Gender-Diverse Youth with Turner Syndrome: Special Management Considerations.

Turner syndrome (TS) is a sex chromosome abnormality characterized by short stature and primary hypogonadism with increased risk for cardiovascular disease, osteopenia, metabolic syndrome, diabetes mellitus, abnormal liver enzymes, and impairment of nonverbal learning skills. Gender-diverse youth include youth who have a gender identity that is different from their sex assigned at birth. They have an increased risk of suicidality, which is decreased in those who receive gender-affirming care. There have been no prior reports on the association or management of gender-diverse youth with TS. We describe 3 cases of gender-diverse youth with TS that highlight the importance of discussing gender identity in patients with hypogonadism in need of sex hormone replacement. Goals of care should be discussed to determine whether estrogen or testosterone replacement aligns best with gender identity. If a patient chooses to start testosterone, special considerations of risks such as erythrocytosis, osteopenia, and cardiovascular disease should be discussed in relation to their TS.

Treatment of hypothalamic obesity in people with hypothalamic injury: new drugs are on the horizon.

Hypothalamic obesity (HO) is a complex and rare disorder affecting multiple regulatory pathways of energy intake and expenditure in the brain as well as the regulation of the autonomic nervous system and peripheral hormonal signaling. It can be related to monogenic obesity syndromes which often affect the central leptin-melanocortin pathways or due to injury of the hypothalamus from pituitary and hypothalamic tumors, such as craniopharyngioma, surgery, trauma, or radiation to the hypothalamus. Traditional treatments of obesity, such as lifestyle intervention and specific diets, are still a therapeutic cornerstone, but often fail to result in meaningful and sustained reduction of body mass index. This review will give an update on pharmacotherapies of HO related to hypothalamic injury. Recent obesity drug developments are promising for successful obesity intervention outcomes.

Case Report: Nine-year-old with parathyroid adenoma within the piriform sinus.

We present the case of a 9-year-old girl who presented with symptomatic hypercalcemia from primary hyperparathyroidism (PHPT). Laboratory results revealed elevated serum calcium 12.1 mg/dl (ref: 9.1-10.4), elevated ionized calcium 6.8 (ref: 4.5-5.6) mg/dl, phosphorus 3.8 (ref: 3.3-5.1) mg/dl, 25-OH vitamin D 20.1 (30-100) ng/ml, and elevated intact PTH 70 (15-65) pg/ml, consistent with the diagnosis of PHPT. She had persistent hyperparathyroidism after bilateral neck exploration, left thyroid lobectomy, and transcervical thymectomy. Neither inferior gland was identified. No parathyroid tissue was seen on histology. Repeat preoperative imaging identified a 7-mm × 5-mm adenoma on 4DCT not seen on 99Tc-sestamibi parathyroid scan. The patient then underwent a successful redo parathyroidectomy with removal of a submucosal left parathyroid adenoma at the superior aspect of the thyroid cartilage in the piriform sinus. Her biochemical work-up remains consistent with surgical cure 6 months after surgery. Herein, we also review common locations for ectopic parathyroid adenomas. Clinical Trial Registration: NCT04969926.

Influence of puberty on relationships between body composition and blood pressure: a cross-sectional study.

BACKGROUND: Fat mass (FM) and fat-free mass (FFM) are positively associated with blood pressure (BP) in youth. Yet, how puberty, independent of age, affects these relationships remains unclear. Given puberty may be a crucial period for cardiometabolic health, we examined how pubertal development moderates the associations of FM/FFM with BP. METHODS: Pubertal development, resting BP, and body composition were assessed in a convenience sample of youth (5.5-17 years). General linear models were conducted to assess if pubertal development moderated the relationships between FM/FFM and systolic/diastolic BP standardized for age, sex, and height (SBPz/DBPz). RESULTS: Among participants (N = 1405; age: M = 13.3 ± 2.9 years; 65.4% female; 53.2% racial/ethnic minority), FM/FFM were positively associated with SBPz and DBPz (ps ≤ 0.02). Pubertal development moderated the associations between FFM and BPz (ps ≤ 0.01), but not FM (ps > 0.43). For early/mid and late pubertal participants, there were positive associations between FFM and BP (DBPz: ßs = 0.10-0.18, ps ≤ 0.01; SBPz: ßs = 0.33-0.43, ps < 0.001); however, these relationships were attenuated, especially for prepubertal DBPz (DBPz: ß = 0.01, p = 0.91; SBPz: ß = 0.24, p = 0.001). CONCLUSIONS: Puberty moderated the relationships between FFM and SBPz/DBPz in analyses that separately modeled the contributions of age and sex. These data suggest that the FFM-DBPz association may potentially be impacted by increasing sex hormone concentrations during puberty. IMPACT: Fat mass (FM) and blood pressure (BP) were positively associated throughout puberty. Fat-free mass (FFM) and BP were positively associated throughout puberty; however, puberty moderated the FFM-BP relationship, such that there was a positive relationship in early/mid and late puberty, but the relationship was attenuated for prepubertal children. These findings contribute further insight into physiological and cardiometabolic changes occurring during puberty. Changes in hormone concentrations may explain the impact puberty has on the FFM-BP relationship. Understanding predictors of BP are important as childhood BP is associated with future cardiometabolic outcomes.

Circadian variation of serum leptin and adipose tissue changes in children.

BACKGROUND: Higher morning serum leptin values are associated with larger adipose tissue gains in children; however, it is unclear if leptin circadian variation is itself associated with adipose tissue changes during growth. OBJECTIVE: We studied the association of circadian variation in leptin with change in total body fat mass (TBFM), total body percentage fat (%FM), and trunk fat mass (TrFM). METHODS: Baseline serum samples for leptin were obtained every 3 h for 24 h from 130 children (baseline age 9.6 ± 2.5y; 51.1% male; BMI-Z 1.59) with mean follow-up of 11.1 ± 4.0y and underwent dual-energy x-ray absorptiometry. ANCOVA models examined change in TBFM, %FM, or TrFM as dependent variables and number of years of follow-up, sex, race, baseline age, pubertal status, initial visit body composition, and initial visit serum leptin circadian variables (maximal diurnal leptin [acrophase], diurnal amplitude, and percentage change of amplitude) as independent factors. RESULT: Although initial visit mesor (24 h average) leptin was positively associated with initial visit TBFM (r2  = 0.78, p < 0.001), %FM (r2  = 076, p < 0.001), and TrFM (r2  = 0.71, p < 0.001), none of the circadian leptin variables studied was significantly associated with change in TBFM, %FM, or TrFM. CONCLUSION: We found no evidence that circadian variation in serum leptin concentrations during childhood is associated with long-term changes in children's adiposity.

State negative affect in relation to loss-of-control eating among children and adolescents in the natural environment.

Affect regulation theory proposes that loss-of-control (LOC)-eating is preceded by increases and followed by decreases in negative affect (NA), but empirical tests of this theory among pediatric samples in the natural environment are needed. Using an ecological momentary assessment approach, we conducted post-hoc analyses to examine LOC-eating severity reported during post-meal surveys in relation to the intensity of composite NA and NA components (anger, anxiety, depression, guilt) throughout the day for two weeks in a cohort of healthy children and adolescents. Multilevel models tested the associations among LOC-eating severity and NA components reported at pre-meal surveys (t-1), post-meal surveys (t), and lagged post-meal surveys (t+1). Models were adjusted for sex, age, race/ethnicity, height, fat mass, socioeconomic status, and time between the occurrence and report of eating episodes; post-meal analyses were also adjusted for pre-meal NA. Participants age 8-17 (N = 100; 55% female; 45% male; 12.83 ± 2.73y; 24% with overweight/obesity) recorded 2410 eating episodes. Pre-meal composite NA and NA components were not associated with LOC-eating severity at the subsequent meal. LOC-eating severity was positively associated with post-meal depression (ß = 0.042, 95% CI = 0.007, 0.076) and guilt (ß = 0.056, 95% CI = 0.017, 0.095), but not composite negative affect, anger, or anxiety. The positive association among LOC-eating severity and guilt persisted in lagged post-meal analyses (ß = 0.075, 95% CI = 0.021, 0.128). Contrary to affect regulation theory and laboratory data, but consistent with prior ecological momentary assessment data in children and adolescents, pre-meal NA was not linked to subsequent LOC-eating. Increased guilt following meals may be a mechanism for the development of exacerbated disordered eating. Longitudinal studies may elucidate how NA is implicated in the etiology of pediatric eating disorders.

Retrieval-induced forgetting in children and adolescents with and without obesity.

BACKGROUND/OBJECTIVES: Previous research indicates that youth with obesity exhibit deficits in executive functioning (EF), which often take the form of impaired response inhibition. One aspect of EF not previously studied in obesity is the adaptive process known as retrieval-induced forgetting (RIF), the suppression/inhibition of intrusive or non-target items by the retrieval of specific items from memory. The present study investigated if child or adolescent obesity disrupts the ability to inhibit retrieval of intrusive memories. SUBJECTS/METHODS: We compared the manifestation of RIF in children (ages 8-12) and adolescents (ages 13-18) as a function of their weight status and sex. We also evaluated the effects of these variables on simple recall of items from episodic memory under conditions where competition from intrusive items was reduced. RESULTS: Children with obesity did not demonstrate significant RIF, whereas RIF was exhibited by preteens without obesity and by teenage participants with- and without obesity (Weight Status × Age Group interaction p = 0.028). This pattern of results did not differ as a function of sex for either age group. No differences in episodic memory were found. Additional analyses using Age as continuous covariate (and not as a nominal group) comparing participants who exhibited RIF with those who did not, found that the no RIF group consumed fast-food meals more frequently (p = 0.024) and had higher percentages of total body adiposity and android fat compared to the RIF group (p's < 0.05). CONCLUSIONS: The findings expand what is known about the effects of childhood obesity on cognitive functioning, identify impaired RIF with specific behavioral and dietary factors and increased adiposity, and suggest the possibility that impairments in the ability to inhibit intrusive memories of food and eating may contribute to poor early-life weight control.

A comparison of negative affect and disinhibited eating between children with and without parents with type 2 diabetes.

BACKGROUND: Children whose parents have type 2 diabetes (T2D) are at high-risk for developing T2D. In youth, negative affect has been shown to predict insulin resistance (IR), and disinhibited-eating behaviors have been linked to IR. It is unknown if youth with a parent with T2D (P-T2D) report greater psychological and behavioral symptoms than those without a P-T2D. OBJECTIVE: To compare youth with and without a P-T2D on symptoms of negative affect and disinhibited-eating. METHODS: Nine-hundred thirty-two youth (13.3 ± 2.6 years; BMIz 1.06 ± 1.06; 67.8% female; 53.6% people of color; 10.7% with a P-T2D) completed questionnaires of anxiety and depressive symptoms, eating in the absence of hunger, and emotional-eating. Loss-of-control (LOC)-eating was assessed by interview. In two separate subsamples, energy intake was explored using laboratory test meals simulating eating in the absence of hunger and LOC-eating, respectively. Analyses were adjusted for age, sex, race/ethnicity. In follow-up analyses, fat mass (kg) and height, and IR were included as covariates, respectively. RESULTS: Adjusting for all covariates including adiposity and IR, compared to youth without a P-T2D, youth with a P-T2D reported more anxiety and depression symptoms, greater eating in the absence of hunger, and emotional-eating (ps < 0.05). No significant differences were found for LOC-eating, or in exploratory analyses of energy intake for either test meal (ps > 0.16). CONCLUSIONS: Self-reported negative affect and disinhibited-eating may be higher among youth with P-T2D compared to those without P-T2D. Prospective studies should examine, among those with a P-T2D, what role such symptoms may play for their subsequent risk for T2D.

Associations of sleep with food cravings and loss-of-control eating in youth: An ecological momentary assessment study.

BACKGROUND: Inconsistent sleep patterns may promote excess weight gain by increasing food cravings and loss-of-control (LOC)-eating; however, these relationships have not been elucidated in youth. OBJECTIVE: We tested whether sleep duration and timing were associated with food cravings and LOC-eating. METHOD: For 14 days, youths wore actigraphy monitors to assess sleep and reported severity of food cravings and LOC-eating using ecological momentary assessment. Generalized linear mixed models tested the associations between weekly and nightly shifts in facets of sleep (i.e., duration, onset, midpoint, and waketime) and next-day food cravings and LOC-eating. Models were re-run adjusting for relevant covariates (e.g., age, sex, adiposity). RESULTS: Among 48 youths (12.88 ± 2.69 years, 68.8% female, 33.3% with overweight/obesity), neither weekly nor nightly facets of sleep were significantly associated with food cravings (ps = 0.08-0.93). Youths with shorter weekly sleep duration (est. ß = -0.31, p = 0.004), earlier weekly midpoints (est. ß = -0.47, p = 0.010) and later weekly waketimes (est. ß = 0.49, p = 0.010) reported greater LOC-eating severity; findings persisted in adjusted models. CONCLUSIONS: In youth, weekly, but not nightly, shifts in multiple facets of sleep were associated with LOC-eating severity; associations were not significant for food cravings. Sleep should be assessed as a potentially modifiable target in paediatric LOC-eating and obesity prevention programs.

Longitudinal associations between facets of sleep and adiposity in youth.

OBJECTIVE: Beyond sleep duration, other facets of sleep such as variability and timing may be associated with obesity risk in youth. However, data are limited. Using a longitudinal design, this study tested whether multiple facets of sleep were associated with fat mass gain over 1 year. METHODS: A convenience sample of non-treatment-seeking youth (age 8-17 years) wore actigraphy monitors for 14 days. Average weekly sleep duration, within-person sleep duration variability, weekend catch-up sleep, bedtime and wake time shift, social jet lag, bedtime, wake time, and sleep midpoint were calculated. The association of each facet of baseline sleep with 1-year fat mass, adjusting for baseline fat mass and height, was examined. RESULTS: A total of 137 youths (54.0% female; mean [SD], age 12.5 [2.6] years; 28.4% non-Hispanic Black or African American; baseline fat mass = 15.3 [8.9] kg; 1-year fat mass = 17.0 [10.0] kg; 28.5% with baseline overweight or obesity) were studied. Wake time (p = 0.03) and sleep midpoint (p = 0.02) were inversely associated with 1-year fat mass, such that earlier wake time and midpoint were associated with higher 1-year fat mass. No other facet of sleep was significantly associated with 1-year fat mass (p > 0.09). CONCLUSIONS: Using objective measures, youth with earlier wake times and sleep midpoints had greater gains in fat mass. Additional research is needed to determine whether sleep timing may be a modifiable target to prevent pediatric obesity.

Food cravings and loss-of-control eating in youth: Associations with gonadal hormone concentrations.

OBJECTIVE: Among youth with overweight, food cravings (FC) are associated with loss-of-control (LOC)-eating, but the impact of sex-associated biological characteristics on this relationship is unknown. We examined whether sex and gonadal hormone concentrations moderated the relationships between FC and LOC-eating severity among healthy boys and girls across the weight strata in natural and laboratory environments. METHOD: Using ecological momentary assessment (EMA), FC, and LOC-eating severity were reported 3-5 times a day for 2 weeks. In the laboratory, participants reported FC, consumed lunch from a buffet test meal designed to simulate LOC-eating, and rated LOC-eating severity during the meal. RESULTS: Eighty-seven youth (13.0 ± 2.7 years, 58.6% female, 32.2% with overweight/obesity) participated. EMA measured general and momentary FC were positively associated with LOC-eating severity (ps < .01), with no differences by sex (ps = .21-.93). Estradiol and progesterone significantly moderated the relationships between FC and LOC-eating such that general FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) estradiol (p = .01), and momentary FC and LOC-eating severity were only positively associated among girls with greater (vs. lower) progesterone (p = .01). Boys' testosterone did not significantly moderate the associations between FC and LOC-eating severity (ps = .36-.97). At the test meal, pre-meal FC were positively related to LOC-eating severity (p < .01), without sex or hormonal moderation (ps = .20-.64). DISCUSSION: FC were related to LOC-eating severity in boys and girls. In the natural environment, gonadal hormones moderated this relationship in girls, but not boys. The mechanisms through which gonadal hormones might affect the relationship between FC and LOC-eating warrant investigation.

Bridging executive function and disinhibited eating among youth: A network analysis.

OBJECTIVE: Poorer executive function (EF) has been linked to disinhibited eating in youth, suggesting poor EF predisposes toward obesity, yet the specific nature and extent of interconnections between facets of these domains is unclear. Network analysis provides a promising framework for elucidating the relationship between poor EF and disinhibited eating, and offers insights into potential maintenance processes. METHOD: Among youth ages 8-17 years, a regularized partial correlation network of EF and disinhibited eating facets was estimated to examine expected influence centrality and bridge expected influence. Computerized neurocognitive tasks assessed EF variables, including decision-making, general and food-related inhibitory control, delayed gratification, cognitive flexibility, and working memory. Disinhibited eating variables included total carbohydrate-fat intake at a laboratory test meal and self-reported eating in the absence of hunger, emotional eating, and loss-of-control eating severity. RESULTS: In the current sample (N = 248; Mage = 12.5; 54.8% female; 43.5% non-Hispanic White; 25.8% non-Hispanic Black; BMI %ile = 65.8 ± 27.8), emotional eating in response to depressive symptoms emerged as a central symptom in the network. Carbohydrate-fat intake had the highest bridge expected influence and was most strongly connected to general inhibitory control (part r = .14). DISCUSSION: The link between general inhibitory control and objective palatable food intake may be particularly salient in maintaining maladaptive eating behavior. Interventions targeting behavioral disinhibition may disrupt associations among a network of disinhibited eating facets in youth and should be targets for longitudinal research.

Surgical Treatment of Type 2 Diabetes Mellitus in Youth.

Bariatric surgery is currently the most effective weight loss treatment of severe obesity and its associated comorbidities and is being increasingly used to treat children and adolescents with severe obesity, including those with Type 2 Diabetes (T2D). This review focuses on the conventional management of T2D in children and adolescents, comparison of various types of bariatric surgeries, effect of bariatric surgery on gastrointestinal physiology and metabolism, current literature on the use of bariatric surgery to treat youth with severe obesity and T2D, and the potential complications of bariatric surgery in this population.

Quetiapine-Induced Central Hypothyroidism.

Hypothyroidism has been associated with quetiapine, but the underlying mechanism is not well understood and has been presumed to result from thyroid gland dysfunction (primary hypothyroidism). We present a case of symptomatic quetiapine-induced hypothyroidism due to hypothalamic/pituitary gland dysfunction (central [secondary] hypothyroidism).

Coombs Positive Thrombotic Thrombocytopenic Purpura in a Male Pediatric Patient: An Urgent Diagnostic Challenge.

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy often caused by deficiency of von Willebrand (vW) factor cleaving protease, ADAMTS-13, leading to large vW multimers and intravascular platelet aggregation. Hemolysis in TTP is mechanical and nonimmune mediated, thus Coombs testing is usually negative. We report a case of an adolescent with thrombocytopenia and Coombs positive anemia, diagnosed with Evans syndrome, but ultimately found to have TTP. TTP should be considered in children with thrombocytopenia and Coombs positive anemia who are refractory to steroids or develop signs of microangiopathy.  Recognition of this presentation can lead to life-saving treatment with plasma exchange.

The IRE1alpha-XBP1 pathway of the unfolded protein response is required for adipogenesis.

Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARgamma and C/EBPalpha. Here we demonstrate that the IRE1alpha-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1alpha knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPbeta, a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1alpha is required as only the spliced form of XBP1 (XBP1s) rescues the adipogenic defect exhibited by XBP1-deficient cells. Taken together, our data show that the IRE1alpha-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis.