states such as primary ovarian insufficiency and Turner syndrome suggest that estrogen status may be an important modulator of mood and emotions. In this study we compared depressive and anxiety symptoms between adolescent and young adult female oligo-amenorrheic athletes (AA) and eumenorrheic females (EM), and explored structural, and functional changes in related brain areas during reward processing, a behavioral construct that is altered in depression and anxiety. Methods: We included (i) 24 AA participating in ≥4 hours/week of aerobic exercise or running ≥20 miles/week for ≥6 months in the preceding year, with lack of menstrual cycles for ≥3 months within at least 6 preceding months of oligo-amenorrhea, OR in premenarchal girls, absence of menses at >15 years), and (ii) 27 EM aged 14-25 years. Participants completed the Beck Depression Inventory-II (BDI-II), State and Trait Anxiety Inventory (STAI), and Mood and Anxiety Symptoms Questionnaire (MASQ). Structural MRI and brain activation during a functional MRI (fMRI) task that probes reward and punishment processing was examined in a subset of 10 AA and 23 EM. Results: Median (IQR) age and BMI of AA and EM groups were 20.6 (19.0-22.6) vs. 20.6 (19.2-23.7) years, p=0.6 and v 20.3 (18.8-21.5) vs. 21.9 (19.6-23.5) kg/m2, p=0.005, respectively. While groups did not differ for BDI-II scores, AA had higher anhedonic depression MASQ scores (p=0.04), and STAI (p=0.03) scores vs. EM. In the fMRI subset, AA had higher caudate volumes vs. EM [F(1, 29)=9.930, p=0.004]. Lower activation observed in the right caudate during reward anticipation in AA compared with EM (p=0.036) suggests blunted reward processing in the striatum in estrogen deficient states. Conclusion: Athletes with amenorrhea had higher depressive and anxiety symptomatology compared to eumenorrheic young women. Exploratory analyses demonstrated increased caudate volumes and decreased caudate activation during reward processing in athletes with amenorrhea suggesting that estrogen may play a role in reward processing.

Intranasal Carbetocin Reduces Hyperphagia, Anxiousness, and Distress in Prader-Willi Syndrome: CARE-PWS Phase 3 Trial.

CONTEXT: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. OBJECTIVE: To evaluate safety and efficacy of intranasal carbetocin in PWS. DESIGN: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. SETTING: Twenty-four ambulatory clinics at academic medical centers. PARTICIPANTS: A total of 130 participants with PWS aged 7 to 18 years. INTERVENTIONS: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. MAIN OUTCOME MEASURES: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). RESULTS: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. CONCLUSIONS: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. CLINICAL TRIALS REGISTRATION NUMBER: NCT03649477.

Care for Transgender Young People.

Clinicians of all disciplines, including pediatric endocrinologists, are likely to encounter transgender and gender-diverse (TGD) young people in their practice regardless of whether they specialize in gender-affirming medical care. Because of this, it is important to be aware of the ways in which medical professionals can affirm these individuals. Although gender-affirming therapy should always include affirmation including proper use of names and pronouns, the transition journey will look different for each patient. The gender-affirming care of TGD young people may include both medical and nonmedical interventions (e.g., social transition). Therapies utilized for medical gender transition such as gonadotropin-releasing hormone agonists and/or gender-affirming hormones have implications for growth, bone health, cardiovascular health, and fertility, although these impacts are not yet completely understood. This review provides an overview of the care of transgender young people as well as a summary of what is known about the outcomes of these therapies. Clinicians should advise TGD young people and their families of the known and unknown risks and work together with patients to decide upon a treatment and follow-up regimen that aligns with their individual gender affirmation and health goals.

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

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.

Depressive and anxiety symptoms and suicidality in adolescent and young adult females with moderate to severe obesity before and after weight loss surgery.

Data are conflicting regarding the impact of weight loss on mood and anxiety in adolescent and young adult females with moderate to severe obesity (OB), who are at increased risk for mood dysfunction compared with normal-weight females (NW). We examined depressive and anxiety symptoms in 94 females 13-21 years old: 39 in the NW group (body mass index [BMI]: 5th -85th percentiles) and 55 in the OB group (BMI >40 kg/m2 or >35 kg/m2 with comorbidities). Fifteen participants in the OB group who underwent bariatric surgery (gastric bypass or sleeve gastrectomy) and 15 getting routine care were re-assessed after 6 months. The Beck Depression Inventory-II (BDI-II) and State-Trait Anxiety Inventory (STAI) assessed depressive and anxiety symptoms, respectively. The OB group had higher BDI-II and STAI T-scores (P < .0001), a higher prevalence of clinical depression and anxiety (P < .001), and reported greater suicidal ideation (P = .02) vs the NW group. The bariatric surgery and non-surgical groups did not differ for changes in BDI-II and STAI T-Scores and suicidality over 6-month follow-up, despite greater weight loss in the former. Depressive and anxiety symptoms and suicidality were more frequently observed in the OB vs NW group. These symptoms did not improve following bariatric surgery despite significant weight loss, underscoring the need to investigate determinants of emergence and resolution of these symptoms in the OB group.

Oestrogen replacement improves bone mineral density in oligo-amenorrhoeic athletes: a randomised clinical trial.

OBJECTIVE: Normal-weight oligo-amenorrhoeic athletes (OAA) are at risk for low bone mineral density (BMD). Data are lacking regarding the impact of oestrogen administration on bone outcomes in OAA. Our objective was to determine the effects of transdermal versus oral oestrogen administration on bone in OAA engaged in weight-bearing activity. METHODS: 121 patients with OAA aged 14-25 years were randomised to receive: (1) a 17ß-estradiol transdermal patch continuously with cyclic oral micronised progesterone (PATCH), (2) a combined ethinyl estradiol and desogestrel pill (PILL) or (3) no oestrogen/progesterone (NONE). All participants received calcium and vitamin D supplementation. Areal BMD was assessed at the lumbar spine, femoral neck, total hip and total body less head using dual-energy X-ray absorptiometry at baseline, 6 and 12 months. Intention-to-treat (ITT) and completers analyses were performed. RESULTS: Randomised groups did not differ for age, body mass index or BMD Z-scores at baseline. For ITT analysis, spine and femoral neck BMD Z-scores significantly increased in the PATCH versus PILL (p=0.011 and p=0.021, respectively) and NONE (p=0.021 and p=0.033, respectively) groups, and hip BMD Z-scores significantly increased in the PATCH versus PILL group (p=0.018). Similar findings were noted in completers analysis. CONCLUSION: Transdermal estradiol over 12 months improves BMD in young OAA, particularly compared with an ethinyl estradiol-containing contraceptive pill/oral contraceptives. TRIAL REGISTRATION NUMBER: NCT00946192; Pre-results.

Bone Parameters in Anorexia Nervosa and Athletic Amenorrhea: Comparison of Two Hypothalamic Amenorrhea States.

Objective: We have reported low bone mineral density (BMD), impaired bone structure, and increased fracture risk in participants with anorexia nervosa (AN) and normal-weight oligoamenorrheic athletes (OAs). However, data directly comparing compartment-specific bone parameters in participants with AN, OAs, and controls are lacking. Design: A total of 468 female participants 14 to 21.9 years old were included: 269 with AN, 104 OAs, and 95 normal-weight eumenorrheic controls. Dual-energy x-ray absorptiometry was used to assess areal BMD (aBMD) of the whole body less head (WBLH), spine, and hip. High-resolution peripheral quantitative computed tomography was used to assess volumetric BMD (vBMD), bone geometry, and structure at the non-weight-bearing distal radius and weight-bearing distal tibia. Results: Participants with AN had lower WBLH and hip aBMD z scores than OAs and controls (P < 0.0001). Participants with AN and OAs had lower spine aBMD z scores than controls (P < 0.01). At the radius, total and cortical vBMD, percentage cortical area, and thickness were lower in the AN and OA groups than in controls (P ≤ 0.04); trabecular vBMD was lower in participants with AN than controls. At the tibia, participants with AN had lower measures for most parameters compared with OAs and controls (P < 0.05); OAs had lower cortical vBMD than controls (P = 0.002). Participants with AN and OAs had higher fracture rates than controls. Stress fracture prevalence was highest in OAs (P < 0.0001); nonstress fracture prevalence was highest in participants with AN (P < 0.05). Conclusion: AN is deleterious to bone at all sites and both bone compartments. A high stress fracture rate in OAs, who have comparable WBLH and hip aBMD measures to controls, indicates that BMD in these women may need to be even higher to avoid fractures.

Update on endocrine aspects of childhood obesity.

PURPOSE OF REVIEW: Although childhood obesity has leveled off in the last decade, 'severe obesity' continues to be on the rise. Various genetic, environmental and hormonal factors contribute to obesity. This article reviews the most current understanding of obesity's multifactorial origin and recent recommendations for its management in childhood and adolescence. RECENT FINDINGS: Epigenetics plays a key role in transmitting obesity risk to offspring. Single-nucleotide polymorphisms at genetic loci for adipokines and their receptors are associated with obesity. Gut microbiota is an important regulator of weight status, and Bifidobacterium species improves metabolic status. The incidence of comorbidities including prediabetes and type 2 diabetes has increased. Novel biomarkers such as alpha-hydroxybutyrate and branched-chain amino acids correlate with insulin sensitivity and predict glycemic control in adolescents. Lifestyle modifications and pharmacotherapy can produce small BMI changes. Bariatric surgery induces substantial weight loss and remission of comorbidities. SUMMARY: Alterations in genetics, epigenetics and microbiota influence childhood obesity. Lifestyle modification remains the mainstay of management and pharmacotherapy with Food and Drug Administration approved medications is recommended only for patients resistant to lifestyle changes and for comorbidities. Bariatric surgery produces sustained weight loss and cardiovascular benefits and is an effective option for adolescents with severe obesity.

Oxytocin secretion is pulsatile in men and is related to social-emotional functioning.

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 5min over a period of 10h 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±1.2years, and BMI was 21.7±0.4kg/m2 (mean±SEM). Assuming a basal secretion of zero and a half life of five to seven minutes, we demonstrated the following: OXT AUC: 5421±1331pg/ml, mean OXT level: 9.1pg/ml, mean pulse number: 22±3/10hr, mean pulse height: 1.81±0.48pg/ml, mean pulse mass: 30.34±10.29pg/ml and mean inter-pulse interval: 27±4min. 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.

Macronutrient intake associated with weight gain in adolescent girls with anorexia nervosa.

OBJECTIVE: Adolescents and women with anorexia nervosa (AN) are known to severely restrict total calorie and fat intake. However, data are limited regarding specific macronutrient intake associated with weight gain in AN. OBJECTIVE: To prospectively investigate dietary macronutrient composition associated with weight gain in adolescent girls with AN. METHOD: A prospective naturalistic study of 90 girls 12-18 years old; 45 with AN and 45 healthy normal-weight-controls over a 6-12-month period. Participants completed four-day food diaries and underwent body composition assessment using dual energy X-ray absorptiometry. Weight gain was defined as a ≥10% increase in body mass index (BMI) from baseline. RESULTS: Baseline clinical characteristics did not differ between girls with AN who did not gain weight (AN-0) versus those who did (AN-1) over the following 6-12 month period except for percentage of calories from proteins (p = 0.046). At 6-12 month follow-up, AN-1 consumed a lower percentage of total calories from protein (p = .001), and a higher percentage of total calories from fat (p = .02) compared to AN-0. AN-1 had a significant increase in the percentage of total calories obtained from and poly-unsaturated-fatty acids (PUFA) (p = 0.006) compared to AN-0, between baseline and follow-up. Within the AN group, BMI at follow-up was associated positively with percentage of total calories obtained from fat, MUFA, and PUFA (p < .05) at 6/12 months, and inversely with the percentage of total calories obtained from carbohydrates and proteins (p = .03). DISCUSSION: Consuming a greater proportion of total calories from fat is associated with weight gain in adolescent girls with AN.

Effects of Anorexia Nervosa on the Endocrine System.

Anorexia nervosa (AN) is characterized by severe undernutrition associated with alterations in multiple endocrine axes, which are primarily adaptive to the state of caloric deprivation. Hormonal changes include growth hormone (GH) resistance with low insulin like growth factor-1 (IGF-1) levels, hypothalamic hypogonadism, relative hypercortisolemia and changes in appetite regulating hormones, including leptin, ghrelin, and peptide YY. These alterations contribute to abnormalities in bone metabolism leading to low bone mass, impaired bone microarchitecture, and increased risk for fracture, and may also negatively impact cognition, emotions and mood. The best strategy to improve all biologic outcomes is weight and menstrual recovery. Physiological estrogen replacement improves bone accrual rates and measures of trait anxiety in adolescents with AN. Other therapies including testosterone and IGF-1 replacement, and use of DHEA with oral estrogen-progesterone combination pills, bisphosphonates and teriparatide have also been studied to improve bone outcomes.

Estrogen Replacement Improves Verbal Memory and Executive Control in Oligomenorrheic/Amenorrheic Athletes in a Randomized Controlled Trial.

OBJECTIVE: Both estrogen and exercise may have cognition enhancing benefits; however, young oligomenorrheic/amenorrheic athletes (OA) with estrogen deficiency have not been evaluated for cognitive deficits. Our objective was to determine whether 6 months of estrogen replacement will impact cognitive domains in OA. We hypothesized that estrogen replacement would improve verbal memory and executive control in OA. METHODS: We performed cognitive assessments at baseline and after 6 months in 48 OA (14-25 years) randomized to estrogen (EST+) (oral 30 µg ethinyl estradiol [n = 16] or transdermal 100 µg 17-ß-estradiol patch [n = 13]) or no estrogen (EST-) (n = 19) in an ongoing clinical trial. Neurocognitive testing included California Verbal Learning Test-Second Edition (CVLT-II) (for verbal memory) and Delis-Kaplan Executive Function System Color-Word Interference Test (D-KEFS-CWIT) (executive control). RESULTS: On average, subjects (mean ± SEM age: 19.9 ± 3.1 years, body mass index: 20.6 ± 2.3 kg/m²) participated in 10.3 ± 5.9 hours per week of weight-bearing activities of their lower limbs. The EST+ group performed better for CVLT-II verbal memory scores for immediate recall over 6 months of therapy compared to EST- (P < .05) even after controlling for baseline scores and age. Changes in D-KEFS-CWIT scores over 6 months did not differ between the groups. However, the EST+ group had greater improvements in inhibition-switching completion time over 6 months compared with the EST- group after controlling for baseline scores and age (P = .01). CONCLUSIONS: OA show improvements in verbal memory and executive control following 6 months of estrogen replacement. These findings in athletes, who are in their prime of neurocognitive development, underscore the need for future studies exploring cognition in OA. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00946192.

Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders.

Patients with autism spectrum disorder (ASD) are at increased risk for fracture, and peri-pubertal boys with ASD have lower bone mineral density (BMD) than controls. Data are lacking regarding BMD in older adolescents with ASD. We compared BMD using dual-energy X-ray absorptiometry in 9 adolescents/young adults with ASD against 9 typically developing matched controls. Patients with ASD and controls were excluded if they had other underlying conditions that may affect bone. Compared to controls, patients with ASD had (i) lower femoral neck and hip BMD Z-scores, and (ii) lower spine, femoral neck and hip height adjusted BMD Z-scores even after controlling for BMI. Understanding the underlying pathophysiology will be key to developing therapies to improve BMD and reduce fracture risk.

Leptin secretory dynamics and associated disordered eating psychopathology across the weight spectrum.

OBJECTIVE: Leptin secretory dynamics across the weight spectrum and their relationship with disordered eating psychopathology have not been studied. Our objective was to compare leptin secretory dynamics in 13 anorexia nervosa (AN), 12 overweight/obese (OB) and 12 normal-weight women using deconvolution analysis. METHODS: In this cross-sectional study conducted at a tertiary referral center, serum leptin levels were obtained every 20  min from 2000 to 0800  h. Dual energy X-ray absorptiometry was used to measure percent body fat. Disordered eating psychopathology was assessed by the Eating Disorders Examination-Questionnaire (EDE-Q) and the Eating Disorders Inventory-2 (EDI-2). RESULTS: The groups differed for basal leptin secretion (BASAL) (P=0.02). Mean leptin pulse amplitude, pulse mass, total pulsatile secretion (TPS) and area under the curve (AUC) were significantly different between groups before and after adjustment for BASAL (P<0.0001 for all). Leptin AUC correlated strongly with TPS (r=0.97, P<0.0001) and less with BASAL (r=0.35, P=0.03). On multivariate analysis, only TPS was a significant predictor of leptin AUC (P<0.0001). TPS was inversely associated with most EDE-Q and EDI-2 parameters and the associations remained significant for EDE-Q eating concern (P=0.01), and EDI-2 asceticism, ineffectiveness and social insecurity (P<0.05) after adjusting for BASAL. These relationships were not significant when controlled for percent body fat. CONCLUSION: Secretory dynamics of leptin differ across weight spectrum, with mean pulse amplitude, mean pulse mass and TPS being low in AN and high in OB. Pulsatile, rather than basal secretion, is the major contributor to leptin AUC. Decreased pulsatile leptin is associated with disordered eating psychopathology, possibly reflecting low percent body fat in AN.

Bone parameters in relation to attitudes and feelings associated with disordered eating in oligo-amenorrheic athletes, eumenorrheic athletes, and nonathletes.

OBJECTIVES: Disordered eating may negatively impact bone in athletes. However, it is not known whether this effect is independent of the associated amenorrhea and relative hypercortisolemia. We aimed to compare attitudes, feelings, and cognitions associated with disordered eating using the Three-Factor Eating Questionnaire (TFEQ) and Eating Disorder Inventory-2 (EDI-2) in normal-weight oligomenorrheic athletes (OA), eumenorrheic athletes (EA), and nonathletes, and determine the associations with bone independent of confounders. METHOD: 109 OA, 39 EA, and 36 nonathletes (14-25 years) completed the TFEQ and EDI-2. Dual-energy X-ray absorptiometry was used to assess spine bone mineral density (BMD), and high-resolution pQCT to assess radius microarchitecture. We measured integrated cortisol (q 20', 11 PM-7 AM), bone formation (procollagen Type 1 N-terminal propeptide, P1NP), and resorption (C-telopeptide, CTX) markers in a subset. RESULTS: OA had lower spine BMD Z-scores than EA. Cognitive eating restraint (CER), drive for thinness (DT), ineffectiveness, and interoceptive awareness (IA) were higher in OA than EA (p < 0.05); CER was higher in OA versus nonathletes (p = 0.03). Pulsatile cortisol was positively associated with DT, ineffectiveness, and IA (p < 0.03). CER was inversely associated with BMD Z-scores and P1NP, and ineffectiveness with radius cross-sectional area even after controlling for age, BMI, amenorrhea duration, and cortisol (p < 0.03). DISCUSSION: Higher CER in athletes independently predicts lower BMD.

Diagnosis of pediatric hyperthyroidism: technetium 99 uptake versus thyroid stimulating immunoglobulins.

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 (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. METHODS: We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc 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. (99m)Tc 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: (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

A decade of temporal trends in overweight/obesity in youth with type 1 diabetes after the Diabetes Control and Complications Trial.

BACKGROUND: Youth with type 1 diabetes (T1D) are at risk for weight gain due to the epidemic of childhood overweight/obesity and common use of intensive insulin therapy; the latter resulted in weight gain in the Diabetes Control and Complications Trial. OBJECTIVE: To assess overweight/obesity prevalence and intensive insulin therapy use in youth with T1D over a decade and identify factors associated with weight status and glycemic control. METHODS: We obtained cross-sectional data from four unique cohorts (1999, 2002, 2006, and 2009). Youth (N = 507, 49% male) were 8-16 yr old with T1D duration ≥6 months, A1c 6.0-12.0% (42-108 mmol/mol), and daily insulin dose ≥0.5 U/kg. RESULTS: Across cohorts, age, body mass index (BMI) percentile, and A1c ranged from 12.0 ± 2.2 to 12.8 ± 2.3 yr, 70 ± 22 to 72 ± 21, and 8.3 ± 1.0 (67 ± 11) to 8.5 ± 1.1% (69 ± 12 mmol/mol), respectively. Intensive insulin therapy use increased from 52 to 97% (p < 0.001) between 1999 and 2009. However, prevalence of overweight/obesity remained similar, 27% (1999), 36% (2002), 33% (2006), and 31% (2009) (p = 0.54), as did z-BMI. In multivariate analysis, higher A1c was related to higher insulin dose (p < 0.01), less frequent blood glucose monitoring (p < 0.001), and non-white race (p < 0.001); A1c was not related to z-BMI, intensive insulin therapy, or cohort. z-BMI was related to insulin dose (p < 0.005) but not intensive insulin therapy or cohort. CONCLUSIONS: Despite near-universal implementation of intensive insulin therapy, overweight/obesity prevalence in youth with T1D remained stable over a decade, similar to the general pediatric population. However, A1c remained suboptimal, underscoring the need to optimize T1D treatment to reduce future complication risk.