bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT336 A Successful Ovulation Induction And Embryo Generation In A Woman With P450-oxidoreductase Deficiency From Mutation G539R, Which Preferentially Impairs 17,20-lyase Activity
Authors: Charoensri Suranut , Thakur Mili , Auchus Richard J 
Published: October 2023

Abstract
Disclosure: S. Charoensri: None. M. Thakur: None. R.J. Auchus: None.
Introduction: Cytochrome P450 oxidoreductase (POR) deficiency is an autosomal recessive disorder causing decreased activity of several P450 enzymes, including CYP21A2, CYP17A1, and CYP19A1 that are essential for steroidogenesis in the adrenals and gonads. Female POR deficiency patients are typically manifested with genital ambiguity, abnormal menstruation, and infertility. Very few pregnancies have been documented from these patients.
Case presentation: During an evaluation for infertility, a 35-year-old woman with late menarche, irregular cycles, and unruptured ovarian follicles was diagnosed with POR deficiency due to compound heterozygous pathogenic variant c.1615G&gt;C (G539R) and a large deletion c.1669+5_1669+32del in the POR gene. Because mutation G539R preferentially impairs the 17,20-lyase activity of CYP17A1, she underwent in-vitro fertilization (IVF) with the protocol that has been used successfully to achieve pregnancy in incomplete 17-hydroxylase deficiency. Oral dexamethasone of 0.5 mg/day was given to suppress the adrenal-derived progesterone. After one menstrual cycle induced with estradiol and progesterone priming, leuprolide acetate was used to down-regulate endogenous gonadotropin secretion, then the oocyte maturation was induced with recombinant follicle-stimulating hormone (rFSH) and highly purified menotrophin. In the first cycle, 6 eggs were retrieved, 2 that were mature and fertilized with intracytoplasmic sperm injection (ICSI); however, none advanced to the blastocyst stage. She underwent the same protocol in a second IVF cycle with higher rFSH dosing. Despite increasing dexamethasone to 1.5 mg/day, progesterone rose to 4.9 ng/mL, while estradiol peaked at 120 pg/mL, consistent with progesterone accumulation in the developing ovarian follicles due to POR deficiency. From 6 eggs retrieved, 5 eggs were mature and all fertilized, and 3 developed past day 3. On day 6, one embryo (grading 5BB) was biopsied for preimplantation genetic testing and frozen. The second phase of the treatment plan is to lower adrenal-derived progesterone with a combination of hydrocortisone and prednisolone, prepare the endometrium with estradiol followed by progesterone, and perform embryo transfer. Conclusions: Very few examples of pregnancy in women with POR deficiency have been reported, and we describe the first example of successful ovulation induction and embryo generation in a woman with POR deficiency caused by the G539R mutation, which preferentially impairs 17,20-lyase activity. The complex array of steroid excess and deficiencies, from both adrenal and ovarian origin, must be systematically managed during assisted reproduction treatment for these women.
Presentation: Saturday, June 17, 2023
THU418 Steroid Profiles And Its Implication In Bone Mass And Quality In Premenopausal Women With Adrenal Tumors With Autonomous Cortisol Secretion
Authors: Nakao Hiroshi , Nakatani Kohta , Yokomoto-Umakoshi Maki , Umakoshi Hironobu , Kaneko Hiroki , Iwahashi Norifusa , Ogata Masatoshi , Fukumoto Tazuru , Masamichi Fujita , Tatsuki Ogasawara , Matsuda Yayoi , Sakamoto Ryuichi , Izumi Yoshihiro , Bamba Takeshi , Ogawa Yoshihiro 
Published: October 2023

Abstract
Disclosure: H. Nakao: None. K. Nakatani: None. M. Yokomoto-Umakoshi: None. H. Umakoshi: None. H. Kaneko: None. N. Iwahashi: None. M. Ogata: None. T. Fukumoto: None. F. Masamichi: None. O. Tatsuki: None. Y. Matsuda: None. R. Sakamoto: None. Y. Izumi: None. T. Bamba: None. Y. Ogawa: None.
Context: Osteoporosis is a major complication in adrenal tumors with autonomous cortisol secretion (ACS). We conducted steroid profiling to elucidate how steroid metabolites affect bone mass and quality in patient with ACS. Methods: Ninety patients with ACS and 91 with non-functioning adrenal tumors (NFAT) were included, of whom 73 ACS (18 pre-, 26 postmenopausal women, and 29 men) and 85 NFAT (12 pre-, 34 postmenopausal women, and 39 men) were evaluated for 21 plasma steroid metabolites using liquid chromatography-tandem mass spectrometry. Results: Premenopausal women with ACS had lower lumbar spine (LS)-bone mineral density (BMD) and trabecular bone score (TBS) than those with NFAT. The discriminant and principal component analyses clearly separated ACS from NFAT in premenopausal women, but not in men and postmenopausal women. In premenopausal women, 8 steroid metabolites differed between ACS and NFAT, with 11-deoxycorticosterone having the largest effect size (Cohen’s d=1.600, false discovery rate (FDR)=1e-04). In premenopausal women with ACS, 11-deoxycorticosterone showed a negative correlation with LS-BMD Z-score (r=-0.603, FDR=0.064), and DHEA-S and androsterone-glucuronide showed a positive correlation with TBS (DHEA-S, r=0.647, FDR=0.019; androsterone-glucuronide r=0.681, FDR=0.020). The correlation of 11-deoxycorticosterone with LS-BMD Z-score and that of androsterone-glucuronide with TBS remained significant after adjustment for confounders. In men and postmenopausal women with ACS, no steroid metabolites evaluated were significantly correlated with BMD and TBS. Conclusion: This study provides the evidence for distinct steroid profiles in premenopausal women with ACS, suggesting that elevated 11-deoxycorticosterone, a mineralocorticoid metabolite, induces bone loss, and decreased androsterone-glucuronide, an androgen metabolite, deteriorates bone quality.
Presentation: Thursday, June 15, 2023
THU423 Recognizing Secondary Contributors Of Osteoporosis In A Hip Fracture Cohort In Singapore
Authors: Tay Wei Lin , Kwang Donovan Tay Yu 
Published: October 2023

Abstract
Disclosure: W. Tay: None. T.Y. Donovan: None.
Osteoporotic fractures pose a considerable burden on a country’s healthcare system. Identifying and managing secondary contributors is essential in optimizing the response to osteoporosis treatment. The reported prevalence of secondary osteoporosis is heterogeneous and maybe country-specific and recommendations on screening for these contributors in guidelines are variable. Knowing the frequency of underlying disorders can facilitate development of suitable and cost-effective recommendations specific to a population. We aimed to examine the prevalence of secondary contributors of osteoporosis in a multi-ethnic cohort of Singaporean women and men presenting with hip fracture and to also identify the extent of treatment gap. A retrospective cohort study of 493 consecutive adult patients admitted to a regional hospital in Singapore for a hip fracture were evaluated for secondary contributors. All patients were enrolled in a standard electronic hip fracture clinical pathway. Laboratory investigations were standardised. Deidentified data was extracted from the electronic health intelligence system (eHINTS) using the Oracle Business Intelligence and Enterprise Edition (OBIEE) software. The eHINTS is a data repository that consolidates healthcare, operational and finance data from multiple healthcare system uploaded on the web-based business intelligence software. Demographics, clinical data and laboratory investigations, bone mineral density and current medication were extracted. Approval was obtained from the centralized institutional board of our institution.
The mean age of the cohort was 78 ±11 years. The majority (67.3%) of the cohort were female. Mean BMI was 22.3± 9.2 kg/m2. The mean T score at the lumbar spine was -1.87± 1.55; total hip -2.32±1.42; femoral neck -2.50 ± 1.28. 45.2% of the cohort had at least a secondary contributor of osteoporosis. 30.6% had vitamin deficiency (25OHD &lt;20µg/L). 12.2% were on at least 1 medication implicated in the pathogenesis of osteoporosis such as aromatase inhibitors, glucocorticoids, anti-epileptics, levothyroxine, anti-depressants, warfarin, gonadotropin-releasing hormone (GnRH) therapy. 6.9% had primary hyperparathyroidism. 2.6% had primary hyperthyroidism. In male patients, 2.5% had hypogonadism. 1 patient had hypercalciuria. 13.6% had a BMD done prior to the hip fracture admission and only 11.8% of patients were on osteoporosis treatment prior to admission.
Secondary contributors to osteoporosis are common and this should be considered in the evaluation of patients presenting with hip fractures. A significant treatment gap still exists and future studies should address the reasons behind the treatment inertia.
Presentation: Thursday, June 15, 2023
THU424 A Diagnostic Predictive Model For Secondary Osteoporosis In Patients With Fragility Fracture: A Retrospective Cohort Study In A Tertiary Care Hospital
Authors: Phudphong Pitchaporn , Phimphilai Mattabhorn , Manosroi Worapaka , Adulkasem Nath , Kaewchur Tawika 
Published: October 2023

Abstract
Disclosure: P. Phudphong: None. M. Phimphilai: None. W. Manosroi: None. N. Adulkasem: None. T. Kaewchur: None.
Introduction: Although primary osteoporosis is the leading etiology of osteoporosis in asymptomatic elderly presenting with fragility fractures, secondary osteoporosis can be accounted for one-third of patients. Establishing whether a fragility fracture is secondary to a specific cause of osteoporosis is crucial for treatment outcomes. This study aimed to develop a simple screening tool for secondary osteoporosis in the elderly who are presented with fragility fractures. Methods: A retrospective cohort study of 456 patients diagnosed with non-traumatic hip and clinical vertebral fractures between January 2017 and July 2022 was conducted. Demographic, clinical, biochemical, and final diagnostic data were retrieved. Potential predictors for secondary osteoporosis were identified via multivariate logistic regression analysis. Subsequently, we developed a predictive model for secondary osteoporosis using the identified potential predictors. Results: This study included 343 females and 113 males with a mean age of 76.9±11.0 years. One hundred and twenty-one patients (26.5%) were diagnosed with secondary osteoporosis. Vitamin D deficiency (71.9%) was the most common cause of secondary osteoporosis, followed by glucocorticoid-induced osteoporosis (23.9%) and primary hyperparathyroidism (9.9%). The developed prediction model for secondary osteoporosis demonstrated an acceptable discriminative ability with an AuROC of 0.75 (95%CI 0.69 to 0.81) using the patient’s age, body mass index (BMI), corrected serum calcium, serum phosphate, thyroid stimulating hormone (TSH) level, and BMI-based FRAX score. With a cut-off level of 0.22, the proposed predictive model revealed a sensitivity of 74.4% and a specificity of 65.8%. Finally, the developed prediction model was derived into a web-based screening tool available at: https://www.calconic.com/calculator-widgets/secondary-osteoporosis-screening-tool/62f7c112d5da86001f8e3a25?layouts=true. Conclusion: A predictive model for screening secondary osteoporosis was constructed using simple clinical and biochemical parameters. This newly developed predictive model may provide clinicians with guidance to perform further advanced investigations for secondary causes of osteoporosis.
Presentation: Thursday, June 15, 2023
THU427 The Benefits Of Oral Bisphosphonates For Elderly Patients With A History Of Long Term Aromatase Inhibitor Use
Authors: Dominguez Lorena D , Acosta Sebastian Everett , Alejandro Angel Rodolfo 
Published: October 2023

Abstract
Disclosure: L.D. Dominguez: None. S.E. Acosta: None. A.R. Alejandro: None.
Aromatase Inhibitors (AI) are commonly used to treat estrogen receptor-positive breast cancer as they reduce the risk of recurrence and mortality. The AIs, however, can lead to a decrease in bone mineral density (BMD), resulting in fractures. According to the Journal of Bone Oncology (JBO), postmenopausal women on AIs with two or more risk factors for fractures should be placed on antiresorptive treatment (1). Our objective was to compare the BMD of at-risk patients that have been treated with antiresorptive treatment versus the BMD of patients not treated. An EMR chart review was conducted from 6/14/2022-8/20/2022, in which 295 patients were analyzed by the medications prescribed and their BMD. Our sample size was limited to 90 patients that had obtained DXA scores from the same GE Hologic densitometer. We hypothesized that patients on AIs and antiresorptive treatment would show more improvement in BMD than patients on AIs and not on treatment. Patients were analyzed in the comparison of their BMD. Of the 65 patients on AIs, only 17 were placed on antiresorptive treatment (26%). 94% of these patients showed improved BMD. The increase in BMD for the spine was significant (.030) as it exceeds the least significant change (LSC) of .027 g/cm^2. The improvement of .012 in the hip was not significant (.022 g/cm^2 LSC). 68.75% of patients on AI’s and not on treatment worsened by .025 in the hip (.022 g/cm^2 LSC) and by .017 in the spine (.027 g/cm^2 LSC). Alendronate (76%), Zoledronic acid (18%) and Ibandronate (6%) were commonly prescribed. The patients on Alendronate and Ibandronate, improved by .015 in the hip (.022 g/cm^2 LSC) and improved significantly by .028 in the spine (.027 g/cm^2 LSC). Patients on intravenous(IV) treatment improved significantly in the spine by .041(.027 g/cm^2 LSC) but only improved by .006 in the hip (.022 g/cm^2). Although IV administration of treatment is recommended for patients starting treatment (2), most patients showed a trend of improvement on oral bisphosphonates. Hence, to improve the care offered to at-risk patients who cannot obtain IV bisphosphonates, we can advocate for the use of oral bisphosphonate treatment.
References:
(1)Hadji, Peyman, et al. “Manage of Aromat.” JBO, 2017,doi:10.1016/j.jbo.2017.03.001
(2)”Mottaghi P. Intrav bisphos.” Res Med. 2010 May;1515(3):175-84
Presentation: Thursday, June 15, 2023
THU428 Association Of Bone Turnover Markers Monitoring With Osteoporosis Medication Adherence In Korea: A Nationwide Cohort Study
Authors: Ahn Seong Hee , Park So Young , Kwak Mi Kyung , Kim Se Hwa , Kim Tae-Young , Kim Ha Young , Hong Seongbin 
Published: October 2023

Abstract
Disclosure: S. Ahn: None. S. Park: None. M. Kwak: None. S. Kim: None. T. Kim: None. H. Kim: None. S. Hong: None.
Objective: Bone turnover markers (BTMs) are non-invasive and useful biomarkers for predicting the risk of fractures and monitoring the adherence and response to medical treatment in patients with osteoporosis. However, the contribution of BTMs in the improvement of osteoporosis medication adherence has not been well studied. Therefore, we investigated the association of BTMs monitoring with medication adherence in Korean osteoporosis patients. Methods: We used data from the Korean National Health Insurance Service. Among 1,440,538 osteoporosis patients ≥50 years who started with medical treatment during 2010-2014, we selected 118,598 patients who monitored BTMs at least once during 2 years of follow up (BTM group) and 362,794 age-, sex-, and medication initiation year-matched controls who never measured BTMs (NO-BTM group). Adherence to medical treatment was defined as medication possession ratio ≥80%. Multivariable logistic regression analysis was used to determine the association of BTMs monitoring with adherence at 2 year follow up. Results: Among BTM group, 92.5% and 87.1% patients monitored bone resorption or formation markers at least once during 2 years of follow up, respectively. However, only 36.0% of patients monitored BTMs more than twice. MPRs at 2 year follow up were higher in BTM group than in NO-BTM group (41.4% vs. 26.5%, P&lt;0.001). Among BTM group, MPRs were higher in patients who monitored bone resorption markers than in patients who never monitored them (41.7% vs. 36.1%, P&lt;0.001) and in patients who monitored BTMs more than twice than in patients who monitored them only once (55.6% vs. 32.9%, P&lt;0.001). BTMs monitoring showed positive association with MPRs at 2 year follow up (β = 3.055, SE = 0.137, P&lt;0.001) after adjusting for confounders. BTMs monitoring was associated with increased OR (1.17, 95% CI 1.15-1.20, P&lt;0.001) for better adherence to medical treatment at 2 year follow up after adjusting for confounders. Conclusion: In this retrospective study, monitoring of BTMs was associated with better adherence to medical treatment in Korean patients with osteoporosis.
Presentation: Thursday, June 15, 2023
THU301 Natural History Of Pregnancy And Pregnancy Outcomes In Subjects With Lipodystrophy
Authors: Neal Trinity J , Startzell Megan S , Cochran Elaine , Lightbourne Marissa , Brown Rebecca J 
Published: October 2023

Abstract
Disclosure: T.J. Neal: None. M.S. Startzell: None. E. Cochran: None. M. Lightbourne: None. R.J. Brown: None.
Lipodystrophy syndromes are a group of rare heterogenous disorders characterized by deficiency of adipose tissue in a regional distribution (Partial Lipodystrophy, PL) or all of the body (Generalized Lipodystrophy, GL), leading to severe insulin resistance, diabetes, hypertriglyceridemia, non-alcoholic steatohepatitis, and polycystic ovarian syndrome. During pregnancy in patients with lipodystrophy, insulin resistance worsens during late gestation, leading to pregnancy complications that may threaten the lives of the fetus and mother. Case reports have suggested increased risk of pregnancy complications such as pre-eclampsia in patients with lipodystrophy. We sought to systematically examine pregnancy complications and offspring outcomes in lipodystrophy through a prospective study involving structured interviews with patients with known lipodystrophy and past pregnancy.
Data were collected in 7 patients with PL (2 LMNA, PPARG, 4 unknown genetic cause) and 1 with GL (AGPAT2). These 7 patients had 21 pregnancies (mean 2.6), including 19 singleton and 2 twin gestations. 14 pregnancies (67%) were spontaneous and 7 (33%) required fertility treatment. 10 pregnancies (48%) in 6 patients resulted in 12 live births (7 term, 3 preterm; 3 vaginal and 8 C-section delivery) and 11 (52%) resulted in miscarriage (9 first trimester, 2 second trimester in 1 patient due to cervical insufficiency). There were no episodes of acute pancreatitis during pregnancy. Among the 10 pregnancies resulting in live birth, 100% were complicated by diabetes. 5 (50%) had pre-gestational diabetes and 5 (50%) had gestational diabetes that resolved after delivery. 8 (80%) required insulin during pregnancy (of whom none required insulin pre-pregnancy). 5 (50%) of these pregnancies were complicated by pre-eclampsia. Among all 21 pregnancies, metformin was used in 8 (38%), insulin in 8 (38%), metreleptin in 4 (19%) pregnancies (all 4 of which were in 1 patient with GL), and fenofibrate in 2 (9.5%). Among 12 offspring, 1 (8%) was small for gestational age (GA), 8 (67%) were appropriate for GA and 3 (25%) were large for GA. 6 (50%) had neonatal hypoglycemia.
In summary, pregnancies in women with lipodystrophy showed high complication rates, including very high rates of miscarriage, diabetes, and pre-eclampsia. Larger studies are needed to determine how management of these patients during pregnancy, including with newer treatments such as metreleptin for GL, affects pregnancy and offspring outcomes.
Presentation: Thursday, June 15, 2023
FRI652 Type 2 Diabetes Management: More GLP1 Agonists And Less Metformin?
Authors: Lopez Maldonado Francisco J , Cota Rene A 
Published: October 2023

Abstract
Disclosure: F.J. Lopez Maldonado: None. R.A. Cota: None.
Case presentation: A 41-year-old male patient with family history of T2DM in both parents and brother, personal history of mild alcohol consumption and a sedentary job (public accountant), and obesity since age 30 presented to the endocrinology clinic due to failure to lose weight after 1 year of treatment with a nutritionist. During his first visit, the was asymptomatic and had acanthosis nigricans, his blood pressure was measured at 142/92 mmHg, weight was 100.8 kg, waist circumference was 128 cm, and serum glucose was at 280 mg/dL with an HbA1c of 11.9%. Further laboratory tests showed elevated levels of triglycerides (310 mg/dL), LDL (139 mg/dL), AST (96 U/L), and ALT (65 U/L). Two days later, glucose and HbA1c were repeated with similar results. A liver ultrasound was ordered which revealed diffuse hyperechogenicity of the liver and severe fatty liver disease. The ASCVD risk score was 5.4%. The patient was diagnosed with T2DM, obesity, mixed dyslipidemia, and fatty liver disease. The patient received education, nutrition support, exercise, and pharmacotherapy management with stepped-dose oral semaglutide without metformin. The dose was increased monthly starting at 3 mg and reaching the target dose of 14 mg QD. After three months, the patient demonstrated significant improvements in various parameters such as blood pressure (−10/−8 mmHg), weight (−9.8 kg), waist circumference (−25 cm), serum glucose (−179 mg/dL), HbA1C (−5.7%), triglycerides (−154 mg/dL), LDL (−18 mg/dL), AST (−60 U/L), and ALT (−38 U/L), along with an increase in HDL (+6 mg/dL). After approximately 4 months on the target dose the patient showed further improvements in several parameters including ASCVD risk score (2.1%), blood pressure (−20/12 mmHg), weight (−14.8 kg), waist circumference (−30 cm), serum glucose (−183 mg/dL), HbA1C (−6%), LDL (−25 mg/dL), AST (−63 U/L), and ALT (−40 U/L), and HDL (+10 mg/dL), except for triglyceride levels (−130 mg/dL). Follow-up liver ultrasound showed significant improvement in fatty liver disease. Real-world experiences with newly introduced drugs should be reported, as they may have beneficial effects beyond the ones studied. Oral semaglutide, the first oral GLP-1 analog, has been shown to be non-inferior to other subcutaneous GLP-1 analogs. In this case, improvements were observed in glycemic control, weight loss, lipid levels, and a reduction in cardiovascular risk, as well as an improvement in fatty liver disease.
Presentation: Friday, June 16, 2023