bluuebunny/crossref_metadata_2025_split huggingface dataset:
Paraganglioma
Authors: Aluko Oluwatomisin A , Ruby Edward 
Published: May 2021

Abstract
Introduction: Paragangliomas are rare neuroendocrine tumors arising from extra-adrenal medullary neural crest derivatives. The terms pheochromocytoma and paraganglioma are often used interchangeably because morphologically and functionally these entities are almost the same. However, paragangliomas that arise in the adrenal medulla are called pheochromocytomas and those outside the adrenal gland are called paragangliomas. Paragangliomas are often discovered incidentally during imaging studies performed for other reasons. We report a case of a patient who had incidental finding of retroperitoneal paraganglioma on imaging done for evaluation of thigh and gluteal cellulitis.
Clinical Case: A 24-year-old female presented with chief complaints of episodic headaches, multiple skin abscesses, fever and malaise. She has a history of Type 1DM and had been non-compliant on insulin. Vitals on presentation was significant for tachycardia with heart rate of 124, blood pressure of 119/81, respiratory rate of 16. Initial labs were consistent with DKA. CT abdomen and pelvis done for further evaluation of gluteal and thigh abscess showed incidental finding of a 3.4 cm retroperitoneal/para-aortic well-circumscribed rim-enhancing mass with central hypoenhancing component, suspicious for neoplasm such as paraganglioma. Biochemical testing was performed. 24-hour urine catecholamine levels obtained showed elevated urine norepinephrine level of 1008μg/day (reference range 15-100μg/day), urine dopamine 410μg/day (reference range 65- 400μg/day), urine epinephrine less than 2μg/day (reference range 0-20μg/day). Total urine catecholamines was elevated 1008μg/day (reference range 15-100μg/day). These results confirmed diagnosis of paraganglioma. Treatment options were discussed with the patient including surgery for removal of paraganglioma which she has currently declined.
Conclusion: Diagnosis of a paraganglioma can usually be made using biochemical and radiographic testing. All patients with paraganglioma should be tested for hypersecretion of catecholamines in a 24-hour urine or serum collection, even if they do not present with a clinical picture of catecholamine hypersecretion. Importantly these extra-adrenal tumors do not have the enzymatic capacity to form epinephrine from norepinephrine as was exemplified by our case. For catecholamine-secreting tumors, biochemical diagnosis should be followed by radiological evaluation (typically either CT or MRI of the abdomen and pelvis) to locate the tumor. Treatment options are dependent on location of tumor, size, presence of symptoms and if there is metastatic disease present.
Unraveling Secretory Mechanisms that Control Pentraxin 3 Secretion in Adipocytes During Inflammation
Authors: Lin Te-Yueh , Chen XiaoLi 
Published: May 2021

Abstract
As a soluble pattern recognition receptor, Pentraxin 3 (PTX3) plays an important role in innate immunity and obesity-associated metabolic inflammation. PTX3 is abundantly expressed and secreted in adipocytes in response to lipopolysaccharide (LPS) stimulation. Appropriate regulation of PTX3 secretion is critical for maintaining inflammatory homeostasis. This study aims to unravel the mechanisms that control PTX3 secretion in adipocytes during LPS-induced inflammation. Upon 6h treatment of LPS, PTX3 expression and secretion were significantly induced in 3T3-L1 and stromal-vascular (SV) differentiated adipocytes, but to a lesser extent in SV cells or 3T3-L1 fibroblasts. However, LPSdoes not significantly stimulate PTX3 expression and secretion in macrophages. Using chemical inhibitors of conventional and unconventional protein secretion, we explored the mechanisms for controlling LPS-stimulated PTX3 secretion. 3T3-L1 adipocytes were treated with LPS for 6h in the presence or absence of various inhibitors blocking protein secretion from the Golgi complex (Monensin and Brefeldin A), mitochondrial oxidation (carbonyl cyanide 3-chlorophenylhydrazone [CCCP]), autophagy-lysosome (chloroquine and 3-methyladenine) and inflammasome (Bay 11–7082 and wedelolactone) activation, or exosome synthesis and trafficking (GW4869, manumycin A, calpeptin, and Y-27632). There were no significant effects of all inhibitors except for Monensin, Brefeldin A, and CCCP on intracellular and secreted levels of PTX3 in adipocytes. We found that Monensin and Brefeldin A significantly blocked LPS-stimulated PTX3 secretion, resulting in cellular PTX3 accumulation in adipocytes. Disrupting mitochondrial membrane potential by CCCP caused the reduction in PTX3 secretion from adipocytes. Additionally, we detected PTX3 in exosomes isolated from LPS-treated adipocytes. Inhibiting exosome synthesis by Manumycin A attenuated LPS-stimulated PTX3 secretion in both adipocyte culture media and isolated exosomes but not in the non-exosomal fraction of media, suggesting the involvement of the exosomal pathway in PTX3 secretion. However, the levels of exosomal PTX3 were significantly lower than that of the non-exosomal PTX3, and only 4.3% of secreted PTX3 was detected in the exosomal fraction of cultural media. Inhibiting the Golgi complex pathway blocked both the exosomal and non-exosomal secretion of PTX3 in adipocytes. After further fractionation of isolated crude exosomes by the iodixanol density gradient centrifugation, we showed that the majority of PTX3 was found in the non-extracellular vesicular (EV) fractions; only a small portion of secreted PTX3 overlapped with the exosomal marker CD63 in the small EV fractions. We conclude that PTX3 is secreted mainly through the conventional protein secretion pathway and minimally through the exosomal or EV pathway in response to LPS stimulation.
Pituitary Lymphoma Presenting as Diabetes Insipidus
Authors: Bashir Bilal , Jacob Deepa Liza , Banerjee Moulinath 
Published: May 2021

Abstract
Introduction: Primary CNS lymphomas are rare accounting for 1-3% of CNS neoplasms. They lack specific clinical or radiological features and are diagnosed histologically. We describe a case of Primary CNS lymphoma involving pituitary gland presenting with confusion and diabetes insipidus. Case: 74-year-old presented with anorexia, weight loss, visual hallucinations and acute confusion. Initial evaluation revealed hypernatremia (148 mmol/L), an old cerebral infarct and new extensive thrombus in aorta and lower limb deep vein thrombosis. During hospital stay, he sustained a fall and a CT head showed a new high attenuation change around the temporal horn and left temporal lobe. MRI head was done to characterize the lesion but because of confusion and irritability, this was inconclusive. Patient continued to have hypernatremia with serum sodium ranging from 148 - 154 mmol/L (135-145 mmol/L) that failed to improve after rehydration. He continued to have negative fluid balance and urine output &gt;2.5 litres a day with dilute urine and urine osmolarity of 134 mosm/L. Due to confusion, we were unable to conduct a water deprivation test. Anterior pituitary profile was consistent with secondary hypothyroidism (TSH was 0.09 (0.02-6.00), Free T4 8.2 (8.0-18.0) and (Free T3 was 2.8 (3.0- 4.8)), and secondary hypogonadism (Testosterone 0.9 nmol/L (6.1-27.1), FSH 1.0 IU/L and LH was &lt;0.2 IU/L). Hypothalamic- adrenal axis was intact as cortisol showed adequate increment after corticotropin stimulation (Cortisol at 0 min 386 nmol/L, 30 minutes 584 nmol/L and 60 minutes 640 nmol/L). Further CT Head with contrast was carried out in view of new findings of hypopituitarism that showed smooth hyperattenuating pituitary gland that was consistent with diabetes insipidus and intense contrast enhancement seen in the periventricular regions and the caudate and dentate nuclei bilaterally. Based on clinical and radiological picture, diagnosis of CNS lymphoma and diabetes insipidus was made and commenced on desmopressin nasal spray. We were unable to perform brain biopsy or quantify the response to desmopressin due to rapid deterioration of patient who died 9 weeks after his initial presentation. An autopsy was carried out and histopathology of pituitary yielded normal anterior pituitary but posterior pituitary was completely infiltrated by Non-Hodgkin’s Lymphoma of Diffuse large B cell type that was also infiltrating parts of the cerebellum, temporal cortex and the basal ganglia hence proving diagnosis of Primary CNS lymphoma. Conclusion: Sudden onset of DI with pathological appearance of posterior pituitary and equivocal/non diagnostic CNS imaging should raise the suspicion of CNS lymphoma. Although diagnosis is histopathological, early detection with high index of suspicion and treatment and lead to better outcomes.
Postpartum Cranial Diabetes Insipidus
Authors: Cairns Ross Andrew , Azharuddin Mohammed K 
Published: May 2021

Abstract
Cranial Diabetes Insipidus is a rare diagnosis and rarer still postpartum. We present the case of 24-year-old woman who developed CDI following pregnancy. The patient had developed persistent polydipsia and polyuria 5 months following her first pregnancy. The pregnancy had been complicated by Gestational Diabetes Mellitus, Obstetric Cholestasis and a Postpartum Haemorrhage which had required a 3 unit transfusion of blood. The patient reported feeling fatigued and lightheaded and stated that she had needed to drink water frequently: around 8 litres throughout the day and 4 litres overnight. She reported that she had been unable to breastfeed but the rest of her systemic enquiry was unremarkable. The patient had attributed her symptoms of lethargy to sleepless nights with her new born baby and the polyuria as a consequence of labour and as such had presented for review at her primary care Physician 18 months following delivery.
Initial investigations revealed a fasting blood glucose of 4.9 mmol/l, an Adj. Calcium of 2.23 mmol/l and a fasting urine osmolality of 85 mmol/kg. A diagnosis of DI was suspected and was confirmed by water deprivation test: the patient had an inappropriately dilute urine osmolality of 111 mmol/kg when compared to the serum osmolality of 301 mOsm/Kg at the start of the test and her urine failed to concentrate as water was withheld. Administration of DDAVP resulted in appropriate concentration of urine and therefore confirmed the diagnosis specifically as Cranial Diabetes Insipidus.
Blood tests revealed normal anterior pituitary function: TSH was 2.78 mU/L, Prolactin was 361 mU/l, LH and FSH were 23.6 U/L and 5.3 U/L, IGF and GH were 197 ug/L and 0.1 ug/l and ACTH was 10 mU/L. Her basal cortisol was 392 nmol/l and was stimulated to 593 nmol/l by SST. MRI Pituitary revealed an unusually flat and broad pituitary gland with a possible tiny lesion in the posterior pituitary suggestive of an adenoma. The patient was established on DDAVP replacement therapy and her quality of life improved: she enjoyed restful sleep and reported less exhaustion. There was no anterior pituitary hormone deficiency 28 months following delivery. DI is a rare diagnosis with an estimated prevalence of 1 in 25000 people. CDI has been commonly reported as being caused by infiltrative or inflammatory pituitary disease, as an iatrogenic sequelae of pituitary surgery or as a result of a congenital defect in the production of vasopressin. We suspect that in this case the patient’s PPH may have resulted in isolated cranial diabetes insipidus though the significance of the MRI scan findings remains unclear. The learning points highlighted by this case are that CDI can occur following pregnancy in an isolated form without anterior pituitary hormone deficiency. We also highlight that patients may misattribute significant symptoms and signs of DI as being a normal part of the postpartum period resulting in a delayed diagnosis.
Rituximab as an Alternative Treatment for Refractory Granulomatous Hypophysitis
Authors: Nokhbehzaeim Mahrokh , Panjirkaran Lloyd , Washington Terri 
Published: May 2021

Abstract
Background: Although glucocorticoids have been adopted as the main stay treatment for granulomatous hypophysitis, refractory cases have been treated by infliximab with success in multiple reported case.[1,2,3] Given the low prevalence, incidence of granulomatous hypophysitis[4] and the advent of biologics, evidence of rituximab’s efficacy are largely based on a handful of case reports[1,2,3] and needs more evidence to label its utility. We describe a case of recurrent primary granulomatous hypophysitis in a 48-year-old female who had significant treatment challenge until there was good response after initiation of rituximab. Clinical Case: Patient was a known case of granulomatous hypophysitis and had undergone total hypophysectomy. Despite this approximately a year after her surgery she had become symptomatic and had MRI changes. She was started on a succession of immunosuppressive agents and high dose steroids to control recurrent symptoms. Due to treatment failure and very high steroid dose, patient was eventually started on Rituximab and patient had significant improvement of her symptoms as well as resolution of the MRI changes. Conclusion: Although there is a lack of prospective, double blind and controlled studies this case study highlights the utility of Rituximab as a potent alternative treatment for refractory given the adverse effect associated with the steroids and other immunosuppressive agents. Reference statement: 1. Schreckinger M, Francis T, Rajah G, Jagannathan J, Guthikonda M, Mittal S. Novel strategy to treat a case of recurrent lymphocytic hypophysitis using rituximab. J Neurosurg. 2012 Jun;116(6):1318-23. doi: 10.3171/2012.2.JNS111456. Epub 2012 Mar 23. PMID: 22443503. 2. Xu C, Ricciuti A, Caturegli P, Keene CD, Kargi AY. Autoimmune lymphocytic hypophysitis in association with autoimmune eye disease and sequential treatment with infliximab and rituximab. Pituitary. 2015 Aug;18(4):441-7. doi: 10.1007/s11102-014-0592-7. PMID: 25224140. 3. Gu WJ, Zhang Q, Zhu J, Li J, Wei SH, Mu YM. Rituximab was used to treat recurrent IgG4-related hypophysitis with ophthalmopathy as the initial presentation: A case report and literature review. Medicine (Baltimore). 2017 Jun;96(24):e6934. doi: 10.1097/MD.0000000000006934. PMID: 28614220; PMCID: PMC5478305. 4. Angelousi A, Alexandraki K, Tsoli M, Kaltsas G, Kassi E. Hypophysitis (Including IgG4 and Immunotherapy). Neuroendocrinology. 2020;110(9-10):822-835. doi: 10.1159/000506903. Epub 2020 Mar 4. PMID: 32126548
Urea Use for SIADH: A Case Report and Review of the Literature
Authors: Flores Monica , Broome David Tyler , Makin Vinni 
Published: May 2021

Abstract
Introduction: Hyponatremia is the most frequent electrolyte abnormality among hospitalized patients associated with increased morbidity and mortality. There is a demanding need for affordable and well-tolerated therapies, and urea is a compelling alternative for the syndrome of inappropriate diuretic hormone (SIADH). Urea increases renal water excretion due to osmotic diuresis and reduce urinary sodium leading to an increase in serum sodium. This case illustrates the effect and safe use of urea in a hospitalized patient with SIADH. Clinical Case: An 80-year-old male with history of recurrent anterior chest wall chondrosarcoma despite 3 chest wall resections presented to the hospital for a 4th anterior chest wall resection with reconstruction. Physical examination was notable for euvolemia with no neurologic deficits. Pre-operative labs were significant for a plasma sodium (PNa) 118 mmol/L, potassium 4 mmol/L, BUN 9 mg/dL, Cr 0.72 mg/dL, TSH 2.9 mIU/L, cortisol 21.3 mcg/dL, serum osmolality 267 mOsm/kg, urine osmolality 423 mOsm/kg, and urine sodium 115 mmol/L. Underlying SIADH was initially treated with water restriction of 800 mL/24 h. Previously, he was given a trial of salt tabs, which he did not tolerate due to nausea and emesis. Due to profound hyponatremia, he was started on 2% hypertonic saline. Once PNa levels reached 130 mmol/L, 2% saline was discontinued. Repeated PNa showed a decrease to 128mmol/L. Tolvaptan was not initiated due to lack of insurance coverage and hepatotoxicity, and demeclocycline was not considered due to his known allergy. He was ultimately started on urea powder at 15 g/day and tittered to 30 g/day. In one week PNa improved to 135 mmol/L and remained stable until discharge. Clinical Lessons: The cornerstone of therapy for SIADH relies on reducing free water intake but this is not always feasible or sufficient. Winzer et al. [1] showed that fluid restriction is effective in only 59% of the patient with SIADH. As a result, pharmacology therapy is often needed. European guidelines, as compared to American guidelines, recommend the use of urea instead of vaptans therapy as second-line treatment. The above is based on different studies [2] that have shown that urea has similar efficacy, is more cost-effective, and safer since it does not cause liver toxicity like vaptans. Given this response, it appears that urea should be considered as a second-line therapy to fluid restriction given its tolerability and cost-effectiveness when compared to its alternatives. References: 1. Winzeler B, Lengsfeld S, Nigro N, Suter-Widmer I, et al. Predictors of nonresponse to fluid restriction in hyponatremia due to the syndrome of inappropriate antidiuresis. J Intern Med 280: 609–617, 20162. Soupart A, Coffernils M, Couturier B, Gankam-Kengne F, et al. Efficacy and tolerance of urea compared with vaptans for long-term treatment of patients with SIADH. Clin J Am Soc Nephrol 7: 742–747
Body Composition and Nuchal Skinfold Thickness in Pediatric Brain Tumor Patients
Authors: Peng Junxiang , Boekhoff Svenja , Eveslage Maria , Sowithayasakul Panjarat , Bison Brigitte , Muller Hermann Lothar 
Published: May 2021

Abstract
Obesity, cardiovascular disease, and relapse/progression have major impact on prognosis in pediatric brain tumor patients. Cranial MRI is part of routine follow-up. In a cross-sectional study, we analyzed nuchal skinfold thickness (NST) by a standardized method on MRI performed for brain tumor follow-up monitoring as a novel parameter for body composition and cardiovascular disease in 177 brain tumor patients (40 WHO grade 1-2 brain tumors; 31 grade 3-4 brain tumors; 106 craniopharyngioma), and 53 healthy controls. Associations of NST with body mass index (BMI), waist-to-height ratio, caliper-measured skinfold thickness, and blood pressure were analysed in brain tumor patients and healthy controls. Craniopharyngioma patients showed higher BMI, waist-to-height ratio, NST and caliper-measured skinfold thickness when compared with brain tumor patients and healthy controls, whereas these differences were not detectable between brain tumor patients and healthy controls. However, WHO grade 1-2 brain tumor patients were observed with higher BMI, waist circumference and caliper-measured triceps skinfold thickness when compared to WHO grade 3-4 brain tumor patients. NST showed high correlations with BMI, waist-to-height ratio, and caliper-measured skinfold thickness. NST, BMI and waist-to-height ratio had predictive value for cardiovascular disease in terms of increased blood pressure, and in multivariate analysis, only BMI was selected for the final model resulting in an odds ratio of 1.25 (1.14-1.379). In craniopharyngioma patients with hypothalamic involvement/lesion or gross-total resection, rate and degree of obesity were increased. As monitoring of MRI and body composition play an important role in follow-up after brain tumor, we conclude that NST could serve as a novel useful parameter for assessment of body composition and cardiovascular disease risk in brain tumor patients.
Characterizing Immune Checkpoint Inhibitor-Induced Hypophysitis and Obstacles in Diagnosis
Authors: Johnson Jake , Abdallah Dua’A , Kotwal Anupam , Ganti Apar Kishor , Goldner Whitney Sears 
Published: May 2021

Abstract
Background: Immune checkpoint inhibitors (ICI) are used in the treatment of multiple cancers. ICI-induced endocrinopathies are known side effects of many of these agents due to their immunogenic properties. The primary aim of this single institution analysis was to characterize the population who developed hypophysitis and secondary adrenal insufficiency (AI) related to ICI therapy, and identify diagnostic challenges.
Methods: We performed a retrospective cohort study of adult cancer patients who received ICI therapy from 12/1/2012- 12/31/2019. We identified 839 patients who received CTLA-4, PD-1, PDL-1 inhibitors, or a combination during this time. Hypophysitis (H) was defined as low ACTH and low serum cortisol ± other pituitary hormone deficiencies.
Results: Sixteen patients (1.9%; 16/839) developed hypophysitis after a median of 7 months from ICI initiation. The underlying cancers included: uroepithelial (1/48; 2.1 %), neuroendocrine (1/10; 10%), melanoma (9/156; 5.8%), renal cell carcinoma (4/74; 5.4%), and non-small cell lung carcinoma (1/247; 0.4%). Four patients were excluded since they had isolated secondary AI due to exogenous steroids. Two patients with hypophysitis also had exogenous steroid usage. However, these patients had central hypothyroidism + secondary AI so were included. The median age at start of ICI was 61.3 years and 57% were males. Patients who developed hypophysitis were younger compared to the non-hypophysitis (NH) patients (median age: 57 years vs. 65 years; p=0.0113). Time from initiation of ICI to death/last follow-up was longer in the H group (20 months vs. 10.8 months; p=.0013). 87.5% of group H as compared to 47.3% of NH were alive at end of data collection (p=0.0008). In the H cohort, 43.8% (7/16) received combination CTLA-4/PD-1 inhibitors, 43.8% (7/16) PD-1 monotherapy, 6.25% (1/16) CTLA-4 monotherapy, and 6.25% (1/16) PD-L1 monotherapy. Forty-six percent (6/13) of group H had radiographic evidence of hypophysitis on MRI that resolved on follow up imaging. Six patients had concurrent thyroiditis, 2/16 had concurrent type 1 diabetes, 9/16 had central hypothyroidism, 1/16 had secondary hypogonadism, and 2/16 had GH deficiency. In 15/16 patients, secondary AI presented as the first endocrinopathy, while one patient presented with central hypothyroidism.
Conclusions: Development of hypophysitis following ICI therapy was associated with a longer survival. Deficiencies in multiple pituitary hormones occurred in the majority and non-pituitary endocrinopathies occurred in half the cases. High dose steroid usage can also present as secondary AI, making the diagnosis of ICI induced hypophysitis difficult. Further pituitary evaluation must be conducted to differentiate secondary AI due to exogenous steroids from hypophysitis from ICI therapy.