bluuebunny/crossref_metadata_2025_split huggingface dataset:
8553 Gdf-15 Levels In Patients With Prostate Cancer On Androgen Deprivation Therapy
Authors: Carmen Jaramillo-Quiroz Sofia del , Caeiro Lucas , Jayne Anderson Lindsey , Manuel Garcia Jose 
Published: October 2024

Abstract
Disclosure: S.D. Jaramillo-Quiroz: Other; Self; VAPSHCS: Director Fund Research Fellowship/UW Abrass Family Fellowship Fund. CDMRP (PC170059).. L. Caeiro: None. L.J. Anderson: None. J.M. Garcia: None.
Growth Differentiation Factor 15 (GDF-15) is a stress-induced cytokine known to induce anorexia and cachexia and a biomarker of biological aging, mitochondrial dysfunction, and worse hand grip strength and poor survival in different settings. Also, GDF-15 has pleiotropic functions at all stages of tumorigenicity and is suggested as a marker to differentiate BPH from PCa. Androgen Deprivation Therapy (ADT) is the standard treatment for advanced prostate cancer (PCa), but it also decreases muscle mass and function and Quality of life (QOL). The role and effects of GDF-15 in prostate cancer patients undergoing ADT are not well characterized and was explored in this longitudinal, 6-month, observational study that recruited men with (PCa) starting ADT (n=60, mean age 69). Body composition [dual energy X-ray absorptiometry (DEXA), body weight history], physical performance [handgrip strength (HGS), 6-minute walk test (6MWT), energy expenditure (indirect calorimetry and actigraphy)], were assessed before, at 3 and 6 months after starting ADT. QoL was assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30). GDF-15 was measured by ELISA. Mean differences performed with standard error of the mean, repeated measures ANOVA and Tukey’s Post Hoc test. Correlations were assessed by Spearman’s. After 6 months of ADT, fat mass was increased (mean difference: 1.14 ±0.38, p=0.0029), and lean muscle mass (mean difference: -1.214 ± 0.38, p=0.005), appendicular lean mass (ALM, mean difference: -0.879 ± 0.19, p=&lt;0.0001). HGS (mean difference: -2.927 ± 0.59, p=&lt;0.0001), and VO2 max decreased (mean difference -3.31 ± 0.83, p=0.0007). Baseline GDF-15 (mean 1456.59 ± 1022.80) was correlated with the changes in weight (r: -0.38, p=0.01), BMI (r: -0.33, p=0.01), ALM (r: -0.29, p=0.04), and fatigue (r: -0.38, p=0.004). As shown, baseline GDF-15 was inversely correlated with changes in weight, appendicular lean mass, and fatigue in subjects undergoing ADT, highlighting the possibility of its role as a biomarker and therapeutic target of body composition and patient-reported outcomes in this setting.
Presentation: 6/1/2024
8277 Pregnancy-Induced Cushing Syndrome
Authors: Al Allawi Sarah , Okigbo Chinelo , Osman Radwa 
Published: October 2024

Abstract
Disclosure: S. Al Allawi: None. C. Okigbo: None. R. Osman: None.
Introduction: Pregnancy is uncommon in women with Cushing syndrome (CS), as hypercortisolism typically leads to anovulatory infertility. CS during pregnancy can be challenging due to the physiological changes in the hypothalamic-pituitary-adrenal axis, overlapping features with pregnancy, and the potential for misdiagnosis as gestational diabetes or hypertension. Pregnancy-induced Cushing is rarely reported, and can sometimes completely remit postpartum, although some cases recur with subsequent pregnancies. Here, we describe a case of pregnancy-induced hypercortisolism with postpartum remission. Clinical Case: A 26-year-old primigravida with a reported history of PCOS, presented to the hospital at 25 weeks of gestation due to concerns for pre-eclampsia. Prior to her pregnancy, she had a history of oligomenorrhea and had an intrauterine device (IUD) in place until a month before conception. In the first trimester, she developed severe facial acne and excessive hirsutism. An abdominal MRI obtained due to abdominal pain, revealed an enlarged right ovary with a 4.2 cm dominant cyst and a slight asymmetric prominence of the left adrenal, indicating hyperplasia. At 18 weeks, she was diagnosed with pre-eclampsia and subsequently developed severe hypokalemia and muscle weakness. This prompted a workup for hypercortisolism which revealed elevated morning cortisol level of 55 mcg/dL, elevated 24-hour urinary cortisol 2,282 mcg/24 hr, suppressed ACTH &lt; 5 pg/mL, elevated total testosterone 337 ng/dL and plasma renin activity (8.13 ng/mL/hr) with normal DHEAs and aldosterone levels. Repeat workup showed similar findings. A diagnosis of ACTH-independent Cushing syndrome was made. At 25 weeks, she was admitted for severe pre-eclampsia. Physical exam revealed cushingoid features with facial fullness, plethora, dorsocervical fat pads, generalized violaceous striae, and severe acne. A decision was made to initiate Metyrapone, but the patient quickly developed HELLP syndrome which led to premature delivery at 26 weeks, with a concomitant right ovarian cystectomy. Pathology revealed a benign serous cystadenoma. On Postpartum day 2, workup showed a drop in morning cortisol to 26 mcg/dL, ACTH 4.9 pg/mL, total testosterone 25 ng/dL. Three months postpartum, the patient had an improvement in the cushingoid features. Hormonal reassessment demonstrated morning cortisol of 9 mcg/dL, suppressed ACTH &lt; 5 pg/mL, and total testosterone 47 ng/dL. Conclusion: Cushing's syndrome in pregnancy is rare, leading to a low suspicion among physicians and delayed diagnosis, posing risks for both mother and fetus. Over 260 cases of CS in pregnancy have been reported, with only 15 cases of pregnancy-induced Cushing's. Maintaining a high index of clinical suspicion can facilitate prompt diagnosis and early intervention, thereby minimizing maternal and fetal morbidity and improving pregnancy outcomes.
Presentation: 6/3/2024
6620 Serum Steroid Profiling For The Diagnosis Of Adrenocortical Carcinoma: A Prospective Cross-Sectional Study From A Tertiary Center
Authors: Yu K , Athimulam S , Saini J , Kaur R , Singh R J , Grebe S K , Xue Q , Bancos I 
Published: October 2024

Abstract
Disclosure: K. Yu: None. S. Athimulam: None. J. Saini: None. R. Kaur: None. R.J. Singh: None. S.K. Grebe: None. Q. Xue: None. I. Bancos: Advisory Board Member; Self; AstraZeneca, Corcept, Novo Nordisk, HRA Pharmaceuticals, Neurocrine, Diurnal, Recordati, Sparrow, Xeris, Spruce, Adrenas. Research Investigator; Self; HRA Pharmaceuticals, Recordati.
Context: Early diagnosis is essential to assure a better prognosis in patients with adrenocortical carcinoma (ACC). Guidelines suggested performing urine steroid profiling in patients with indeterminate adrenal tumors to make a noninvasive diagnosis of ACC. However, urine steroid profiling is not widely available. Accuracy of clinically available serum steroids in diagnosing ACC has not been established. Objective: To determine the accuracy of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone in diagnosing ACC. Design: Prospective single-center cohort study. Participants: Between 2015 and 2023, consecutive patients with adrenal mass were prospectively enrolled in the prospective registry and biobank study. Patients who agreed to contribute a fasting serum sample were included in the study. Exclusion criteria were congenital adrenal hyperplasia, exogenous glucocorticoid use, absence of unenhanced Hounsfield unit measurements (HU), and lack of established reference standard (histopathology, imaging characteristics, 2-year imaging follow up, or 5-year clinical follow up). Measures and Outcomes: measurements included 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone by liquid chromatography–mass spectrometry. Localized Generalized Matrix Learning Vector Quantization (LGMLVQ) analysis was used to develop serum steroid score and assessed with area under receiver operating curve (AUROC). Results: Of 263 patients with adrenal masses, 44 (17%) were diagnosed with ACC, 161 (61%) with adrenocortical adenomas (ACAs), 27 (10%) with other adrenal malignancies, and 31 (12%) with other. HU ≥ 20 were demonstrated in all ACCs, in all but one other adrenal malignancy, and only in 58 (31%) ACAs. All 3 steroids were higher in patients with ACCs vs nonACCs, including when comparing ACCs with functioning ACAs, and with ACAs with HU ≥ 20 (P&lt;0.0001 for all). LGMLVQ analysis yielded a serum steroid score that discriminated between ACC and non-ACC groups with a mean threshold fixed AUROC of 0.823. Serum steroid score of 0.29 demonstrated a mean false negative rate of 0% and a score of 0.61 demonstrated a mean false positive rate of 0%. Conclusions: We showed that measurements of 11-deoxycortisol, 17OH-progesterone, and 17OH-pregnenolone could be valuable in diagnosing ACC. After appropriate validation, serum steroid score could be integrated in clinical practice.
Presentation: 6/2/2024
12515 Single-Nuclei Multiome Analysis Of The Adrenal Gland Identifies Putative Novel Regulators Of Zone-Specific Steroidogenesis
Authors: Marcondes Lerario Antonio , Rege Juilee , Blinder Amy , Hammer Gary D , Rainey William E 
Published: October 2024

Abstract
Disclosure: A.M. Lerario: None. J. Rege: None. A. Blinder: None. G.D. Hammer: None. W.E. Rainey: None.
The human adrenal cortex comprises three distinct histological zones: the outer zona glomerulosa (ZG), responsible for aldosterone production, the middle zona fasciculata (ZF), producing cortisol, and the inner zona reticularis (ZR), contributing to the synthesis of DHEAS. One key mechanism of zone-specific steroidogenesis lies in the selective expression of membrane receptors for the endocrine regulators AngII and ACTH in the ZG and ZF/ZR, respectively. Activation of these receptors drives zone-specific expression of CYP11B2, CYP11B1, and SULT2A1, the steroidogenic enzymes responsible for the final step of aldosterone, cortisol, and DHEAS biosynthesis, respectively. While the downstream intracellular signaling pathways governing the expression of these enzymes are well characterized, the transcriptional regulatory mechanisms remain incompletely understood. To identify potential transcriptional regulators and chromatin regions controlling the zone-specific expression of steroidogenic enzymes, we conducted a single-nuclei multiome study (RNAseq and ATACseq) in three adrenal glands from adult kidney donors with normal zonation confirmed by immunohistochemistry. As expected, our analysis revealed distinct cell populations with gene expression profiles characteristic of each histological zone, displaying zone-specific expression patterns of CYP11B2, CYP11B1, and SULT2A1. Furthermore, within each zone, subpopulations of cells exhibited variable expression of steroidogenic enzymes, indicative of diverse states of differentiation or cellular activation. Moreover, we identified zone-specific changes in chromatin accessibility spanning the promoters and putative distal regulatory regions of CYP11B2, CYP11B1, and SULT2A1. Transcription factor binding motif analysis of these regions identified known and potentially novel transcriptional regulators controlling the expression of these genes. Our analyses underscore the complexity of the regulatory network that controls the transcription of zone-specific steroidogenic enzymes, highlighting the interplay between promoter-bound transcriptional regulators and distal cis-regulatory elements.
Presentation: 6/2/2024
12444 Steroid Profiling And Circadian Cortisol Secretion In Patients With Mild Autonomous Cortisol Secretion: A Single-Center Cross-Sectional Study
Authors: Saini Jasmine , Singh Sumitabh , Ladefoged Ebbehøj Andreas , Zhang Catherine D , Nathani Rohit , Fell Vanessa , Atkinson Elizabeth , Achenbach Sara , Rivard Ann , Jit Singh Ravinder , Gunther Grebe Stefan Karl , Bancos Irina 
Published: October 2024

Abstract
Disclosure: J. Saini: None. S. Singh: None. A.L. Ebbehøj: None. C.D. Zhang: None. R. Nathani: None. V. Fell: None. E. Atkinson: None. S. Achenbach: None. A. Rivard: None. R.J. Singh: None. S.K. Grebe: None. I. Bancos: None.
Abstract Context: Mild autonomous cortisol secretion (MACS) is diagnosed based on post-dexamethasone cortisol&gt;1.8 mcg/dL. Scarce evidence exists on steroid circadian secretion and steroid metabolome in MACS. Objective: To characterize 24-hour urine steroid metabolome in patients with MACS and determine circadian differences in urine steroid profiling and cortisol concentrations in patients with MACS versus referent subjects. Design: Cross-sectional study, 2018-2023. Setting: Referral center Participants: 72 patients with MACS and 72 age-, sex-, BMI-, and menopausal status-matched referent subjects. Measurements: Urine was collected over a 24-hour (h) period in separate day- and night-time collections. High-resolution mass spectrometry assay was used to measure 25 steroids. A subgroup of patients and referent subjects were admitted for every 2-hour serum measurement of free and total cortisol. Outcomes: Steroids, sums, and ratios Results: Patients with MACS had lower mcg/24h median androgens (2084 vs 3283, P&lt;0.001), higher glucocorticoids (15754 vs 12936, P&lt;0.001), and higher glucocorticoid/androgen ratio (8.7 vs 3.9, P&lt;0.001). Steroid day/night ratios were lower in patients when compared to referent subjects, reflecting a higher relative nocturnal steroid production in MACS. In a subgroup of 12 patients with MACS and 10 referent subjects, the 24-hour area under the curves for total and free cortisol were similar. However, nocturnal mean total (5.3 vs 4.0 mcg/dL, P=0.056) and free (0.2 vs 0.1 mcg/dL, P=0.035) cortisol were higher in patients vs referent subjects. Conclusion: Patients with MACS demonstrate an abnormal urine steroid metabolome, with a high glucocorticoid to androgen ratio, and a higher nocturnal steroid production.
Presentation: 6/3/2024
7325 Adjuvant Denosumab Therapy For Adult-Onset Central Giant Cell Granuloma
Authors: Khalid S , Whitlatch H 
Published: October 2024

Abstract
Disclosure: S. Khalid: None. H. Whitlatch: None.
Introduction: Central giant cell granulomas (CGCG) are rare, expansile non-neoplastic bone lesions involving the mandible or maxilla. These lesions consist of a mix of mononuclear and multinucleated giant cells in a mesenchymal stromal background. CGCG typically occurs before the age of 20 years and is more common in females. Conventionally, surgery has been the mainstay of treatment, ranging from curettage to aggressive resection. Unfortunately, curettage is associated with a recurrence rate of up to 49%. While surgical resection lowers recurrence rate to 6%, it can be associated with substantial morbidity, especially with larger lesions. This has led to the investigational use of medical adjunctive therapy, including intralesional corticosteroids, bisphosphonates, and calcitonin. Recently, there have been case reports involving the successful use of denosumab, a monoclonal antibody to receptor activator of nuclear factor-ΚB ligand (RANK-L). Here, we describe an unusual case of adult-onset CGCG treated with surgery and denosumab. CASE: A 24-year-old female presented to the oral maxillofacial surgery clinic with progressive left-sided mandibular swelling of 2 years duration. On examination, she was noted to have left lower third facial swelling and asymmetry. Intraoral exam showed buccal and labial expansion extending from tooth 19 to 27. CT scan revealed a large, multiloculated, expansile lytic lesion of the left mandible measuring up to 4.2 cm. Biopsy of the lesion was rich in giant cells, and the appearance favored giant cell granuloma. Biochemical evaluation included PTH 29 mg/dL (normal 15 mg/dL - 65 mg/dL), calcium 9.2 mg/dL (8.7 mg/dL -10.2 mg/dL), phosphorus 4.7 mg/dL (3 mg/dL -4.4 mg/dL) and alkaline phosphatase 94 mg/dL (44 mg/dL -121 mg/dL). She underwent enucleation and curettage of the lesion. 3 months after the surgery, she started her course of denosumab 120 mg weekly for 4 weeks, followed by monthly dosing with planned 1 year course. She noted improvement in pain after 2 doses of denosumab, and x-ray imaging at 1 month showed improved bone fill. Conclusion: Denosumab exerts its therapeutic effect in giant cell lesions by inhibiting osteoclast maturation, thereby suppressing osteolysis and giant cell formation. Our case suggests it could be considered first line adjuvant treatment for patients with large CGCG lesions.
Presentation: 6/2/2024
8056 Burosumab Treatment In McCune Albright Syndrome: New Therapeutic Perspectives And Gaps To Be Filled
Authors: Barbato A , Vaiasuso R , Del Medico G , Stagi S 
Published: October 2024

Abstract
Disclosure: A. Barbato: None. R. Vaiasuso: None. G. Del Medico: None. S. Stagi: None.
Background: McCune Albright syndrome (MAS) is a sporadic genetic condition associated with bone dysplasia, multiple endocrine over-function, and café au lait skin macules. It is caused by postzygotic mosaic activating mutations of GNAS gene located on chromosome 20q13.3, leading to increased activity of Gs α protein. Fibrous dysplasia (FD) is one of the key features of this syndrome and causes bone deformities with pathologic fractures. In pediatric age, therapies for FD are only able to control pain and reduce burden of disability but not to modify the course of the disease. FGF23 production is increased in MAS and negatively influences bone metabolism. Anti-FGF23 antibody, burosumab, has been recently introduced as a potential new treatment for FD. Case presentation: an 11 years old boy with MAS was referred to our Center for periodic follow-up and treatment of severe FD. He was diagnosed with FD at the age of 1 year and 8 months and since then underwent 4 pathological fractures and 2 surgical interventions for correction of bone deformity. At the age of 6 years old subclinical hyperthyroidism was diagnosed. At the same age he started treatment with endovenous neridronate every three months with partial control of the pain but progression of bone deformity. One year later he developed hypophosphatemia (nadir 3.1 mg/dl) with increased FGF23 levels (144 pg/ml). Because of the clinical worsening of the disease with persistent laboratory alterations (phosphate 3.1 mg/dl, FGF23 251 pg/ml, alkaline phosphatase (ALP) 2188 UI/l, 25-OH vitamin D 58 ng/ml, and PTH 38 pg/ml), at 9 years old he started periodic treatment with burosumab (0.4 mg/kg). The same year the patient developed a central precocious puberty therefore treatment with GnRH was started. After 1 year of treatment with burosumab (0,8 mg/kg) we observed an increase in phosphate levels to 4.2 mg/dl and a reduction of ALP to 1490 UI/L while FGF23 remained stable 243 pg/ml, as did 25 OH vitamin D 31 ng/ml, and PTH 44 pg/ml. At periodic X-rays we documented a slower but still present progression of the FD. Conclusion: burosumab showed beneficial effect on bone tissue metabolism in our patient without significant adverse reactions but did not manage to completely stop FD progression and reduce FGF23 levels. This finding highlights how FGF23 acts as exacerbating factor rather than sole determinat of FD, leading to only a partial clinical response to anti-FGF23 therapy. Furthermore, the presence of FD reduces the efficacy of ALP as a marker of laboratory response, requiring a more disease specific approach to laboratory monitoring of response to burosumab in MAS. New target therapies are needed for Gs α over-function.
Presentation: 6/1/2024
7390 Case Study Of New Lesion Formation In FOP Patients By 18F-NaF PET/CT Imaging
Authors: Trotter D Gonzalez , Srinivasan D , Mohammadi K , Economides A N , Herman G , Mellis S 
Published: October 2024

Abstract
Disclosure: D. Gonzalez Trotter: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. D. Srinivasan: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. K. Mohammadi: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. A.N. Economides: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. G. Herman: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals. S. Mellis: Employee; Self; Regeneron Pharmaceuticals. Stock Owner; Self; Regeneron Pharmaceuticals.
Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare disorder characterized by the deposition of bone in soft tissues, known as heterotopic ossification (HO). The formation of HO lesions is sporadic and is sometimes associated with painful swellings (flares), which subside over time. LUMINA-1, a phase 2, randomized, double-blind study (NCT03188666), evaluated the safety and efficacy of garetosmab, an anti-activin A antibody, versus placebo in adult patients with FOP. This case series uses [1]8F-NaF PET/CT imaging to follow the evolution of new HO lesions in placebo-treated patients during the double-blinded period of the study, during which patients were imaged at baseline, Week 8, and Week 28 from randomization. Six patients were selected to represent the observed range of aggregate positive new lesion volume burden. Lesion characteristics over time were reported according to their number, time of initial observation, location, and size. A total of 21 new lesions were detected: three appearing at Week 8 and 18 appearing at Week 28. Individual patients accumulated nine (left shoulder, humerus, and scapula), two (left femur and forearm), one (left pelvis), four (right thigh), three (right thigh), and two (right tibia) new lesions by Week 28, with an aggregate volume of 84.8, 36.0, 14.7, 14.5, 3.2, and 1.1 cm3, respectively. All three lesions that were first observed at Week 8 were detected at Week 28 and had increased in size by an average of 277% (10.0 cm3). This case series illustrates the tendency of new lesions to appear in clusters at disparate locations, with those initially observed at Week 8 persisting into Week 28. These findings suggest that after their initial formation new HO lesions generally do not regress spontaneously, indicating the need for therapeutic interventions that inhibit the initial formation of new HO lesions in FOP patients.
Presentation: 6/2/2024