bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-244 Inflammatory Rathke Cleft Cyst Caused Hypothalamic Panhypopituitarism
Authors: Mariko Tangiku , Ishizuka Tatsuo , Fujioka Kei , Inui Saori , Tani Hideki , Maruyama Takako , Yamada Kouji 
Published: May 2020

Abstract
Background: Hypothalamic panhypopituitarism was a rare disease which was caused by brain tumors such as Rathke cyst, germinoma, malignant lymphoma and craniopharyngioma, and vascular accidents such as thrombosis and hemorrhage. We have found a rare case of hypothalamic panhypopituitarism occurred by the inflammation of Rathke cyst. Case presentation: A 77-year-old woman was admitted to our hospital because of severe headache, nausea, vomiting and fever. Hyponatremia (Na 131 meq/L) and increased CRP level (0.20 mg/dl) and no finding of gastroenterological examination and abdominal CT scanning were observed. Endocrinological examination revealed low levels of anterior pituitary hormones such as GH, LH, FSH and ACTH and increased PRL levels and low level of serum cortisol. Simultaneous CRH, TRH and LH-RH stimulations tests indicated low responses of TSH, LH, FSH and PRL and hyperesponse of ACTH (from 2.4 to 251 pg/ml). Radiological examination by enhanced MRI revealed high intensity of T2-weighted images and low and partial high intensities of T1-weighted images in swelling of pituitary gland and vanishment of high intensity of posterior lobe in T2-weighted images suggesting that the inflammatory wall of Rathke cyst. We searched previous data of ACTH and cortisol levels which showed normal level of ACTH (55.2 pg/ml) and cortisol 18.8 μ;g/dl) when headache and nausea arouse on 50 days before. Based on above results patient was diagnosed as hypothalamic hypopituitarism due to inflammatory Rathke cyst. Therefore, patient was treated with hormone replacement therapy by 20 mg of hydrocortisone. After these treatment, polyuria, urinary low osmotic pressure and hypernatremia appeared due to partial diabetes insipidus caused by the impairment of posterior lobe in pituitary gland, and diagnosed by the examination of vasopressin test. This patient was also treated by the oral desmopressin acetate hydrate (60 μ;g/day), and has been well-tolerated in the outpatient clinic. Conclusion: These results suggested that inflammatory Rathke cyst with inflammatory changes in hypothlamo-pituitary system raised a rare case of hypothalamic panhypopituitarism.Reference: Nishioka H. et al.: Clin Endocrinology (Oxf) 2006:64:184–188
SUN-196 Persistent Hyperkalemia After Unilateral Adrenalectomy for Aldosteronoma
Authors: Ammana Hima Reddy , Yuditskaya Susan 
Published: May 2020

Abstract
Introduction
Following unilateral adrenalectomy, some patients experience persistent hyperkalemia. This has been attributed to hypoaldosteronism due to severe suppression of aldosterone synthesis in the contralateral adrenal gland. Additionally, excess aldosterone leads to glomerular hyperfiltration masking kidney dysfunction, which can then manifest after cure with CKD-related hyperkalemia.
Case Presentation
We report a case of 51-year-old male who was diagnosed with hypertension in his late 30s. He required a beta-blocker and calcium channel blocker (CCB) for 10 years, and eventually developed hypertensive nephropathy. With worsening lower extremity edema, he was switched from a CCB to an angiotensin receptor blocker. Soon afterwards, he presented with hypertensive emergency and was discovered to have significant hypokalemia (K 2.1 mmol/L), prompting work up for primary aldosteronism.
Biochemical evaluation revealed an elevated aldosterone to renin ratio of 38 [(ng/dL)/(ng/mL/hr)] and adrenal protocol CT scan revealed a 1.9 cm left adrenal nodule with benign characteristics. Adrenal vein sampling showed marked lateralization of excess aldosterone to the left adrenal gland, with proper catheter placement demonstrated in each adrenal veins (5-fold cortisol gradient bilaterally). He was started on spironolactone and 6 weeks later, underwent an uncomplicated laparoscopic left adrenalectomy. Spironolactone was discontinued
Serum K level was normal at 4.8 mmol/L immediately postoperatively. Ten hours later, his K went up to 6.6 mmol/L which was confirmed by repeat blood work, accompanied by worsened renal function (Cr 2.5 mg/dL up from a of baseline 2.0). His hyperkalemia persisted in the 5.0 – 6.0 range despite IV Calcium Gluconate, Insulin and D50. Oral potassium binders were avoided due to concerns about ileus. Upon recognition of the possibility of hypoaldosteronism, we recommended a NaHCO3 gtt, with subsequent normalization of serum K. We avoided initiating fludrocortisone in the short term, due to uncertainty about duration of hypoaldosteronism, & because he was still requiring two antihypertensive agents. Plasma aldosterone 2 wks after surgery was fully suppressed, confirming suspicion of hypoaldosteronism. He has been managed successfully with oral sodium bicarbonate tablets, remaining normokalemic at 3 weeks post-surgery.
Conclusion:
Here we present a case of persistent hyperkalemia following resection of a signficantly biochemically active and long-standing aldosteronoma, which was successfully managed with sodium bicarbonate. We attribute the post-operative hyperkalemia in this patient to a combination of hypoaldosteronism due to deep suppression of the mineralocorticoid production of the contralateral adrenal, as well as unmasking of more severe kidney dysfunction than was he previously thought to have once aldosterone excess was withdrawn.
OR12-06 Nuclear Receptor CAR Protects Female Mice from the Development of Diet-Induced Nonalcoholic Fatty Liver Disease
Authors: Oliviero Fabiana Layla , Lukowicz Céline , Mary Lucile , Lakhal Laila 
Published: May 2020

Abstract
NAFLD (Non Alcoholic Fatty Liver Disease) has become the most common cause of chronic liver disease in many developed countries worldwide and represents a major health concern. The prevalence of NAFLD is sexually dimorphic with men suspected to be more susceptible to the development of hepatic steatosis than women. Women are mostly protected until hormonal imbalance induced by menopause. Nuclear receptor CAR (Constitutive Androstan Receptor) is at the crossroads between endocrine and metabolic regulations and could therefore represent an interesting therapeutic target. It is primarily expressed in the liver and involved in the catabolism of hormones such as thyroid hormones, corticosteroids and estrogens. In addition, several studies reveal a metabolic role of CAR through regulation of major hepatic pathways such as neoglucogenesis, beta-oxidation and de novo lipogenesis. Our research is aimed at better understanding the role of CAR using a mouse model genetically deficient for CAR. To explore the metabolic functions of CAR, knock-out male and female mice were subjected to a high fat diet (HFD) for 16 weeks. Concomitant CAR deletion and high fat diet induces sexually dimorphic metabolic disorders. Knock-out of CAR in males exacerbates HFD-induced fasted hyperglycemia whereas in females, it aggravates body weight gain and adipose tissue accumulation. In accordance with epidemiological studies revealing a protection of women from the development of hepatic steatosis, HFD-fed WT female mice present less important hepatic steatosis than HFD-fed WT male mice. However, following CAR deletion, HFD-fed female mice develop a severe steatosis along with important hepatic injury. Ongoing studies aim to understand the transcriptomic and endocrine dysregulations that may explain these phenotypes. These results reveal a previously unrecognized dimorphic role of CAR in energy homeostasis and highlights its involvement in the protection of female mice towards the development of hepatic steatosis. Overall, this research provides further insights in the pathogenesis of NAFLD and its dimorphic prevalence.
SAT-061 Severe Hypocalcemia in an Infant with Abnormal Microarray and Dysmorphic Features
Authors: Jo Inha , Mantis Stelios , Minutti Carla 
Published: May 2020

Abstract
Introduction:
In pediatrics, hypocalcemia is observed most often in an ICU setting. It can be associated with acute or chronic illnesses. We present a 1 month old male infant with abnormal microarray who presented to the PICU for seizures secondary to severe hypocalcemia.
Case presentation:
A 1 month old male was admitted to PICU with new onset seizures. Past history was remarkable for NICU hospitalization for respiratory distress, dysmorphic features with genetic evaluation revealing chromosome 10p15.3p14 deletion and chromosome 6p25.3p24.3 duplication with normal karyotype, muscular VSD, neonatal cholestasis, left hydronephrosis and congenital hypothyroidism. Labs obtained during NICU stay did not reveal hypocalcemia at the time. Basic lab work-up done at time of admission showed low Ca level of 5.6, elevated Phos of 9.3 and Mag level of 1.6. Thyroid work-up was within normal.
Pediatric endocrinology was consulted for hypocalcemia.
Further work-up showed Ca of 7.2, drawn after calcium gluconate riders and on calcium infusion rate at 5 mg/kg/hr, Mg of 1.8, Phos of 6.4, PTH of 36.2 and vitamin D-25 OH of 10, which was most consistent with hypoparathyroidism, likely due to his underlying genetic mutation, given inappropriately normal PTH. We recommended to continue Ca infusion as needed up to 80 mg/kg/day to maintain normal Ca levels and to provide 2000 units of vit D for 6-12 weeks and Calcitriol 0.25 mcg daily for 1 week with monitoring of levels.
Patient’s remainder of hospital course was complicated by need for intubation, arrhythmia unrelated to hypocalcemia, sepsis, acute tubular necrosis, which prolonged patient’s need for IV calcium and length of hospitalization. Patient’s electrolytes were normalized and he was able to transition to 25 mg/kg/day PO supplements and 1000 units of vit D with improved levels. He was discharged on these supplements with follow-up.
Conclusion:
This is a case of severe hypocalcemia secondary to primary hypoparathyroidism from underlying genetic mutation with chromosome 10p15.3p14 deletion. Patient’s complicated hospital course including sepsis and acute tubular necrosis had prolonged the need for calcium infusion until he was eventually transitioned to PO calcium supplementation. It is interesting that to note the association of his underlying genetic mutation and hypoparathyroidism as there has not been any specific pediatric case described with patient’s genetic mutation.
1.
SUN-520 Graves Disease and T3 Thyrotoxicosis: A Case Report
Authors: thalambedu Nishanth , iqbal Iqra , khanal Shristi , Khan Muhammad Atique Alam 
Published: May 2020

Abstract
Introduction: Hyperthyroidism is one of the common problems in the world of endocrinology. Identifying the type of thyrotoxicosis is crucial before starting treatment. We present a case of a 37-year-old woman presented with hyperthyroidism and was started on methimazole. Her symptoms persisted and further workup showed T3 thyrotoxicosis. Her symptoms improved after switching her to PTU. She eventually underwent thyroidectomy.
Case description: Thirty-seven-year old African American woman presented to her primary care physician(PCP) with symptoms suggestive of hyperthyroidism for three months. Her past medical history is significant for recent delivery one year ago. Her Physical exam is pertinent for hypertension of 160/80 with a heart rate of 120. Her neck is diffusely enlarged with bilateral bruits. Bilateral lid retraction with lid lag was noted along with left lid proptosis. There were no tremors or leg swelling noted. Her Initial workup showed sinus tachycardia in the electrocardiogram. Her TSH level was &lt;0.010 and a free T4 level of 3.48. Ultrasound showed diffuse enlargement of the thyroid gland with no focal nodule. She was started on methimazole 10mg twice daily and metoprolol 25mg twice daily.
Three months later, she presented to the emergency room(ER) with tachycardia of 130 and hypertension of 170/85. Work up showed a TSH level of &lt;0.010 and a free T4 level of 3.94. She was compliant with medications. When free T3 levels were checked it turned out to be &gt;30. She was diagnosed with T3 Thyrotoxicosis and was started on propylthiouracil 150mg every 8 hours. Her metoprolol was increased to 50mg every 12 hours. Her symptoms improved and she finally underwent surgery for thyroidectomy.
Discussion: Hyperthyroidism is seen in about 1 in 5000 with a strong female predominance. Graves disease, the most common cause of hyperthyroidism is due to excess production of TSH receptor stimulating antibodies. Hyperthyroid patients with graves disease sometimes have a disproportionate increase in serum T3 levels when compared to serum T4. This is thought to be due to increased T3 production or extrathyroidal conversion of T4 to T3. It is very crucial to identify the free hormone levels in a new patient with hyperthyroidism because of the difference in management. Antithyroid drugs are traditionally the first-line treatment option along with beta-blockers prior to definitive therapy like radioactive iodine or thyroidectomy. The main drugs used are methimazole and propylthiouracil(PTU). Methimazole is more commonly used than PTU because of its rapid efficacy, longer duration of action and less adverse effects. For patients with T3 thyrotoxicosis, PTU is preferred as it is known to reduce the peripheral conversion of T4 to T3. Our patient medication was changed from methimazole to PTU, after which she started to notice improvement. She eventually underwent definitive treatment with thyroidectomy.
SUN-028 Concomitant Mutations in the POR and AR Genes in a Boy Presenting with Micropenis and Premature Adrenarche
Authors: Dermitzaki Eleni , Manolakos Emmanouil , Kleanthous Kleanthis , Mastorakos George , Papadimitriou Dimitrios T 
Published: May 2020

Abstract
Background: Micropenis is caused either by a defect in androgen synthesis, conversion to Dihydrotestosterone, or action due to mutant androgen receptor. Premature adrenarche is caused by excess of adrenal androgens.
Clinical case: A 6,5-year-old boy presented to our pediatric endocrinology clinic due to increased body weight and hyperthyreotropinemia. Physical examination revealed premature adrenarche with testicular volume 1,5 ml, micropenis (4cm, &lt;-2 SDS) and acanthosis nigricans. His linear growth presented an acceleration the last 2 years from +0.85 to +1.81 SD and his bone age was advanced by 2 years with a statural height at -0.5 SD, not in accordance with the mean parental height (+0.90 SD). At the same time, his BMI was increased from +1,36 to +3,64 SDS.
Laboratory investigations for premature adrenarche with synacthen test revealed mild elevation of compound-S 15,4 ng/dl at 60’, which could be theoretically attributed to partial 11-β-hydroxylase deficiency (CYP11B1). DHEA was also elevated 2,1 ng/ml with an increased DHEA/Δ4 ratio at 20 (normal &lt; 10) which could be explained in the case of partial 3-β-Hydroxysteroid dehydrogenase deficiency.
Method: Whole exome sequencing was preformed targeted to a gene panel related to premature adrenarche.
Results: A heterozygous mutation c.[1174C&gt;T]+[1174C&gt;T]; p.[Pro329Ser]+[Pro329Ser] in exon 1 in Androgen Receptor (AR) gene (X-linked) was found to the patient and his mother. The mutation, according to Human Gene Mutation Database, can cause disorder of sex development (DSD), partial androgen insensitivity syndrome (PAIS), infertility and hypospadias. Additionally, sequencing of the coding region of the P450 oxyreductase (POR) gene revealed a heterozygous mutation c.[642-5C&gt;G] in exon 7, which in homozygosity can cause steroidogenesis disorder due to oxyreductase deficiency. This heterozygous POR mutation was found to the patient and his father.
Discussion: Our patient caries mutations in the AR and in POR genes. The AR mutation is obviously responsible for micropenis in our patient. CYP11B1 and 3β-Hydroxysteroid dehydrogenase genes were normal. POR deficiency is a disorder of steroidogenesis with phenotypic spectrum ranging from PCOS to ambiguous genitalia and glycocorticosteroid deficiency or even to classic Antley-Bixler syndrome (1).
Conclusion: The genetic and hormonal results in our case imply a role for POR in the CYP11B1 gene expression, which is reported for the first time to our knowledge.
1.
Concomitant Mutations in the P450 Oxidoreductase and Androgen Receptor Genes Presenting with 46,XY Disordered Sex Development and Androgenization at Adrenarche. J Clin Endocrinol Metab. 2010 Jul; 95(7): 3418-3427
MON-271 Identification of IGF-1 Variants in a Clinical Study of 307,000 Specimens: Discrepancies with General Population and Novel Discoveries
Authors: Motorykin Ievgen , McPhaul Michael John , Clarke Nigel J , Wu Zengru 
Published: May 2020

Abstract
High resolution accurate mass (HRAM) mass spectrometry (MS) is a highly specific and robust method for identifying and quantifying intact IGF-1. However, protein variants with mass-to-charge ratios differing from wild type (WT) are not included in quantification. Previously, we developed a naming convention for isotopic peaks, called the Isotopic Peak Index (IPi) that helps identify variants by comparing their IPis. This method cannot differentiate some variants; however, the relative retention time (rRT), which is defined as the difference between the chromatographic RT of a variant and that of the WT, may help in some cases. We report IGF-1 variants detected using rRT and IPi; we also compare expected and observed frequency of common variants A67T and A70T. For IPi, 4 variant groups (VGs), each monitored at a single m/z ratio, were identified to make detection of 15 variants more efficient. Variants within each VG could be distinguished if they had different IPis. To distinguish some variants in the same VG with the same IPi, we used rRT. We also developed a tandem mass-spectrometry (MS/MS) method that uses specific fragment ions generated during fragmentation to distinguish between the most abundant variants, A67T and A70T. Of the 307,269 samples we analyzed, 1,266 (0.4%) variants were identified. IPi identified variants with different indices and the rRT approach distinguished between pairs of variants that IPi could not (A38V vs A67V; R55K vs R36Q). The following variants (and their count) were identified: R50W/T4M/A67T/A70T (1,210), A67V (23), A38V (9), P66A (6), R36Q/R50Q (5), V17M/V44M (5), A67S (4), R55K/R56K (3), T29I/T41I (1), S34N (1), S33P (1), Y31H (1). We observed a different relative frequency of A67T and A70T variants than expected based on a general population ExAC DNA database. We expected to detect 2.1-fold more A67T than A70T counts. However, DNA sequencing of 74 samples in this study identified 1.6-fold more A70T occurrences (46) than A67T (28). Overrepresentation of A70T may suggest its clinical significance. The A38V variant was predicted to occur 5.1-times in the population studied, but it was detected 9 times. The A67V variant was not present in the ExAC database, but it was detected in 23 patients. We detected 2 variants that did not match WT or expected variants; DNA sequencing identified them as new variants (S33P, Y31H). DNA sequencing also identified 3 new variants (R50Q, R56K, T41I) at different positions than expected. Using a few test samples, the tandem MS technique has shown its ability to distinguish between A67T and A70T. It will be applied to this patient set. IPi and rRT can be used together to identify and differentiate IGF-1 variants. Such an approach may provide improved estimates of variant frequencies and identify new variants.
SUN-645 Cornus Officinalis Promotes IGFBP2 and Autophagy in Human 1.1B4 Pancreatic Cell Line as Revealed by Employing a Global Proteomic Approach via Mass Spectrometry
Authors: Tawfik Arielle Elizabeth , Guergues Jennifer , Stevens Stanley M , Burkhardt Brant Roger 
Published: May 2020

Abstract
Type 1 diabetes (T1D) results in the loss of pancreatic beta cells and subsequent loss of insulin production. Exogenous insulin is the only effective treatment, but there is still no cure or interventional therapy available to inhibit progression of T1D. Successful T1D interventional therapy must protect pancreatic beta cells from autoimmunity while enhancing beta cell survival and function. Our data suggests Cornus officinalis (CO) may be a candidate for interventional therapy to protect pancreatic beta cells from autoimmune attack and increase their function. CO has been used in traditional Chinese medicine (TCM) for over 2,000 years and has shown characteristics of anti-diabetic effects in vitro and in vivo but never examined in the application of T1D. Our prior publication (Mol. and Cell. Endo.2019:494:110491), has shown increased proliferation and protection against Th1 cytokine attack upon CO treatment using a human pancreatic beta cell line, 1.1B4. From this, we sought to define precise molecular mechanism by employing a global and phosphorylation mass spectrometry (MS) approach. We applied CO to 1.1B4 cells for 2, 6, 12, and 24h then collected the cell lysates for MS analysis. Our global MS analysis revealed a 12-fold increase in beta cell functional regulator, IGFBP2, at multiple time points. IGFBP2 has been shown to display a T2D protective effect and regulate glucose metabolism. The ingenuity pathway analysis program (IPA) predicted an increase in insulin starting at 2h and the NRF2-mediated oxidative stress pathway at 12h and 24h. Furthermore, NRF2 is an upstream regulator of P62 which was significantly hyperphosphorylated at multiple timepoints from our MS analysis. Nrf2 is responsible for activating antioxidant enzymes upon oxidative stress, which is caused by proinflammatory cytokines in T1D. P62 aids in this pathway by targeting proteins for autophagy upon oxidative stress in order to keep cellular homeostasis within beta cells rather than cells progressing through apoptosis. Autophagy is critical for beta cell function and survival as it promotes survival under beta cell stress which would otherwise lead to cell death. The recovery and protection of autophagy in beta cells of patients in the pre-diagnosed stages of T1D could provide a beneficial interventional therapy in order to delay or inhibit the onset of T1D. Altogether, our proteomic analysis revealed an increase in IGFBP2 and predicted an increase in the NRf2-mediated oxidative stress pathway upon CO induction. Further analysis will examine the IGFBP2 and Nrf2-mediated oxidative pathway as a mechanism of CO induced protective and proliferative effects in pancreatic beta cells.