bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR29-01 Long-Term Safety in Adults with X-Linked Hypophosphatemia (XLH) Treated with Burosumab, a Fully Human Monoclonal Antibody Against FGF23: Final Results of a Phase 3 Trial
Authors: Perwad Farzana , Portale Anthony A , Carpenter Thomas O , Briot Karine , Imel Erik Allen , Kamenicky Peter , Weber Thomas Joseph , Pitukcheewanont Pisit , Cheong Hae Il , De Beur Suzanne Marie Jan , Imanishi Yasuo , Ito Nobuaki , Lachmann Robin , Tanaka Hiroyuki , Zhang Lin , Skrinar Alison , Rees Linda , Insogna Karl Leonard 
Published: May 2020

Abstract
Burosumab, a fully human IgG1 monoclonal antibody to FGF23, is approved in Canada and Brazil to treat XLH in patients ≥1 year of age and in the US to treat XLH in patients ≥6 months of age. Burosumab has also received conditional marketing authorization in Europe to treat XLH with radiographic evidence of bone disease in children ≥1 year of age and in adolescents with growing skeletons. Burosumab significantly improved serum phosphorus, fracture/pseudofracture healing, stiffness, and physical functioning in a phase 3, double-blind, multicenter study (CL303, NCT02526160). In this trial, subjects were randomized 1:1 to receive burosumab or placebo subcutaneously every 4 weeks. At Week 24, subjects in the placebo group crossed over to receive burosumab (total duration ≥96 weeks). Here, we report final long-term safety results from this trial. Most (119/134, 89%) subjects completed 96 weeks and received 1 mg/kg burosumab; protocol-specified dose reductions were required for 11/134 (8.2%) subjects to effectively manage hyperphosphatemia (all mild [Grade 1]). Mean (±SE) baseline serum phosphorus was 1.98 (±0.03) mg/dL and was 2.97 (±0.05) mg/dL at Week 94 (midpoint of dose interval). Mean (±SE) iPTH level was 96 (±3.8) pg/mL at baseline and progressively declined to 79 (±3.3) pg/mL at Week 96. Nephrocalcinosis score at Week 96 changed by 0 in 101 subjects, -1 in 9 subjects, +1 in 10 subjects (14 subjects not available). There were no meaningful changes in ectopic mineralization. There were no neutralizing antibodies. No treatment-emergent adverse events led to study or treatment withdrawal. Serum phosphorus was maintained with long-term burosumab treatment, with no evidence of loss of effect in adults with XLH. Burosumab dose reductions effectively managed mild hyperphosphatemia. Frequency, severity, and types of AEs reported were consistent with previous burosumab trials.
SAT-384 Identification of Heterozygous LRP5 Mutation and a TGFβ-1 Variant of Unknown Significance in a Patient with Hearing Loss, High Bone Mass, and Oropharyngeal Exostoses
Authors: Cheng Cheng , Avery James , Gottesman Gary , Mumm Steven , Whyte Michael P 
Published: May 2020

Abstract
Background: Manifestations of the high bone mass (HBM) disorders not only include strong bones, but also excessive bones causing cranial nerve palsies and oropharyngeal exostoses. Due to overlap of clinical phenotype in dense bone diseases, one or more distinct genes may be involved. Up-regulation in bone formation can result from gain of function mutation of the low-density lipoprotein receptor-related protein 5 (LRP5), which mediates activation of the canonical Wnt pathway via co-binding with the frizzled protein, but may also be a consequence of activating mutations in the transforming growth factor β1 (TGFβ-1) gene that associate with stimulated osteogenesis. Clinical Case: Here we report a 41 year-old woman referred for incidentally found dense bones on screening dual-energy X-ray absorptiometry (DXA) that led to subsequent revelation of several family members sharing similar histories including inability to float in water, strong bones on skeletal surgery, and presence of palatal exostoses. Her childhood history included mandibular pain developing at age 15 years due to bony overgrowth of her lower jaw requiring multiple drilling for removal. At age 33, she manifested trigeminal neuralgia initially responsive to medical management but eventually needed microvascular decompression for unremitting pain. Preoperative brain magnetic resonance imaging (MRI) noted significant hyperostosis of the skull as well as mild narrowing of internal auditory canals, for which auditory testing showing mild mixed hearing loss in her right ear. Skeletal survey revealed diffuse thickening of axial and appendicular skeleton with characteristic endosteal hyperostosis. DXA demonstrated Z scores of +8.3 and +5.3 in the lumbar spine and total hip, respectively. Torus palatinus was also identified on exam. Mutational analysis disclosed a heterozygous LRP5 missense mutation, c.844A&gt;G, p.Met282Val, together with a variant of unknown significance in TGFβ-1 (c.887G&gt;A, p.Arg296Gln) possibly linked to Camurati-Engelmann disease (progressive diaphyseal dysplasia). As transmission in both conditions follows an autosomal dominant pattern, multigenerational family history was elicited from patient that her mother, who underwent knee replacement in her 80’s, was described by the surgeon as “having bones of a 30-year old man,” and that her deceased maternal grandmother possibly had “thickened” bones. Half of patient’s 18 siblings reportedly also carry features suggestive of high bone mass phenotype. Genetic testing of family members is planned. Conclusion: While HBM disorders protect against fractures, it is important to recognize that these relatively benign conditions may present with neurological and oropharyngeal complications prompting the need for their surveillance and surgical precautions during orthopedic procedures.
SAT-202 Hypoglycemia Following Unilateral Pheochromocytoma Resection in the Immediate Post-Surgical Period
Authors: Ghosh Raisa , Dalwadi Sanketkumar , Luo Hongxiu 
Published: May 2020

Abstract
Introduction
Hypoglycemia in the immediate post-resection period of unilateral pheochromocytoma is a potential complication but not very well recognized.
Clinical Case
A 47 year old female with past medical history of Hypertension, coronary artery disease, Myocardial infarction, Depression, Systemic lupus erythematosus presented to the hospital initially for elective robotic assisted Left adrenalectomy. CT scan showed a big left adrenal mass with normal right adrenal gland. It was clinically diagnosed as Pheochromocytoma as outpatient by primary internist. Biochemical studies showed elevated serum metanephrines and normetanephrines, and urine normetanephrine.
Post-surgery (&lt; 24 hours) patient had episodes of fasting hypoglycemia with blood glucose levels as low as 68 mg/dl, accompanied with neuroglycopenic symptoms like tremors, sweating and palpitations.
High dose ACTH stimulation test was performed. Serum cortisol levels were tested as 5.1, 11.7 and 14.4 mcg/dl within 0, 30 minutes and 60 minutes of Cosyntropin 250 mcg IV injection.
The patient was started on Prednisone 5 mg daily to prevent any further episodes, which was successful, and was stopped by the patient one week after discharge, without any more hypoglycemia episodes. Further endocrinology work up could not be done as the patient did not follow up.
Post-surgical pathology showed a 7x 5.5 x4 cm mass, which was confirmed as pheochromocytoma histopathologically and immunohistochemically by positive chromogranin, synaptophysin and BCl2 and negative for calretinin and S100.
Discussion and Conclusion
The etiology of hypoglycemia after resection of unilateral pheochromocytoma can be explained by impaired glucagon secretion and decreased gluconeogenesis due to the suppression from higher catecholamine levels in the blood pre-operatively. The second mechanism is rebound insulin secretion from the pancreas due to sudden withdrawal of catecholamines.
In our patient, the transient hypocortisolemia could be another reason. The lack of immunohistochemical evidence in post-surgical pathology report excluded cortisol- secreting tumor. Another rare situation, ACTH-secreting pheochromocytoma, has been reported but was not checked in the case.
In a word, hypoglycemia is common after surgical removal of unilateral pheochromocytoma. Careful monitoring of patients’ glucose level in immediate post-resection period is essential to prevent transient hypoglycemia
References
1.Akiba M, Kodaba T, Ito Y, Obara T, Fujimoto Y. Hypoglycemia induced by excessive rebound secretion of insulin after removal of pheochromocytoma. World J Surg; 14(3):317-24
2.Chen Y, Hodin RA, Pandolfi C, Ruan DT, McKenzie TJ. Hypoglycemia after resection of pheochromocytoma.Surgery;156(6): 1404-09
MON-446 Anaplastic Thyroid Cancer Presenting with Brain Metastasis: 17-Year Progression Free Survival
Authors: Howard Kathryn Kay , Lapkus Morta , Johnson Natalie , Nagar Sapna , Czako Peter 
Published: May 2020

Abstract
Background: Anaplastic Thyroid Cancer is the most aggressive thyroid cancer with a median survival of just five months. Long term survival has been reported in locally aggressive cases, but has yet to be reported in metastatic disease.
Case Information: A 34-year-old male presented with symptoms of dizziness, confusion, intermittent headaches, and erratic behavior for two weeks. CT of the head revealed a 1 cm ring enhancing lesion in the left parietal lobe with surrounding vasogenic edema. He was taken to the operating room for a left parietal craniotomy and a vascular, solid mass was removed. Initial pathology suggested papillary thyroid origin due to positive staining for thyroid transcription factor (TTF) and thyroglobulin (Tg). On exam, he had a palpable 3 cm mass in the right thyroid lobe with no associated adenopathy. He underwent thyroidectomy to optimize post-operative radioactive iodine treatment. Intraoperative frozen section revealed anaplastic thyroid cancer and final pathology revealed anaplastic carcinoma identical to the brain lesion. The tumor pathology showed extension through the thyroid capsule with lymphovascular invasion and one of two positive lymph nodes. Post-operatively, he underwent 15 cycles of whole brain radiation therapy for a total of 35 Gy. Two additional brain lesions were identified after thyroidectomy and a third was identified after whole brain radiation. He underwent stereotactic radiosurgery of these three lesions less than two months after thyroidectomy. The patient went on to receive modified mantle field irradiation (46 cycles, total 55.2 Gy) to the neck, thyroid bed, and the upper mediastinum. Additionally, he received chemotherapy with doxorubicin 6-8 weeks and temozolomide for 2 years. Thyroid uptake studies showed minimal residual iodine-avid disease and, in the setting of chemotherapy-induced cytopenias, radioactive iodine treatment was not administered. The patient has currently survived 17 years post-treatment. His persistent, but stable, brain lesions are being followed with serial imaging. He remains clinically and neurologically asymptomatic.
Conclusions: This is the first case presenting with long-term survival in a patient with metastatic anaplastic thyroid carcinoma. A multidisciplinary course with early aggressive surgical removal, adjuvant treatment with chemotherapy and radiation, and long term imaging follow up may be an acceptable treatment plan for stable patients.
References:
Smallridge RC, Ain KB, Asa SL, Bible KC, Brierley JD, Burman KD, et al. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012;22(11):1104-39.
MON-122 Introduction of an Ambulatory Curriculum in Endocrinology Diabetes and Metabolism for Internal Medicine Trainees
Authors: White Caitlin A , Cardillo Serena 
Published: May 2020

Abstract
Internal Medicine (IM) training programs are disproportionately weighted to inpatient learning opportunities. IM residents‘ exposure to outpatient internal medicine subspecialties, such as Endocrinology, Diabetes and Metabolism (EDM), is limited. This may contribute to gaps in medical knowledge in these content areas in spite of the frequent occurrence of EDM disorders. Further, reduced exposure during training may adversely impact interest in pursuing fellowship training in these fields, in spite of increased societal need.
In July 2015 the IM residency program at the University of Pennsylvania switched to a “6 + 2” training model. In this training module, trainees are grouped into four cohorts, each of which have 6 weeks of inpatient rotations, followed by 2 weeks of an ambulatory experience. This model allowed the introduction of an organized ambulatory curriculum during the 2-week outpatient blocks, which was named the Interactive Learning Module (ILM). This creates the opportunity to deliver a standardized curriculum to all residents. Through this module we coordinate an immersive experience in five distinct outpatient themes: General Internal Medicine, Infectious Disease, EDM, Nephrology, and Rheumatology. The EDM ILM is co-led by a core faculty member and senior endocrinology fellow with interest in pursuing a career in medical education.
During the EDM ILM, IM interns receive 12 hours of interactive didactics in high yield content areas including: Diabetes Workshop, Adrenal and Pituitary Diseases, Osteoporosis, Thyroid Diseases, Women’s Health, Calcium Disorders, Obesity and Endocrine Emergencies.
Interns are given 3-4 opportunities to work with an EDM faculty member in the outpatient setting. Interns are also asked to read and review three publications within the field, which are discussed as a group.
The EDM ILM has been consistently praised by IM interns, and feedback for the curriculum has been overwhelmingly positive. 97% of interns agreed the breadth of content was comprehensive and 94% agreed that the content was applicable to their delivery of ambulatory primary care. The quality of the teaching was rated high among 96% of interns. 89% reported improved understanding of EDM. Four years after the institution of the curriculum, we have not yet noted an increase in graduating IM residents choosing fellowship in EDM. However, all three of our IM residents who have matched into EDM fellowship over the past four years have chosen to stay at our institution.
Faculty have thrived with these teaching opportunities: their consistently high evaluations have been an important criterion for academic promotion.
Co-leading this course has been an important opportunity for senior EDM fellows to build expertise in medical education; three out of four participating fellows accepted academic positions with GME support.
SUN-004 Case Study: A 17-year-old Girl with HAIR-AN Syndrome, T2DM and Primary Amenorrhea
Authors: Alsaeed Abdulghani Habib , Harthi Hayat Al 
Published: May 2020

Abstract
Introduction: HAIR-AN syndrome is a sub-type of polycystic ovarian syndrome which consists of virilization, insulin resistance and acanthosis nigricans. It may be associated with menstrual irregularity, and hyperandrogenic features such as hirsutism and masculinization. Aim: We report an adolescent girl with HAIR-AN syndrome, T2DM, a very high testosterone level (male range) and primary amenorrhea Case report: A 17-year-old female who had been investigated by pediatric endocrinology since the age of 13 because of hyperpigmentation which was proven to be acanthosis nigricans on skin biopsy. The patient was found to have insulin resistance with initially normal glucose level. She has hirsutism and hypertrichosis. There is no similar condition in her family, she has three siblings all are well. She developed T2DM with at the age of 14. She was started on Metformin 2 gram daily and them pioglitazone 30 mg was added when she was 16 years. She never had menarche. The clinical examination revealed an adolescent girl with normal BP 106/68 mmHg, and BMI 19.6kg/m2. She scored 24 onFerriman-Gallwey hirsutism scoring system. She had severe acanthosis nigricans on both axillae. She also had back and upper limbs hyperpigmentation.Lab tests revealed normal thyroid function tests, prolactin, cortisol, DHEA-S, and 17 hydroxy progesterone. Fasting glucose 7.2, insulin 123 μU/ml (2.6-24.9), c-peptide 964, HbA1c 8.2%. Total testosterone 24.61 nmol/L (0.069-2.715), SHBG 184.9 nmol/L, and Free testosterone index 13.31 (0.51-6.53). Her LH 8.9 and FSH 4.7.Radiological investigations revealed polycystic ovaries on pelvic ultrasound. MRI abdomen showed normal adrenals, and mildly enlarged ovaries with peripherally located follicles consistent with polycystic ovarian syndrome. The patient was started in Diane-35 (cyproterone acetate and ethinyl estradiol) oral pills. She started to have menarche three months after using Diane-35. Her Total testosterone had dropped from 24.61 to 1.69 nmol/L (0.069-2.715), SHBG 579 nmol/L, and Free testosterone index 0.29 (0.51-6.53). She reported that the hirsutism is getting less than before starting the treatment.Conclusion: Primary amenorrhea might be a manifestation of in HAIR-AN syndrome due to sever hyperandrogenism. The management of such condition is challenging. In addition to controlling the metabolic parameters, combined oral pills with antiandrogen effect might be effective.
SAT-217 Paraganglioma in Two Unrelated Kinyarwanda-Speaking Patients in Anatomically Distinct Sites
Authors: Ejaz Sadia , Nandam Neeharika , Styner Maya 
Published: May 2020

Abstract
Introduction: Capable of generating excess catecholamines, untreated extra-adrenal paragangliomas (PGL) result in severe cardiovascular morbidity and mortality. Increasingly, a hereditary basis can be identified to underlie PGLs, though such data is largely absent in non-Caucasian populations.
Case 1: A 43 yr. old Kinyarwanda-speaking woman from DR Congo presented with left lower extremity edema and hypertension, with blood pressure of 154/86 while on spironolactone, HCTZ and furosemide. Ultrasound was negative for a DVT; abdominal CT revealed a 3 cm necrotic mass, inferior to the duodenum and abutting the IVC and aorta, as well as 2 bladder wall lesions. EUS-guided FNA revealed a keratin-negative neuroendocrine tumor. Urinary 24hr norepinephrine (NE) was high at 185 mcg [15–80]. Urinary 24hr normetanephrine (NM) was high at 1404 mcg [119-451; hypertensive &lt;900]. MIBG scan confirmed avidity in the aortocaval mass. Despite lack of bladder uptake on MIBG, pathology similarly pointed to PGL. Surgery included excision of bladder, pelvic nodes, uterus, and aortocaval tumor. Post-op, urinary 24hr NE was 18 mcg and NM was 297 mcg, both normal. One year later, MIBG/SPECT and CT of the abdomen were negative for recurrence. A GeneDx panel of 12 PGL/PCC mutations was negative.
Case 2: An unrelated 41 yr. old Kinyarwanda-speaking woman from Rwanda, with prior history of preeclampsia and multiple miscarriages, presented with palpitations, headaches and hypertension. Echo showed a 4 cm mass posterior to the left atrium; the mass was18F-FDG PET-avid. Video-assisted thoracoscopy was performed yet the tumor’s vascularity precluded a biopsy. Biopsy of mediastinal mass after performing thoracotomy was consistent with PGL. Plasma NM was high at 7.1 nmol/l (&lt;0.90), consistent with PGL and she underwent complete removal of the tumor. Testing for SDHB mutation was negative. Symptoms resolved and antihypertensives were discontinued. Follow-up plasma NM was 0.55 nmol/l 1-year post op and remained normal for six years of follow-up.
Discussion: Less than 10% of PGLs are known to involve the mediastinum or bladder (1). In familial PGL, the most commonly identified non-syndromic mutations involve SDHD, SDHAF2, SDHB, SDHD, SDHC, VHL, and MAX. Tumorigenesis in a sizable fraction of PGLs is not well understood.
Conclusion: We present two cases of extra-adrenal PGL, both exhibiting similar age, sex and geographic ancestry. Our cases raise questions that require active investigation regarding additional environmental and/ or genetic factors which might predispose to PGLs in uncommon anatomic sites.
References: (1) Erickson D et al. J Clin Endocrinol Metab, 2001 (2) Martins et al. Int J of Endocrinol, 2014
OR27-03 Duration of Testosterone-Induced Acyclicity Influences Corpora Lutea Formation and Stromal Changes in a Transgender Mouse Model
Authors: Kinnear Hadrian M , Hashim Prianka H , Rubenstein Gillian , Brunette Margaret A , Padmanabhan Vasantha , Shikanov Ariella , Moravek Molly B 
Published: May 2020

Abstract
The impact and reversibility of long-term gender-affirming testosterone (T) therapy on the reproductive axis of transgender men has not been well-established. Little is known about outcomes for transgender men interested in pausing T therapy to harvest oocytes or get pregnant. We previously established a translational mouse model to investigate T-induced acyclicity and ovarian perturbations. We hypothesized that the duration of T-induced acyclicity would impact the reversibility of cyclic and ovarian changes. To test this hypothesis, T-treated mice were assigned to two groups: (SHORT) 6 weeks of T therapy with immediate reversibility (1.5 mg T propionate pellet implant/removal, n = 5) and (LONG) 6 weeks of T therapy with a prolonged T washout phase (subcutaneous oil injections of T enanthate at 0.9 mg once weekly, n = 5). Control groups (placebo pellets n = 5, sesame oil vehicle injections n = 5) were run in parallel. Estrous cycles were monitored using daily vaginal cytology. Following cessation of T therapy, mice were sacrificed in diestrus after resumption of cyclicity for 4 cycles and ovarian histology examined. Data were analyzed in GraphPad Prism using Welch’s t-test or Mann-Whitney where appropriate. T therapy led to persistent diestrus within a week after T administration for all T-treated mice and none of the controls. The total duration of acyclicity was 6±1 weeks for the SHORT group, which was significantly shorter than the 11±2 weeks for the LONG group (mean ± s.d., p = 0.0079). With resumption of cyclicity, both the SHORT and LONG groups had a significantly lower percentage of days in estrus and higher percentage of days in metestrus as compared to their parallel age-matched controls. Ovarian histology for the SHORT group all showed regular corpora lutea and minimal stromal changes, however, 3/5 mice in the LONG group lacked corpora lutea and 4/5 revealed marked stromal cell hypertrophy. Similar stromal cell changes were not seen in control mice. In conclusion, the length of time of T-induced acyclicity appears to impact the development of stromal cell hypertrophy and formation of corpora lutea even after resumption of cyclicity with similar alterations to the estrous cycles. These findings may have clinical relevance for transgender men interested in fertility, based on duration of gender-affirming T therapy. Future work will aim to separate out the respective contributions of T exposure and acyclicity to the stromal phenotype.