bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP386 Growth Velocity and Growth Hormone Deficiency During Puberty
Authors: Currais Carolina , Seeherunvong Tossaporn 
Published: November 2022

Abstract

Background
A subnormal growth velocity (GV) is a characteristic feature of growth hormone deficiency (GHD). During puberty growth hormone (GH) levels increase markedly in response to sex hormone secretion. The normal range for GV declines during childhood, increases during puberty with peak levels at mid-puberty. Hence, pubertal status rather than age alone must be considered in the evaluation of GV in children and adolescents. In most cases, a diagnosis of GHD is established by a subnormal response in GH levels following a stimulation with two pharmacological agents.

Objective
We determined the reliability of GV as a predictor of GHD during puberty.

Methods
We conducted a retrospective study of pubertal children and adolescents who underwent a GH stimulation test in our pediatric endocrinology clinic. Seventy-nine subjects (57 boys and 22 girls) were included in this study. Bone age was determined for all patients. Serum levels of insulin like growth factor-1 (IGF-1) were obtained prior to GH stimulation test. Serum IGF-1 levels, expressed as a standard deviation score were compared to the IGF-1 levels expected chronological age (CA), height age (HA), and bone age (BA). Serum GH levels were determined following the administration of arginine and levodopa. GHD was established by a peak GH level &lt;10 ng/mL. IBM SPSS Statistics software version 28. 0. 0. 0 (190) was used for data analysis.

Results
Subjects ranged in age from 7.3-17.9 years. Thirty-nine patients (49.4%) had GV &lt; 10 th percentile for CA; Forty patients (50.6%) had GV &lt;10 th percentile for BA. Sixty percent of patients with GV &lt;10 th percentile for CA had GHD. A similar number (59%) of patients with normal GV for CA also had GHD. Among patients with GV &lt;10 th percentile for BA, 72.5% of subjects had GHD. By contrast, the percentage of patients who had normal GV for bone age and GHD (46.2%) was significantly less than that of subjects with GV &lt;10 th percentile for BA (p = 0. 015). Positive predictive value, negative predictive value, sensitivity and specificity for GV &lt;10 th percentile for BA in the diagnosis of GHD were 72.5%, 53.8%, 61.7%, and 65.6%, respectively. With respect to the diagnostic value of serum IGF-1, when the area under the ROC curve was used to measure how well the serum IGF-1 standard deviation score distinguished between GHD and normal, serum IGF-1 standard deviation score for CA, HA, and BA were not predictive of GHD (p = 0.1, 0.47, and 0.27, respectively).

Conclusions
During puberty, slow growth velocity for bone age (but not slow growth velocity for chronological age) was useful to predict a diagnosis of growth hormone deficiency.
Presentation: No date and time listed
ODP389 Lipid Peroxidation System Reactivity in Adolescents During Constitutional Obesity Non-drug Therapy
Authors: Darenskaya Marina , Rychkova Lyubov , Kolesnikov Sergey , Kravtsova Olga , Semenova Natalya , Nikitina Olga , Kolesnikova Lyubov 
Published: November 2022

Abstract

Background
In recent years, there has been a worldwide trend toward preventing and controlling childhood obesity by non-drug therapy. The success of this trend largely depends on better understanding the various metabolic and regulatory systems functions. Lipid peroxidation (LPO) - antioxidant defense (AOD) nonspecific system reactivity should be of special attention. The aim of the study was to reveal the lipid peroxidation and antioxidant defense parameters changes in different sex's adolescents during constitutional obesity non-drug therapy.

Materials and methods
Adolescents of 12-17 years old with constitutional obesity (CO) (22 boys and 24 girls) before and after constitutional obesity non-drug therapy were examined. The therapy included routine recommendations for food consumption modification, motivational education in the School of Rational Eating, a steady diet, a low-calorie diet, aerobic physical exercises (running track), impulse physiotherapy on the rectus abdominis. Healthy teenager's data (20 boys and 16 girls) were used as a control. We analyzed the content of LPO products - diene conjugates (DC), ketodienes and conjugated trienes (KD and CT), TBA-active products and AOD factors activity: total antioxidant activity (TAA), α-tocopherol, retinol, reduced (GSH) and oxidized (GSSG) glutathione, superoxide dismutase activity (SOD). Spectrophotometric and fluorometric methods were used.

Results
The boys with CO had decreased values of primary LPO products – DC (by 1.35 times lower, p=0. 001) and AOD factors: TAA (by 1.16 times lower, p=0. 036) and SOD activity (by 1.49 times lower, p&lt;0. 0001), against the increased background values of secondary products - KD and CT (by 1.42 times higher, p=0. 046) in comparison with control results. Boys with CO therapy did not lead to normalization of the studied parameters. The girls with CO had decreased values of TAA values (by 1.4 times lower, p=0. 0001), SOD (by 1.42 times lower, p&lt;0. 0001) and α-tocopherol (by 1.33 times lower, p=0. 012) compared to the control group. After the course of therapy, there was an increase in GSSG levels (by 1.14 times higher, p=0. 029).

Conclusions
This study showed the presence of negative changes in the pro- and antioxidant status in adolescents with CO, which did not normalize after a course of non-drug therapy. Additional pharmacological correction by prescription of antioxidant drugs becomes relevant in addition to the course of non-drug therapy.
Presentation: No date and time listed
ODP391 Neurodevelopmental and Growth Outcome of Congenital Hypothyroidism: A National Investigation of Birth Cohort Study
Authors: Jung Mo Kyung , Cha Hye Ryeong , Lee Seung Won , Ha Eun Kyo , Kim Ju Hee , Yoo Eun-Gyong , Han Man Yong 
Published: November 2022

Abstract

Objectives
The purpose was to investigate the neurodevelopmental and growth status of Congenital hypothyroidism (CH) patients compared to normal children using population-based cohort study.

Methods
The National Investigation of Birth Cohort in Korea study 2008 (NICKs-2008) consisted of the Korean National Health Insurance System (NHIS) and the National Health Screening Program for Infants and Children (NHSPIC) databases comprising children born in 2008 (n=469,248) and 2009 (n=448,459). The CH patients were enrolled with International Classifications of Diseases-10 codes and drug classification (levothyroxine over 5 years) codes. We investigated their developmental outcomes using the Korean-Ages and Stages Questionnaire (K-ASQ), and serial changes of BMI (BMI-z) and height (height -z) were compared in children with and without CH. Risk ratios were obtained using a modified Poisson regression and weighted risk differences using binomial regression.

Results
Of the 919,707 newborns, 433 children (boys, 47.7%) were diagnosed as CH (1: 2,124 of prevalence). The risk ratio (RR) for delayed development based on the results from the 5th–7th K-ASQ was higher for the total developmental area (adjusted RR = 2.77, 95% CI: 1.507-5.118) in CH patients. There was significant difference between patients with CH and controls in the assessment of gross motor, fine motor and problem-solving areas (P &lt; . 0001). At 66-71 months of age, short stature (height-z &lt; -1.63) were increased in the CH group compared with normal children (adjusted RR 2.27, 95% CI 1.328-3.865). Obese children (BMI-z &gt; 1.63) were not increased.

Conclusions
The adequate large cohort data showed that prevalence of developmental delay and short stature were higher in CH patients than normal. Careful and early intervention is needed.
Presentation: No date and time listed
OR05-1 Testicular Magnetic Resonance Imaging (MRI) Findings and Predictive Factors of Gonadal Neoplasia in Complete Androgen Insensitivity Syndrome
Authors: Carvalho Filomena Marino , Coelho Fernando Morbeck Almeida , Costa Elaine Maria Frade , Craveiro Flora Ladeira , Dantas Patricia Perola , Domenice Sorahia , Mendonca Berenice Bilharinho , Viana Publio Cesar Cavalcante , Batista Rafael Loch 
Published: November 2022

Abstract

Introduction
Complete Androgen Insensitivity Syndrome (CAIS) is characterized by a complete external genitalia appearance and testicular development in 46,XY individuals carrying inactivating mutations in the AR gene. Prophylactic gonadectomy versus saving gonads has been debatable in CAIS management, mainly due to the absence of an accurate biomarker for testicular germ cell tumors (GCT).

Objective
to cross the preoperative pelvic MRI data with the histological gonadal findings from CAIS patients who underwent prophylactic gonadectomy to identify predictive factors of GCT development.

Methods
We evaluated 30 gonads from 15 CAIS patients with proven AR mutation. All performed pelvic MRI before gonadectomy through the same MRI machine and were included in the MRI data analysis. Three blinded radiologists specialized in urology performed image analysis. The immunohistochemical markers PLAP, c-KIT, OCT3/4, SALL4, ER, alpha-inhibin, CD99, and calretinin were performed.

Results
Nine (60%) performed gonadectomy after puberty (&gt;16 years old). We identified one case of classical seminoma and one case of Sertoli cell neoplasia (at 18 and 19 years of age, respectively). Overall, the prevalence of neoplasia was 13.3%. No case of premalignant intratubular germ cell neoplasia was detected.Histological data revealed a high prevalence of benign lesions (n=12; 80%). Leydig Cell Hyperplasia (67%), stromal fibrosis (53%), Sertoli Cell nodules (47%), hamartomatoums nodules (40%) and paratesticular cysts (67%) which are more frequent after puberty (p&lt;.01). MRI detected heterogeneity in all cases harboring hamartomatoums nodules, Sertoli cell nodules, and testicular neoplasia. Benign lesions were bilateral in all cases. Regarding the MRI data, the presence of testicular cystic mass (by tumoral necrosis) on MRI and tumor size (higher among malignancies) correlated with malignancy (p=.008 and p=.03, respectively), whereas gonadal location (inguinal/abdominal), presence of solid nodules, T2WI and postcontrast features, nodule diffusion restriction, and presence of perigonadal cysts did not. Chronological age &gt;16 years was associated with malignancy with a 4.3 OR (1.6–11.69).

Conclusion
Pelvic MRI is sensitive to detect gonadal nodules in CAIS patients, regardless of the gonad position, but most nodules are benign. Testicular malignancy should be suspicious in the presence of testicular cystic mass and large testis size in CAIS patients &gt;16 years old.
Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.
OR05-4 Case Series of Transmasculine Adolescents Who Developed Polycythemia on Gender Affirming Hormone Therapy
Authors: Latysheva Natalya 
Published: November 2022

Abstract

Study Objective
This case series was designed to describe cases of polycythemia among transgender male adolescent patients undergoing treatment with testosterone.

Methods
Retrospective data was collected for our Pediatric Gender Clinic between Jan 2014 and June 2021. Variables assessed included demographic and laboratory data, presence of comorbidities, testosterone dose and level at the time of polycythemia, concurrent treatment with other hormonal treatments, and duration of therapy. Polycythemia in children was defined as hematocrit (HCT) +2 SD above mean for age and gender. Male reference range was used for HCT after 3 months of treatment.

Results
Seven of 131 patients were identified with polycythemia (5.3%). The mean age was 17.9 ± 3.7 (SD) years at the time of polycythemia and 6 of 7 patients were overweight or obese. All patients were receiving testosterone by injection. The mean testosterone dose was 51.4 ± 13.3 (SD) mg/m2/2wks or 92.9 mg/2wk ±22.1 (SD). All patients developed polycythemia developed at doses below 75 mg/m2/2wks. The mean testosterone level at the time of polycythemia was 588 ± 315.3. (SD) ng/dL and the mean length of treatment before polycythemia occurred was 18.6 ± 6.2 (SD) months; the shortest duration of treatment was 10 months. Two patients have received concurrent treatment with progestin therapy. Obstructive sleep apnea (OSA) was identified in 1 patient.

Conclusion
Polycythemia occurred in 5.3% of our transgender male patients receiving testosterone therapy. This is a known complication of testosterone therapy that may appear with a relatively low dose and after a relatively short duration of treatment. Patient 1Patient 2Patient 3Patient 4*Patient 5Patient 6Patient 7Age at time of polycythemia, years19.116.616.721.816.917.616.6BMI at time of polycythemia, kg/m225.239.634.130.949.619.426.7Smoking/vaping NNNVapingNNNComorbidities: Asthma, OSANAsthma, mild OSAAsthmaNNNNAdditional hormonal therapyNMedroxyprogesterone acetate injectionEtonogestrel implantNNNNHCT level at baseline, %46.544.143.050.444.245.841.1HCT level at the time of polycythemia, %
55.050.150.053.050.550.650.8Testosterone level at the time of polycythemia, ng/dL3997033455254821253416Length of Tx with testosterone, months10141426182523Dose of testosterone, mg/2wk801008060130100100Dose of testosterone, mg/m2/2wk47.369.741.231.249.664.556.5Table 1. Characteristics of patients with polycythemia.* Patient was taking an injectable dose of testosterone for 6-8 months prior to the first visit to our clinic
Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.
PMON193 Reactive oxygen species in the development of gonadal failure in late-onset transaldolase deficiency
Authors: Zangen David , Florsheim Natan , Lavi Eran , Kerem Liya , Renbaum Paul , Cahan Ranit , Libdeh Abdulsalam Abu , Levi-Lahad Efrat , Mendelsohn Espen Eliyahu 
Published: November 2022

Abstract

Background
Deficiency in Transaldolase, an essential enzyme in regulating NADPH and ribose 5-phosphate production, has been reported in only 39 patients to date. Most patients present already prenatally/neonatally with intra uterine growth retardation, hepato(spleno)megaly and consequent liver failure, anemia, thrombocytopenia, dysmorphic facial features, cardiac and skin abnormalities and hypergonadotropic hypogonadism in cases of late-onset presentation. The mechanism underlying gonadal dysfunction is not fully understood.
Clinical case, methods and results
A 15y old male from an Indian-Jewish background, with atrial-septal-defect, renal tubulopathy, mild facial dysmorphism and transient liver enzymes abnormalities presented with absence of pubertal development. His gonadotropins levels were elevated (LH – 22 IU/L, FSH 103 IU/L) while testosterone was low. Whole exome sequencing revealed homozygous variant in a novel T167M missense mutation in TALDO1 (transaldolase) gene whereas both parents were heterozygote carriers. Proteine structure analysis indicate that Threonine 167 is part of transaldolase catalytic site and critical for its function. As transaldolase activity is required for nucleic acids production, NADPH synthesis and reduction of cellular Reactive Oxygen Species (ROS) we measured the ROS accumulation using 2′,7′-dichlorodihydrofluorescein diacetate, in fibroblasts derived from the patient and normal controls. The affected patient's fibroblasts showed a significantly increased accumulation of ROS (207%, P=0.007), compared to controls indicating an increased susceptibility to oxidative stress.

Conclusion
The novel T167M missense mutation in the transaldolase (TALDO1) gene causes a unique clinical presentation including a relative mild liver involvement and hypergonadotrophic hypogonadism. The compromised TALDO1 activity in preventing cellular ROS accumulation in actual patient's fibroblasts is shown here for the first time and may indicate the therapeutic use of antioxidants in all patients with TALDO1 dysfunction. The high expression of TALDO1 in the testis and the gonadal failure suggests its tissue specific requirement in preventing the accumulation of ROS during steroidogenesis.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON307 Adipokines and Bone Health in Hispanic Children
Authors: Shawar Reem , Ayash Heba E , Puyua Maurice , Bacha Fida 
Published: November 2022

Abstract

Introduction
Leptin and adiponectin are adipocytokines with important metabolic functions. Leptin to adiponectin ratio is a marker of adipose tissue dysfunction and is associated with insulin resistance and cardiometabolic risk. We previously reported a negative effect of adiposity on bone health. We examined the relationship of adipokines to bone mass in a large cohort of Hispanic youth. We hypothesized that adipocytokine dysregulation in childhood may contribute to adverse bone health in children with obesity.

Methods
We studied 501 (237 males and 264 females) children and adolescents from the Viva la Familia Study. They were all pubertal; mean age (SD) 14.1 (2.5) years; 27% were normal weight (NW), 20% overweight (OW) and 53% obese (OB). They underwent measurement of body composition, total body less head bone mineral content (BMC) and density (BMD) by DXA scan; fasting leptin and adiponectin. The leptin to adiponectin ratio was calculated.

Results
Leptin concentration and leptin to adiponectin ratio were higher in OW and OB compared to NW (p&lt;.001) whereas adiponectin was lower in OW and OB compared to NW (p&lt;.001). After adjusting for sex, age, Tanner stage and lean mass, BMC was inversely related to leptin (r = -0.15, p =.001) and leptin to adiponectin ratio (r = -0.20, p &lt;.001) but positively related to adiponectin (r = 0.12, p =.007). Similar relationships were found for BMD.
In a regression model with BMC as the dependent variable, together and independently of sex, age, Tanner stage, lean mass and fat mass, leptin to adiponectin ratio negatively contributed (β = -0.060, p=.002) to the variance of BMC (R2 = 0.877, p &lt;.001). Similar findings were seen with BMD as the dependent variable.

Conclusion
Elevated leptin to adiponectin ratio, a manifestation of adipokine dysregulation, may contribute negatively to bone health (BMC and BMD) in children with overweight/obesity.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON325 Rare Presentation of Precocious Puberty Secondary to LH-Secreting Adenoma
Authors: Uhing Anna , Salamat Shahriar , Chen Melinda 
Published: November 2022

Abstract

Background
Normal male puberty begins after 9 years of age with a concurrent rise in luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These play distinct roles, with LH acting on Leydig cells to stimulate testosterone and secondary sex characteristics, while FSH promotes testicular growth by stimulating the maturation of seminiferous tubules.

Clinical Case
An 8-year 9-month-old male TV presented with a 1.5 year history of facial hair and 9 months of phallic growth, body odor and acne. Physical exam revealed phallic enlargement, Tanner stage I pubic hair and firm, borderline pubertal testes (4 cc bilaterally). Bone age was 9 years at a chronological age of 8 years 6 months. Laboratory evaluation was inconsistent with typical puberty – LH (9 mIU/mL, RR 0.0-0.3 mIU/mL) and testosterone (519 ng/dL, RR 2-8 ng/dL) were elevated while FSH was pre-pubertal (&lt;0.1 mIU/mL, RR 0.0-2.8 mIU/mL) and androgens were only mildly elevated (androstenedione 0.363 ng/mL, RR 0.03-0.3; 17-OHP 155 ng/dL, RR&lt;63 ng/dL). Head MRI revealed an anterior pituitary adenoma measuring 8×12×10 mm. After failing to respond to leuprolide, TV was initiated on spironolactone and anastrozole to minimize pubertal progression prior to transsphenoidal adenomectomy. Surgical pathology was positive for steroidogenic factor 1 but negative for LH, FSH and thyroid-stimulating hormone immunoreactivity. However, he had post-operative reduction of LH (0.4 mIU/mL, RR 0.0-0.3 mIU/mL) and testosterone (16 ng/dL, RR 2-8 ng/dL).

Conclusions
Normal male puberty follows a predictable sequence, beginning with testicular enlargement followed by body odor, pubic hair growth, phallic enlargement, voice change, and increased growth velocity. In TV, hypersecretion of LH led to testosterone production, causing secondary sex characteristics. However, his pre-pubertal FSH did not stimulate the testicular growth that typically heralds the onset of puberty. Digression from typical pubertal sequence and isolated high LH raised concern for a pathologic cause. Central precocious puberty (CPP) is most often idiopathic in females, although more commonly associated with CNS lesions in males. Rarely, precocious puberty results from a functioning gonadotroph adenoma. Less than 1% of these are hormonally active. If active, these more often secrete FSH or co-secrete FSH and LH, and typically require surgical resection given limited success of medical therapies. This case illustrates the distinct roles of FSH and LH in pubertal development. Departures from the typical sequence of development should expand one's differential to include etiologies resulting in nonconcurrent secretion of gonadotropins.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSAT118 Elevated Serum IgA at Onset of Type 1 Diabetes in Children
Authors: Thakkar Amruta , Redondo Maria , Hajjar Joud , Minard Charles , Huang Xiaofan , Hwu Kathy 
Published: November 2022

Abstract

IgA is the most produced antibody in the body. There are two major forms of IgA, monomeric serum IgA and dimeric mucosal (secretory) IgA. During infection or inflammation, IgA binding to its antigen induces crosslinking of FcaRI, which activates immune effector cells to carry out their functions and can thus induce pro-inflammatory responses, which is hypothesized to occur when IgA titers are high. (1,2) Elevated serum IgA has been associated with autoimmune diseases (3) including type 1 diabetes (T1D) but its role in disease pathogenesis is not well known. To address this gap in knowledge, we aimed to test the hypothesis that at diagnosis of T1D, children and adolescents with elevated serum IgA have different demographic, clinical and laboratory characteristics than those with normal serum IgA.
We analyzed 612 children 9.7 [4.2] (mean [SD]) years old (59% Non-Hispanic White, 20% Hispanic, 16% Black, 5% Other) with new onset T1D diagnosed between 1/2008-2/2012 at a large, academic pediatric hospital. Serum IgA values above age-adjusted normal ranges were defined as elevated serum IgA. Patients with low IgA were excluded because of known association between IgA deficiency and autoimmune disease. Demographic and clinical variables were compared between youth with and without elevated serum IgA. Univariable and multivariable regression models were used to compare baseline characteristics that were associated with elevated serum IgA. A significance level of 0.05 was used.
We found that elevated serum IgA was present in 21% (128/612) of the children at T1D onset. By multivariate analysis, compared to children with normal IgA, those with elevated IgA were more likely to be of Hispanic ethnicity (Odds Ratio (OR)=3.27, 95% Confidence Interval (CI)=2.00, 5.35) and had a higher hemoglobin A1c (A1c) (OR=1.13, 95% CI=1.01, 1.26). They also had higher odds of having insulin autoantibody (IAA) positivity at diagnosis (OR=1.65, 95% CI=1.10, 2.45) and lower odds of GAD autoantibody (GADA) positivity (OR= 0.57, 95% CI=0.36, 0.93) (all, p&lt;0.05), while there were no significant associations with age, glucose level or presence of DKA.
In sum, at diagnosis of T1D, 21% of youth have elevated serum IgA and this was associated with Hispanic ethnicity, higher A1C and positivity for IAA. Our findings suggest that elevated serum IgA may help identify youth with T1D, islet autoimmunity and insulin deficiency. Further studies are warranted to investigate potential pathogenic correlates and persistence over time. This knowledge may lead to new targeted strategies to preserve or improve beta-cell function in individuals with clinical or pre-clinical T1D.

References
(1) Hansen IS et al. Cell Mol Life Sci. 2019 Mar;76(6): 1041-1055. PMID: 30498997 (2) Leong KW et al. DNA Cell Biol. 2014 Dec;33(12): 823-9. PMID: 25188736 (3) Kerr MA. Biochem J. 1990 Oct 15;271(2): 285-96. PMID: 2241915
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.