bluuebunny/crossref_metadata_2025 huggingface dataset:
PMON54 Exosomes Isolated from Conditioned Media of Immortalized Kisspeptin Neurons Exert Diverse Effects on Central and Peripheral in Vitro Cell Models.
Authors: Chappell Patrick , Ewton Jessica , James Teagan , Karthikeyan Varsha , Starman Alia
Published: November 2022

Previous work in our laboratory explored the proteomic contents of exosome-like extracellular vesicles (EVs) released into the media in vitro from immortalized Kisspeptin (KP) neuronal cell lines KTaV-3 (derived from female mouse AVPV) and KTaR-1 (derived from KNDy neurons in the ARC). EVs were isolated from conditioned media via ultracentrifugation or filtration kit and validated using a NanoCyte, and LCMS-MS analysis revealed that relative abundance of exosomal cargo varied dependent upon estrogen (E2) exposure in vitro, with ∼150-170 proteins up-regulated and ∼200-220 proteins downregulated by E2 in EVs of KTaR-1 and KTaV-3 KP neurons.

Since E2-regulated KP exosomal proteins included candidates implicated in the regulation of synaptic plasticity and signaling (i.e. annexins, semaphorins, connexins), we investigated the effects of exposure to purified EVs on gene expression in immortalized GnRH neurons (GT1-7 cells). Notably, EVs from 24h E2-treated KTaV-3 neurons induced increased expression of kiss1r in GT1-7 cells, in contrast to KTaV-3 neurons not exposed to E2, suggesting that AVPV KP neurons may signal an increase in KP receptivity in GnRH neurons in vivo via non-neuronal communication. Additionally, increases in expression of the synaptic scaffolding protein PSD-95 (dlg4) were seen in GT1-7 cells treated with E2-treated KTaV-3 EVs, suggesting AVPV KP neurons may use extracellular vesicles to modulate GnRH neuronal synaptic plasticity over the estrous cycle. While EVs isolated from KTaR-1 conditioned media did not alter GT1-7 kiss1r or dlg4 levels, treatment (24h) resulted in induction of selective gap junction hemichannel expression in GT1-7 cells. KTaR-1 (but not KTaV-3) EVs increased expression of Cx26 (gjb2) irrespective of E2 exposure, while induction of Cx43 (gja1) expression in GT1-7 cells was only observed following treatment with E2-deprived KTaR-1 EVs.

Further, we found that KTaR-1 media and EVs can affect osteoblast function in vitro, including increases in sp7 and runx2 expression, E2-dependent modulation of wnt10b, and formation of bone matrix (evaluated by Alizarin Red assay) in cultured osteoblast lines, supporting recent studies implicating ARC KP neurons in bone remodeling. Lastly, we found significant levels of immunomodulatory pentraxins (PTX3) in KP EVs, with abundance dependent upon prior E2 exposure in KTaR-1 KP neurons, as revealed by ELISA. Together, results from these studies suggest that EVs may represent additional intercellular communication pathways utilized by Kiss-1 neurons to elicit changes in nearby neuronal populations and potentially even in the periphery, affecting inflammation and bone remodeling. Future studies will address mechanisms involved in the E2 regulation of exosomal cargo in these critical neuronal populations.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON81 A Case of Hypophysitis Associated With SARS-CoV2 Vaccination
Authors: Ankireddypalli Anvitha , Chow Lisa S , Radulescu Angela , Kawakami Yasuhiko , Araki Takako
Published: November 2022

Objective

Although SARS-CoV2 vaccines have been developed with multiple novel technologies and rapidly disseminated worldwide, the full profile of adverse effects has not been known. Recently, there are sporadic but increasing reports of endocrinopathies in relation to SARS-CoV2 vaccination. Here, we report a rare case of hypophysitis with acute onset of diabetes insipidus after SARS-CoV2 vaccination.

Case Report

A 48-year-old female who had been in her usual state of health until she received the first SARS-CoV2 vaccine. Two days after the vaccination, she started to have flu-like symptoms including severe headache and myalgia as well as persistent headache, polydipsia and polyuria. On presentation, her vital signs were stable, with her pulse being 81 bpm, BP: 122/84 mm Hg, temperature: 98.6F. Her physical examination was unremarkable. Laboratory evaluation revealed normal values of the basic metabolic panel including sodium level of 142 mmol/L and normal complete blood count. Due to her prolonged and worsening headache, she underwent a brain MRI which revealed a 4 mm round shape of thickening pituitary stalk and partial empty sella. The polydipsia, polyuria, and the thickening of the pituitary stalk led to further pituitary work-up. She underwent the overnight water deprivation test followed by the desmopressin challenge test. Her overnight water deprivation test revealed hypernatremia (Na 147 mmol/L), elevated serum osmolarity (309 mmol/kg), and low urinary osmolarity (83 mmol/kg) which were compatible with diabetes insipidus. Her IGF1 level revealed low normal range (66 ng/mL). Her 250 mcg cosyntropin test showed appropriate response without adrenal insufficiency. DDAVP was started. 3 months after the vaccination, her symptoms have partially improved, and on repeating the MRI brain she has persistent pituitary stalk thickening.

Discussion

We report a rare case of diabetes insipidus from hypophysitis associated with SARS-CoV2 vaccine. Mechanisms of SARS-CoV2 vaccination-associated endocrinopathy is unknown. From our literature search, we found increasing numbers of the cases of endocrinopathy reported after the SARS- CoV2 vaccination. The thyroid seems the most frequently reported endocrine organ (83%), followed by the pituitary (11%) and adrenal (6%). Average onset is 1-5 days after the vaccinations and reported with all types of SARS-CoV2 vaccines. More mid-age (average age 46) female (78%) cases have been reported. Although associations are not confirmed, endocrinopathies may be underestimated in the post vaccinated population. Further studies are warranted to better understand SARS-CoV2 vaccinations and potential associations of endocrinopathy.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP037 Effects of DHCR24 Inhibitor on Excessive Adrenal Steroidogenesis in db/db mouse
Authors: Kamigaki Risa , Kameda Hiraku , Shibayama Yui , Nomoto Hiroshi , Cho Kyu Yong , Nakamura Akinobu , Jin Shigeki , Matoba Kotaro , Miyoshi Hideaki , Atsumi Tatsuya
Published: November 2022

Background and purpose

Patients with type 2 diabetes have an elevated basal level of cortisol, which has been suggested to be involved in the exacerbation of hyperglycemia and the progression of organ complications. Furthermore, it has been reported that adrenal steroidogenesis increases in db/db mice, an animal model of type 2 diabetes. However, the mechanism of the increased adrenal steroidogenesis in type 2 diabetes is unclear. In this study, we aimed to elucidate the mechanism of increased adrenal steroidogenesis in db/db mice and examine whether it is a therapeutic target.

Experiment 1: Methods

Gene expression in adrenal glands of 10-week-old male db/db mice and db/+ mice was examined by DNA microarray and real-time PCR.

Results

In the adrenal glands of db/db mice, expression of Acc and Scd1, which are involved in fatty acid synthesis, was decreased by 3.7-fold and 2.6-fold, respectively, compared with db/+ mice. However, expression of Cpt1α, which is involved in acetyl-CoA production by lipolysis, was increased by 1.8-fold and expression of Dhcr24, the final enzyme of the de novo cholesterol synthesis system, was increased by 2.5-fold. Thus, fatty acid degradation and endogenous cholesterol synthesis had increased in the adrenal glands of db/db mice.

Experiment 2: Methods

8-week-old male db/db mice were divided into two groups, PBS administration (P) and 10mg/kg DHCR24 inhibitor (U18666A) administration (U) groups. PBS or U18666A was injected intraperitoneally into mice once a week. 4 weeks later, the mice were euthanized, blood corticosterone was measured by LC-MS/MS, and gene expression in adrenal glands was measured by real-time PCR.

Results

The blood corticosterone level was 196.6±12.7ng/mL in the U group and 245.8±15.4ng/mL in the P group, which was significantly lower in the U group (unpaired t-test, p<0. 05). mRNA expression of Acc and Scd1 was increased by 3.1-fold and 1.3-fold, respectively, in the U group compared with the P group.

Conclusion

These results suggest that increased endogenous cholesterol synthesis may be a cause of steroid overproduction in the adrenal glands of db/db mice and a DHCR24 inhibitor suppresses the increase in steroid hormone synthesis. This study indicates that changes in adrenal fatty acid metabolism and endogenous cholesterol synthesis might play a major role in understanding the mechanism of increased adrenal steroidogenesis and finding a new therapeutic target to prevent organ complications of type 2 diabetes.

Presentation: No date and time listed
RF13 | PMON48 A novel missense variant in the gene encoding Fatty Acid Synthase (FASN) associated with a unique multi-system disorder including hypopituitarism and hypoparathyroidism
Authors: Dattani Mehul , Eaton Simon , Gregory Louise , Krywawych Steven
Published: November 2022

A male patient presented with a unique complex phenotype including panhypopituitarism, short stature with failure to respond to GH [IGF-1 generation test: no response to 2.8 mg/m2/day GH], sensorineural deafness, hypoparathyroidism, retinal dystrophy, and intellectual disability. He was 127cm tall at the age of 21 and was completely prepubertal (LH 0.8 U/L, FSH 2.6 U/L, Testosterone <0.69 nmol/L) with a bone age of 12 years. A trial of recombinant IGF-1 failed to improve growth. He died at the age of 26 years following a collapse of unknown etiology.

Exome sequencing and subsequent variant calling on this patient revealed a novel heterozygous de novo missense variant (c.6395C>T, p.A2132V) at a highly conserved residue in FASN encoding Fatty Acid Synthase. The variant was not present in any control database, including the GnomAD browser. Human embryonic brain expression analysis using in situ hybridisation, revealed FASN mRNA transcript staining in the diencephalon and hypothalamus at Carnegie stages (CS) 16, 19, 20 and 23, and in Rathke's pouch (primordium of the anterior pituitary) at CS16 only.

Fatty acid synthase (FASN), a crucial multienzyme with seven different catalytic activities, converts acetyl-CoA and malonyl-CoA into long-chain saturated fatty acids such as palmitate, in the presence of NADPH. Murine null mutant Fasn-/- embryos die before implantation and Fasn+/- embryos at various stages in the early postnatal period. Fasn is expressed in multiple tissues including the brain, parathyroids, liver and adrenal.

Biochemical investigation of the patient revealed high triglyceride concentrations (3.81-6.49 mmol/L; NR 0.38-2) at all time points during an 18 hour fast. He mobilised free fatty acids but did not generate an increase in 3-hydroxybutyrate, suggesting a defect in fatty acid oxidation or ketone body synthesis. He maintained normoglycaemia with normal hormone responses to fasting, except for an undetectable IGF-1 (<25 ng/ml) and IGFBP-3 (1.17 mg/L).

We measured de novo fatty acid synthesis in cultured patient and control fibroblast cells with 13C-Glucose, with and without the C75 fatty acid synthase inhibitor. Cell pellets were collected at three time-points, and 13C-fatty acids derived from 13C-glucose were analysed by mass spectrometry. Preliminary data showed that more C13-glucose was incorporated into de novo synthesised palmitic acid in control cells, suggesting reduced fatty acid synthesis in the patient.

Our data suggest that FASN p.A2132V is pathogenic and contributed significantly to the complex patient phenotype, consistent with recent studies suggesting that neural stem/progenitor cells (NSPCs) in the rodent brain are governed by Fasn-dependent de novo lipogenesis for proliferation.

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.
LBMON185 Isthmin-1 As A Modulator Of Metabolic Health
Authors: Zhao Meng , Danneskiold-Samsøe Niels Banhos , Voilquin Laetitia , Jiang Zewen , Svensson Katrin J
Published: November 2022

Insulin resistance involves impaired glucose clearance capacity by the skeletal muscle and adipose tissue and is also associated with muscle loss. However, the underlying mechanistic link between diabetes and muscle loss is not well understood. Here, we identify Isthmin-1 (Ism1) as a secreted signaling protein with multi-organ actions. By performing untargeted phosphoproteomics revealing the global signaling actions of Ism1, we identify that Ism1 stimulates adipose and skeletal muscle glucose uptake and an increase in skeletal muscle protein synthesis. Mechanistically, Ism1 activates pAKT-mTOR-S6 signaling independently of insulin or the insulin receptor. In mice, Ism1 ablation results in impaired glucose clearance capacity and reduced insulin sensitivity, demonstrating an endogenous function for Ism1 in systemic glucose regulation. Notably, the administration of recombinant Ism1 is sufficient to ameliorate diabetes in a diet-induced obese mouse model. Ism1 ablation also results in smaller skeletal muscle fiber size and lower muscle protein content, demonstrating that Ism1 is required for muscle proteostasis. These findings reveal a new secreted protein hormone that activates anabolic pathways in muscle and adipose tissue.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON192 Impact of Gender-Affirming Care Learning Module on Medical Students’ Knowledge and Self-Efficacy
Authors: Mokatrin M×Raneem , Joshi Weena , Patterson Mary , Marinkovic Maja
Published: November 2022

While evidence supports the need for increased provider education on gender-affirming care, few medical curricula address the healthcare needs of transgender and non-binary (TGNB) patients. To bridge this knowledge gap, we developed an online learning module to educate medical students (MS) in the care of this underserved population. The module included topics such as TGNB health disparities, gender dysphoria, and gender-affirming therapy.

We hypothesized that learners would possess greater knowledge and self-efficacy following completion of the module.

A cohort of 272 first- (MS1) and second-year medical students (MS2) from a single institution received protected time during their academic training to complete the mandatory online module (total duration: 60 minutes). Of those, 90 learners consented to participate in our IRB approved study and completed pre- and post-module surveys. Surveys assessed the impact of the educational module on self-reported knowledge and self-efficacy pertaining to learning objectives. Most participants self-identified as cisgender (97%), while 40% of those who chose to answer reported being part of LGBTQIA+ community. Baseline knowledge scores ranged from 7 (not knowledgeable) to 35 (knowledgeable). Following completion of the module, the median knowledge score significantly increased by 9 points (23 to 32; p<0.0001). At baseline, self-efficacy scores ranged from 9 (not confident) to 45 (confident) and similarly increased by 9 points (31 to 40; p<0.0001). Feedback from participants indicated that the module was well-received.

Our data showed that an online educational module on gender-affirming care was successful in increasing knowledge and self-efficacy in surveyed MS1 and MS2 at our institution. Education of healthcare providers is a key step towards improving care for TGNB patients. Therefore, more institutions should adopt formal curricula for MS on gender-affirming care to mitigate health disparities in this vulnerable population. Similar modules could be adapted to educate already practicing clinicians and support staff to ensure a more gender-inclusive healthcare environment.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP053 Serum Free Cortisol and Free Cortisol-to-Cortisone Ratio Increase After 10 Days of Overfeeding and After 10 Days of Fasting
Authors: Colling Caitlin , Bredella Miriam , Fazeli Pouneh , Pachón-Peña Gisela , Singh Ravinder , Klibanski Anne , Rosen Clifford , Miller Karen
Published: November 2022

Introduction

Chronic caloric deprivation and obesity are complicated by elevations of serum total cortisol levels. The effects of acute overfeeding and fasting on circulating free cortisol levels and interconversion of cortisone to free cortisol are unknown. We hypothesized that serum free cortisol and free cortisol-to-cortisone ratio (a surrogate measure of 11β-hydroxysteroid dehydrogenase [11β-HSD] activity) would increase after both overfeeding and fasting.

Methods

We prospectively studied 22 healthy volunteers who underwent a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-week wash-out period, in a Clinical Research Center. Fasting morning free and total cortisol and free cortisone levels (liquid chromatography-tandem mass spectrometry, Mayo Labs) and percent body fat (dual-energy x-ray absorptiometry) were performed at baseline before and after 10 days of each intervention.

Results

High-calorie feeding increased total and free cortisol and the free cortisol-to-free cortisone ratio (p<0. 001 to p=0. 046). Total and free cortisol, the free cortisol-to-free cortisone ratio, and the free cortisol-to-total cortisol ratio increased after fasting (p=0. 001 to 0. 021). During the high-calorie protocol, there was no significant interaction between sex and time for any of the cortisol parameters. During the fasting visit, the changes in free cortisol and free-to-total cortisol ratio were modified by sex (p=0. 014 and 0. 004, respectively for interaction term), with a trend toward a significant interaction between sex and time in the change in free cortisol-to-free cortisone ratio (p=0. 054). In subset analyses stratified by sex examining the effect of fasting on free cortisol and the free-to-total cortisol ratio, there were significant increases in men (p<0. 001) but not women (p=0.898 and 1. 000, respectively). Baseline percent body fat, measured at the start of the fasting visit, was inversely associated with change in free cortisol (ρ=-0.52, p=0. 013), free cortisol-to-total cortisol ratio (ρ=-0.49, p=0. 021) and free cortisol-to-cortisone ratio (ρ=-0.47, p=0. 029) during fasting.

Conclusion

Overfeeding and fasting both increase circulating free cortisol levels and appear to alter 11β-HSD activity. The effect of fasting, but not overfeeding, on free cortisol levels is modified by sex. Greater percent fat mass may be relatively protective against starvation-induced hypercortisolemia in women. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility.

Presentation: No date and time listed
RF02 | PMON323 Pituitary stalk interruption syndrome, polydactyly, polymicrogyria and a ZRSR2 variant
Authors: Jacobs An , Hannes Laurens , Rochtus Anne , Casteels Kristina , Atzori Marta , Attanasio Catia , Pelgrims Elise , Breckpot Jeroen , de Zegher Francis
Published: November 2022

Background

Pituitary stalk interruption syndrome (PSIS) may associate with brain midline defects and also with polydactyly (GLI2 mutations) but rarely with brain cortex anomalies.

Clinical Case

We report a boy referred at age 19 months because of growth failure. Bilateral postaxial polydactyly, syndactyly of the toes, and a nodule on the tongue were noted at term birth. The neonatal course was complicated by marked but transient hypoglycemia. During infancy, the acquisition of gross motor skills was slightly delayed. Upon referral, body length was 4.1 SD below the level of mid-parental height. Extremely low concentrations of circulating IGF-I (8 mcg/L) and IGFBP-3 (861 mcg/L) were suggestive of growth hormone (GH) deficiency which was corroborated by glucagon test (peak GH 3.3 mcg/L, peak cortisol 14.6 mcg/dL) in an euthyroid and normoprolactinemic state, and in the absence of polydipsia or polyuria. Brain MRI disclosed not only a PSIS triad (with a virtual absence of the pituitary stalk and the anterior pituitary, and with an ectopic position of the posterior pituitary) but also abnormal sulcation and polymicrogyria (pointing to abnormal lamination in the cortex) on both sides in the posterior cingulum. Familial history is positive for holoprosencephaly and polydactyly in two male relatives, who died neonatally.

Whole exome sequencing showed a rare maternally inherited variant in ZRSR2 on the X chromosome (c. 1207_1208delAG (p.Arg403Glyfs*24)) (OMIM 300028). ZRSR2 isdepleted from loss-of-function variants in the reference population, and has not been associated with congenital anomalies or with pituitary dysfunction. This ZRSR2 variant escapes nonsense mediated decay and segregates in this family according to an X-linked recessive pattern. X-inactivation studies and gene expression studies are ongoing to correlate the ZRSR2 variant to the patient's phenotype.

Conclusion

This case describes a toddler with polydactyly and short stature, based on GH deficiency due to PSIS, in combination with polymicrogyria. Studies are ongoing to link the patient's phenotype to a rare variant in ZRSR2.

Presentation: Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Saturday, June 11, 2022 1:30 p.m. - 1:35 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP054 The Impact of SGLT2-inhibitors on Renin-Aldosterone axis and Adrenal Incidentaloma's work up: Case study and literature review
Authors: Alkhaddo Jamil , Tipu Ali
Published: November 2022

Introduction

SGLT2 inhibitors (SGLT2i) are being increasingly used in patients with Type 2 DM given their glycemic effects along with cardio-protective and reno-protective effects. SGLT2i exert these effects through various mechanisms, mainly through the RAAS (Renin-Angiotensin-Aldosterone System) with diuresis, leading to transient elevation of renin levels with minimal effect on aldosterone levels. We present a case where elevated aldosterone levels improved stoppage of SGLT2i. Case 52 year male with history of GERD and Sleep apnea who was referred for evaluation of right adrenal incidentaloma of 2 cm found on CT abdomen in 12/2019 as part of renal stone work up. Initial work up in 3/2020 showed elevated aldosterone of 87.1, renin of 2.3 with ratio of 37.9. Repeat work up in 7/2020 showed elevated aldosterone of 66 with renin levels of 2. High urine aldosterone of 64.7 was noted but urine sodium of 171 mg only. Urine metanephrine and normetanephrine levels were in the reference range. He was started on spironolactone considering hyperaldosteronism and mild hypertension, but developed hyperglycemia and type 2 diabetes mellitus which was initially treated with insulin and later switched to Jardiance. Follow up CT abdomen with adrenal protocol in 8/2020 showed stable right adrenal nodule, consistent with adrenal adenoma. His repeat aldosterone levels remained elevated at 70 with renin levels of 2.8 in 6/2021 after holding spironolactone for 2 weeks. Patient was advised to stop Jardiance as well as continue holding Spironolactone in 9/2021 and repeated labs showed an improvement in aldosterone levels of 43 in 10/2021 and 21 in 12/2021 with renin levels of 2.79 and 2.95 respectively.

Discussion

SGLT2 inhibitors are known to reduce heart failure hospitalization in the clinical trials. Use of SGLT2i leads to early diuresis with natriuresis and systemic RAAS activation rather than intra-renal RAAS activation. Effects are mainly mediated through transient natriuresis with volume depletion in short term, leading to RAAS activation with transient renin elevation but no significant effects on aldosterone levels, possibly due to other controlling factors like ACTH and K levels along with circadian rhythm. Our case presents unique scenario where elevated aldosterone with normal (non-suppressed) renin levels were noted in the context of adrenal incidentaloma work up and Jardiance use. Even though the improvement of aldosterone levels might be related to multiple factors but with increasing use of SGLT2i, much attention should be paid to the impact of these agents on renin-aldosterone axis and possible need of holding these agents if elevated renin-aldosterone levels are noted.

Presentation: No date and time listed
RF26 | PSAT109 The Prevalence of Abnormalities in Cranial MRIs in Children with Short Stature Prior to Growth Hormone Therapy
Authors: Epstein Benjamin , McGuirk Liam , Krasnow Matthew , Manely Sarah , Sayegh Emily , Patale Tara , Schefflein Javin , Mehta Hasit , Mehta Shilpa , Tenner Michael , Noto Richard
Published: November 2022

Background

MRIs of the brain in patients with short stature have shown a number of abnormalities. Some of these radiological findings can have clinical significance. Here we have looked at MRI results in such a population.

Objective

To review the value and significance of the prevalence of all abnormal MRI findings of children with short stature who are to undergo growth hormone therapy (GHT).

Materials and methods

This study involved a retrospective review of MRI findings in all children prescribed GHT within a pediatric health network's database from Jan 2020 to Aug 2021. Post-gadolinium contrast enhanced brain and pituitary MRIs utilizing 2 mm slices were used to calculate pituitary volume. Pituitary volume was calculated using the ellipsoid formula (LxWxH/2). Pediatric patients diagnosed with non-acquired GHD or ISS, with MRIs having been performed between Jan 2020 and Aug 2021 and having been prescribed GHT by Aug 2021 were included in this study. Patients who experienced other endocrine abnormalities such as SGA, Turner Syndrome, and Noonan Syndrome were excluded. Patients with obstruction of sellar and parasellar religion due to movement artifacts or magnetic interference on their MRIs were also excluded.

Results

Of one hundred and twelve patients found, eighty one met criteria for inclusion in this study. Of the eighty one MRIs reviewed, twenty eight children, 34.6%, had normal pituitary anatomy and fifty three, 65.4%, had a pituitary abnormality. Out of the fifty three with a pituitary abnormality, forty three subjects, 81.1%, were determined to have a small pituitary volume, including significant pituitary hypoplasia. Ten subjects (18.9%) had an enlarged pituitary volume (pituitary hyperplasia). Of these ten patients who had an enlarged pituitary volume, eight were pubertal (80%). Nine children with a pituitary abnormality (16.9%) had additional structural anomalies on their MRIs. One had a small left frontal developmental venous anomaly. Two had Rathke's cleft cysts. Two had pars intermedia cysts. One had a small right parietal developmental venous anomaly. One had a small left parietal developmental venous anomaly. One had a left cerebellar tonsillar ectopia bordering on chiari malformation (.5 mm away on the coronal plane). One had a small lobulation (semi-bulbous projection) of the anterior pituitary gland, superior and anterior to the infundibular stalk.

Conclusion

Prevalence of brain abnormalities in children with short stature who are to undergo GHT is significant and warrants MRI evaluations in these subjects.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:58 p.m. - 1:03 p.m.
LBODP091 The Reasons For Loss To Follow-up Of Patients With Gender Dysphoria
Authors: Kadioglu Pinar , Uysal Ayten Cavus , Durcan Emre , Uysal Serhat , Sulu Cem , Turan Senol
Published: November 2022

Aim

To assess the effect of social function, motivation, support, and traumatic childhood experiences on follow-up behavior of patients with gender dysphoria (GD). Method: All the patients with GD who came to our clinic for endocrinological visit between September 2020 and July 2021 were asked to participate in this cross-sectional study. People with GD that provided consent were included in trans group. We also assigned age-matched cis-gender healthy controls. Data regarding gender transition process were collected retrospectively from medical charts. All the participants were administered Social Adaptation Self-evaluation Scale (SASS), Childhood Trauma Questionnaire (CTQ), and Multidimensional Scale of Perceived Social Support (MSPSS). The results were compared between groups.

Results

The study included 50 male-to-female with GD (MtF), 50 female-to-male with GD (FtM), 48 cis-females, 28 cis-males. The ratio of regular follow-up was higher in FtMs (n=48, 77.1%) than MtFs (n=39, 56.4%) (p<0. 05). Among lost to follow-up patients with GD, MtFs (n=17, %64.7) had a higher suicide rate than FtMs (n=11, %9.1) (p<0. 05). MtFs had lower CTQ and emotional abuse scores and higher sexual abuse scores than FtMs (p<0. 05).

Conclusion

Childhood traumas, emotional and sexual abuse may serve the reason for the loss to follow-up of MtFs.

Presentation: No date and time listed
LBSAT133 Dilemmas In The Diagnosis Of Osteoporosis In Transgender Population
Authors: Vasanthaakumar Vijaykiran P , De La Torre Sebastian , Vietor Nicole O , Shakir Mohamed K M , Hoang Thanh Duc
Published: November 2022

Although hormone therapy is associated with an increase in the bone mineral density (BMD) in transgender (TG) women the clinical significance of this on fracture risk is unknown. There are also no clear guidelines to define the interpretation of BMD data by DXA scan in the TG population. We are reporting three cases to illustrate the dilemmas involved in the interpretation of BMD in this population.

Case 1

A 30-year-old TG female to male (FTM) was started on testosterone treatment and 12 months later patient noted deepening of voice, facial hair growth and, increased muscle strength. Laboratory: serum testosterone 533 ng/dL, sex hormone binding globulin (SHBG) 23.2 nmol/L, FSH 7.1 mIU/mL, LH 8.2 mIU/mL estradiol 59.3 pg/mL, leptin 24.4 ng/mL. A DXA done 12 months after the initiation of treatment: Male Z scores LS spine -1. 0, femoral neck -0.8, total hip 0.2, forearm -2.8. Female: LS spine -0.6, femoral neck -0.4, total hip 0.9, forearm 0.4.

Case 2

A 25-year-old TG FTM was started on testosterone treatment for the last 9 months. Patient developed hair growth on the face and voice changes. Laboratory done 9 months later: serum testosterone 714 ng/dL, SHBG 22.5 nmol/L, FSH 4. 0 mIU/mL, LH 2.37 mIU/mL, estradiol 45.6 pg/mL, leptin 18.5ng/mL. A DXA done 9 months after the treatment: male Z scores LS spine 0.5, femoral neck -0.4, | total hip 0. 0, forearm -2.5. Female: LS spine 1. 0, femoral neck 0.2, total hip 0.8, and forearm -0.1.

Case 3

A 29-year-old TG MTF taking estradiol and spironolactone for 8 months and with this treatment she noted breast development and decreased facial hair. Laboratory done 9 months later: estradiol 139 pg/mL, serum testosterone 11.9 ng/dL, SHBG 70.3 nmol/L, FSH 1. 0 mIU/mL, LH 0.87 mIU/mL, leptin 8.2 ng/mL. DXA done 9 months after estradiol treatment: male Z scores A-P spine -2.5, femoral neck -1.6, total hip -1.3, forearm -1.3. Female: LS spine -2. 0, femoral neck -1.3, total hip -1.1, forearm 0.9.

Discussion

In these three patients when the BMD were analyzed in the current assigned gender and it showed discrepancies and presently there are no guidelines to select the BMD interpretation ie whether to depend on the native gender or current gender. Additionally, it is not clear whether treatment will alter the fracture risk in this population. Further studies are needed.

Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP423 Postmenopausal Virilization Secondary to A Rare Left Ovarian Androgen-Secreting Leydig Cell Tumor Localized Using Ovarian Vein Sampling
Authors: Shuster Shirley , Awad Sara
Published: November 2022

Introduction

Postmenopausal virilization can be caused by androgen-secreting tumours from either the adrenal glands or ovaries. Ovarian androgen-secreting tumours are rare, accounting for <0.2% of all cases of hyperandrogenism, and <1% of ovarian tumours. Leydig cell tumours account for <0.1% of all ovarian tumours and may represent a diagnostic challenge given their small size and difficulty to visualize radiologically.

Clinical Case

A 57-year-old female with a past medical history of hypertension presented with a 10-year history of hirsutism, and a 4-year history of virilization. She denied exogenous testosterone or supplement use. Examination was significant for voice deepening, excessive hair growth on her face, back, chest, and upper leg (Ferriman-Gallwey score of 20), male pattern baldness, and clitoromegaly. Investigations revealed markedly elevated total testosterone 11.5nmol/L (reference range (RR)=0.3-1.3) and bioavailable testosterone 7.19nmol/L (RR=0.1-0.6). DHEAS was normal at 4. 0umol/L (RR=0.8-4.9). TSH, prolactin, 17-OH-progesterone, ACTH, IGF-1 and GH were normal, and cortisol suppressed to <50nmol/L after 1-mg dexamethasone. Abdominal and transvaginal ultrasound, and adrenal and pelvic MRI did not identify adrenal or ovarian masses. Given normal DHEAS, there was a high suspicion for an ovarian source despite unremarkable imaging, thus ovarian vein sampling was undertaken. This revealed lateralization to the left gonad with total testosterone level of 780nmol/L (RR=0.3-1.8) and right gonadal testosterone level of 18.6nmol/L (RR=0.3-1.3). Left-to-right ovarian ratio was 41.94 (>15 is a strong lateralization to the left ovary as the likely source). After discussion with Gynecology, the patient underwent bilateral salpingo-oopherectomy given she was postmenopausal. The ovarian pathology revealed a left ovarian Leydig cell tumour with normal right ovarian pathology. Post-operatively, her total testosterone normalized to 0.4nmol/L, and the patient's virilizing symptoms improved.

Conclusion and Implications for Practice

This case illustrates the importance of considering rare androgen-secreting ovarian tumours in the differential diagnosis of post-menopausal virilization. It also demonstrates the diagnostic challenge associated with such tumours particularly given their difficulty to visualize radiologically. This demonstrates the importance of considering ovarian vein sampling as a diagnostic tool for localization when there is a high suspicion for an ovarian tumour, even when not identified on imaging studies.

Presentation: No date and time listed
ODP059 Torn Between Two Adrenal Cancers: A Case Report
Authors: Beronio Rae Angeli , Pingoy Noel , Galia Analyza
Published: November 2022

The adrenals are affected by Non-Hodgkin's lymphoma (NHL) in only 1 percent of cases. We report a rare case of NHL presenting as a large irregular mass at the adrenal gland in an elderly male. A 62-year-old male with hypertension and diabetes presented with 6-month history of vague right sided abdominal pain with recent extension to the left flank accompanied by body malaise and unintentional weight loss. Abdominal ultrasound revealed a 9-cm left suprarenal mass in addition to bilateral nephrolithiases and prostate enlargement. There was also left-sided minimal pleural effusion. CT scan and MRI contrast studies both confirmed a large left adrenal mass with infiltration of the spleen, pancreatic tail, and left kidney. High-Resolution CT scan of the chest confirmed left-sided pleural effusion with subsegmental atelectasis. Hormonal tests showed normal 24-hour urinary metanephrines, 24-hour urinary free cortisol, aldosterone-renin ratio, and serum DHEAS. Intact PTH and calcium were also normal. Multidisciplinary consultations involving endocrinology, medical oncology, hematology, pulmonology, surgical oncology, urology, thoracic cardiovascular surgery, anesthesiology, radiology, and pathology were done. He underwent exploratory laparotomy with resection of left adrenal mass and en bloc left nephrectomy, splenectomy and distal pancreatectomy. Histopathologic findings and immunostaining were consistent with diffuse large B-cell lymphoma. He completed R-CHOP chemotherapy and adjuvant radiotherapy with good clinical response and he has been on remission for two years.

Presentation: No date and time listed
PMON206 Pregnancy Rate and Outcomes Following a Randomized Controlled Three-component Lifestyle Intervention in Women with PCOS
Authors: van der Ham Kim , Jiskoot Geranne , Louwers Yvonne , Beerthuizen Annemerle , Busschbach Jan , Laven Joop , de Loos Alexandra Dietz
Published: November 2022

PCOS (polycystic ovary syndrome) is associated with overweight and obesity. Women with PCOS and overweight or obesity present with more pronounced reproductive derangements. Moreover, when pregnant, pregnancy complications such as gestational diabetes, hypertensive disorders and preterm birth seem to be more prevalent in this population. The present study is a one-year randomized controlled trial to investigate the effect of a three-component (cognitive behavioral therapy, healthy diet and physical therapy) lifestyle intervention (LSI) with or without Short Message Service (SMS) on pregnancy leading to live birth, pregnancy complications and outcomes within 24 months after the start of the lifestyle intervention compared to care as usual (CAU). We hypothesized that pre-pregnancy weight loss and the adoption of a healthy lifestyle would cause more pregnancies, shorter time to conception and less pregnancy complications. Women diagnosed with PCOS according to the Rotterdam 2003 criteria and a BMI above 25 kg/m2 were included. A total of 183 participants were randomly assigned to three groups: 1) three-component lifestyle intervention with SMS (LSI SMS+); 2) three-component lifestyle intervention without SMS (LSI SMS-); 3) care as usual (CAU): encourage to lose weight autonomously (control group). Pregnancy and neonatal outcomes were collected from the Dutch Bureau of Statistics (CBS) combined with the Dutch Perinatal registry (Perined). Within 24 months after the start of the intervention the pregnancy rate leading to live birth was 41.7% (25/60) within SMS+, 38.1% (24/63) within SMS- and 38.3% (23/60) within CAU. This was non-significant between the groups. Mean time to pregnancy for SMS+ was 18.3 months, 19.1 months for SMS- and 19.4 months for CAU (p=0.775). Gestational diabetes (LSI: 8.2% vs CAU: 21.7%, p=0.133), hypertensive disorders (LSI: 8.2% vs CAU: 13.0%, p=0.673) and preterm birth (LSI: 12.2% vs CAU: 17.4%, p=0.716) rates were all lower in the LSI groups (SMS+ and SMS- combined) compared to CAU. This trial demonstrated a non-significant positive trend in pregnancy outcomes in favor of the lifestyle intervention groups. We believe that a pre-pregnancy three-component lifestyle intervention in overweight or obese women with PCOS supports the attempts to get a healthy pregnancy by creating weight loss with positive effects on their physical and mental health.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON275 GONAD-on-CHIP to study early gonad development and DSD
Authors: Bashamboo Anu , Gonen Nitzan , Eozenou Caroline , Mitter Richard , Bernardo Andreia Sofia , Chervova Almira Chervova , Frachon Emmanuel , Commère Pierre-Henri , Brailly-Tabard Sylvie , Mazen Inas , Gobaa Samy , Smith James , McElreavey Kenneth , Lovell-Badge Robin
Published: November 2022

During embryonic development, mutually antagonistic signaling cascades determine the fate of the bipotential gonad towards a testicular or ovarian identity. Errors in this process result in human Disorders of Sex Development (DSDs), where there is discordance between chromosomal, gonadal, and anatomical sex. The absence of an appropriate, accessible in-vitro system is a major obstacle in understanding mechanisms of sex-determination/DSDs. Here, we describe protocols for differentiation of mouse and human pluripotent cells towards gonadal progenitors. Transcriptomic analysis reveals that the in-vitro-derived murine gonadal cells are equivalent to E11.5 in-vivo progenitors. Using similar conditions, Sertoli-like cells derived from 46,XY human induced pluripotent stem cells (hiPSCs) exhibit sustained expression of testis-specific genes, secrete AMH, migrate and form 3D tubular structures on a specially designed microfluidic device. The cells derived from a 46,XY DSD female hiPSCs, carrying a NR5A1 variant, show aberrant gene expression and absence of tubule formation. CRISPR/Cas9-mediated correction of the variant rescued the phenotype. This is a robust tool to understand mechanisms of sex-determination and model DSDs.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
ODP067 Long-term Systemic Steroid Use And Its Impact on In-hospital Outcomes Among Patients Admitted With Acute Pericarditis
Authors: Kumi Dennis , Ramirez Marcelo , Akaho Elikplim , Soon-shiong Raquel , Shrestha Prajwal , Karki Sadicchya , Nissan Ninos , Patel Birju
Published: November 2022

Background

Early use of systemic steroids in the acute setting of acute pericarditis has been associated with increased recurrence rate and a longer course of treatment. It is not clear if long-term systemic steroids use, has a similar unfavorable impact in patients admitted for acute pericarditis. Our study aimed to determine if the presence of long-term systemic steroid use as a comorbidity during admission for acute pericarditis, was associated with worse outcomes. Method: A retrospective cohort study was designed using data obtained from the 2016 to 2018 combined National Inpatient Sample (NIS) database. The international diseases classification code, tenth revision (ICD-10), was used to identify patients admitted with a principal diagnosis of acute pericarditis who were further dichotomized into 2 cohorts, based on the presence of a secondary diagnosis of long-term systemic steroid use. Primary outcomes of the study were, mortality rate, length of stay (LOS) and total hospital charge. Secondary outcomes assessed included rates of pericardial effusion, cardiac tamponade, cardiogenic shock, pericardial window, and cardiac arrest. A multivariate linear and logistic regression were used to adjust for confounders.

Results

Our sample included a total of 36,570 adult hospitalizations for acute pericarditis, out of which 2.24% had associated long-term systemic steroid use as a secondary diagnosis. There was a 3- fold increased odds of mortality among patients with long-term systemic steroid use compared to the group without, (2.44% vs 0.84%, AOR: 2.92, 95% CI: 1. 06 to 8. 01, p: 0. 038). Both length of stay (LOS) and total charge were increased among patients with long-term systemic steroid use compared to their counterpart cohort, with an adjusted mean difference of 0.2 days and 1,693.65 USD respectively but these did not meet statistical significance. There was no statistically significant difference in terms of secondary clinical outcomes including, pericardial effusions, cardiac tamponade, cardiogenic shock, rate of pericardial window and cardiac arrest between the two groups analyzed.

Conclusion

The presence of long-term corticosteroid therapy as a comorbidity during admission for acute pericarditis was associated with a 3–fold increased odds of mortality during hospitalization and there was a trend towards increased LOS and total charge among such patients, though the latter did not meet statistical significance. Further prospective studies need to be done on this topic to better improve understanding and to assess its impact on patient care.

Presentation: No date and time listed
RF10 | PMON204 Eucaloric High Fat Diet Does Not induce insulin Resistance But May Stimulate Fat Oxidation in Normal Weight Women
Authors: Schauer Irene , Kuhn Katherine , Fought Angela , Pretzel Shannon , Bradford Andrew , Santoro Nanette
Published: November 2022

Obesity and metabolic syndrome are associated with defects in the hypothalamic pituitary ovarian (HPO) axis termed the reprometabolic syndrome. We have previously shown that lipid infusion induces insulin resistance and the reprometabolic syndrome of obesity in normal weight women. We hypothesized that the induced insulin resistance is the underlying cause of the attenuation of the hypothalamic pituitary ovarian (HPO) axis. 16 women of normal BMI (18-24.9g/m2), mean age 29.7 ± 6.4, were recruited for a study including a 30-day, prescribed, eucaloric, high fat (48% of calories from fat) dietary intervention. Diet was adjusted to ensure that participants remained weight stable throughout the study. Insulin sensitivity was measured by 2 stage euglycemic hyperinsulinemic clamp (8 and 40 mU/m2*min) pre and post diet. Final stage 2 glucoses were not different pre vs post diet (mg/dL, 86±7 vs 89±6, p=0.08). Muscle insulin sensitivity (glucose infusion rate, mg/kg*min) was different pre versus post diet (10.9±3.3 vs 10.6±3.5, p=0.013) after exclusion of one participant for multiple protocol deviations. Adipose insulin sensitivity as measured by fatty acid suppression during the low insulin infusion stage of the clamp was also not different pre versus post diet [final fatty acid level in µEg/L; median 115 (IQR 84, 224) vs 158 (IQR 67,274; p>0.99). However, the final high insulin stage 2 fatty acid suppression trended towards greater suppression after high fat diet [median 17.8 (IQR 9.8,33.8), vs 11.7 (IQR 7.7, 18.7) p=0.06]. This may reflect higher fatty acid oxidation on the high fat diet.

We have previously reported that this diet, like the lipid infusion, did attenuate the HPO axis (reduced baseline early follicular LH and FSH and reduced LH response to GnRH). In contrast to lipid infusion, however, this dietary intervention did not induce the same degree of insulin resistance, possibly due to the emphasis on neutral energy balance, suggesting that the suppression of the HPO axis by high fat diet may be partially independent of insulin sensitivity.

Presentation: Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
RF34 | PMON229 TNFa-Induced Altered miRNA Expression Links to Inflammation in Endometriosis
Authors: Chowdhury Indrajit , Driss Adel , Taylor Robert N , Nezhat Ceana , Sidell Neil , Thompson Winston E , Xu Wei , Banerjee Saswati , Chowdhury Indrajit
Published: November 2022

Endometriosis is a common gynecological inflammatory disorder, which is characterized by immune system dysregulation with initiation and progression. It affects 5% to 15% of reproductive-age women and is present in as many as 30% to 50% of patients with infertility and/or pain. In previous studies, including ours, have demonstrated that several cytokines have been associated with the evolution of endometriosis, including tumor necrosis factor-a (TNFa). TNFa is a non-glycosylated protein which has potent inflammatory, cytotoxic, and angiogenic potential. Therefore, in the current studies, we examined the effects of TNFa over a time course in the regulation of proinflammatory and proangiogenic microRNAs (miRNAs) in primary cultures of normal endometrial stromal cells (NESC) and compared with the untreated cells derived from eutopic endometrium of endometriosis subjects (EESC). miRNAs are short, 18- to 22-nucleotide– size, non-coding RNAs that act as post-transcriptional modulators of gene expression and are involved in the pathogenesis of endometriosis. Using NanoString nCounter-based assays and quantitative RT-PCR, we have identified levels of several proinflammatory and proangiogenic miRNAs higher in EESC than NESC. NESC treatment with TNFa significantly altered the expression of proinflammatory and proangiogenic miRNAs in a time-dependent manner. Notably, TNFa significantly decreased phosphorylation of the PI3K, AKT, and ERK signaling pathways. Moreover, treatment of EESC and NESC with curcumin (diferuloylmethane, CUR), an anti-inflammatory folk medicine in Asian countries, significantly increased the expression of anti-inflammatory and anti-angiogenic miRNAs in a dose- and time-dependent manner. These findings demonstrate higher inflammatory, and proangiogenic miRNA production in EESC may be due to a higher concentration of TNFa than NESC under basal conditions. Therefore, suppressing TNFa may reduce the inflammatory and angiogenic miRNA associated with endometriosis.

Sources of Research Support: This study was supported in part by National Institutes of Health Grants 1SC3 GM113751, U01, 1SC1 GM130544, HD66439, 1R01HD057235, U54 CA118948, HD41749, S21MD000101 and G12-MD007602. This investigation was conducted in a facility constructed with support from Research Facilities Improvement Grant #C06 RR018386 from NIH/NCRR.

Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.