bluuebunny/crossref_metadata_2025 huggingface dataset:
ODP395 Relationship of serum total insulin-like growth factor-binding protein-3 with triglyceride to high-density lipoprotein cholesterol ratio and glucose tolerance in Korean children and adolescents
Authors: Choi Iee H , Kim Minsun , Kim Sun-Young
Published: November 2022

Objectives

We investigated the relationships between serum IGF-I/ IGFBP-3 levels and degrees of triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio in Korean children and adolescents who underwentoral glucose tolerance test.

Methods

children and adolescents without known diabetes were checked an oral glucose tolerance test and collected the clinical and laboratory data. Serum IGF-I and total IGFBP-3 levels, TG/HDL ratio, total cholesterol, low-density lipoprotein cholesterol (LDL),AST, ALT, C-peptide levels, homeostasis model assessment of insulin resistance (HOMA-IR) index, and glycated hemoglobin (HbA1c) levels were measured.

Results

Serum TG/HDL ratio and IGF-I/ total IGFBP-3 levels were significantly higher in individuals with type 2 diabetes (DM) than in those with normal glucose tolerance (NGT) (P<0. 05). TG/HDL ratio was not related with age and IGF-I levels and it was correlated with serum IGFBP-3 levels, HbA1c, C-peptide, HOMA-IR, and body mass index. However, these relationships were altered in patients with insulin resistance state, especially in those with DM. In the DM group, TG/HDL ratio and total IGFBP-3 levels were positively correlated stronger than no-DM groups. In addition,TG/HDL ratio and total IGFBP-3 levels were positively correlated with total cholesterol and LDL levels but not with age.

Conclusions

TG/HDL ratio, the marker of small dense LDL particles, is related with IGFBP-3, especially in patients with type 2 diabetes. The IGF-I-IGFBP-3 axis, especially IGFBP-3, may play roles in the pathogenesis and metabolic control of lipid metabolism.

Presentation: No date and time listed
ODP619 Trends in Obesity in Gender Diverse Adolescents in Northern Nevada
Authors: Miah Faria , Brereton Caroline , Kelley Erin , Eckert Kathryn
Published: November 2022

Obesity in the pediatric population is increasing with 19.3% of adolescents having a body mass index (BMI) at or above 95th percentile. Childhood obesity impacts physical and psychological health, increasing the risk of developing various diseases. Studies show that prevalence of gender diverse (GD) adolescents is increasing and is estimated to be 7 per 1000 in the US. GD adolescents are at increased risk for cardiovascular disease and mental health disorders. GD adolescents who are diagnosed with obesity are at an increased risk for poor health outcomes. There is a lack of research regarding the prevalence of obesity and the impact of hormone therapy in GD adolescents. A retrospective chart review was conducted at Renown Regional Medical Center in Reno, NV. A total of 119 adolescents, aged 8-21, diagnosed with gender dysphoria prior to June 2021, were enrolled using ICD-10 codes. Patient demographics including age, sex assigned at birth, gender identity, BMI, and use of puberty blockers or hormone therapy were retrieved. Patients were categorized into two groups - no treatment and treatment with puberty blockers and/or testosterone. Average change in BMI was calculated. Fisher exact tests were conducted using SAS version 9.4. Nineteen of the 119 GD patients enrolled were classified as obese using age and sex appropriate BMI charts (15.9%). Thirteen participants were assigned female at birth (AFAB) and six were assigned male at birth (AMAB). Of these participants, 12 had no medical interventions and 7 were treated with puberty blockers and/or without testosterone. No participants received estrogen therapy. The average change in BMI was +1.84 (no treatment group) and + 3.70 (treatment group). The average change in BMI for AFAB participants was +2.24 and +3.16 for AMAB participants. Association of obesity with treatment compared to no treatment was not found to be statistically significant (p=0.4125). The prevalence of obesity in this population was similar to the prevalence of obesity in non-GD adolescents regionally. In Nevada, obesity in adolescents age 10-17 increased from 12.9% to 16% from 2018-2021. We expected to observe a higher prevalence of obesity in the adolescent GD population compared to the non-GD pediatric population. Additionally, we expected to see a greater increase in BMI in the group of GD patients receiving treatment. Although the results were not statistically significant, patients undergoing treatments did experience a greater average increase in BMI compared to those who had no medical intervention. The lack of statistical significance is likely due to having a small sample size. Further research is needed to observe obesity trends in adolescent GD populations, as well as the effects of hormone therapy on BMI.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
OR05-6 Designing a Gender Affirming Hospital: Patient Perspectives on Gender Inclusive Care
Authors: Fisher Erin , Gist Lauren , Inwards-Breland David , Marinkovic Maja , Marino-Kibbee Bixby , Patel Aarti , Rhee Kay , Richardson Tay , Yeh Debra
Published: November 2022

Background

Studies have shown transgender and non-binary individuals encounter discrimination and harassment in medical settings leading to delays in seeking care and worse physical and mental health outcomes. Organizations, including the American Academy of Pediatrics, published recommendations for medical centers to foster respectful and inclusive care through systems, environmental, and educational changes. However, it is unclear whether health systems are making these changes and what the impact may be for transgender and non-binary youth.

Objective

To explore perspectives of transgender and non-binary patients regarding the current state of gender inclusive care at our medical center and identify areas for improvement.

Design/Methods

A qualitative study was conducted at a large academic center. Participants aged 13-21 years were recruited from the Center for Gender Affirming Care to participate in a semi-structured interview and demographics survey regarding their experiences across various clinical settings within the medical center. Interviews were audio-recorded and transcribed verbatim. Survey results were analyzed using descriptive statistics. Two independent coders reviewed the transcripts, developed a preliminary coding scheme, and reached consensus on any coding discrepancies. ATLAS.ti® was used for thematic analysis.

Results

Thirty participants completed an interview and survey. Mean age of participants was 17 years, with 30% identifying as female/trans female, 47% male/trans male, and 23% identifying as nonbinary or gender fluid. Several key themes emerged. Overall participants are satisfied with their care and attributed improvements to societal progress and systems/environmental changes. Parent advocacy and diversity among staff promoted positive and affirming experiences. However, participants identified personnel, systems, and environmental areas needing improvement including: 1) Provider training on use of pronouns, gender affirming terminology, and exam techniques, 2) Reliable and accurate display of chosen name and pronouns in the electronic medical record (EMR) and patient labels, and standardized check-in processes to prevent misnaming/misgendering, 3) Desire for more LGBTQ-inclusive décor and resources.

Conclusions

While national recommendations were published more than 5 years ago, it is clear from our participants that not all recommendations have been implemented consistently across all clinical settings. Eliciting feedback from patients may provide tangible ways to improve care for this population.

Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.
OR18-5 A Prospective Clinical Trial of Vosoritide in Selected Genetic Causes of Short Stature
Authors: Boucher Kimberly , Dham Niti , Kanakatti Shankar Roopa , McCarthy Tara , Merchant Nadia , Zhang Anqing , Dauber Andrew
Published: November 2022

Objectives

Vosoritide is a C-type natriuretic peptide analog which binds its receptor on chondrocytes, leading to increased chondrocyte proliferation and differentiation via its inhibition of the ERK1/2-MAPK pathway. It was recently approved for increasing linear growth in children with achondroplasia. Our study aims to assess the safety and efficacy of vosoritide in children with genetic mutations in 6 categories: hypochondroplasia, Rasopathies (including Noonan syndrome), aggrecan deficiency, carriers of heterozygous NPR2 mutations, CNP deficiency, and SHOX deficiency.

Methods

This is a prospective, Phase II study with a goal N of 35 subjects. All subjects must have a documented genetic mutation in one of the 6 categories, be prepubertal between the ages of 3 and 11 for boys and 3 and 10 for girls, and have a height < -2.25 SD. Subjects are followed for a 6-month observation period to establish a baseline annualized growth velocity (AGV) and then receive daily subcutaneous vosoritide (15 mcg/kg/day) for 12 months. The primary outcomes are rate of AEs and change in AGV from baseline. Pharmacokinetic studies and pharmacodynamic studies, using cGMP production as a pharmacodynamic marker, are completed at Day 1 and Months 6 and 12.

Results

To date, 27 subjects have enrolled in the trial (20 hypochondroplasia, 3 Noonan, 2 NPR2, 2 Aggrecan). Median baseline height is -3.1 SD (IQR -3.6, -2.6). 14 subjects have initiated on vosoritide, and 10 completed 6 months of therapy. Median increase in AGV was 3.9 cm/yr (IQR 2.2, 4.6). The two subjects with NPR2 mutations had increased AGVs of 4.4 and 9.2 cm/yr. The two subjects with Noonan syndrome had an increase in AGV of 7.5 and 3.3 cm/yr. One subject with Noonan syndrome, a 4-year-old male, had previously been treated with growth hormone (GH) for 2 years. His AGV was 6.7 cm/yr while on GH, 4.1 cm/yr during the 6-month observation period, and 11.6 cm/year during the first 6 months of vosoritide treatment. There were no serious adverse events related to vosoritide treatment. One subject had a brief episode of syncope with her first injection which self-resolved, and she continued on therapy with no further incidents. PK parameters were similar to previously published parameters for vosoritide in children with achondroplasia. In preliminary data, vosoritide Cmax and AUC correlated strongly with peak increase in cGMP (r=0.70, p=0.01;r=0.84, p<0.01, respectively) but not with increase in AGV (r=0.35, p=0.32).

Conclusions

This is the first clinical trial of vosoritide for children with genetic short stature who do not have achondroplasia. Vosoritide treatment may work as a precision therapy to improve growth in multiple genetic conditions which interact with the ERK1/2-MAPK pathway.

Presentation: Monday, June 13, 2022 12:00 p.m. - 12:15 p.m.
PMON313 Hyperinsulinemic Hypoglycemia and Growth Hormone Deficiency Secondary to 20p11 Deletion
Authors: Wee Erica , Dileepan Kavitha , Tsai S L , Paprocki Emily
Published: November 2022

Introduction

Hyperinsulinism (HI) and growth hormone deficiency (GHD) are known causes of hypoglycemia but not commonly found together. We present a 4-month-old boy with hypoglycemia found to have both HI and GHD with subsequent genetic diagnosis of 20p11 deletion. This deletion has been associated with panhypopituitarism. This case represents a few to report HI as a manifestation of this deletion. Treatment with both recombinant human growth hormone (rhGH) and Diazoxide led to blood glucose (BG) normalization.

Clinical Case

A 4-month-old, full-term, large for gestational age (96th percentile), born to a nondiabetic mother presented with hypoglycemic seizures. He had transient hypoglycemia at birth, normal newborn screen, and exclusively breastfeeding with normal growth and development. He had a negative 60-hour video EEG. Further work-up was significant for serum glucose of 54 mg/dL despite blood draw being 20 minutes after a breastfeed, prompting endocrinology evaluation. Physical exam showed no dysmorphism and normal genitalia. He had a serum glucose of 39 mg/dL while asymptomatic. Critical sample revealed detectable insulin (3.2 mcIU/mL), low beta hydroxybutyrate (145.6 mcmol/L) and low growth hormone (GH) (4.2 ng/dL). He had normal cortisol, lactic acid and ammonia. A glucagon challenge showed an increase in BG of 26 mg/dL (35-->61 mg/dL). He had a GH stimulation test with arginine (peak GH 3.8 ng/dL) and glucagon (peak GH 6.6 ng/dL). He had mildly elevated liver enzymes that resolved on repeat testing. Plasma amino acid, plasma acylcarnitine profile, urine organic acids, and brain MRI were normal. He was initially started on rhGH with continued hypoglycemia, hence, Diazoxide, and chlorothiazide were added. His BG was monitored until dextrose infusion was successfully weaned, while maintaining normoglycemia. Genetic testing with next-generation sequencing revealed 20p11.22-p11.21 deletion. He was discharged on Diazoxide (12 mg/kg/day), chlorothiazide, and rhGH (0.27 mg/kg/week).

Conclusion

It is important to determine the cause of hypoglycemia so specific treatment can be provided. HI is a common cause of hypoglycemia in infants due to abnormal insulin secretion in the pancreatic beta cells. GHD can also cause hypoglycemia and be associated with other pituitary hormone deficiencies. Evaluation of our patient's hypoglycemia revealed HI, GHD and 20p11 deletion. This deletion has been associated with hypoglycemia due to GHD and few reports with HI. This patient will need to be regularly screened for other pituitary hormone abnormalities. Other features of 20p11 deletion include cognitive delay, craniofacial dysmorphisms, gastrointestinal and genitourinary anomalies. While hypoglycemia is often the result of a single cause, this case shows that there are pathological conditions that can present with both GHD and HI, so the differential diagnosis for hypoglycemia should remain broad.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON318 Nephrogenic syndrome of inappropriate antidiuresis in a 19 months old child with gross developmental delay
Authors: Bargman Renee , Gavryutina Irina
Published: November 2022

Case report

19 months old African American boy with nonsignificant past medical history presented with inability to walk, hypotonia chewing difficulties and speech delay. Initial laboratory evaluations demonstrated serum hyponatremia of 120-129 mEq/dl, low serum osmolality 261 mosm/kg (normal serum osmolality 275-295 mosm/kg) with inappropriately high urine osmolality 445 mosm/kg) (normal urine osmolality 300-1000 mosm/kg). Blood work for thyroid, adrenal, and pituitary function was unremarkable. Vasopressin level of 2.4 pg/ml (normal 0.0 - 4.7 pg/mL) did not support the diagnosis of Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH). Fludrocortisone challenge test ruled out aldosterone deficiency with insufficient decrease in urine sodium and no response in serum sodium. Renal ultrasound and brain MRI were normal. Genetic testing revealed AVPR2 X-linked mutation c.409C>T p.R137C, consistent with nephrogenic syndrome of inappropriate antidiuresis (NSIAD). The patient was discharged on sodium chloride tablets 2g every 8 hours and remained stable, asymptomatic. One month after discharge patient showed significant neurological improvement.

Discussion

Sodium is known to play a significant role in growth and maturation of the whole body, especially of the nervous system. Moderate (120-129 mEq/L) to severe (<120 mEq/L) hyponatremia can present with nausea, malaise, headache, lethargy, motor and speech delay, seizures and even death due to brain herniation. Normal fluid and electrolyte balance is achieved by the thirst mechanism and free water excretion in kidneys. This is mediated by Vasopressin, which acts through V2R receptor in distal renal collecting duct. Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the most common cause of hyponatremia. Reset osmostat syndrome with a congenitally low serum osmolality threshold is one of the rare disorders on the differential. Hereditary nephrogenic syndrome of inappropriate antidiuresis is very rare mutation in vasopressin receptor, which clinically resembles SIADH except for normal/low vasopressin levels in set of hyponatremia. It causes gain of function and inappropriately high water retention.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON322 Gigantism in 13-Year-Old Male With Pituitary Tumor
Authors: Senguttuvan Rajan , Huante David , Ricoy Giselle
Published: November 2022

Background

Pituitary gigantism is caused by excess growth hormone [GH] secretion from the pituitary gland when the growth plates are open leading to excessive linear growth and tall stature in the pediatric population. It is extremely rare with a reported incidence of 8 cases per million person-years.

Clinical Case

The patient is a 13-year-old male who presented with concerns of accelerated growth rate and tall stature. His father noticed the patient's tall stature when he passed his own height the last year. The patient was seen by his PCP who referred the family to pediatric endocrinology. His symptoms included snoring and bi-weekly headaches, but no vision changes. Review of his growth charts showed linear growth tracking at greater than the 95th percentile since the age of 9 years. His clinical features included large hands, large feet, prominent jaw, testicular volume >25 ml, tall stature [Ht > 99%, Z= +4.59 SD]. The patient's mid-parental height is 69.1 inches [175.5 cm] and the patient measured 76.6 inches [194.5 cm]. His predicted height was 7 feet 1.5 inches [217.2 cm] based on his bone age. His clinical features were strongly concerning for Gigantism.

Initial labs showed IGF-1 of 924 ng/mL [168–576], prolactin of 20.1 ng/mL [2.8–11.0], and IGF-BP3 8.7 mg/L [3.1–9.5]. Cortisol, ACTH, TSH, FT4, LH, FSH, Testosterone were within normal limits. Bone age was concordant with chronological age. MRI showed enlarged pituitary gland measuring 1.3 cm in height, suspicious for macroadenoma. Cardiac evaluation including echocardiogram came back normal. GH suppression test resulted in a 2-hour GH level of 27.3 ng/mL [<1] and he was diagnosed with Gigantism due to GH-secreting pituitary tumor. The parents decided to consult neurosurgery team at a different facility, where transsphenoidal resection of the pituitary tumor was performed. He did not develop any postoperative complications, including Diabetes insipidus or any pituitary hormone deficiencies, and was discharged home shortly after. Follow-up MRI of the pituitary showed no evidence of residual tumor. Pathology of the macroadenoma expressed GH and prolactin on immunohistochemical stains and was negative for TSH, LH/FSH, and ACTH. Genetic studies obtained were negative, lowering the likelihood of inherited predisposition to endocrine neoplasms. The patient has remained well post-operatively and has been able to continue school and play basketball without issues.

Conclusion

Pituitary gigantism occurs in the pediatric population prior to skeletal epiphyseal closure and is caused by GH excess. Initial screening tests should evaluate for pituitary function including IGF-1 and prolactin levels. The gold standard for diagnosing GH excess is the GH suppression test. Even though rare, it is important for clinicians to keep a high level of suspicion for quick recognition and management of overgrowth syndromes.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSAT104 Predicting Response to Growth Hormone Therapy with Pituitary Volume and The Growth Hormone Stimulation Test
Authors: McGuirk Liam , Epstein Benjamin , Krasnow Matthew , Manely Sarah , Patale Tara , Sayegh Emily , Tenner Michael , Mehta Shilpa , Schefflein Javin , Mehta Hasit , Vanier Cheryl , Noto Richard
Published: November 2022

Background

Patients with diminished growth hormone (GH) secretion are candidates for GH therapy (GHT). The GH stimulation test (GHST) is considered the gold standard for the diagnosis of GH deficiency (GHD), yet its efficacy has been questioned. In this study we explore the GHST and PV's ability to define GHD and determine their individual ability to predict GHT outcomes.

Subjects and Methods

A database at a Pediatric Endocrinology center was queried for patients aged 6-18 yrs who underwent a GHST, MRI, and GHT between 1/2018 - 1/2021. Patients with a first follow up (FU) between 3 and 9 months were included; of these patients, second FUs were included if they occurred between 9 and 15 months. Patients with relevant comorbidities, those with GHST peak ≥ 10.0 ng/mL, and nonadherent patients were excluded. MRIs were acquired on a Philips 1.5 or 3.0 T scanner (2mm slices) and PV was calculated using the ellipsoid formula (LxWxH/2).

PV and height were converted to SDS. Response to treatment was defined as change in height SDS over the assessed time interval. A multiple linear regression was utilized to analyze the response to GHT relative to peak GH and PV, with initial height and age at stimulation included as covariates. The relationship between peak GH and PV SDS was analyzed with a Pearson correlation

Results

The first FU ranged between 3.1 and 8.9 months, and the second FU ranged between 9.0 and 14.9 months. 145 patients had one FU, and 83 patients had two FUs. Peak GH and PV SDS were not correlated (r=0.03). Patients who were relatively shorter for their age and gender at stimulation had higher growth rates in the first interval, but not in the second interval. Both PV and peak GH provided information about response to GHT. PV SDS negatively predicted the relative growth response to treatment in the first interval (slope=-0.03, p=0.048). However, PV only explained 3.7% of variation in growth. PV SDS was not a useful predictor of response in the second interval (slope=-0.01, p=0.693). Peak GH was a predictor of response to GHT in the first interval only after accounting for age at stimulation and initial height (slope=-0.01, p=0.032; r2=0.01). Peak GH was a predictor of response in the second interval (slope=-0.02, p=0.040), explaining 5.1% of the variation in growth.

Conclusion

Since peak GH and PV were not correlated, they likely reflect different physiological processes. PV and peak GH both provide information about response to GHT, so they should both be utilized to determine eligibility for GHT.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT107 Evaluating Pituitary Volume and the Growth Hormone Stimulation Test in Siblings. Both Together Better Define the Etiology of Short Stature.
Authors: Sayegh Emily , McGuirk Liam , Patale Tara , Krasnow Matthew , Manely Sarah , Epstein Benjamin , Tenner Michael , Mehta Shilpa , Schefflein Javin , Mehta Hasit , Noto Richard
Published: November 2022

We have shown that short children have significantly reduced pituitary volume (PV)s and have speculated PV as a cause for diminished chronic growth hormone (GH) secretion and poor growth. In this study, we further elucidate the role of PV in the etiology of short stature (SS) in a larger cohort of siblings (SBs).The database of a Peds Endo Center between 2013-21 was queried for siblings with SS who underwent a GH Stimulation test (GHST) and MRI evaluation. Their results were compared with normal controls (NCs) as previously reported. 129 SBs of 60 families were compared to 170 NCs. SBs were divided into 3 groups (GPs). GP1 (n=79) consisted of families with only GHD. GP2 (n=12) contained families with only ISS SBs. GP3 (n=38) comprised families with mixed GHD and ISS. SBs <11 yrs and >11 yrs were considered prepubertal (prePB) and pubertal (PB), RSP. The mean (MN) and median (MD) age for both prePB and PB SBs were significantly different (p 0.05). The 32 PB patients in GP3 had a mean PV of 316.17± 197.53 mm3, which was significantly different from that of the PB NCs of 424.6 ± 138.4 mm3 (p<0.001). Out of 38 children in GP3, 18 passed the GHST and 11 of those children who passed demonstrated a small pituitary gland (61%). 78% of prePB SBs had small PVs, while 88% were GHD. 66% of PB SBs had small PVs, while 70% of PB SBs were GHD. 71% of all SBs had small PVs, while 77% were GHD. When combined, GHST and PV identify the etiology for SS in 92% of subjects. The GHST and PV together identify more patients of SS who should qualify and benefit from GH therapy than the GHST alone. Since ages were significantly different and present as a limitation to this study, future studies should strive for age match control

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF14 | PMON328 The Effect of Pituitary Cysts on Pituitary Volume in Patients with Growth Hormone Deficiency and Idiopathic Short Stature
Authors: Patale Tara , McGuirk Liam , Krasnow Matthew , Epstein Benjamin , Manely Sarah , Sayegh Emily , Tenner Michael , Schefflein Javin , Mehta Hasit , Noto Richard
Published: November 2022

Background

Pituitary cysts (PCs) may be related to the development of diminished growth hormone secretion because they may limit the proliferation of somatotrophs. This study seeks to investigate the mass effect of PCs on the pituitary function.

Methods

Patients aged 6-18 with cysts and follow-ups between 2007–21 were compared to normal controls (NCs) aged 6-18 from a neuroradiology center. Pituitary volume (PV) is the volume of the pituitary gland including the cyst, while net pituitary volume (netPV) is the volume of the pituitary gland excluding the cyst. Since NCs did not have PCs, only PV was utilized. PVs and netPVs are reported in mm3. Data were stratified into prepubertal (age < 11 yrs) and pubertal (age > 11 yrs). The Kruskal-Wallis One Way ANOVA on Ranks was utilized to compare multiple means, and the Kruskal-Wallis Multiple-Comparison Z Value test (with Bonferroni adjustment) was utilized for pairwise comparisons.

Results

The mean and median PVs of prepubertal GHD (n=37), ISS (n=5), and NCs (n=58) were 290.2 ± 109.7 and 305.0, 314.4 ± 100.8 and 299.8, and 246.8 ± 63.7 and 241.6, respectively. The difference between mean PVs of prepubertal GHD, ISS, and NCs was not significant.

The mean and median PVs of pubertal GHD (n=58), ISS (n=33), and NCs (n=112) were 391.5 ± 163.5 and 370.2, 409.2 ± 215.8 and 382.9, and 424.2 ± 138.9 and 402.7, respectively. The difference between mean PVs of pubertal GHD, ISS, and NCs was not significant.

For netPV, the mean and median values for prepubertal GHD and ISS patients were 252.2 ± 83.3 and 272.2, and 245.2 ± 85.7 and 244.9, respectively. The difference between mean netPVs of prepubertal GHD, ISS, and NCs was not significant.

For netPV, the mean and median values for pubertal GHD and ISS patients were 332.7 ± 121.3 and 346.4, and 333.9 ± 146.1 and 330.7, respectively. The mean netPVs of pubertal GHD and ISS patients were both significantly lower than the mean PV of pubertal NCs.

The mean and median PVs for cyst patients were 364.8 ± 170.0 and 347.8 which was not significantly different from the NCs. The mean and median netPVs for cyst patients were 307.3 ± 122.9 and 289.0 which was significantly different from the NCs (p<0.001).

Conclusion

When considering the functional component of the pituitary gland, cyst volume should be subtracted from the overall pituitary gland.

Presentation: Sunday, June 12, 2022 12:36 p.m. - 12:41 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
LBODP068 Double Trouble: Co-occurrence Of Epididymal Cyst With Testicular Hydrocele And Varicocel In Patient With Kallmann
Authors: Shaaban Noreen Hamed , Angueira Eugenio , Gone Jayanthraj , Kodali Yukthi , Vallepu Shirisha R , Gonzalez Javier A , Lozada Arianna , Pinto Rohan
Published: November 2022

Background

We present a patient with central and peripheral hypogonadism, decreased libido, and erectile dysfunction, who was previously diagnosed with Kallmann syndrome confirmed by serum hormone panel and ultrasonography.

Clinical Case

A 27-year-old male with a past medical history of hypogonadotropic hypogonadism, Kallmann syndrome, obesity, and dyslipidemia presented to the clinic with concerns about his reproductive health. There was no family history of hypogonadism. He was diagnosed with Kallmann syndrome at the age of 14 due to short stature and had been treated using testosterone therapy. He had paused therapy for 6 months prior to the visit for the trial of a new medication, Menopur, to improve his fertility. However, the therapy had failed to improve his sperm count. Laboratory tests showed a subclinical total testosterone level of 7 ng/dL which was consistent with hypogonadism, so testosterone therapy was restarted with weekly 200 mg/mL testosterone cypionate intramuscular injections. Results were also significant for dyslipidemia with total cholesterol 299 mg/dL, triglycerides 240 mg/dL, HDL 38 mg/dL, LDL-c 217 mg/dL, and elevated BMI of 38.52 kg/m2, for which the patient was started on rosuvastatin 20 mg daily and counseled on lifestyle modification. HbA1c levels were in the pre-diabetic range of 5.8%, and he was started on metformin 500 mg BID. On a repeat visit, the patient complained of painless testicular swelling, for which ultrasonographic imaging was ordered. The results showed bilateral small testes for age measuring 1.9×1.4×1.2 cm on right and 2.5×1.4×1.4 cm on left with a 0.6×0.4 cm left epididymal cyst and evidence of mild right hydrocele and left varicocele. The patient was referred to a genitourinary specialist for further investigation. On follow-up visit, the patient presented with new labs showing improvement with total testosterone 943 ng/dL, free testosterone 255.6 pg/mL, FSH <0.7 mIU/mL, and estradiol 64 pg/mL. The patient continued with testosterone therapy over the long term after failing the trial of Menopur for fertility improvement.

Conclusion

Failing of hormonal replacement in improving the fertility inpatient with central hypogonadism warranty the importance of gonadal examination. This is a patient with a past medical history of hypogonadotropic hypogonadism, who had been treated with testosterone since the time of diagnosis to improve his short stature and secondary sexual characteristics. Given the clinical picture of his testes and failed trial of a new drug regimen, there was a low chance of regaining fertility for this patient.

Presentation: No date and time listed
ODP056 The Treatment of Opioid Addiction Leading to Secondary Adrenal Insufficiency
Authors: Morgan Farah , Shah Aditi
Published: November 2022

Background

As we continue to learn about the opioid crisis in America, more patients are seeking treatment for their opioid addictions. This treatment includes buprenorphine/naloxone, a partial opioid agonist and opioid antagonist. Though there is known evidence of opioid-induced secondary adrenal insufficiency, there is scarce data regarding the effect of buprenorphine/naloxone on the hypothalamic-pituitary-adrenal (HPA) axis. Here we describe a case of secondary adrenal insufficiency in a patient who is on long-term treatment for her opioid addiction with buprenorphine/naloxone.

Clinical Case

A 30 year old female with a past medical history of ADHD, OCD, PTSD, and menorrhagia presented with extreme fatigue, 100-pound weight gain, hair loss, and intermittent red flushing on hands and face over the past year. Labs showed low androstenedione (21 ng/dL, n 41 - 262 ng/dL), low testosterone (6.5 ng/dL, n 10. 0 - 55. 0 ng/dL) and low DHEA-S levels (55.6 ug/dL, n 84.8 - 378. 0 ug/dL). Further history revealed that the patient had been on Buprenorphine/Naloxone for 4 years for opioid addiction. Testing revealed a low morning cortisol level (5.6 ug/dL, n 6.2 - 19.4 ug/dL). The patient was started on hydrocortisone 10mg in the morning and 5mg in the afternoon with improvement of symptoms. Repeat testing after holding hydrocortisone revealed a cortisol level (6.6 n 6.2 - 19.4 ug/dL) and an inappropriately low-normal ACTH level (16 pg/mL, n 6 - 50 pg/mL). Cosyntropin stimulation test did not show an adequate response with a baseline cortisol level of 3.4 ug/dL, (n 5. 0 - 23. 0 ug/dL), 30 minute cortisol level of 6.9 ug/dL and 60 minute cortisol level of 8.2 ug/dL (n >18. 0 ug/dL). ACTH drawn at that time was low (<5 pg/mL n 6 - 50 pg/mL). Pituitary MRI was completed and findings were insignificant. Due to continued fatigue, the hydrocortisone dose was increased to 15mg in the morning and 5mg in the afternoon with improvement in symptoms with a plan to retest the adrenal axis as she continues to wean off the Buprenorphine/Naloxone.

Conclusion

This case calls attention to secondary adrenal insufficiency caused by the treatment of opioid addiction with buprenorphine/naloxone. Further investigation of adrenal insufficiency secondary to buprenorphine/naloxone use is warranted given the frequency of use of this combination to treat the ongoing opiate addiction crisis in America.

Presentation: No date and time listed
ODP402 Adult height and reproductive outcome of Klinefelter men with a 46,XX/47,XXY mosaicism
Authors: Schepper Jean D , Gies Inge , Staels Willem , Unuane David , Vloeberghs Veerle , Wampers Alicia
Published: November 2022

Background

Mosaicism in Klinefelter Syndrome (KS) is reported in 15–20%, but 46,XX/47,XXY mosaicismis extremely rare and presents either during infancy with ambiguous genitalia or during adolescence with gynecomastia or microorchidism. In view of the scarce data on adult outcomes (1,2), we here comprehensively report the skeletal and reproductive health outcome in two individuals with 46,XX/47,XXY KS. Clinical cases The first case was born at 40 weeks after a spontaneous conception with a birth length of 49 cm. At birth right cryptorchidism, but a normally developed penis and scrotum was present. Surgical intervention at the age of 1 year, showed a right abdominal testicular nubbin. He was investigated at the age of 17 years for left microorchidism (6ml) contrasting with a normal genital development (Tanner G5). Hormonal investigation showed hypergonadotropinemia with a normal serum testosterone. Peripheral blood karyotype showed mosaicism 46,XX (60%)/47,XXY (40%). At the age of 18 years, standing height was 164.5 cm (mid-parental height (MPH) 173.5 cm). BMI was 19 kg/m2. Hormonal evaluation showed an unmeasurable serum inhibin B, elevated gonadotropins (LH 43 IU/L and FSH 65 IU/L), but a normal testosterone and estradiol. Ultrasound of the left testis showed a normal echo pattern. Azoospermia was documented. Lumbar spine bone mineral density (LS-BMD) was -1 SDS. The second case was born at 37 weeks after ICSI with a birth length of 49 cm. External genitalia at birth were normal. However, routine karyotyping after ICSI conception showed a mosaicism 46,XX (50)/ 47,XXY (50). A normal pubertal development apart from an arrest in testicular development at the age of 15 years was documented. At the age of 18 years, his height was 176.8 cm (MPH 184 cm), BMI 26 kg/m2, Tanner stage G5 and testes volumes 8/8 ml. Hormonal evaluation showed low inhibin B (43.4 ng/l), slightly elevated gonadotropins (LH 16.1 IU/L and FSH 12.5 IU/L), and normal testosterone and estradiol. Ultrasonography of the scrotum showed normal testicular structure. LS-BMD SDS was 1.

Conclusion

46,XX/47,XXY KS men, who present with normal male genitals at birth, can have a normal pubertal progression with the exception of a mid-pubertal testicular regression, but in contrast to men with a 46,XY/ 47,XXY constitution, appear at risk for a shorter stature than expected for parental height. References Velissariou V et al., European Journal of Medical Genetics (2006) 49, 331-337Matsuki S, Journal of Urology (1999) 161 (5), 1573-74

Presentation: No date and time listed
ODP404 Effects of Empagliflozin on Serum Androgens Levels in Men Without Diabetes
Authors: Kosinski Christophe , Salamin Olivier , Kuuranne Tiia , Nicoli Raul , Pitteloud Prof Nelly , Zanchi Anne
Published: November 2022

Introduction

Sodium-glucose cotransporter (SGLT) 2 inhibition is a well-known target for type 2 diabetes treatment, chronic heart failure and chronic kidney disease. SGLT2 is encoded by SLC5A2 (Solute Carrier Family 5 Member 2) gene, which is highly expressed in the kidney cortex(x36.9). Notably, SLC5A2is also overexpressed in the testes (x8.1), where glucose uptake could be crucial for androgen production and spermatogenesis. We hypothesized that the SGLT2 inhibitors use could interfere with testosterone production in healthy men.

Method

This is a post-hoc analysis of a double-blind, randomized, placebo-controlled study, in 27 healthy men who received empagliflozin 10mg once a day during 4 weeks. All weight categories were included: 15 normal weight, 15 overweight, 15 obese. In each group, 5 were randomized to the placebo and 10 to the empagliflozin. Serum samples were analyzed using an ultra-high-performance LC (UHPLC)–MS/MS method for quantification of total testosterone (TT) and dihydrotestosterone (DHT). TT and sex hormone-binding globulin were used to calculate free testosterone (FT).

Results

No significant changes were observed in total serum TT (Δ 2.1 nmol/L; p>0.1), DHT (Δ 0. 03 nmol/L; p>0.1) and FT (Δ 0.35 nmol/L; p>0.1) after one month of empagliflozin.

Conclusion

The use of a highly selective SGLT2 inhibitor, empagliflozin, in men without diabetes did not change serum androgen levels, regardless of body mass index category. Studies on seminiferous tubule function in healthy men are ongoing to further clarify the role of SGLT2 in spermatogenesis.

Presentation: No date and time listed
ODP409 Exercise Increases Microbiota Diversity in Women with Polycystic Ovary Syndrome: A Secondary Analysis of a Pilot Randomized Controlled Trial
Authors: Benham Jamie , Ramay Hena , Reimer Raylene , Booth Jane , Friedenreich Christine , Rabi Doreen , Sigal Ronald
Published: November 2022

Background

Women with polycystic ovary syndrome (PCOS) have reduced diversity and altered composition of gut microbiota (all microorganisms in the intestine) compared with healthy women. Shifts in gut microbiota with exercise may mediate some of the beneficial (e. g. anti-inflammatory) effects of exercise.

Objective

To evaluate the effect of exercise training on gut microbiota diversity (number of different species) and composition in women with PCOS.

Methods

18–40-year-old women with PCOS were randomly assigned to six months of thrice-weekly high-intensity interval training (HIIT), continuous aerobic exercise training (CAET) or no-exercise control. Stool samples were collected pre- and post-intervention. Bacterial DNA was extracted from stool samples and microbial sequencing performed on the MiSeq Illumina platform with amplification of the V3 and V4 regions of the 16S rRNA gene. The IDTAXA classifier was used to classify reads with the Silva rRNA database. Alpha diversity (within sample diversity) was measured using Shannon and Simpson indices. Changes in bacterial community structure (beta diversity) were based on Bray-Curtis dissimilarity and visualized using principal coordinates analysis.

Results

Data were available for 19 women pre- and post-intervention: control (n=8), CAET (n=6) and HIIT (n=5). In all samples, Firmicutes were the most abundant bacterial phylum followed by Bacteroidetes. The abundance of Actinobacteria, Verrucomicrobia and Proteobacteria decreased with exercise training in both exercise groups. Alpha diversity increased for all HIIT participants, but the effect was inconsistent in CAET participants with an increase in 3 (50%) participants. There were no statistically significant changes in beta diversity.

Conclusion

Exercise training may change the relative abundance of bacteria taxa of gut microbiota, and increase alpha diversity but not beta diversity in women living with PCOS. Further larger studies are needed to determine the effect of exercise training on gut microbiota in this population.

Presentation: No date and time listed
ODP413 Impact of Gestational Weight Gain according to 2009 IOM Recommendations on Neonatal Anthropometrics in Asians: A Pilot Study from Malaysia
Authors: Tai Yong Ting , Lim Quan Hziung , Ratnasingam Jeyakantha , Paramasivam Sharmila Sunita , Tan Peng Chiong , Omar Siti Zawiah , Chinna Karuthan , Lim Lee-Ling , Vethakkan Shireene Ratna
Published: November 2022

Introduction

Gestational Weight Gain (GWG) modulates pregnancy outcomes and long-term offspring metabolic health [1,2]. Thus far, the widely used 2009 Institute of Medicine (IOM) recommendations on GWG have largely been evaluated in Caucasian populations and some monoethnic East Asian cohorts. We designed this study to determine if IOM GWG thresholds are applicable in a multi-ethnic Asian cohort of Malaysian mothers.

Methods

In this prospective observational study, 875 mothers were recruited from a Malaysian tertiary urban center during screening for gestational diabetes. Amongst data collected were Total GWG (maternal weight at delivery – self-reported pre-gravid weight) and neonatal anthropometrics. BMI was stratified by Caucasian (overweight ≥25kg/m 2, obese ≥30 kg/m 2) and Asian (overweight ≥23kg/m 2, obese ≥27.5kg/m 2) thresholds, and patients categorized by 2009 IOM GWG recommendations.

Results

This study included 67% Malay, 23% Chinese and 10% Indian mothers. There was a high prevalence of overweight/obesity regardless of cut-offs used (Asian 56.9% vs Caucasian 44%). When Asian BMI cut-offs were used, excessive GWG prevalence increased (34.1% → 40.6%) whilst inadequate GWG declined (30% → 24.9%). Prevalence of LGA, macrosomia, Birth Weight(BW)/Neonatal Fat Mass(NFM)/Sum of Skinfold Thickness(SSFT) >90th centile was highest (p<0. 05) in those with excess GWG whether stratified by Caucasian or Asian BMI cut-offs. Upon multivariate analysis adjusting for age, parity, race, GDM, Ln HOMA2%S and baby gender, excessive GWG (by Asian BMI categories) was associated only with increased risk of SSFT >90th centile (aOR 5.7, 95% CI 2.33–14. 03). Excessive GWG (by Caucasian BMI categories) was associated with increased risk of macrosomia (aOR 8.65, 95% CI 1. 07–70. 01), NFM >90th centile (aOR 2.14, 95% CI 1. 02–4.45) and SSFT >90th centile (aOR 3.88, 95% CI 1.77–8.51). SGA status was associated with insufficient GWG by both Caucasian (aOR 4.26, 95% CI 2.46–7.38) and Asian BMI cut-offs (aOR 3.55, 95% CI 2. 07–6.10).

Conclusion

The 2009 IOM recommendations, using either Caucasian or regional Asian BMI thresholds, are applicable in our multi-ethnic Asian cohort in terms of predicting increased neonatal adiposity and SGA status.

References: 1. Rasmussen K, Yaktine AL, eds; Institute of Medicine; National Research Council. Weight Gain During Pregnancy: Reexamining the Guidelines. Washington, DC: National Academies Press; National Academy of Sciences; 2009.2. He Y, Tam CH, et al. Optimal gestational weight gain for Chinese women - analysis from a longitudinal cohort with childhood follow-up. Lancet Reg Health West Pac. 2021 Jul 6;13: 100190.

Presentation: No date and time listed
OR06-1 Cyclophosphamide Depletes Primordial Follicles via the p63 Apoptotic Pathway
Authors: Dong Rosemary , Elesh Ibrahim , Kim So-Youn , Xu Pauline , Yu Seok-Yeong , Luan Yi
Published: November 2022

Cancer therapies often cause serious side effects, affecting the quality of life for cancer survivors. The ovary can be affected by cancer therapies, causing premature ovarian insufficiency, leading to endocrine dysfunction and infertility. Thus, maintaining ovarian function against cancer treatment is an unmet need for female cancer patients. Cyclophosphamide (CPA), a common chemotherapeutic agent, is metabolized in vivo and forms DNA crosslinks, inducing apoptosis in rapidly proliferating tumor cells. However, the underlying mechanism of the CPA-induced oocyte death in ovarian reserve remains unclear. This study aims to investigate the mechanism of oocyte death in primordial follicles by generating oocyte-specific Abl1 and p63 knockout and Pik3ca* knockin mouse models using Gdf9-iCre+. Postnatal day 7 female mice were i.p. injected w/wo CPA. Notably, we found CPA drastically reduced the number of primordial follicles without increasing the number of growing follicles. The quantification of surviving follicles validated that 90% of the primordial follicles from oocyte-specific Abl1 knockout mice were lost following CPA treatment in vivo and in vitro. Concurrently, high expression of CHK2 was detected in the oocytes of the ovary cultured with CPA metabolite in vitro. This implied CHK2 rather than ABL is a possible tyrosine kinase for CPA-induced oocyte death. Most of all, p63 was a key player for CPA-induced oocyte death, supported by the result that p63 knockout oocytes were rescued after CPA treatment. To clarify whether the ovaries lose follicles via activation or apoptosis pathway, PIK3CA* mice were examined with CPA. As expected, primordial follicles and primordial follicles with activated oocytes in the ovary of PIK3CA* mice survived against CPA due to constitutive PI3K activity in them. This indicates activated follicles resist gonadotoxic reagents, although p63 is expressed inside their oocytes. Accordingly, the apoptosis markers, BAX and cleaved PARP were highly induced with CPA injection in a time-dependent manner in the ovaries from wild-type female mice but not from the p63 knockout. The double-strand break also occurred in the nucleus of oocytes post CPA administration as γH2AX was detected. Interestingly, OPA1, a protein required for mitochondrial fusion, was highly induced inside the oocyte cytoplasm of p63 knockout, while oocytes in wild-type mice time-dependently lost the OPA1 expression by CPA treatment. This indicates that oocytes without p63 in the nucleus survive and induce mitochondrial fusion to escape apoptosis by mitochondrial damages. In conclusion, CPA induces depletion of oocytes of primordial follicles through the CHK2-TAp63 apoptotic pathway.

Presentation: Saturday, June 11, 2022 11:30 a.m. - 11:45 a.m.