bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP047 Intramuscular ACTH stimulation test in a patient with liver disease
Authors: Khurram Daniyeh , Dadlani Apaar , Krishnasamy Sathya 
Published: November 2022

Abstract

Introduction
High dose (250 mcg) ACTH stimulation test is the gold standard dynamic testing to diagnose primary adrenal insufficiency (PAI). While the current guidelines do not elaborate on the preferable route of administration of corticotropin (intravenous or intramuscular), most published studies have been conducted on healthy people using the intravenous route. We present a patient with non-alcoholic steatohepatitis cirrhosis and hypotension who was thought to have suboptimal response with intramuscular ACTH stimulation test.

Case
62-year-old male with cirrhosis, presented with dizziness, and was found to be hypotensive. Lab tests showed normal cell counts, electrolytes, renal function and lactic acid. His albumin was 2.6 g/dL. His blood pressure did not improve with intravenous fluids. Workup initiated for adrenal insufficiency showed 8 am cortisol level of 7. 0 mcg/dL, and ACTH level of 26 pg/mL. He underwent ACTH stimulation test with 250 mcg intramuscular cosyntropin, after which the 30-minute cortisol level was 13.7 mcg/dL and the 60-minute level was 15.1 mcg/dL (level immediately before the test 7.2 mcg/dL). Due to the patient not having signs of adrenal insufficiency and low albumin level due to liver disease, the cortisol response was considered adequate.

Discussion
Per the current Endocrine Society Clinical Practice Guidelines, the standard method of performing the ACTH stimulation test involves measuring baseline cortisol level, administration of 250 mcg of cosyntropin, and then measuring cortisol level 30 and 60 minutes post administration. Traditionally, an appropriate response is characterized by peak cortisol level above 18 mcg/dL, with lower values indicative of AI. While the responses can vary due to multitude of factors including time of testing etc., the individual response to the intravenous versus intramuscular injections is similar. However, the cut-off points between the two administration methods may differ. In a study on 64 healthy adult men who were administered 250 mcg cosyntropin intramuscularly, Longui et al. demonstrated lower cut-off values of 12.6 mcg/dL and 16.3 mcg/dL at 30 and 60 minutes respectively. In addition, with the introduction of newer monoclonal antibody and LC-MS/MS assays having greater specificity for cortisol, a study by Jarvosky et. al. recommends a new lower cut-off of 14-15 mcg/dL. Furthermore, several studies have shown higher prevalence of low total cortisol levels in cirrhosis and other liver disease leading to overdiagnosis of PAI, due to deficiency of cortisol binding globulin and albumin. In our patient, we hypothesize that the combination of all these factors could have caused a falsely low cortisol peak level without any underlying PAI. Our case highlights the need for additional studies on patients with underlying liver disease and hypoalbuminemia who undergo testing with intramuscular cosyntropin administration, and analysis with the new assays available.
Presentation: No date and time listed
PMON187 Worsening Hypertriglyceridemia in an Adolescent Female with Type 1 Diabetes Mellitus despite Improvement in Glucose Control
Authors: Figueredo Veronica , Sanchez Janine 
Published: November 2022

Abstract

Background
Chylomicronemia syndrome with severe hypertriglyceridemia may be the result of genetic abnormalities, aggravating factors or a combination of both.

Clinical case
The patient is a 17-year-old overweight female (BMI of 90th percentile) with a history of type 1 diabetes mellitus (T1D) for eleven years, PCOS, vitamin D deficiency and hypertriglyceridemia. Her father has a history of hypertriglyceridemia that improves with dietary modifications. Her mother and younger sister (who also has T1D) have normal serum lipid levels. Although the patient has a history of poor compliance (HbA1c ranging between 9-11%), glucose control had been improving (HbA1c most recently between 8.1-8.6%). Her serum triglyceride level had been slightly abnormal for the past few years (200-300 mg/dL; normal range: &lt; 90 mg/dL) and had increased to 413 mg/dL, despite the improvement in glucose control. She subsequently started taking omega-3, 1000 mg daily. At that time, she also began treatment with combined oral contraceptives (COCs) for PCOS. The serum triglyceride level three months later increased to 1,322 mg/dL. She consistently denied alcohol or recreational drug use. The omega-3 dose was increased to 4 gm daily. Atorvastatin 10 mg daily was also started and COCs were discontinued. Three weeks later, a repeat triglyceride level was found to be 2,813 mg/dL. Fenofibrate 160 mg daily was added. Atorvastatin was discontinued and she began a low-fat diet. After further questioning, patient admitted to heavy alcohol intake during the weekends. She reported specifically drinking grain alcohols to avoid carbohydrates. Three weeks after cessation of alcohol, her triglyceride level declined to 302 mg/dL.
Clinical lesson: This patient had multiple risk factors for chylomicronemia syndrome including poorly controlled T1D, overweight and estrogen containing contraceptive therapy. Although alcohol abuse was a problem at the time hypertriglyceridemia worsened, the history of excessive alcohol consumption was not given until many other treatments had been initiated.
This case highlights the importance of screening for alcohol abuse in patients with hypertriglyceridemia who do not respond to standard therapies, especially in adolescent patients who may be reticent about discussing alcohol abuse with their physicians.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON331 The Natural History of Pituitary Cysts in Patients with Growth Hormone Deficiency and Idiopathic Short Stature
Authors: Krasnow Matthew , McGuirk Liam , Krasnow Nicholas , Patale Tara , Manely Sarah , Sayegh Emily , Epstein Benjamin , Tenner Michael , Mehta Shilpa , Schefflein Javin , Mehta Hasit , Noto Richard 
Published: November 2022

Abstract

Background
Pituitary cysts may be implicated in short stature and affect growth hormone secretion. The natural history of cysts is not known in patients with GHD and ISS.

Objective
To characterize the progression of cyst volume (CV) and percentage of the gland occupied by the cyst (POGO) over time in GHD and ISS patients.

Subjects and Methods
A pediatric health system's database was queried for patients diagnosed with short stature and a cyst with at least one follow up MRI between 2007-21. Data up to 7 years after first follow up was included in this study. The mean and median follow up time were 1.32±1.24 and 1.00. Cysts with a POGO≤15% were considered small, while a POGO&gt;15% were considered large.

Results
The mean and median %ΔCV for all patients for all their follow up MRIs were 38.27%±179.14 and 0%. The mean and median %ΔPOGO for all patients were 38.32%±219.85 and -5.79%. The mean and median %ΔCV for patients with a small cyst (SC) (n=34) were 61.49%±215.60 and 0%. The mean and median %ΔPOGO for patients with a SC were 61.62%±267.25 and -2.89%. The mean and median %ΔCV for patients with a large cyst(LC)(n=14) were -0.4% ±-79.25 and 0%. The mean and median %ΔPOGO for patients with a LC were -1.08%±90.50 and -15.67%. 5 of the 35(14.3%) SCs grew into LCs and stayed large while 6 of the 14 LCs shrunk into SCs. 4 cysts fluctuated between large and small: 3 started large and 1 started small. CV of patients with LCs has a significant negative correlation with time (-0.37, p=0.01). The slope of the regression line is -0.01 mm3/month. The CV of patients with SCs does not show any change in time (-0.02, p=0.84). There is no significant difference in POGO (p=0.86) or in CV (p=0.96) in GHD and ISS patients. In GHD and ISS patients, the difference in POGO is different in each group at each MRI date (p=0.02), but not in CV (p=0.38). GHD patients had an average ΔPOGO of -1.05, while ISS patients had an average ΔPOGO of 1.26.

Conclusion
POGO can change greatly over time. LCs tend to take up less of the gland over time. SCs tend not to change significantly over time, but a minority can still enlarge and need to be monitored. So far, there have been no significant clinical consequences related to these cysts.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PSAT116 Perceived Facilitators and Barriers Using Telemedicine for Gender-Affirming Care in Youth: A Qualitative Study
Authors: Inwards-Breland David , Yeh Debra , Richardson T , Marinkovic Maja , Marino-Kibbee Bixby , Rhee Kay 
Published: November 2022

Abstract

Background
Multi-disciplinary gender-affirming care centers (GACC) are seeing increasing numbers of transgender and non-binary (TNB) youth seeking medical care. In the wake of the COVID pandemic, telemedicine use in clinical settings, including GACC, have increased. There is a paucity of research in the provision of care by telemedicine for gender care as well as TNB youth's perspectives on its use.

Objective
To explore perspectives of TNB youth in the use of telemedicine for gender-affirming care.

Methods
Participants aged 13-21 years, who identified as TNB, were recruited from gender center at a large academic center to participate in a semi-structured interview and demographics survey. 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 discrepancies. ATLAS.ti® was used for thematic analysis.

Results
TNB youth (n=30) had a mean age of 17 years; 30% identified as female/trans female, 47% as male/trans male, and 23% as non-binary or gender fluid. Overall, participants favored in-person visits over telemedicine because of connection with their provider. Patients also had a lack of perceived knowledge about telemedicine despite having good working knowledge of technology. They had mixed feelings regarding clinic staff's role in telemedicine (some felt it was a waste of time, others found it helpful to orient and offer future visits). There were minimal concerns around confidentiality and having a secure line. Advantages to telemedicine included convenience (no travel time or missing school), and discussion of hormone therapy, medication changes, and lab results. However, it was not optimal for full assessment of treatment progress because there was no physical exam.

Conclusions
Despite participants’ preference for in-person visits, telemedicine is a viable option for TNB youth in receiving gender-affirming medical care because of convenience and perceived confidentiality. Efforts to increase telemedicine use could center on providers and clinic staff providing education on the technical aspects of telemedicine use and promoting its availability for discussion-based visits.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF14 | LBMON195 Once-weekly Somapacitan Is Effective And Well Tolerated In Children With GH Deficiency: A Randomized Phase 3 Trial
Authors: Miller Bradley , Blair Joanne C , Højby Rasmussen Michael , Böttcher Volker , Juul Kildemoes Rasmus , Maniatis Aristides , Beck Bang Rikke , Mori Jun , Polak Michel , Stagi Stefano , Horikawa Reiko ,   on behalf of the REAL4 study group
Published: November 2022

Abstract
Growth hormone (GH) replacement therapy usually requires daily subcutaneous (s.c.) injections that can be burdensome for patients and their caregivers. Somapacitan, a long-acting reversible albumin-binding GH derivative, is in development for once-weekly s.c. administration in children with GH deficiency (GHD). REAL4 is a randomised, multi-national, open labelled, and active-controlled parallel group phase 3 trial, comprising a 52-week main phase and three-year extension period (NCT03811535). Two-hundred GH-treatment-naïve, prepubertal children with GHD (74.5% male) were randomly assigned in a 2: 1 ratio to receive 0.16 mg/kg/week s.c. somapacitan (n=132) or daily s.c. GH (0.034 mg/kg/day Norditropin®; n=68). The 52-week main trial results are presented here. The primary endpoint was annualized height velocity (HV) after 52 weeks of treatment. At week 52, the estimated mean HV was 11.2 cm/year for somapacitan compared to 11.7 cm/year for daily GH. The estimated treatment difference was -0.5 [95% CI -1.1 to 0.2] cm/year, confirming non-inferiority (non-inferiority threshold: -1.8 cm/year). Secondary height-related endpoints supported the primary endpoint. Insulin-like growth factor-I standard deviation score (IGF-I SDS) showed consistent increases for both somapacitan and daily GH over the 52 weeks, with change differences from baseline not statistically significant between treatment groups. At week 52, mean IGF-I SDS levels were similar between somapacitan (+0.28) and daily GH (+0.10) and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or local tolerability issues identified. There were no clinically relevant findings with respect to changes in glucose metabolism, no neutralizing anti-somapacitan or anti-GH antibodies were detected, and a low number of patients reported injection-site reactions, with similar proportions for somapacitan (5.3%) and daily GH (5.9%). In both treatment groups, 1.5% of patients reported injection site pain. Adherence was high for both treatments. The mean and median adherence for somapacitan treatment were 95.8% and 100%, respectively. The mean and median adherence for the daily GH group were 88.3% and 96.9%, respectively. In conclusion, once-weekly somapacitan has a similar efficacy and safety profile as daily GH with similar mean IGF-I levels in treatment-naïve children with GHD.
Presentation: Sunday, June 12, 2022 1:06 p.m. - 1:11 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF26 | PMON335 Once-Weekly Somapacitan Versus Daily Growth Hormone in Children Born Small for Gestational Age: Results From a Randomized Phase 2 Trial
Authors: Juul Anders , Backeljauw Philippe , Højby Michael , Kawai Masanobu , Kildemoes Rasmus Juul , Linglart Agnès , Zuckerman-Levin Nehama , Horikawa Reiko 
Published: November 2022

Abstract
Treatment of persistent short stature in children born small for gestational age (SGA) requires daily growth hormone (GH) injections that can be burdensome for patients and caregivers. Once-weekly somapacitan is a long-acting GH currently in phase 3 development for replacement therapy in children with GH deficiency. We report the 26-week results of the first phase 2, multinational, randomized, open-label, controlled, dose-finding trial (NCT03878446) investigating the efficacy and safety of somapacitan as treatment for short stature in children born SGA compared with daily GH (Norditropin®, Novo Nordisk A/S). A total of 62 (35.5% female) GH-treatment-naïve, prepubertal children received 0.16, 0.20 or 0.24 mg/kg/week subcutaneous (s.c.) somapacitan, or 0.035 or 0.067 mg/kg/day s.c. daily GH for 26 weeks (main phase). All children are subsequently included in an extension to this trial.
The primary outcome was annualized height velocity (HV). At week 26, the estimated mean HV was: 8.9, 11.0 and 11.3 cm/year for 0.16 mg/kg/week (n=12), 0.20 mg/kg/week (n=13) and 0.24 mg/kg/week (n=12) somapacitan, respectively, versus 10.3 and 11.9 cm/year for 0.035 mg/kg/day (n=12) and 0.067 mg/kg/day (n=13) daily GH, respectively. A dose-dependent response in the estimated mean HV was observed with both somapacitan and daily GH. The effect of somapacitan on HV was not statistically significantly different compared with daily GH. A similar pattern was observed for change from baseline in height standard deviation score (SDS) and change from baseline in HV SDS. Consistent dose-dependent increases were observed in insulin-like growth factor-I (IGF-I) SDS with both somapacitan and daily GH. Exposure-response modeling of somapacitan exposure versus HV and IGF-I SDS vs. HV indicated an exposure-dependent increase in HV for both these parameters.
Somapacitan was well tolerated at all doses investigated, with no safety or local tolerability issues identified. There were no clinically relevant findings with respect to glucose metabolism, and no detection of anti-drug antibodies in any of the dose groups.
In conclusion, all investigated doses of weekly somapacitan were efficacious and well tolerated throughout the study period. Based on the totality of data on improvements in height-based parameters combined with exposure-response analyses, a somapacitan dose of 0.24 mg/kg/week appears as the most efficacious dose, providing similar efficacy, safety and tolerability to daily GH 0.067 mg/kg/day after 26 weeks of treatment.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 12:51 p.m. - 12:56 p.m.
OR25-2 RBFOX2 Copy Number Variation Disrupts Urethral Development Causing Hypospadias
Authors: O'Neill Marisol , Ruiz Rojano Fredi , Ruthig Victor , White Jeffrey , Lamb Dolores 
Published: November 2022

Abstract
Despite the frequency of hypospadias (1: 125 live male births) often the etiology is not known. The Lamb Laboratory previously determined that RNA Binding Fox-1 Homolog 2 (RBFOX2) copy number variation (CNV) is associated with clinical cases of upper and lower tract genitourinary (GU) anomalies, including hypospadias. RBFOX2 encodes a RNA binding protein that regulates mRNA splicing. The hypothesis was tested that altered RBFOX2 gene dosage impacts the developing penis transcriptome via mRNA splicing, specifically the mesenchymal to epithelial transition critical for penile urethra formation, resulting in hypospadias.Searches, in publically available and local clinical databases, centered on hypospadias occurance with gene CNV: identified the RBFOX2 locus as a gene dosage sensitve region. To identify developmental pathways regulated by RBFOX2 in the GU system, Rbfox2 haploinsufficient and null mouse models were developed, and penises were collected for RNA-seq, in situ hybridization, and micro-CT analysis of urethral development. In situ hybridization together with re-analysis of published scRNA-seq datasets were employed to define the anatomical regions of Rbfox2-specific expression in the developing mouse penis [Amato & Yao, PNAS 118(25): e2103856118, 2021; Armfield & Cohn, Dev Biol 477: 145-154.2021].Publicly available clinical data identified 17 patients (0.068% n=24,896) with pathogenic RBFOX2 CNVs: 4 were noted to have hypospadias. Results from our cohort of non-syndromic GU birth defect patient samples identified 11 patients (2.4% n=450) with RBFOX2 CNVs: 21% of whom have hypospadias. RNA immunoprecipitation agianst RBFOX2 in human kidney cells validated mRNA transcipt targets previously identified in cardiac cells [Verma 2016]. Micro-CT analysis on fetal Rbfox2-haploinsufficient mice validated the modeled clinical phenotype. Combined in situhybridization and scRNA-seq spatial analysis on mouse samples revealed, after penile sex determination (E15.5), Rbfox2 expression becomes restricted to the penile urethral mesenchyme. Differential gene expression and transcript usage analysis on the Rbfox2-loss mouse penis transcriptome identified mis-expression of gene products associated the estrogen signalling pathway.Alterations in RBFOX2 gene dosage clinically correlate with upper and lower tract genitourinary anomalies, specifically hypospadias. Data from human cell lines and mouse models seemingly indicate the phenotype seems is partially the product of an RBFOX2 role in directing the mesenchymal to epithelial transition. Specifically our data support the a direct role of RBFOX2 in balancing the competing male and female pathways at the level of estrogen and androgen signaling pathways. We are currently using immunofluorescence experiments to define the changes in androgen-receptor, estrogen-receptor, and RBFOX2 patterning throughout perinatal penis development.
Presentation: Monday, June 13, 2022 11:15 a.m. - 11:30 a.m.
OR25-6 In Men on Testosterone Therapy, Baseline Testosterone Level of &lt;264 ng/dL is Associated with Greater Improvement in Body Composition, While Level of ≥264 ng/dL Favors Improvement in Metabolic Profile
Authors: Aguirre Lina , Armamento-Villarea Reina , Ballato Elliot , Chen Rui , Colleluori Georgia , Qualls Clifford , Villareal Dennis T , Deepika Fnu 
Published: November 2022

Abstract

Context
Male hypogonadism adversely affects body composition, bone mineral density (BMD), and metabolic health. A previous report showed that pre-treatment testosterone (T) levels of &lt;200 ng/dL is associated with greater improvement in spine BMD with T therapy. However, to date, there is no study investigating whether baseline T levels also influences body composition and metabolic response to T therapy.

Objective
To determine if there are differences in the changes in body composition, metabolic profile, and bone turnover markers, in addition to BMD, in response to T therapy in men with baseline T level of &lt; 264 ng/dL compared to those with levels ≥264ng/dL Methods: Secondary analysis of single-arm, open-label clinical trial (NCT01378299) on pharmacogenetics of response to T therapy conducted between 2011-2016 involving 105 men (40-74 years old), with average morning T &lt; 300 ng/dL, given intramuscular T cypionate 200 mg every 2 weeks for 18 months. Subjects were divided into those with baseline T levels of &lt; 264 ng/dL (N=43) and those with ≥264 ng/dL (N=57). T and estradiol (E2) were measured by liquid chromatography/mass spectrometry; serum bone turnover markers (C-telopeptide [CTX], osteocalcin, sclerostin), adiponectin, and leptin by enzyme-linked immunosorbent assay; glycated hemoglobin (HbA1c) by high-performance liquid chromatography, areal BMD, and body composition by dual-energy x-ray absorptiometry (DXA).

Results
Men with T &lt; 264 ng/dL showed greater increases in total fat-free mass (FFM) at 18 months compared to those with T ≥ 264 ng/dL (4.2±4.1 vs 2.7±3.8%; p=0.047) and unadjusted appendicular FFM at 6 and 18 months (8.7±11.5 vs 4.4±4.3%, 7.3±11.6 vs 2.4±6.8%; p=0.033 and p=0.043, respectively). Men with T ≥ 264 ng/dL showed significant decreases in HbA1c at 12 months (-3.1±9.2 vs 3.2±13.9%; p=0.005), fasting glucose at 18 months (-4.2±31.9 vs 13.0±57.3%; p=0.040), LDL at 6 months (-6.4±27.5 vs 12.8±44.1%; p=0.034), leptin at 18 months (-40.2±35.1 vs -27.6±31.0%; p=0.034) compared to those with T &lt; 264 ng/dL. No significant differences in BMD and bone turnover markers were observed.

Conclusion
T therapy results in improvement in body composition irrespective of baseline T levels but T &lt;264 ng/dL is associated with greater improvement in FFM, whereas T level of ≥264 ng/dL favors improvement in metabolic profile.
Presentation: Monday, June 13, 2022 12:15 p.m. - 12:30 p.m.