bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP366 Copeptin Improves Prediction of Treatment Response in Children With Monosymptomatic Nocturnal Enuresis
Authors: Sailer Clara O , Gaisl Odile C , Beglinger Svetlana , Sommer-Joergensen Vivienne , Frech-Dörfler Martina , Christ-Crain Mirjam 
Published: November 2022

Abstract

Background
Monosymptomatic nocturnal enuresis, bedwetting of children older than 5 years, affects 10% of children, and increases psychosocial burden. Monosymptomatic nocturnal enuresiscan be treated with DDAVP, a vasopressin analogue. Not all children respond to DDAVP treatment, and no reliable treatment predictor has yet been established. We hypothesise that plasma copeptin, a surrogate marker for vasopressin, can be used to predict treatment response to DDAVP in children with monosymptomatic nocturnal enuresis.

Methods
In this prospective observational study, we included 28 children with monosymptomatic nocturnal enuresis. Number of wet nights were assessed prior to starting, 4 weeks, and 12 weeks following treatment with DDAVP. Plasma copeptin was measured in the morning and evening prior to starting DDAVP treatment and after 4 weeks of treatment. Initial daily dose wasDDAVP 120 mg and was increased to DDAVP 240 mg in children where treatment response was insufficient after 4 weeks. Treatment response was defined as &gt;50% reduction in wet nights and divided into partial treatment response (50-99% reduction of wet nights per week) and complete treatment response (100% reduction of wet nights). The primary endpoint was prediction of treatment response following 12 weeks of treatment with DDAVP using plasma copeptin ratio (evening/morning copeptin) at baseline.

Results
Median [IQR] age of children with monosymptomatic nocturnal enuresis was 10 years [8. 0, 11.2], 75% were male. Median [IQR] number of wet nights at baseline was 5. 0 [2.8, 7. 0]. 18 children responded to DDAVP treatment at 12 weeks (partial treatment response 10 children, complete treatment response 8 children). To predict overall treatment response, the best copeptin ratio cut-off was 1.34 (sensitivity 55.56%, specificity 94.12%, AUC 70.6%). To predict partial treatment response, the best copeptin cut-off was 1.3 (sensitivity 55.56%, specificity 100%, AUC 73. 0%). To predict complete treatment response, the best copeptin cut-off was 1.34 (sensitivity 31.25%, specificity 90%, AUC 54.1%). In contrast, neither number of wet nights at baseline, age, BMI, or serum sodium alone or in combination with plasma copeptin improved outcome prediction.

Discussion
Our results indicate that plasma copeptin ratio is the best predictor for treatment response in children withmonosymptomatic nocturnal enuresis. Plasma copeptin ratio could thus be useful to identify children with the highest benefit of DDAVP treatment and improve individualized treatment of monosymptomatic nocturnal enuresis.
Presentation: No date and time listed
ODP576 A pilot randomized clinical trial of intranasal oxytocin to promote weight loss in children, adolescents, and adults with hypothalamic obesity
Authors: Bamba Vaneeta , Cilenti Nicolette , Crowley Julia , Dedio Anna E , Fisher Michael J , Hocking Matthew C , Lawson Elizabeth A , Plessow Franziska , Roizen Jeffrey D , Vetter Victoria L , Wade Kristin L , Wang Zi C , Xiao Rui , McCormack Shana 
Published: November 2022

Abstract
Many individuals with brain tumors affecting the hypothalamus and pituitary gain weight excessively after tumor treatment. There is currently no FDA-approved treatment for this condition, which is called hypothalamic obesity. In animals and in some preliminary studies in humans, the hypothalamic hormone oxytocin impacts metabolism, and may be deficient in individuals with hypothalamic obesity. Therefore, we performed a randomized, double-blind, placebo-controlled, cross-over trial to test the effects of 8 weeks of intranasal administration of oxytocin as compared to placebo on body weight in children, adolescents, and young adults (ages 10-&lt;35y) with excess weight gain related to hypothalamic/pituitary brain tumors (N=13). We did not detect an effect of oxytocin on body weight or other metabolic measures. Overall oxytocin appeared well-tolerated, with most side effects being mild and not different from placebo. Our pilot study yielded several other lessons. First, affected individuals have many other medical problems. Also, individuals with hypothalamic obesity also differ from each other with respect to factors that impact body weight (e. g., appetite and eating behavior) and thus future larger studies could test different individualized dosing strategies, combination therapies, and a wider scope of outcomes to examine further the potential value of oxytocin treatment in this disorder. Keywords: Craniopharyngioma, Hypothalamic Dysfunction, Hypothalamus, Obesity, Weight Loss.
Presentation: No date and time listed
ODP587 A Case of Rathke'S Cleft Cyst Presented With Central Diabetes Insipidus In A Young Female
Authors: Das Niladri , Baidya Arjun , Tarenia Silima Subhasnigdha , Hathi Deep , Gaikwad Prashant Manohar , Pathak Yashaswi , Banerjee Abhirup , Chatterjee Mounam , Goswami Soumik , Sengupta Nilanjan 
Published: November 2022

Abstract

Introduction
Rathke's cleft cysts (RCC) are cystic sellar and suprasellar lesion derived from remnant of Rathke's pouch. RCC are mainly asymptomatic, but can present with headache, visual disturbance, panhypopituitarism, hypothalamic dysfunction when it enlarges causing compression to the surrounding structure. Diabetes insipidus as a presenting feature of RCC is rare. Even it presents with diabetes insipidus, it occurs more in elderly.

Clinical Case
A 32-year-old married female, mother of one child, having normal menstrual cycle presented with polyuria, polydipsia of recent onset. Clinical examinations was normal. Serum creatinine, potassium, calcium, plasma glucose were within normal range. Anterior pituitary hormonal evaluation was normal. Serum sodium was in the upper range of normal. Basal urine osmolality and serum osmolality were 87.49 mosm/kg (150 -1150 mOsm/kg) and 287 mOsm/kg (275 -295 mOsm/kg) respectively. Water deprivation test followed by vasopressin challenge test was done, which revealed partial central DI. Magnetic resonance imaging revealed a sellar cystic lesion hyperintense on both T1 and T2 weighted images, suggestive of rathke's cleft cyst and posterior pituitary bright spot was not visible. Tablet desmopressin 50 mcg twice daily was given and within two days patient responded well to the treatment. Urine volume reduced to 2.5 litres/day and water intake reduced to 3. 0 litres/day.

Conclusion
This is a rare case of Rathke's cleft cyst, presenting as diabetes insipidus as the sole manifestation in a young lady.
Presentation: No date and time listed
ODP653 DNA Methylation Markers Detected in Liquid Biopsy Specimens Differentiate Pituitary Neuroendocrine Tumors from Other Sellar and CNS Diseases
Authors: Castro Ana Valeria , Herrgott Grayson , Asmaro Karam , Wells Michael , Sabedot Thais , Barnholtz-Sloan Jill , Sloan Andrew , Selman Warren , Noushmehr Houtan , Rock Jack 
Published: November 2022

Abstract

Background
DNA methylation abnormalities are pervasive in pituitary neuroendocrine tumors (PitNETs). The feasibility to detect these molecular alterations in circulating cell-free DNA (cfDNA) has been reported for several central nervous system tumors but not across PitNETs.

Hypothesis
PitNET-specific methylation signatures detected in liquid biopsy specimens differentiate PitNETs from other sellar diseases.

Method
We profiled the cfDNA methylome (EPIC array) of 44 serum and 34 plasma liquid biopsy (LB) specimens from patients with PitNETs and other CNS (craniopharyngiomas, other pituitary diseases, gliomas, meningiomas) or nontumor conditions, grouped as non-PitNET.

Results
Our results indicated that, despite quantitative and qualitative differences between serum and plasma cfDNA composition, both sources of LB showed that patients with PitNETs presented a distinct methylome landscape compared to non-PitNETs. In addition, LB methylome captured epigenetic features reported in PitNET tissue. Using LB-derived PitNETs-specific signatures as input into a machine-learning algorithm, we generated a score that distinguished PitNETs from other pituitary and CNS diseases with high accuracy in an independent set.

Conclusions
Our results underpin the potential application of a methylation-based LB as a noninvasive approach to identify clinically relevant epigenetic markers to diagnose and potentially impact the management of patients with PitNETs.
Presentation: No date and time listed
OR27-1 11-Oxygenated C19 Steroids Are the Predominant Androgens Responsible for Hyperandrogenemia in Cushing's Disease
Authors: Adaway Jo , Auer Matthias , Bidlingmaier Martin , Braun Leah , Hawley James , Keevil Brian , Lottspeich Christian , Reincke Martin , Reisch Nicole , Schilbach Katharina , Tschaidse Lea , Vogel Frederick , Nowotny Hanna 
Published: November 2022

Abstract

Background
Symptoms of hyperandrogenism are common in patients with Cushing's disease (CD), but they cannot be sufficiently explained by measured concentrations of circulating androgens. In this study we analyzed the contribution of 11-oxygenated (11oxC19) androgens to hyperandrogenemia in female patients with CD as well as the influence of treatment with steroidogenesis inhibitors osilodrostat and metyrapone on 11oxC19 and classic androgens.

Methods
In this single-center study, we assessed saliva day profiles of 23 females with treatment naïve CD, 26 female controls, 5 females with CD treated with metyrapone and 5 treated with osilodrostat for cortisol, cortisone, androstenedione (A4), 11-hydroxyandrostenedione (11OHA4), testosterone (T), 11-ketotestosterone (11KT) by by liquid chromatography tandem mass spectrometry as well as morning baseline levels of gonadotropins and estradiol, sex hormone-binding globulin, cortisol anddehydroepiandrosterone sulfate (DHEAS) in serum and adrenocorticotropic hormone in plasma.

Results
Treatment naïve females with CD showed significantly elevated area under the curve (AUC) of 11OHA4 and 11KT throughout the day compared to controls (11OHA4 mean rank difference (mrd) 18.13, p = 0.0002; 11KT mrd 17.42; p = 0.0005) whereas A4, T and DHEAS were comparable to controls. Patients with more symptoms of hyperandrogenism displayed higher concentrations of 11oxC19 androgens and had significantly lower SHBG concentrations. Gonadotropin levels were normal in all patients with CD (LH 7.18 U/l (SD 14.28 U/l); FSH 7.68 U/l (SD 12.0 U/l)) and did not correlate with any other parameters. Treatment with osilodrostat and metyrapone efficaciously blocked 11oxC19 synthesis. In metyrapone but not in osilodrostat treatment a trend towards increased concentrations of T and significantly increased A4-concentrations were observed (A4 mrd 23.07, p = 0.0119).

Conclusion
Hyperandrogenemia in CD is predominantly caused by excess of 11oxC19 androgens. Due to lower compensatory increase of A4 and T, osilodrostat seems to be more suitable for treatment of females with CD and hyperandrogenism than metyrapone.
Presentation: Tuesday, June 14, 2022 9:45 a.m. - 10:00 a.m.
PMON100 IgG4 hypophysitis with granulomatous histopathology
Authors: Gultekin Sakir , Kargi Atil Y , Barrera Francisco 
Published: November 2022

Abstract

Background
IgG4-related disease is characterized by a dense lymphoplasmacytic infiltrate rich in IgG4 plasma cells that may be accompanied by elevated serum IgG4 levels, presence of granulomatous histopathology with multinucleated giant cells has not been reported in patients with IgG4 related hypophysitis.Clinical case: A 39-year-old female with no significant past medical history until April of 2021, when she developed gradual onset of headaches. MRI brain showed a mass in the sella, she was treated for over a month with glucocorticoids by ENT and her headaches improved. She finished the course of glucocorticoids, and soon after, she had a recurrence of her symptoms. Repeat brain MRI revealed a large pituitary mass and she had her first endoscopic endonasal transsphenoidal resection on 8/2021 at an outside hospital. Pathology report of the surgery suggested that she had a colloid cyst of the pituitary and cultures grew actinomyces and streptococcus oralis, likely, as a consequence of contamination from an ethmoid sinus infection/surgical infection, she was treated with antibiotics. Surgery was also complicated by diabetes insipidus for which she is taking desmopressin tablets.She presented to our hospital in November 2021, with persistent symptoms (headaches and worsening vision), and a postoperative brain MRI showing an expansion of the lesion with compression of the optic chiasm, she was evaluated by neurosurgery who recommended repeat revision endoscopic endonasal transsphenoidal resection of this lesion.The patient underwent a second transsphenoidal surgery on 11/29/2021 at our institution. During admission TSH was 0.123 mcIU/ml (0.27-4.2mcIU/ml) with Free T4 0.52ng/dL (0.93-1.7ng/dL). She was discharged on hydrocortisone, desmopressin tablets, and levothyroxine.The pathology report of the second surgery revealed mixed chronic and acute inflammation with granulomatous components containing histiocytic clusters and multinucleated giant cells. Many plasma cells, rare eosinophils, and foci of neutrophils are present. The ratio of IgG4 to IgG is over 70%, with more than 10 IgG4 (+) cells per 10HPF. GMS and AFB were negative for fungi and mycobacteria.Patient's outpatient labs were consistent with panhypopituitarism with AM cortisol of 1.9mcg/dL, ACTH 19pg/mL (6-50 pg/ml), FSH 6.5 mIU/ml, LH 2.4 mIU/ml and estradiol &lt;15pg/ml. TSH was 1.26 mcIU/ml (0.27-4.2mcIU/ml) with Free T4 0.8ng/dL (0.8-1.8ng/dL). IGF-1 level was 72ng/ml (79-259ng/ml). Prolactin was 7.0 ng/ml (3.0-30.0ng/ml). IgG4 serum level was 100.2mg/dL (4.0-86.0mg/dL), IgG1 serum level was 446mg/dL (382-929mg/dL).

Conclusion
This is a unique patient with panhypopituitarism that meets the criteria for IgG4 related hypophysitis but also has secondary granulomatous components developed after the rupture of the colloid cyst during the first surgery. The implications of these findings are unknown in terms of management and prognosis.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON109 A Case of Non-functioning Pituitary Adenoma With Unexpectedly High Prolactin Level
Authors: Mahali Lakshmi Priyanka , Tariq Sana , Abraham Smita 
Published: November 2022

Abstract

Introduction
Lactotroph or prolactin (PRL)-secreting adenomas account for approximately 45% of all pituitary adenomas. They are classified by size as microprolactinomas (&lt;10 mm) and macroprolactinomas (≥10 mm). A giant prolactinoma is arbitrarily defined as an adenoma &gt; 4 cm. PRL levels are often proportional to the size of tumor ranging from &lt;200 ng/mL in adenomas smaller than 1 cm, 200 ng/mL to 1000 ng/mL in 1 cm to 2 cm adenomas and more than 1000 ng/ml in tumors larger than 2 cm. Nonfunctioning pituitary adenomas (NFPA) can cause mild increases in PRL levels due to pituitary stalk compression, however, levels more than 6 times the upper limit of normal have not been reported. We present a rare case of NFPA with significantly elevated prolactin levels Case: 42 yo female presented with headache and left eye blurry vision worsening over 2 years. MRI revealed a pituitary macroadenoma measuring 4.1×4.7×3cm with supra-sellar extension, mass effect including severe compression and displacement of the optic apparatus, and potential cavernous sinus invasion. Initial biochemical profile: TSH 1.01 (0.30–4.20 uU/mL), FT4 0.9 (0.6–1.5 ng/dL), AM ACTH of 20 (7.2-20 pg/ml), peak cortisol 18.8 mg/dl after cosyntropin stimulation, FSH 14.6 mIU/mL, LH 2.4 mIU/mL, IGF-1 71 (52-328 ng/mL) and prolactin 452 (&lt;25.0 ng/mL), confirmed by dilution. PRL levels were concerning for prolactinoma but did not correlate with tumor size making giant prolactinoma an unlikely diagnosis. Yet, levels were higher than those expected from stalk compression. An interdisciplinary decision was made to proceed with operative management. The patient underwent trans-sphenoidal pituitary resection (TSPR). Tumor pathology showed sparsely granulated gonadotroph adenoma with weak LH expression and negative PRL staining, confirming NFPA. PRL level one-month post op was 33.2 ng/mL and vision is improved.

Conclusion
Medical treatment with dopamine agonists is first line treatment for any size prolactinoma with a high remission rate of 90% and prescribed before TSPR even in those with vision disturbance or neurologic symptoms. Giant NFPAs with compressive symptoms are best surgically managed.To our knowledge, this is the first report of significant PRL elevation due to stalk compression. Not only was the PRL higher than that previously associated with stalk compression, but also well above 250 ng/mL, which is typically diagnostic of prolactinoma. This case also highlights the importance of assessing the relationship between PRL level and tumor size to determine the correct course of management.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON112 Primary Pituitary Lymphoma Presenting as Apoplexy
Authors: Abdelaziz Sara , Abrahamson Martin , Mottalib Adham 
Published: November 2022

Abstract

Background
Primary pituitary lymphoma (PPL) in immunocompetent individuals represents a distinct and rare clinical entity.

Clinical Case
A 49-year-old menopausal woman with past medical history of hypertension and obesity who presented to the emergency room with sudden onset loss of vision in her right eye with blurriness on the left. She had been having intermittent headaches and flu-like symptoms over the 2 days preceding her presentation. Her BP was 179/116 mmHg, initial basic metabolic profile was normal, and head CT showed hemorrhage into a bilobed sellar and suprasellar mass measuring 2.2×2.2×3.3 cm. On ophthalmic exam, the right eye showed near-complete visual field loss with some residual island of vision superotemporally while left eye showed temporal hemianopsia. Initial endocrine workup was notable for a normal cortisol 15.9 (ref 2-20) ug/dL and normal prolactin; low-normal TSH 0.73 (ref 0.2-4.2) uIU/mL; low free T4 0.3 (ref 0.9-1.7) ng/dL; low FSH, LH, and IGF-1. She received a pituitary MRI showing hemorrhagic pituitary macroadenoma with significant upward bowing of the optic chiasm and infiltration into the cavernous sinuses. The patient developed diabetes insipidus (DI) before being taken to the operating room for transsphenoidal surgery with debulking and biopsy. Postoperatively and while waiting for pathology results, she developed panhypopituitarism and was being treated with hydrocortisone, levothyroxine, and desmopressin. Her pathology was consistent with diffuse large B-cell lymphoma (DLBCL) of non-germinal center type. She had a complete hematologic workup including whole body PET-CT showing sellar and suprasellar fluorodeoxyglucose avid disease without evidence of disease elsewhere in the head, neck, and torso which confirmed the diagnosis of PPL. The patient was started on chemotherapy using R-CHOP (rituximab, cyclophosphamide, hydroxyadriamycine, vincristine, and prednisone) with high-dose methotrexate. Following the first chemotherapy treatment cycle, she had a modest improvement in her vision; however, her DI was permanent.

Conclusion
This case demonstrates that PPL can present with pituitary apoplexy and can result in panhypopituitarism and permanent DI. Individuals with this condition require a multidisciplinary care team including endocrinology, neurosurgery, hematology, and ophthalmology.

References
A Giustina, M Gola, M Doga, E A Rosei. Primary Lymphoma of the Pituitary: An Emerging Clinical Entity. JCEM. 2001 Oct;86(10): 4567-75.A Tarabay, G Cossu, M Berhouma, M Levivier, R T Daniel, M Messerer. Primary pituitary lymphoma: an update of the literature. J Neurooncol. 2016 Dec;130(3): 383-395.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
PMON127 Neuroendocrine Tumor of the Spinal Cord- A Case Report of Rare Endocrine Tumor Presentation
Authors: Varghese Diana Grace , Yoldy Dorisca , Raygada Margarita , Sedlack Andrew , Anaraki Kimia Saleh , Reilly Karlyne , Widemann Brigitte , del Rivero Jaydira 
Published: November 2022

Abstract

Introduction
Neuroendocrine tumors (NETs) are heterogeneous group of malignant neoplasms arising from neuroendocrine cells distributed throughout the body. The most common sites of NETs are the gastrointestinal tract, pancreas and lungs which account for 82% of all NET cases. Other NET sites are those arising in the parathyroid, thyroid, adrenal, and pituitary glands. Rare NET sites include biliary, prostate, breast, head, and neck. Only a few cases report have been documented in the spinal cord as primary site of origin. Here we present a neuroendocrine tumor case arising from the cervical spinal cord.

Clinical Case
A 60-year-old male presented with posterior cervicalgia and left side facial, neck and shoulder paresthesia. A magnetic resonance imaging (MRI) of the head and cervical spine was performed and demonstrated an heterogenous, non-enhancing mass in the lower brain stem/upper cervical cord. An intramedullary 1.2×1.3×3.4 cm mass was identified with edema surrounding the mass. An MRI of the thoracic and lumbar spine was unremarkable. A fluorodeoxyglucose (FDG)-positron emission tomography (PET)- PET/CT scan only demonstrated a hypermetabolic lesion at the upper cervical spine. A posterior craniotomy and C1 laminectomy was performed with resection of the mass. Surgical pathology revealed a Grade 2 well-differentiated NET with Ki67 proliferation rate approaching 20%. A 68Ga-DOTATATE PET/CT post-surgery only showed a small focus of uptake within the left side of the upper cervical cord, with an SUV max of 3.9. Patient was subsequently treated with 45 Gy of external beam radiation therapy in 25 fractions. Molecular profile was performed on the patient's tumor (TSO 500; TruSight Oncology, Illumina); pathogenic variants were identified in EPHA3 and Tp53, and a copy number gain was found on CCND1. No further therapy was indicated, and patient continued active surveillance.

Conclusion
NETs constitute approximately 2% of all cancer diagnosed in the western world. The incidence has increased sixfold in the past four decades affecting approximately 170000 patients in USA. NETs (primary/ metastatic) are a rare occurrence in the Central Nervous System (CNS), and very few case reports of this condition are described in the literature. Surgery remains the mainstay treatment modality, with the goal of complete resection of the tumor. For residual tumors, somatostatin analogs, targeted molecular therapy (mTOR inhibitors and tyrosine kinase inhibitors) and chemotherapy (capecitabine /temozolomide) are indicated. No consensus guidelines exist for the treatment of spinal NETs and majority of the tumors are treated with surgery and radiation. Further studies are warranted for the diagnosis and management of spinal NETs.
Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.