bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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&lt;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

Abstract
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 &lt;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&gt;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 (&lt;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

Abstract
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

Abstract
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&lt;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&lt;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

Abstract

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&lt;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&lt;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

Abstract

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

Abstract

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

Abstract

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.