bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT265 Stearoyl CoA Desaturase Knockdown Increases Saturated And Monounsaturated Fatty Acid Concentrations In SDHB KD Cells But Not In hPheo1 Wild-type Progenitor Cells
Authors: Ghayee Hans K , Bala Niharika , Xu Yiling , Tevosian Sergei G , Kozuch Marianne , Denslow Nancy D , Alli Abdel Ayube 
Published: October 2023

Abstract
Disclosure: H.K. Ghayee: Other; Self; Royalties form the University of Texas Southwestern Medical Center. N. Bala: None. Y. Xu: None. S.G. Tevosian: None. M. Kozuch: None. N.D. Denslow: None. A.A. Alli: None.
Introduction: Pheochromocytoma and paraganglioma (PPGL) patients with mutations in the succinate dehydrogenase B subunit (SDHB) frequently develop metastatic lesions and have a poor prognosis. The stearoyl-CoA desaturase 1 (SCD1) protein plays an important role in lipid metabolism. SCD1 inhibitors have shown great potential as new treatments for various diseases including cancer. Hypothesis: siRNA mediated knockdown of SCD1 compared to non-targeting siRNA would result in differences in the concentrations of saturated fatty acids and monounsaturated fatty acids in SDHB KD cells compared to hPheo1 wild-type (WT) progenitor cells. Methods: Fatty acid concentrations were assessed by fatty acid methyl ester (FAME) analysis. SCD1 expression was assessed by quantitative polymerase chain reaction (qPCR) and Western blotting analysis. Results: Analyses showed a significant decrease in SCD1 in SDHB KD cells compared to hPheo1 WT cells. Fatty acid methyl ester analysis showed the concentrations of the saturated fatty acids myristic acid, palmitic acid, and stearic acid, and the monounsaturated fatty acids palmitoleic acid and oleic acid are increased at least 2-fold in SDHB KD cells transfected with SCD1 siRNA compared to non-targeting siRNA. Conclusions: Fatty acid changes noted in hPheo1 SDHB KD cells were not seen in hPheo1 WT cells after siRNA mediated knockdown of SCD1. This suggests that SDHB deficiency and loss of FADH2 production interacts specifically with lipid desaturation pathways.
Presentation: Saturday, June 17, 2023
SAT268 Regulation Of Stem/Progenitor Cells Of The HPA Axis During Stress Adaptation
Authors: Siatra Panagiota , Cozma Diana , Berger Ilona , Oikonomakos Ioannis , Theodoropoulou Marily , Bornstein Stefan Richard , Andoniadou Cynthia Lilian , Steenblock Charlotte 
Published: October 2023

Abstract
Disclosure: P. Siatra: None. D. Cozma: None. I. Berger: None. I. Oikonomakos: None. M. Theodoropoulou: None. S.R. Bornstein: None. C.L. Andoniadou: None. C. Steenblock: None.
Chronic stress is a pervasive concern in the modern society. A long-term hyper activation of the hypothalamic-pituitary-adrenal (HPA) axis leads to elevated amounts of stress hormones [e.g. ACTH and glucocorticoids (GCs)]. This can incur maladaptation that eventually contributes to mental illness, cardiovascular dysfunctions, diabetes, cancer and autoimmune diseases. Emerging key players for stress adaptation of the HPA axis are stem/progenitor cell populations. In this study, we aim to unravel the mechanisms involved in the regulation of stem/progenitor cells of the HPA axis during stress adaptation. To that aim, we incorporated an in vitro system of non-adherent spheroids from primary adrenocortical mouse cells that were stimulated with ACTH. The treatment resulted in the increased growth of the spheroids compared to unstimulated controls indicating a potential role of the hormone in cell proliferation and stem cell behaviour. This result is in line with the enlarged adrenals observed in patients with Cushing’s syndrome. To assess the contribution of stem cells during stress adaptation in the adrenal cortex in vivo, we performed immobilization stress and lineage tracing studies using the tamoxifen inducible Gli1:CreERT2/R26R:eYFP mouse line. By combining these results along with single-cell RNA-seq technology, we aim to shed light into molecular factors involved in the adult adrenal cortex regeneration and remodelling. To follow the effect of GC excesses on the negative feedback loop observed during a normal stress response on the pituitary gland, we stimulated adherent primary anterior pituitary colonies with dexamethasone and corticosterone. GC treatment led to downregulation of Pomc expression, a precursor polypeptide for ACTH and other hormones, in the treated colonies compared to the control. This downregulation caused by GCs could be mediated through different gene targets of the glucocorticoid receptor as well as via paracrine signalling from pituitary stem cells. Altogether, our results will provide us with more profound knowledge of mechanisms underlying interactions between stressors and stem/progenitor cells of the HPA axis along with novel therapeutic targets for stress-associated disorders.
Presentation: Saturday, June 17, 2023
SAT300 Use of Overnight Metyrapone Test In Suspected Adrenal Insufficiency: A Retrospective Single Center-Study
Authors: Saini Jasmine , Garcia Raul Gregg , Herndon Justine , Erickson Dana Z , Gruber Lucinda , Bancos Irina 
Published: October 2023

Abstract
Disclosure: J. Saini: None. R. Gregg Garcia: None. J. Herndon: None. D.Z. Erickson: None. L. Gruber: None. I. Bancos: None.
Context: Overnight metyrapone test (OMT) is a dynamic test used to diagnose secondary adrenal insufficiency (SAI). However, it is uncommonly used and the data on the OMT indications and performance are scarce. We aimed to characterize the indications, performance, and safety of outpatient OMT. Methods: Single center retrospective study in adults with OMT between April 1st, 2018 -July 31st, 2022. We evaluated three post-OMT cutoffs diagnostic of SAI: 1) 11-deoxycortisol ≤7 mcg/dL (11D≤7); 2) 11-deoxycortisol ≤10 mcg/dL (11D≤10), or 3) sum of cortisol and 11-deoxycortisol ≤15 mcg/dL (sum≤15), in comparison to pre-test probability and reference standard, defined as clinician-made diagnosis of SAI. When available, OMT-based SAI diagnosis was compared to results from the cosyntropin stimulation test (CST). Results: OMT was performed in 109 patients (76, 70% women) at a median age of 48 (IQR, 37-59) years. Pre-test probability for SAI was high in 13 (12%), moderate in 46 (43%), and low in 49 (45%) patients. Indications for OMT included evaluation of symptoms without clear SAI risk factors (38, 35%), suspected SAI due to chronic opioid use (25, 23%), pituitary pathology/therapies (25, 23%), exogenous glucocorticoid use (8, 7%), other (13, 12%). Overnight metyrapone was administered at a median dose of 2500 (IQR, 2125-3000). Adverse events were reported by 9 (8%) patients and were mild (nausea, fatigue) except for 1 patient who had to be hospitalized.
The final diagnosis of SAI was made in 25 (48%) patients: 92%, 52%, and 12% of patients with high, moderate, and low pre-test probability. When compared to the clinician-made SAI diagnosis, OMT-based diagnosis of SAI was made in 60% of patients using the 11D≤7 cutoff, and in 81% of patients using the other cutoffs (11D≤10 or sum≤15).
In 50 patients with concomitant CST, the final diagnosis of SAI was made in 23 (46%) patients, despite the normal CST results (post-cosyntropin peak cortisol ≥18 mcg/dL) in 12/23 patients. In patients with post-cosyntropin peak cortisol ≥18 mcg/dL, OMT was abnormal in 14% of patients (using post-OMT cutoff 11D≤7), 29% of patients (based on cutoff 11D≤10), and in 30% of patients (based on sum≤15).
Conclusions: Outpatient OMT is well tolerated and was mostly used in patients with low/moderate pre-test probability for SAI. In patients with normal CST, OMT may diagnose SAI in additional 30% of patients, especially if the pre-test probability is high. Post-OMT sum of 11-deoxycortisol and cortisol &lt;15 mcg/dL performs well in diagnosing SAI while allowing confirmation of adequate cortisol suppression.
Presentation: Saturday, June 17, 2023
SAT326 Massive Adrenomyelolipomas Due To Longstanding CAH
Authors: Aziz Qurrat-ul-ain , Champion Amber 
Published: October 2023

Abstract
Disclosure: Q. Aziz: None. A. Champion: None.
Introduction: Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder caused by deficiency in adrenal corticosteroid biosynthesis. 21 Hydroxylase Deficiency is common in 90-95% of CAH cases and have a defect in converting 17 OH Progesterone to 11 deoxycortisol. Therefore, they have an increase in ACTH secretion due to the decrease negative feedback drive along with excess adrenal androgens. Adrenal myelolipoma are common in patients with CAH and the tumors are benign and lipomatous. Clinical Case: Patient is a 47 year old female with past medical history of CAH presents to the clinic for evaluation of generalized fatigue and abdominal pain. She was diagnosed with CAH- 21 hydroxylase deficiency at birth and required vaginal reconstruction surgery. She was on hydrocortisone and fludrocortisone until age 18, but thereafter stopped taking medications or seeing physicians for nearly 30 years. CT abdomen/pelvis showed large bilateral adrenal myelolipomas, right adrenal gland measuring 23.2 cm and left adrenal gland measuring 20 cm. MRI confirmed enlarged adrenal glands. Initial labs included ACTH 299, 17-OH Progesterone &gt;2000, 11 deoxycorticosterone 23.6, total testosterone 160, free testosterone 30.3, DHEA-S 192, Cortisol 2.8. She was started on fludrocortisone 50 mcg and Hydrocortisone 10 mg in the morning and 5 mg in the evening and was referred to an endocrine surgeon out of state, but surgery was not offered due to concerns of medication nonadherence. She returned to clinic 6 months after presentation, she admitted to missing multiple doses of her hydrocortisone. Repeat CT Abdomen and Pelvis showed severe compression of the IVC and right lobe of the liver along with mild compression of the kidneys and pancreas. To improve adherence, she was switched to prednisone, and eventually dexamethasone 0.75mg and fludrocortisone 100mcg. She complains of fatigue but improved abdominal pain. After a period of good adherence with medication administration, she was referred to a local surgical oncologist who agreed to do bilateral adrenalectomy due to mass effect. Conclusion: CAH is a challenging chronic disease with variable penetrance in phenotype, ranging from mild hirsutism to frank adrenal insufficiency. Massive adrenomyelolipomas are thought to be ACTH driven, especially seen in undertreated and longstanding CAH. Without the 21 hydroxylase enzyme to convert 17 OH Progesterone to 11 deoxycortisol, levels of ACTH rise. While these myelolipomas are benign and can generally be monitored, surgery should be considered if the size impairs function of surrounding organs. Bilateral adrenalectomy can also be considered in patients with CAH for refractory hypertension, hyperandrogenism and virilization, Cushing syndrome, infertility, or mass effect.
Presentation: Saturday, June 17, 2023
SAT345 Disappearing Adrenal Masses: A Tale Of Two Lesions
Authors: Arooj Aneela , Lansdown Andrew 
Published: October 2023

Abstract
Disclosure: A. arooj: None. A. Lansdown: None.
Introduction: Adrenal lesions are being increasingly detected on CT scans performed for other reasons. Adrenal lesions that “disappear” on subsequent imaging are rare, most commonly due to adrenal hematomas, cysts or infection.
Case: 1 73-year-old man was admitted with a collapse and fall. CT head & angiogram demonstrated cerebral sinus thrombosis, subarachnoid hemorrhage and right parietal hematoma. Furthermore, high density4cm left adrenal lesion on CT abdomen(Fig 1) Consideration was given to COVID vaccine induced thrombotic thrombocytopenia. ACTH, aldosterone, renin, aldosterone renin ratio normal. Slightly low cortisol (386) after short synacthen test. Later, CT showed the left adrenal lesion had disappeared in Fig 2.
Case 2: 36-year-old man following a road traffic collision, fell from his electric scooter at a speed of 30mph, also noted to have high blood pressure on admission. He had small laceration of the liver which was managed conservatively. CT abdomen and pelvis, showed a low density 28mm right adrenal nodule, measuring 37 Hounsfield Units,(fig 3) that was completely resolved in subsequent imaging (Fig4). His biochemistry reports of dexamethasone suppression test, renin, aldosterone, 24hr metadrenaline urinary profile and urinary cortisol remained normal.
Learning points: "Disappearing", adrenal mass lesions are rare, though reported, and most commonly due to adrenal hematomas, cysts or infection.
References: I G Hermsen , M P J Polak, H R Haak. Disappearing adrenal masses. Endocrine. 2010 Oct;38(2):153-7. doi: 10.1007/s12020-010-9368-7. Epub 2010 Jul 11,
Presentation: Saturday, June 17, 2023
THU393 An Internal NPT2A Cryptic PDZ Motif Is A Novel Regulator of PTH- And FGF23-sensitive Phosphate Transport
Authors: Sneddon Bruce W , Friedman Peter A , Mamonova Tatyana 
Published: October 2023

Abstract
Disclosure: B.W. Sneddon: None. P.A. Friedman: None. T. Mamonova: None.
The Na+-dependent NPT2A (SLC34A1) phosphate co-transporter is a major regulator of phosphate homeostasis. Its most notable structural element is a carboxy-terminal PDZ ligand that binds Na+/H+ Exchanger Regulatory Factor-1 (NHERF1, SLC9A3R1), a multidomain PDZ protein that determines apical NPT2A localization and is required for phosphate transport. NPT2A also possesses an uncharacterized internal PDZ ligand. Two recent clinical reports describe congenital hypophosphatemia in children harboring Arg495His or Arg495Cys variants within the internal PDZ motif. Wild-type internal 494TRL496 PDZ binds NHERF1 PDZ2, which we consider a regulatory domain. Ablating the internal PDZ ligand with a 494AAA496 variant blocked hormone-sensitive phosphate transport. Complementary approaches, including CRISPR/Cas9 technology, side-directed mutagenesis, confocal microscopy, and modeling, showed that NPT2A Arg495 His or Arg495Cys variants do not support PTH or FGF23 action on phosphate transport. CoIP experiments indicate that both variants bound NHERF1 similarly to WT NPT2A. However, in contrast to WT NPT2A, NPT2A Arg495His or Arg495Cys variants remain at the apical membrane and are not internalized in response to PTH. We predict that His or Cys substitution of the charged Arg495 changes the electrostatics, preventing phosphorylation of the upstream Thr494, interfering with phosphate uptake in response to hormone action, and inhibiting NPT2A trafficking. We advance a model where the carboxy-terminal PDZ ligand defines apical localization of NPT2A, while the internal PDZ ligand is essential for hormone-triggered phosphate transport.
Presentation: Thursday, June 15, 2023
THU395 Phosphate Inhibits Calcium-sensing Receptor Expressed Endogenously In TT Cells
Authors: Alghamdi Khaleda Ali , Ward Donald 
Published: October 2023

Abstract
Disclosure: K.A. Alghamdi: None. D. Ward: None.
Calcium-sensing receptor (CaR) is the key controller of parathyroid hormone (PTH) secretion and extracellular calcium homeostasis. Hyperphosphataemia increases PTH secretion and we reported recently that pathophysiologic phosphate (Pi) concentrations can attenuate CaR activity directly in transfected HEK-293 cells and can increase PTH secretion from human and murine parathyroid cells (1). This was investigated further using thyroidal C cell-derived TT cells (ATCC), which express CaR endogenously. Intracellular Ca2+ (Ca2+i) mobilisation was assayed by epifluorescence microscopy, calcitonin secretion by ELISA, protein expression by immunoblotting and CaR mRNA expression by qRT-PCR. Co-stimulation of TT cells with the (CaR-activating) calcimimetic R568 (1µM) and spermine (1mM) elicited robust Ca2+i mobilisation, that was inhibited (33±4%; P&lt;0.001; N=4) by 2mM (pathophysiologic) Pi-containing buffer vs 0.8mM Pi control. In contrast, raising Pi concentration was without effect on carbachol-induced Ca2+i mobilisation (acting via muscarinic receptors) (P=0.89; N=3). Also, 1.2mM (high) sulphate elicited a similar CaR inhibition as for Pi vs 0.3mM control (-28±16%; P&lt;0.05; N=4). Next, it was found that CaR-mediated stimulation of the TT cells with 1µM R568 & 1mM spermine (in 2mM Ca2+ and 0.8mM Pi) increased calcitonin secretion, as expected, whereas the same stimulation in 2mM Pi (in the presence of 2.2mM Ca2+ to correct for any reduction in free Ca2+) significantly blunted this response (-59.7±15%; P&lt;0.05;N=4). Interestingly, CaR mRNA expression was significantly downregulated 45±13%; P&lt;0.05;N=6) after 48 hours treatment with media containing 2mM Pi (vs 0.8mM control). However, while CaR protein expression in the TT cells was confirmed by immunoblotting, its abundance was unaffected by the same 2mM Pi cotreatment (P=0.79; N=8). Therefore, pathophysiologic Pi treatment inhibits endogenous CaR-induced signalling, calcitonin secretion and CaR mRNA expression in thyroidal TT cells but without affecting CaR abundance. These results further support the idea that the CaR represents a mineral sensor, at which Pi acts directly as a non-competitive antagonist to limit CaR-induced suppression of PTH secretion. Reference: (1) Centeno et al. Nat Commun. 2019;10:4693.
Presentation: Thursday, June 15, 2023
THU415 Trabecular Bone Score In Hospitalized Patients With Heart Failure
Authors: Bandeira Francisco , Oliveira Lucian B , Siqueira Mariana A F M , Litvin Mirela A , Garcia Jessica M A , Bandeira Leonardo 
Published: October 2023

Abstract
Disclosure: F. Bandeira: None. L.B. Oliveira: None. M.A. Siqueira: None. M.A. Litvin: None. J.M. Garcia: None. L. Bandeira: None.
Introduction: Heart failure (HF) is a clinical syndrome directly associated with functional impairment, which may be interrelated with skeletal consequences and an increased risk of fractures. The trabecular bone score (TBS) allows an indirect assessment of the bone microarchitecture, a helpful tool in fracture risk stratification. Objective: To evaluate the TBS and its relationship with bone mineral density (BMD) and cardiometabolic parameters in patients admitted with HF. Methods: Cross-sectional study was conducted in a Cardiology center, with patients aged 40 to 85 years hospitalized with HF. Clinical, echocardiographic, laboratory and BMD were evaluated. TBS &lt;1.230 was characterized as bone degradation. Results: A total of 103 patients were evaluated, of which 53.4% were female. The mean age was 64.1 ± 9.4 years. The median left ventricular ejection fraction (LVEF) was 50.0% (interquartile range [IQR] 34.0-61.0%), with 50.5% having preserved LVEF (≥50%), 5.8% having mildly reduced LVEF (41-49%), and 43.7% having reduced LVEF (≤40%). 50.4% of patients had New York Heart Association Functional Classification (NYHA-FC) I-II and 49.6% NYHA-FC III-IV. The majority (67%) of patients had HF of ischemic etiology; 43.7% had diabetes mellitus and 30.0% had prediabetes. Bone degradation indicated by TBS was present in 33.0% of the sample, while BMD in the osteoporosis range was observed in 22.3%. There was no statistically significant difference between genders in the presence of bone degradation (22.9% of men vs. 36.4% of women, p = 0.138). Low TBS was associated with higher mean age (67.5 ± 9.1 vs. 62.7 ± 9.2 years, p = 0.016) and lower T-scores in the lumbar spine (−1.9 ± 1.3 vs. −0.7 ± 1,8, p = 0.001), femoral neck (−1.6 ± 1.2 vs. −1.1 ± 1.2, p = 0.030), and total femur (−1.3 ± 1.1 vs. −0.5 ± 1.3, p = 0.005). There was no association between low TBS and body mass index (28.0 ± 4.4 vs. 27.8 ± 5.3 kg/m², p = 0.828), LVEF (50.0% [30.0-59.0] vs. 55.0% [34.3-61.8], p = 0.183) and hemoglobin A1c (6.4% [5.7-7.9] vs. 6.2% [5.7-8.2], p = 0.920). Patients with NYHA-FC III-IV had lower mean TBS when compared to those with NYHA-FC I-II (1.273 ± 0.138 vs. 1.335 ± 0.149, p = 0.031). Conclusion: We found that bone microarchitecture deterioration was more frequent than osteoporosis in patients hospitalized with HF, with greater symptomatology being associated with lower TBS.
Presentation: Thursday, June 15, 2023
THU432 Severe Osteoporosis Associated With A Novel Plastin 3 (PLS3) Mutation
Authors: Ibrahim Amira , Esper Layal , Gandhi Shruti Mahendra , Nylen Eric S 
Published: October 2023

Abstract
Disclosure: A. Ibrahim: None. L. Esper: None. S.M. Gandhi: None. E.S. Nylen: None.
Early Onset Osteoporosis (EOOP) affects children and young adults and can be caused by endocrinopathies, chronic medical conditions, nutritional deficiencies, and/or genetic mutations. The most common inherited cause is osteogenesis imperfecta(OI), and a rare variant linked to OI includes a defect in the X chromosomal gene encoding Plastin 3 (PLS3). In our case, a 34-year-old male was referred for severe osteoporosis. He had been diagnosed with osteopenia at age 21. At age 24, imaging revealed multiple vertebral compression fractures and DXA scan confirmed severe osteoporosis. He required L3-L5 kyphoplasty and started on oral bisphosphonates for presumed OI despite negative gene mutation (i.e., COL1A1/COL1A2). He continued treatment for only 2 years. 8 years later, he had persistent osteoporosis (DXA L2-4 Z-score -3.6, LFN Z-score -3.2). He had no evidence of kyphosis or scoliosis and no extraskeletal manifestations such as blue-grey sclera or any dysmorphic features. The workup was negative for secondary causes of EOOP and he denied a family history of osteoporosis. Labs showed normal 24-hour urine calcium, bone markers, and bone Alkaline Phosphatase. Karyotyping showed normal XY and gene analysis was again negative for OI. He started treatment with intravenous Zoledronic acid, however, had a 2-year gap between doses initially causing BMD to drop by 6.5% in L2-L4 (Z -4.1) and by 5.7% in LFN (Z -3.1). Subsequently, he received a total of 5 doses of Zoledronic acid to date and had no further fractures. DXA significantly improved by 10.4% in L2-4 (Z -2.6), and 16.3% in LFN (Z -2.0). Repeated expanded gene testing showed a novel PLS3 hemizygous mutation (deletion at site C.234_237+10del of Exon 3). This case demonstrates a novel PLS3 mutation variant to be a plausible cause of adulthood EOOP which was responsive to bisphosphonate treatment. PLS3 is an F-actin binding and bundling protein involved in cytoskeletal remodeling and may have roles in calcium homeostasis, cell migration, endocytosis, DNA repair, and membrane trafficking. Currently, less than 30 loss of function variants of PLS3 have been identified and all lead to severe osteoporosis- particularly in children. However, our patient’s known onset of bone loss occurred much later- in his twenties and he had no evidence of extra-skeletal manifestations. The cause for such late presentation is unclear but may be attributed to this specific variant of PLS3. This case highlights that PLS3 mutation should be on the differential for EOOP even in early adulthood. Our patient’s BMD has markedly improved with bisphosphonates and he sustained no further fractures after starting therapy. Timely diagnosis and earlier detection will allow for appropriate genetic counseling, earlier screening, and treatment of affected family members.
Presentation: Thursday, June 15, 2023