bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT226 A Case Of Congenital Hypopituitarasim Has The Genetic And Phenotypic Features Of Orofacial Syndrome
Authors: Aljasser Abdullah Abdulruhman , Alhashem Amal
Published: October 2023

Disclosure: A.A. Aljasser: None. A. Alhashem: None.

Introduction: Reports on pediatric hypopituitarism are very scarce. The prevalence of hypopituitarism in children is not well documented; there are only pockets of case reports and case series in literature. Pediatric hypopituitarism has multifactorial etiologies and can occur in neonates, infants, children and adolescents. The incidence of congenital hypopituitarasim is 1in 4000-1in 10000. Majority of CH cases are sporadic. howfer small number of familial cases have been identified. A molecular basis has frequently been identified. Between 80-90% cases remain unsolved in terms of molecular genetics. It can be syndromic or isolated congenital hypopituitarism depend on stage of embryogenetic fault. Case: Her we describe a case of Syndromic type of congenital hypopituitarism. A term baby weigh;2.62 kg height; 49 cm and HC 32 cm found to be dysmorphic in form of bilateral cleft lip and palate and flat nose and hypertolirism. She was well until age 2-3 day where she became ill and hemodynamically ill needs ICU in the NICU. Her labs shows: from endocrine point of view: very low ACTH and very low Cortisol and low TSH and low Free T4 (table will be in the poster). After replacement therapy and stabilization, her MRI brain shows absent anterior Pituitary and ectopic neurohypophysis and absent pituitary stalk. Later investigations shows normal chromosomes and CGH array. After evaluation and investigation by our genetic colleges, there was an abnormality in the WES study. See results (table) Conclusion: her we present a positive correlation between the phenotypic and genetic results in our case shows an addition of similar cases reported before

Presentation: Saturday, June 17, 2023
SAT594 Thyroid Dysfunction Is Very Common In Patients With Pheochromocytoma And Paraganglioma: A Cross-sectional Study
Authors: Ramirez-Renteria Claudia , Garcia-Saenz Manuel Ramon , Morin-Martinez Nadia Patricia , Albarran-Sanchez Alejandra
Published: October 2023

Disclosure: C. Ramirez-Renteria: Speaker; Self; Ipsen. M. Garcia-Saenz: None. N. Morin-Martinez: None. A. Albarran-Sanchez: None.

Background: Thyroid function abnormalities are reported in 8-9% of the general population, but the prevalence may change according to different ages, populations, iodine intake, etc. Preoperatory evaluations for pheochromocytoma (Pheo) and paragangliomas (PGN) don’t include routine thyroid function tests, but uncontrolled hypo- or hyperthyroidism may result in adverse effects outcomes during surgery. Aim: to describe the frequency of thyroid function abnormalities in patients evaluated for Pheo and PGN in a referral center. Materials and Methods: All the medical files of adult patients evaluated for Pheo or PGN between January 2018 and December 2022 were reviewed. The available clinical, biochemical, imaging, and pathology data confirming the diagnosis were retrieved. We determined the frequency of patients with a previous diagnosis of thyroid disease, type of disease, and date of diagnosis and recorded the data of patients without a diagnosis but that had their thyroid function tested during the perioperative evaluation. Results: 359 patients with Pheo/PGN were evaluated, 72.7% had a neck PGN, 88% were women and the median age at diagnosis was 56.5 years (IQR 45-66), thyroid function tests were performed in 51.3%, and only 22.8% were normal, 20.9% had primary hypothyroidism, 3.9% had hypothyroidism after a procedure, 2.5% had hyperthyroidism, and 1.1% had thyroiditis. The patients with neck PGN were the most likely to present with hypothyroidism (p=0.006) and they were also the most likely to have hypothyroidism during follow-up, Abnormal thyroid images were found in 19.2%. Thyroid dysfunction was detected before the tumor in 21.5%, during the evaluation of the tumor in 25.8%, and after in 52.7%. Hypertensive cardiomyopathy was more common in patients with abnormal thyroid function (OR 1.969, CI 95% 1.052-3.685, p=0.032), as well as cardiomegaly (OR 2.145, CI 95% 1.200-3.835) and hypertension (OR 1.937, CI95% 1.269-2.956). Conclusions: Pheo/PGN are frequently associated with thyroid dysfunction. Heart disease and hypertension are more common in patients with both comorbidities. Thyroid function tests are suggested during perioperative evaluation in patients with a history of thyroid disease, thyroid abnormalities in imaging, poor blood pressure control, or heart disease. Thyroid function may require an additional evaluation in some cases during the follow-up of Pheo/Para.

Presentation: Saturday, June 17, 2023
SAT615 Long-term Effects Of Transsphenoidal Surgery On Headache In Patients With Pituitary Tumors - A Prospective Study
Authors: Hantelius Victor , Ragnarsson Oskar , Johannsson Gudmundur , Thurin Erik , Skoglund Thomas , Hallen Tobias
Published: October 2023

Disclosure: V. Hantelius: None. O. Ragnarsson: None. G. Johannsson: None. E. Thurin: None. T. Skoglund: None. T. Hallen: None.

Objective: Headache is a common symptom in patients with non-functioning pituitary adenomas (NFPA). The aim of this study was to analyze the long-term effect of transsphenoidal surgery (TSS) on disabling headache in patients with NFPA and to investigate possible predictive factors for headache relief following TSS. Methods: This was a prospective study of 101 patients with NFPA who underwent TSS between September 2015 to December 2021. Headache was assessed preoperatively and 12 months postoperatively with The Migraine Disability Assessment (MIDAS) questionnaire. MIDAS measures the impact of headache on the everyday life during the last 3 months and assess the headache frequency and intensity. Results: Of 101 patients, 27 (27%) experienced disabling headache preoperatively. In these 27 patients, the median (interquartile range) total MIDAS total score improved from 60 (19-140) to 10 (0-49) (p=0.004; max score 270), headache frequency decreased from 45 (25-83) to 6 (3-36) days per 90 days (p=0.002), and headache intensity decreased from 5 (4-7) to 4 (2-7) (p=0.016; on a scale 0-10 at 12 months after surgery. Overall, 18 of 27 patients (67%) had a clinically relevant improvement of their headache, 4 (15%) had a clinically relevant deterioration and 5 (19%) had no clinically relevant change at one year after surgery. No clinical factors that predicted postoperative headache relief were identified. Conclusions: Our study supports that transsphenoidal surgery achieves clinically significant and long-lasting improvement of disabling headache in patients with NFPA.

Presentation: Saturday, June 17, 2023
SAT029 Goldfish Phoenixin: Role In Feeding Control And Its Regulation At The Hepatic Level
Authors: Qin Xiangfeng , Ye Cheng , He Mulan , Wan Ko Wendy Kit , Wong Anderson On-Lam
Published: October 2023

Disclosure: X. Qin: None. C. Ye: None. M. He: None. W.K. Ko: None. A.O. Wong: None.

Phoenixin (PNX), a novel peptide first identified by bioinformatics, is known to have pleiotropic functions and its biological actions are mediated via the orphan receptor GPR173. At present, the study of PNX in non-mammalian species, especially in lower vertebrates, is limited and hormone regulation of PNX as well as the post-receptor signalling involved are still unclear. Using goldfish as a model for bony fish, two forms of PNX, PNXa & b, and one form of GPR173 were cloned. Phylogenetic analysis confirmed that goldfish PNXa, PNXb & GPR173 could be clustered in respective clades of target genes in fish species. Alignment of a.a. sequences and 3D protein modelling also revealed that goldfish PNXa & b were highly comparable to PNX reported in other vertebrates. Using RT-PCR, PNXa/b & GPR173 were found to be ubiquitously expressed at tissue level. For functional testing, PNXa & b were synthesized and tested for their effects on feeding control by IP injection in goldfish. In this case, parallel rises in foraging behaviours and food intake were noted after PNX treatment. Similar results were also obtained with ICV injection of PNXa & PNXb, respectively. In goldfish, food intake could elevate plasma levels of glucose, insulin, growth hormone (GH) and IGF-I with parallel rises in transcript expression of GH in the pituitary and PNXa, PNXb, insulin & IGF-I mRNA in the liver. In goldfish hepatocytes, insulin and IGF-I were both effective in up-regulating PNXa & b mRNA expression via activation of IGF-I receptor (IGF1R) but not insulin receptor. Using a pharmacological approach, IGF-I induced PNXa & b gene expression could be blocked by the inhibitors for PI3K, Akt and mTor but not by the inhibitors for MEK1/2, ERK1/2 and P38MAPK. Our results, as a whole, indicate that (i) PNX & GPR173 are co-expressed in goldfish at tissue level & involved in feeding induction, presumably via central action in the brain, (ii) food intake can up-regulate hepatic expression of PNXa & b via insulin signal caused by glucose uptake and parallel activation of the GH/IGF-I axis after feeding, and (iii) hepatic expression of PNXa & b induced by insulin/IGF-I signal is mediated via IGF1R functionally coupled with the PI3K/Akt/ mTOR but not MEK/ERK & P38MAPK pathways.

Presentation: Saturday, June 17, 2023
THU132 Pediatric Diabetes Virtual Visit Quality And Outcome Not Associated With Social Determinants Of Health
Authors: Bastien Laurence , Zuijdwijk Caroline , Goldbloom Ellen , Webster Richard , Sucha Ewa
Published: October 2023

Disclosure: L. Bastien: None. C. Zuijdwijk: None. E. Goldbloom: None. R. Webster: None. E. Sucha: None.

Word count: 350 Title: Pediatric diabetes virtual visit quality and outcome not associated with social determinants of health Authors: Laurence Bastien, Ellen Goldboom, Ewa Sucha, Richard Webster, IvanTerekov, Caroline Zuijdwijk Objectives: Social determinants of health (SDH) impact diabetes short- and long-term outcomes. In response to COVID-19, virtual care has become a solution to ensure ongoing healthcare access. However, socially disadvantaged groups have less access and skills related to technology, leading to potential increases in health disparities. We aimed to determine the association between SDH and physician-perceived virtual visit quality and outcome in pediatric diabetes patients. Methods: Retrospective chart review of patients who attended a scheduled virtual diabetes follow-up visit at a pediatric tertiary care centre from December 1, 2020 to March 31, 2021. During this time, a quality improvement study required physicians to rate the quality (same/better or worse than in-person) and outcome (successfully replaced in-person visit or not) of each virtual visit. These data, along with patient characteristics, were extracted from the electronic health record. Institut national de santé public du Québec Material and Social Deprivation Index and the Ontario Marginalization Index (Ethnic Concentration) were used to determine SDH based on postal code. Statistical analysis tested for an association between deprivation index quintiles and virtual visit quality and outcome. Results: Data were obtained for 447 patients with mean age 12.7±3.8 years; 47.7% female; 93.1% type 1 diabetes; and mean glucose management indicator 7.96±1.41%. During the study period, 17.9% visits were evaluated as worse than in person, 13.1% visits were unsuccessful in replacing an in-person visit, and 20.7% were rated worse or unsuccessful. The odds of having a worse or unsuccessful visit were not different in those with the highest vs. lowest degree of material deprivation (odds ratio [OR] 1.59, 95% confidence interval [CI] 0.53, 4.76), social deprivation (OR 1.36, 95%CI 0.48, 3.83), or ethnic concentration (OR 0.30, 95%CI 0.30, 1.77). Conclusion: In our pediatric diabetes population, virtual visit quality and outcome were not associated with material or social deprivation. These results show promising success in equitable access and delivery of high quality virtual diabetes care for patients regardless of socioeconomic status, which is important in the context of the current pandemic and sustainable widespread integration of virtual care. Further studies are required to assess this association in other populations.

Presentation: Thursday, June 15, 2023
THU135 Maternal Obesogenic Diet Exposure Affects Post-natal And Pathologic Hepatocyte Proliferation In Offspring
Authors: Ramavath Naresh Naik , Hinrichs Holly , Young Monica , Thompson Michael
Published: October 2023

Disclosure: N. Ramavath: None. H. Hinrichs: None. M. Young: None. M. Thompson: None.

Background: Obesity is a complex metabolic syndrome associated with a wide range of abnormalities in liver known as non-alcoholic fatty liver diseases (NAFLD). Evidence supports that maternal obesity/obesogenic diet exposure programs increased NAFLD offspring. The liver responds to lipotoxic hepatocyte injury through hepatocyte proliferation. It is not clear whether maternal obesogenic diet exposure affects the capacity of offspring hepatocytes to proliferate. We hypothesized that early impact of maternal/ obesogenic diet exposure in early life or utero exposure enhances hepatocyte proliferation capacity in offspring. Methods: Female mice were fed chow or high fat-fructose-cholesterol (HFFC) diet for 6 weeks and bred with lean males Liver and serum samples were collected at different postnatal time periods 5, 10, 15, 20, 25, and 30 days to analyze histological and molecular markers for liver proliferation. In addition, a small group of offspring from each group were weaned to the HFFC diet for 7 weeks to analyze progression of NAFLD (non -alcoholic fatty liver diseases). Results: No significant difference between neonatal body weight and liver weight was observed; however, the liver weight/body weight was increased at day 20 in HFFC offspring compared to chow offspring. The number of ki-67 positive hepatocytes peaked in both groups at day 15. An increase in ki-67 positive hepatocytes was observed at 15, 20, and 30 days in HFFC offspring compared to chow offspring. After 7 weeks of HFFC diet feeding, the number of Ki-67 positive hepatocytes was higher in HFFC offspring in comparison with Chow offspring. Conclusion: Maternal obesogenic diet exposure affected post-natal and NAFLD-associated hepatocyte proliferation in offspring with an increase in hepatocyte proliferative capacity. This could have implications for the ability of maternal obesity exposed offspring to respond to hepatic injury and potential for development of hepatic cancer.

Presentation: Thursday, June 15, 2023
THU139 The Triglyceride-glucose Index Combined With Alanine Aminotransferase Is A Superior Predictor Of The Severity Of Nonalcoholic Fatty Liver Disease In Children And Adolescents
Authors: Yoon Jong Seo , Hwang Il Tae
Published: October 2023

Disclosure: J. Yoon: None. I. Hwang: None.

Background: The triglyceride–glucose (TyG) index is significantly associated with the presence of nonalcoholic fatty liver disease (NAFLD). Alanine aminotransferase (ALT) has been commonly used to screen for NAFLD. Ultrasound fatty liver indicator (US-FLI) is proposed as a non-invasive, semi-quantitative method for predicting NAFLD and accurately identifies histological severity. Objects: We hypothesized that the combination of TyG and ALT would increase the sensitivity and specificity in determining the severity of NAFLD. We evaluated the usefulness of a newly proposed TyG-ALT index for differentiating NAFLD severity and compared it with TyG index. Methods: ALT was used as the screening method for NAFLD (>26 IU/L in boys and >22 IU/L in girls), and the US-FLI was performed on children who met these criteria. US-FLI is a new scoring system ranging 2-8 based on the intensity of liver/kidney contrast, posterior attenuation of ultrasound beam, vessel blurring, difficult visualization of gallbladder wall, difficult visualization of the diaphragm and areas of focal sparing. NAFLD is diagnosed by the minimum score ≥2. The TyG index and the TyG–ALT index were calculated as follows: TyG index=ln(fasting TG [mg/dL]×fasting glucose [mg/dL]/2) and TyG–ALT index= ln(fasting triglyceride [mg/dL]×fasting glucose [mg/dL]×ALT [IU/L]/2). Healthy children of normal weight (body mass index 5-85th percentile) without metabolic comorbidities and no steatosis on ultrasound participated as a control group. Results: A total of 130 NAFLD patients (90 boys and 40 girls) included in this study, with mean age of 11.5±2.29 years. The control group consisted of a total of 28 subjects (17 boys and 11 girls) with mean age of 8.39±1.60 years. Multiple linear regression analysis showed that TyG-ALT index were significantly associated with US-FLI (β=0.356, p<0.001) after controlling for sex, age, and BMI. TyG-ALT index was independent risk factor for NAFLD (odds ratio: 4.218, 95% confidence interval: 1.366-13.020) after controlling for sex, age, and BMI. In the receiver operating characteristic analysis, the area under the curve (AUC) of TyG index was 0.681(p<0.001), 0.681(p<0.001), and 0.782(p<0.001), and AUC of TyG-ALT index was 0.797, (p<0.001), 0.797(p<0.001), and 0.813(p<0.001) in US-FLI ≥4, ≥5, and ≥6, respectively. Conclusions: The TyG–ALT index showed consistently superior detection ability than the TyG index at all severity levels of NAFLD. Further studies are needed to determine its potential role as a noninvasive method for NAFLD screening.

Presentation: Thursday, June 15, 2023
THU144 Highs And Lows: Trends In The Incidence Of Pediatric Type 2 Diabetes Mellitus Related To The COVID 19 Pandemic
Authors: Goroff Julia , Hanley Patrick , Gannon Anthony , Grunwald Tal
Published: October 2023

Disclosure: J. Goroff: None. P. Hanley: None. A. Gannon: None. T. Grunwald: None.

The COVID 19 pandemic and associated lock downs resulted in a definitive change in lifestyle that has had multiple associated outcomes for child health. There has been report of dramatic increases in the incidence of Type 2 Diabetes in the months and years immediately following the start of the pandemic. However, whether this demonstrates an overall upward trend in disease burden, or a discrete spike has yet to be described. In this retrospective cohort study patients younger than 21 years old diagnosed with Type 2 Diabetes from January 2017 to December 2022 at a large stand-alone children’s hospital were compared. Chart review was conducted at participants’ first endocrinology office visit or inpatient hospital stay for new onset Type 2 Diabetes. Diagnosis was confirmed with anti-body status for each participant. Statistical significance between incidences was determined using standard descriptive statistics. A total of 213 new onset Type 2 Diabetes cases were included. The average incidence of Type 2 Diabetes from 2017 to 2019 was 19 cases per year; compared to 65.5 cases per year from 2020 to 2021 representing a statistically significant increase in the incidence of Type 2 Diabetes (p<0.001). 2022 saw a fall in incidence to 25 cases per year. This was a significantly lower incidence rate than 2020 to 2021 (p=0.01). There was no difference in incidence rate of Type 2 Diabetes from 2017 to 2019 and 2022 (p=0.39). These results support a significant increase in Type 2 Diabetes diagnoses with the onset of the COVID 19 pandemic. This may be secondary to sedentary lifestyle, increased mental health and psychosocial stressors or increased BMI. However, we demonstrate that two years after the onset of the pandemic there was a return to pre-pandemic incidences of Type 2 Diabetes. Type 2 Diabetes continues to pose a significant health threat to the pediatric population and burden for the medical system as they age. Nevertheless, if this trend continues and is reflected across other institutions, it is reassuring and may offer insight into modifiable risk factors yet to be investigated.

Presentation: Thursday, June 15, 2023
THU192 Prevalence Of Brain Abnormalities In Children With Central Precocious Puberty
Authors: Bastos Aline Almeida , Machado Canton Ana Pinheiro , Macena Larissa Baracho , Pedrosa Ludmila Fernandes , Mendonca Berenice Bilharinho , Brito Vinicius Nahime , Latronico Ana Claudia
Published: October 2023

Disclosure: A.A. Bastos: None. A.P. Machado Canton: None. L.B. Macena: None. L.F. Pedrosa: None. B.B. Mendonca: None. V.N. Brito: None. A. Latronico: None.

Introduction: Brain magnetic resonance imaging (MRI) is the main tool used to investigate the etiology of central precocious puberty (CPP) in children. A systematic review study showed an overall prevalence of 9% of brain lesions in girls with CPP. Aim: To assess the frequency brain lesions in children with CPP. Patients and Methods: In this retrospective study, we recruited data of 163 brain MRI of children with CPP (140 girls,86%; and 23 boys, 14%) followed in a pediatric endocrinology unit from 1990 to 2022. Brain lesions were classified as congenital or acquired, and causative of CPP or incidental. Results: In girls, normal brain MRI was found in 82/140 (59%). Abnormal brain MRI was identified in the remaining 58 girls (41%), with 26 presenting congenital lesions causative of CPP (11 hypothalamic hamartoma, 7 hydrocephalus, 3 optic pathway gliomas, 2 corpus callosum agenesia, 1 pinealoma, 1 tuberous sclerosis, 1 choroid plexus papilloma), and 32 with incidental findings (microadenomas, pituitary stalk deviation, pituitary hyperplasia, rathke cleft cyst, hippocampal alterations). The overall frequency of incidental findings was 20.8%. In addition, the frequency of brain MRI pathological abnormalities in girls older than 6 years without neuro ophthalmological symptoms was 12%(n=7). In boys, normal brain MRI was found in 6/23 (26%). Abnormal brain MRI was identified in the remaining 17 boys, with 14 presenting congenital lesions causative of CPP (9 hypothalamic hamartoma, 4 hydrocephalus, 1 pineal teratoma) and 1 with acquired lesions (1 pilocytic astrocytoma). Incidental findings were detected in only 2 brain MRI (1 pineal cyst and 1 microadenoma). Incidentalomes were more frequent in girls and lesions that can be associated with CPP were more common in boys. Conclusion: The frequency of pathological brain lesions was higher in CPP boys. Hypothalamic hamartoma was the most frequent congenital lesion identified in both sexes. Based on the frequency of pathological brain alterations in girls older than 6 years we recommend to perform brain MRI in all CPP girls.

Presentation: Thursday, June 15, 2023
THU204 Serum Vascular Endothelial Growth Factor-A Levels According To Pubertal State And Body Weight In Children
Authors: Nam Hyo-Kyoung , Kang Eungu , Rhie Young-Jun , Lee Kee-Hyoung
Published: October 2023

Disclosure: H. Nam: Grant Recipient; Self; Supported by a Korea University Grant. E. Kang: None. Y. Rhie: None. K. Lee: None.

Objectives: Childhood obesity may lead to early puberty in girls, however, it remains unclear whether early thelarche in overweight girls is related to central activation of the gonadotropin releasing hormone-gonadotropin axis. Vascular endothelial growth factor-A (VEGF-A) is essential for governing angiogenesis in adipose tissue. We assessed serum VEGF-A level according to pubertal state and weight in girls. Patients and Methods: Total 165 girls were classified as prepuberty (n=40), puberty with peak LH <5.0 IU/L (n=60), and puberty with peak LH ≥5.0 IU/L (n=65). Serum VEGF-A, sex hormone, gonadotropin level and bone age were analyzed according to pubertal state and overweight including obesity. We measured serum level of VEGF-A using ELISA kit. Results: Their chronological age were similar (7.8±1.2, 7.9±0.8, and 8.0±0.9 years, p=0.410 in prepuberty, puberty with peak LH <5.0 IU/L, puberty with peak LH ≥5.0 IU/L, respectively). The mean VEGF-A level was higher in puberty girls (399.3±206.2, 633.5±473.0, 605.7±392.4 pg/mL, P=0.009) and was significantly correlated with Tanner stage (r=0.224, p=0.004), BMI SDS (r=0.191, p=0.014), and weight SDS (r=0.202, p=0.009). When sub-analysis with the degree of obesity, VEGF-A level (802.2±556.0 pg/mL) was highest in overweight puberty girls with peak LH <5 IU/L and was significantly correlated with peak LH (r=0.397, p=0.044) and peak LH/FSH (r=0.409, p=0.038). Conclusions: Our study showed higher VEGF-A levels in overweight puberty girls. Obesity-associated VEGF-A rise may involve in the progression of precocious puberty. Further studies related to pathophysiological mechanism are needed.

Presentation: Thursday, June 15, 2023
THU230 Consumptive Hypothyroidism Secondary To Hemangioma
Authors: Thirunagari Rajeev , Taha Doris R
Published: October 2023

Disclosure: R. Thirunagari: None. D. Taha: None.

Background: Peripheral Hypothyroidism also known as consumptive hypothyroidism has been rarely described in association with vascular tumors such as hemangiomas. It is due to excessive production of type 3 iodothyronine deiodinase (D3) enzyme by the hemangioma leading to increased rate of deiodination of T4 and T3 to inactive forms. Clinical case: We report a 4-year-old girl who was diagnosed with consumptive hypothyroidism at the age of 2 months. She was born at full term via scheduled C-section. Mother has hypothyroidism. She was admitted to NICU for respiratory distress and needed oxygen supplementation. She had a large hemangioma covering most of her back on exam. An ultrasound of the head/neck soft tissue showed an ill-defined lobular heterogeneous mass measuring 3.4 x 1.2 x 4.5 cm, markedly hypervascular with both arterial and venous flow likely consistent with hemangioma. At follow up plastic surgery clinic she had respiratory distress which necessitated readmission to the NICU for further workup and possible initiation of Propranolol. An abdominal ultrasound showed enlargement of the right adrenal and on further dedicated ultrasound a right suprarenal lobulated mass as well as intrathoracic soft tissue mass were found. MRI of the abdomen and thorax, revealed multiple large bilateral paraspinal masses throughout the thoracic and lower cervical spine(largest measuring 3.3 x 7 x 15 cm AP) invading the neural foramen at multiple levels, and causing mass effect on the spinal cord which is displaced to the left. There was mass effect on adjacent vascular structures without significant vascular compromise. Biopsy was consistent with hemangioma. Thyroid Newborn screening result was normal. Thyroid evaluation done at 3 months age revealed, free T4 level of 1.04 ng/dL and TSH level of 11.3 µIU/mL. She was started on Levothyroxine 50 mcg daily. Reverse T3 was elevated at 139.2 ng/dl (reference range 13-107 ng/dl) 2 weeks after treatment initiation. She was initiated on propranolol and was followed up by plastic surgery and oncology. She had a very good response to Propranolol. Follow up MRI at 4 years shows almost complete resolution of the mass. She continues to be on Levothyroxine but is requiring smaller dose. Conclusion: Infantile hemangiomas can express high levels of type 3 iodothyronine deiodinase (D3), an enzyme that catalyzes the inner-ring deiodination of T4 to reverse T3 (rT3) and of T3 to 3,3'-diiiodothyronine (T2), both of which are biologically inactive. The hypothyroidism is a result of degeneration of thyroid hormones at rates that exceed the synthetic capacity of the infant's thyroid gland. Our case illustrates the importance of closely monitoring thyroid function tests in infants with large hemangiomas even if newborn thyroid screening result is normal. Some infants may require higher Levothyroxine doses than usual. Hypothyroidism usually resolves after resolution of the mass.

Presentation: Thursday, June 15, 2023
THU241 Novel PPARG Pathogenic Gene Variant In Newly Diagnosed Familial Partial Lipodystrophy With Childhood Onset
Authors: Chang Eric K , Greve Katherynne , Escobar Luis
Published: October 2023

Disclosure: E.K. Chang: None. K. Greve: None. L. Escobar: None.

Background: Familial partial lipodystrophy (FPL) is characterized by progressive, selective body fat loss and is often associated with various metabolic complications including insulin resistance. In particular, FPL Type 3 due to PPARG (peroxisome proliferator-activated receptor gamma) mutations is a very rare subtype with a prevalence of less than 1 per 1,000,000 people overall. This case report describes a clinical case of a child presenting with genetic testing revealing a novel PPARG pathogenic gene variant. Clinical Case: A 9 year old female with history of adoption and unknown family history presented with severe abdominal pain and intractable emesis in the setting of COVID19 infection. Her hospital CT scan of the abdomen was remarkable for pancreatitis and hepatosplenomegaly. Glucose was elevated at 356 mg/dL with normal liver function tests. HgA1c was 11%. Triglycerides were above 4425 mg/dL. Her overall clinical picture was consistent with new onset diabetes mellitus and acute pancreatitis. Physical exam was notable for xanthomatosis and acanthosis nigricans. She was later noted to have partial subcutaneous fat loss of the upper and lower extremities, with preserved fat in the face, neck, and truncal region. She was initiated on insulin therapy and discharged to home once symptomatically improved from her pancreatitis with downtrending triglycerides to less than 450 mg/dL. Her diabetes autoantibodies (Glutamic acid decarboxylase, Islet Antigen-2, Zinc transporter 8 antibodies) resulted as normal, and she was able to discontinue insulin with HgA1c trending down to 4.8% within 4 months of hospital discharge. She underwent whole exome sequencing per recommendation of her lipid specialist and geneticist, which identified a likely pathogenic, previously undescribed variant of PPARG: c.1050_1054dup, p.(Glu352Alafs*12) and a variant of uncertain significance for MC4R: c.409A>G, p.(Ile137Val). This particular variant of PPARG represents a frameshift mutation, resulting in a premature stop codon, likely leading to a loss of normal PPARG function. PPARG mutations are specific to FPL Type 3, which is reportedly associated with atypical fat distribution, diabetes mellitus, hypertriglyceridemia, hypertension, and pancreatitis, consistent with many features of this case. Conclusion: This is the first case to describe the unique PPARG variant c.1050_1054dup, p.(Glu352Alafs*12) which is associated with FPL Type 3. This child's clinical course and evaluation can help with identifying affected individuals of this very rare type of FPL.

Presentation: Thursday, June 15, 2023
SAT348 Changes In BMI Z-score After Presentation For Early Breast Budding Is Associated With Rapidly Progressive Puberty And Treatment With GnRH Analogues
Authors: Jung Hae Woon , Cho Ja Hyang , Shim Kye Shik
Published: October 2023

Disclosure: H. Jung: None. J. Cho: None. K. Shim: None.

Introduction: Childhood overweight and obesity are associated with earlier pubertal timing, especially in girls. We aimed to identify different body mass index (BMI) trajectories in patients presenting for breast budding between 5 and 7 years of age, and investigated whether the change in BMI z-scores during follow up is associated with rapid progression of puberty and eventual treatment with gonadotropin-releasing hormone (GnRH) analogues. Methods: We retrospectively reviewed girls who presented with breast budding at 5 to 7 years of age, between March 2016 and May 2021 at a single center. Those 206 girls, who had more than 3 follow up BMI measurements to more than 9 years of age were included in the study. The girls were grouped according to whether BMI z-scores increased or decreased/remain unchanged overall during follow-up. The BMI z-score changes over time (age) were also assessed for latent class trajectories. The risk of progression to rapid progressive puberty requiring treatment with GnRH analogues was analyzed according to overall changes in BMI z-scores and the different BMI trajectory groups, with adjustment for birthweight, gestational age, maternal menarche, maternal height, as well as the initial age, height, and bone age at presentation. Results: The mean age at presentation for breast budding was 7.1±0.7 years. A greater proportion of girls whose BMI z-scores increased during follow up, required treatment with GnRH analogues (n=53, 64%) compared to those whose BMI z-scores decreased or remained unchanged (n=54, 44%). Girls with increases in BMI z-scores during follow up (n=83) had increased risk (OR 4.68, 95% CI 1.88-11.63, p = 0.001) for rapid progressive puberty and treatment with GnRH analogues compared to those girls with decreases/no changes (n=123) in BMI z-scores, even after adjustment for covariates. Further analysis showed that increases in BMI z-scores even in those of normal weight status, were associated with increased OR (4.88) for treatment. Through latent class mixed modelling analysis, we identified 2 different trajectories (high and increasing BMI z-scores, n=72; and decreasing BMI z-scores, n=134). Risk for rapid progression of puberty and eventual treatment with GnRH analogues did not differ significantly between the different latent class trajectories. Conclusions: Increases in BMI z-scores during the follow up period after presentation for early breast budding may be associated with increased risk for rapid progression of puberty and treatment with GnRH analogues. Analysis of a larger group of patients may allow for better assessment of latent class BMI z-score trajectories.

Presentation: Saturday, June 17, 2023
THU630 Improving Diagnostic Precision In Primary Ovarian Insufficiency Using Comprehensive Genetic And Autoantibody Testing
Authors: Vogt Elinor , Bratland Eirik , Berland Siren , Lund Agnethe , Sigridur Bjørnsdottir , Husebye Eystein Sverre , Øksnes Marianne
Published: October 2023

Disclosure: E. Vogt: None. E. Bratland: None. S. Berland: None. A. Lund: None. B. Sigridur: None. E.S. Husebye: None.

Context: Primary ovarian insufficiency (POI) affects approximately 1% of women and has life-changing consequences due to infertility and increased risk of complications related to premature estrogen deficiency. Clinical presentations and pathogenic mechanisms of POI are heterogeneous, but the underlying etiology remains unknown in the majority of cases. Improved diagnostic precision will be an important step towards tailoring future treatments in women with POI. Objective: To evaluate phenotypes and distribution of underlying etiologies in women with newly diagnosed POI. Methods: Prospective cross-sectional study of 100 women with newly diagnosed POI of unknown cause. Standard recommended diagnostic investigations were performed, including screening for chromosomal anomalies and premutations in the fragile X mental retardation 1 gene (FMR1). In addition, we used a two-tiered next generation sequencing (NGS)-based strategy, and assays of autoantibodies against steroid cell autoantigens. Results: We identified chromosomal aberrations in 8%, FMR1 premutations in 3%, genetic variants related to POI in 16%, and autoimmune POI in 3%. A homozygous pathogenic variant in the ZSWIM7 gene (NM_001042697.2) was found in two women, corroborating this as a novel cause of monogenic POI. No associations between phenotypes and genotypes were found. Conclusion: By adding an NGS-based POI-related gene panel, clinical whole exome sequencing, and specific immunoprecipitating autoantibody assays to the recommended diagnostic workup, we were able to determine a likely etiology in one third of the patients.

Presentation: Thursday, June 15, 2023
THU633 Atonal BHLH Transcription Factor 8 (ATOH8) Functions In Decidualization
Authors: Thapa Rupak , Bany Brent
Published: October 2023

Disclosure: R. Thapa: None. B. Bany: None.

ATOH8 is a member of the vast basic helix-loop-helix (bHLH) protein family that is widely known to play a role in various physiological and pathological processes. However, the functional significance of ATOH8 expression in the endometrium during implantation and in the first trimester of pregnancy in women is still lacking. In the mid to late secretory phase of the menstrual cycle, elongated fibroblast-like mesenchymal cells in the uterine endometrium begin to trans-differentiate into polygonal epithelioid-like (decidual) cells. During pregnancy, this process continues more broadly and supports successful embryo implantation and early placental development. We employed an established in vitro model using uterine fibroblast (HuF) cells derived from the decidua parietalis of term patients to investigate the function of ATOH8 during in vitro decidualization. All experiments were carried out using cells isolated from at least six independent patients (N=6). We measured the expression of classical decidualization marker genes and the characteristic shape change from small fibroblast-like cells to large epitheloid-like decidual cells to assess decidualization. Treating cells with steroids plus a membrane-permeable cAMP analog (EPC) for 48h caused in vitro decidualization of these cells, while treatment with vehicle alone had no effect. We discovered that ATOH8 expression was dramatically upregulated during this decidualization at both the mRNA and protein levels, with the protein primarily localized to the nucleus. The functional role of ATOH8 during decidualization was investigated using lentivirus-mediated shRNA knockdown or overexpression of ATOH8. When ATOH8 expression was silenced, we discovered that the ability of the cells to undergo decidualization was greatly and significantly diminished. On the other hand, overexpression of ATOH8 enhanced some aspects of decidualization. The addition of recombinant BMP2 alone had little effect on ATOH8 expression. However, in the presence of EPC it significantly enhanced ATOH8 expression. This effect of BMP2 on ATOH8 expression was inhibited by preincubating the cells with 500 nM DMH-1 (an ALK2/3 inhibitor) for one hr prior to inducing decidualization. Steroids alone did not affect ATOH8 or BMP2 expression. However, the addition of cAMP alone represented the major effect of EPC on ATOH8 expression while having a slight impact on BMP2 expression. A robust increase in BMP2 expression required the presence of both steroids and cAMP together. Our results indicate that ATOH8 plays a crucial role in human endometrial stromal cell decidualization. Further, our results suggest that ALK2/3 receptors are most likely involved in mediating the effect of BMP2 on increasing ATOH8 expression.

Keywords: ATOH8, Decidualization, Embryo Implantation

Presentation: Thursday, June 15, 2023
THU638 Comparison Of Body Composition Changes In Response To A Hypocaloric Dietary Intervention In Women With And Without Polycystic Ovary Syndrome
Authors: Zhang Jie , Carter Faith , Jarrett Brittany Y , Drewes Bailey , Brink Heidi Vanden , Lujan Marla Elaine
Published: October 2023

Disclosure: J. Zhang: None. F. Carter: None. B.Y. Jarrett: None. B. Drewes: None. H. Vanden Brink: None. M.E. Lujan: None.

Lifestyle intervention aimed at weight loss is recommended for women with polycystic ovary syndrome (PCOS) and concurrent obesity to improve reproductive, metabolic, and psychological health and well-being. However, we and others have shown that women with PCOS have perceptions of reduced success of weight loss interventions, and futility related to adoption of healthy lifestyle practices which can affect motivation and adherence to lifestyle change. Empirical data to support reduced success of weight loss interventions in PCOS is lacking. The objective of this study was to contrast the effectiveness of a hypocaloric dietary intervention on weight loss and body composition in women with and without PCOS. Thirty-eight reproductive age females (body mass index ≥25) with (N=22) or without (N=16) PCOS partook in a 4-week baseline assessment (pre-intervention), followed by a 12-week (3MO, N=17) or 24-week (6MO, N=21) commercial hypocaloric dietary intervention. Serial weight assessments were conducted at least twice per week and dual x-ray absorptiometry (DEXA) measured body composition pre- and post-intervention. Random coefficient models were used to compare changes in weight during the intervention. Differences in body composition pre- and post-intervention and across groups were compared using linear regression and analysis of variance. Participants lost an average of 7.8±3.2% and 9.0±5.0% total body weight with the 3MO and 6MO interventions, respectively. Waist circumference (107.1 ± 14.0 vs. 96.9 ± 12.6cm, P<0.001), total lean mass (55.2 ± 7.2 vs. 51.8 ± 6.4cm, P<0.05), total fat mass (43.2 ± 9.7 vs. 38.8 ± 8.9cm, P<0.01) and trunk lean (27.1 ± 3.7 vs. 25.5 ± 3.6kg, P<0.05) and fat mass ((21.7 ± 5.7 vs. 19.6 ± 5.6kg, P<0.05) were decreased post-3MO intervention in women with PCOS, whereas only total (46.3 ± 8.2 vs. 39.4 ± 9.7kg, P<0.05) and trunk fat mass (23.3 ± 5.2 vs. 20.1 ± 6.0kg, P<0.05) were decreased post-6MO intervention in women with PCOS compared to their pre-intervention values. Percent changes in the aforementioned parameters were similar across groups with either the 3MO or 6MO intervention (P>0.05), as was the rate of weight loss (P>0.05). Women with PCOS demonstrated clinically meaningful changes in body composition in response to hypocaloric dietary interventions aimed at weight loss. Similar changes in body compositions and rate of weight loss between women with and without PCOS support comparable effectiveness of short-term hypocaloric dietary interventions in women with and without PCOS. Knowledge of comparable effectiveness to lifestyle change may aid in adoption and adherence to lifestyle interventions in women with PCOS.

Presentation: Thursday, June 15, 2023
THU643 Hyperandrogenism Caused By A Steroid Cell Tumor Of The Ovary In A Postmenopausal Woman
Authors: Mon Myint Myat Su , Pinero-Pilona Antonio
Published: October 2023

Disclosure: M.S. Myint: None. A. Pinero-Pilona: None.

Introduction Steroid cell tumor-not otherwise specified (SCT-NOS) is a subtype of steroid cell tumors which, in turn, is a subtype of sex cord-stroma tumors of the ovary. SCTs are exceedingly rare, account for less than 0.1% of all ovarian tumors, can secrete androstenedione, α-hydroxyprogesterone, and testosterone, and cause hyperandrogenism. We present a case of SCT-NOS, which was revealed postoperatively and was associated with breast cancer. Clinical Case A 74-year-old postmenopausal woman presented approximately a year after the onset of hirsutism, frontal alopecia and an elevated serum total testosterone (TTST) 341 ng/dl (reference range 3 to 41 ng/dL) and free testosterone (FRTST) 10.5 pg/mL (reference range 0.0 to 4.2 pg/mL). She has no clitoromegaly, acne, striae, or changes in voice and no history of infertility or PCOS. Physical examination was significant for cushingoid appearance, frontal alopecia, and hirsutism on the face. Her estradiol level was 213 pg/mL (reference range 0 to 30 pg/mL), FSH and LH levels were in the postmenopausal range, 17-hydroxyprogesterone, DHEA-sulfate, androstenedione, and morning cortisol were normal. Pelvic ultrasonography and CT of the abdomen and pelvis did not reveal an adrenal or ovarian abnormality. We suspected an ovarian source and thus recommended bilateral oophorectomy due to the markedly elevated testosterone level and postmenopausal status. We also started spironolactone. Before setting up for surgery, she was diagnosed with invasive lobular left breast cancer and underwent surgery and radiotherapy. Then, she had bilateral salpingo-oophorectomy. After surgery, TTST dropped to 4 ng/dL and FRTST to 2 pg/mL. Her hyperandrogenic symptoms significantly subsided. Pathology revealed a 1.5 cm red-brown nodule within the left ovary. The nodule contains polygonal cells with vacuolated cytoplasm arranged in nests, cords, and sheets. Cells were positive in calretinin and inhibin and negative in Reinke crystal. A steroid cell tumor, NOS was confirmed. Pathologic features associated with aggressive clinical behavior were not present. Conclusion The incidence of SCT-NOS is highest in women of childbearing age but rare in postmenopausal women. There were only a few case reports of SCT-NOS, most of which are relatively larger and revealed on imaging. In our case, the imaging did not localize the tumor. Sex cord-stromal tumors are often not visualized on imaging. Failure to identify a tumor on imaging does not rule out the presence of a tumor. One should always rule out androgen-secreting tumors in cases of significantly high testosterone. When imaging fails to reveal a tumor, bilateral oophorectomy should be considered in postmenopausal women and an ovarian and adrenal venous sampling in women of childbearing age. It is worth doing so because hyperandrogenism is associated with an increased risk of endometrial and breast cancer.

Presentation: Thursday, June 15, 2023
THU645 Comparison Of LC-MS/MS Testosterone Assays Towards Standardization Of Lower Testosterone Ranges
Authors: Cree Melanie G , Ottey Sasha , Sherif Katherine Devine , Sugahara Otoe , Pokuah Fidelia , Lyle Alicia N , Hubert Vesper
Published: October 2023

Disclosure: M.G. Cree: Consulting Fee; Self; Pollie, Inc. Research Investigator; Self; Eli-Lilly, Amino Co. S. Ottey: None. K.D. Sherif: None. O. Sugahara: None. F. Pokuah: None. A.N. Lyle: None. V. Hubert: None.

Objective: Polycystic ovary syndrome (PCOS) is a common disorder in women. The diagnosis of PCOS often includes elevated concentrations of serum testosterone. Previous work has harmonized the higher range of the testosterone assay and normative cut-offs for low and high testosterone concentrations for the male gender. However, similar work is needed to better align existing Liquid Chromatography Tandem Mass Spectroscopy (LC-MS/MS) methods in the lower range of testosterone and determine upper limits of normal for females. Methods: This is a secondary analysis of a pooled cohort of 60 obese adolescents with and without PCOS, enrolled in 1 of three studies (NCT02157974; NCT03041129; NCT03717935) at the University of Colorado, Anschutz. None of the participants were taking hormonal medication to treat PCOS. Frozen plasma samples collected between 6-7 AM were analyzed by Esoterix hormone branch of LabCorp (Agoura Hills, CA) and by the Centers for Disease Control (CDC) Clinical Standardization Programs with LC-MS/MS. Samples were selected from the available participants to encompass the full range of testosterone concentrations available within the cohort. Results: Within the entire cohort (N=60, Age = 15.8, SD: ± 1.7 years, BMI 35.4, SD: ± 5.5 kg/m2), the means between the assays were statistically, but not clinically different (CDC 48.4 SD: ±24.4 ng/dL vs OL 45.4 SD: ±22.1, p=0.013).Deming regression indicated that the assays were not different with an intercept of 2.05 (-3.69 to 7.79, 95% confidence interval) and slope of 0.895 (0.753 to 1.04, 95% confidence interval). The two assays were highly correlated via linear regression (R2=0.859, p<0.001) and with a Bland-Altman comparison, the CDC assay only had a slight positive bias of 3.04, SD: ± 9.18 ng/dL relative to Esoterix. When divided by PCOS status (PCOS N=52, Hirsutism score 6.5±5.9, Control N=8, Hirsutism score 2.1±4.5), the CDC assay ROC demonstrated discrimination of PCOS status with an AUC of 0.903 (0.800-1.00), p<0.001 and the Youden index was <27.1 ng/dL with a sensitivity of 87.5% and a specificity of 86.5%. However, when the sensitivity was at 100%, the specificity was 57.7% and the cut-off <43.0 ng/dL. Conclusions: The Esoterix, a major commercial lab, assay is very similar to that of CDC LC-MS/MS, and able to discriminate PCOS status at 43.0 ng/dL. Future work is needed to 1) align more clinical assays to the CDC standard and 2) define a common cut-off to describe hyperandrogenism in females across the weight and age spectrum.

Presentation: Thursday, June 15, 2023