bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-270 The Exploding Pituitary - A Case of Atypical Meningitis
Authors: Alhaque Abid , Deininger Kelly , Zabad Manal , Horani Mohamad Hosam
Published: May 2020

Introduction : Pituitary apoplexy is a rare presenting pathology of a pituitary mass. Apoplexy means “sudden attack”, which is a fitting description of the patient’s presentation. Apoplexy is breakdown of the pituitary gland due to insufficient blood flow, leading to ischemia, necrosis, and hemorrhage. Two proposed mechanisms exist: 1. Supra-sellar masses can outgrow their blood supply, 2. Growth inside the suprasellar fossa can constrict blood flow. Patients with pituitary apoplexy typically present with abrupt onset of severe headache, nausea, vomiting, altered level of consciousness, visual impairment and endocrine deficiency. Sheehan took credit for obstetric associated pituitary necrosis however, apoplexy can also be life threatening outside of pregnancy.

Case Presentation : This case features 68-year-old females w history of migraines, bradycardia requiring a pace maker, CAD s/p stents, Rheumatoid Arthritis, and urothelial carcinoma of the left kidney which resulted in unilateral nephrectomy. Following surgery: Patient developed generalized weakness, weight loss, Headache. Presented later to ED with severe headache, photophobia, and hypotension. CT Head showed growth of suprasellar mass, edema of hypothalamus and thalamus. Laboratory tests showed Free T4 0.39 (08-1.7), LH < 0.3, FSH 3.7, Ptolactin diluted 85.7, Low Utine Osm 105, cortisol baseline 6.9, cortisol 60 min value post high dose Cosytropin stimulation was 15.5.Spinal fluid analysis was suggestive of aseptic meningitis. Our patient was treated for 10 days in ICU for Sepsis syndrome and viral meningitis before Endocrine consult was obtained, then he got started on hormonal treatment and referred to pituitary Neurosurgeon. Patient underwent Transphenoidal surgery. Pathology revealed Metastasis of Urothelial cancer to pituitary.

DISCUSSION & CONCLUSION: Apoplexy causing an atypical meningitis is a rare presentation. We theorize apoplexy can lead to aseptic meningitis by leakage of blood or necrotic tissue into the subarachnoid space. Either agent can induce a cytokine mediated response and the presentation of meningitis. Based on CTs, our patient’s pituitary tumor grew significantly in 30 days. Medical management of pituitary apoplexy includes fluid electrolyte balance, glucocorticoids, hemodynamic monitoring, replacement of missing hormones, and the use of Decadron to decreases cerebral edema. Diabetes insipidus was an alarming symptom for possible metastatic cancer to pitutary

CONCLUSION

This case highlights the difficulty in diagnosing pituitary pathologies and the rare presentation of apoplexy. Aseptic meningitis and a decrease in centrally controlled hormones should alert Physicians to include pituitary apoplexy in the differential diagnosis. Metastatic urothelial cancer to pituitary is extraordinarily uncommon.
MON-723 Identification of Thyrotrope Signature Genes and Regulatory Elements
Authors: Daly Alexandre , Cheung Leonard , Brinkmeier Michelle , Camper Sally Ann
Published: May 2020

Recent genome wide association studies have begun to identify loci that are risk factors for sporadic pituitary adenomas, but the genes associated with these loci are unknown. In general, ~90% of GWAS hits are in noncoding regions, making it difficult to transition from genetic mapping to a biological understanding of risk factors. Recent studies that identify enhancer regions by undertaking large scale functional genomic annotation of non-coding elements like Encyclopedia of DNA Elements (ENCODE) have begun to yield a better understanding of some complex diseases. Dense molecular profiling maps of the transcriptome and epigenome have been generated for more than 250 cell lines and 150 tissues, but pituitary cell lines or tissues were not included. Epigenetic and gene expression data are emerging for somatotropes, gonadotropes and corticotropes, but there is very little available data on thyrotropes. We identified the transcription factors and epigenetic changes in chromatin that are associated with differentiation of POU1F1-expressing progenitors into thyrotropes using cell lines that represent an early, undifferentiated Pou1f1 lineage progenitor (GHF-T1) and a committed thyrotrope (TαT1). TαT1 is an excellent cell line for this purpose because it responds to TRH, retinoids, and secretes TSH in response to diurnal cues. We have also used genetic labeling and fluorescence activated cell sorting to purify thyrotropes from pituitaries of young mice and analyzed gene expression using single cell transcriptomics. We used the Assay for TransposaseAccessible Chromatin with sequencing (ATACseq) and Cleavage Under Target and Release Using Nuclease (CUT&RUN) to identify POU1F1 binding sites and histone marks associated with active enhancers, H3K27Ac and H3K4Me1, or inactive regions, H3K27Me3, in GHF-T1 and TαT1 cells. We integrated DNA accessibility, histone modification patterns, transcription factor binding and RNA expression data to identify regulatory elements and candidate transcriptional regulators. We identified POU1F1 binding sites that were unique to each cell line. For example, POU1F1 binds sites in and around Cga and Tshb only in TαT1 cells and Twist1 and Gli3 only in GHFT1 cells. POU1F1 binding sites are commonly associated with bZIP factor consensus binding sites in GHFT1 cells and Helix-Turn-Helix or basic Helix-Loop-Helix in TαT1 cells, suggesting classes of transcription factors that may recruit POU1F1 to unique sites. We validated enhancer function of novel elements we mapped near Tshb, Gata2, and Pitx1 by transfection in TαT1 cells. Finally, we confirmed that an enhancer element near Tshb can drive expression in thyrotropes of transgenic mice. These data extend the ENCODE analysis to an organ that is critical for growth and metabolism. This information could be valuable for understanding pituitary development and disease pathogenesis.
SAT-247 Use of Double Dopamine Agonists in Giant Prolactinomas: A Series of 6 Cases
Authors: Kuan Yueh Chien
Published: May 2020

Dopamine agonist monotherapy is first line therapy in giant prolactinomas even when visual field defect is present. The costlier cabergoline is often preferred over bromocriptine due to higher efficacy and tolerability profile. Described herein combined cabergoline and bromocriptine therapy in 6 cases of giant prolactinomas. Retrospective records review of 6 patients with giant prolactinoma (3 males: M1-M3, 3 females: F1-F3) in a single tertiary centre was performed. Mean age at diagnosis: 29 years (range 17-39). Mean duration of follow up: 7 years (range 3-11). Headache and visual field defect were the presenting symptoms in all cases. Basal prolactin concentration: 100000 to 468851 mIU/L (<300 for male, <600 for female). Three patients have hypopituitarism at presentation, one after surgery and one remained eupitary 5 years after diagnosis. One developed late onset hypopituitarism 4 years after normalisation of prolactin levels. Three patients underwent debulking at presentation because of significant mass effects with obstructive hydrocephalus. In all patients cabergoline 1-1.5 mg/wk was started at diagnosis and gradually increased to 0.5 mg daily, aiming for normoprolactinemia. From May 2017 bromocriptine were given to these patients who continued to have hyperprolactinemia despite cabergoline 3.5-4mg/wk. Bromocriptine was commenced 1.25-5mg/day and gradually increased to 10 mg/day on top of cabergoline with careful monitoring of prolactin levels and side effects. Cabergoline was tapered down to 1.5-2mg/wk if prolactin levels remained stable between 2-3x normal while maintaining dose of bromocriptine. In M1, cabergoline was tapered off while maintaining bromocriptine 10mg/day with stable prolactin levels (~1000 mIU/L). In M2, normoprolactinemia was achieved after adding on bromocriptine and is currently on cabergoline 2mg/week and bromocriptine 10mg/day. In M3, whose prolactin were 4x normal value despite cabergoline 3.5mg/week, decreased 50% with bromocriptine 5 mg/day and remained stable when cabergoline reduced to 1.5mg/week. F1 had transphenoidal section twice due to failure of medical therapy. Her prolactin remained markedly elevated 10000-20000 mIU/L despite cabergoline 3.5 mg/week and bromocriptine 10mg/day, with persistent bitemporal hemianopia. F2 developed erythema nodosum after starting bromocriptine which was stopped and continued with cabergoline 1 mg/week. F3 showed partial response with 50% reduction in prolactin to 4485 mIU/L with bromocriptine 10 mg/day and cabergoline 1.5mg/week. In patients who underwent debulking, residual tumour remained unchanged. Two patients - tumour shrank 40% (F2) and 90% (M3) with medical therapy alone. In conclusion, adding on bromocriptine can be considered when high dose cabergoline is required for treatment of giant prolactinoma with careful monitoring. This reduces cabergoline dose which saves cost.
MON-213 Cardiac Damage and Related Risk Factors in Patients with Primary Aldosteronism
Authors: wang wei
Published: May 2020

Primary aldosteronism (PA) is the most common cause of secondary hypertension. Overseas flow surveys show that compared with essential hypertension (EH), the risk of cardiovascular and cerebrovascular diseases and kidney damages in PA patients is increased, and the mortality rate of cardiovascular events is higher than that in EH patients, in addition,this effect is independent of elevated blood pressure. The difference of cardiac damage between PA and EH patients was analyzed by echocardiography. Methods From April 28, 2017 to April 28, 2019, patients with primary aldosteronism diagnosed by ICD in Department of Endocrinology and Metabolism, Department of Cardiology and Urology were extracted from the adrenal group database of the Department of Endocrinology and Metabolism, West China Hospital of Sichuan University, and ICD diagnosis in Department of Endocrinology and Metabolism during the same period was also extracted. In patients with essential hypertension, the differences of clinical indicators and echocardiography between the two groups were compared, and the differences of cardiac damage and related risk factors between the two groups were explored. Results 295 patients were included in this study, including 148 patients in PA group (50.17%) and 147 patients in EH group (49.83%). There was no significant difference in gender, age, BMI, course of disease and average blood pressure between the two groups (P > 0.05). The levels of serum aldosterone and BNP in PA group were significantly higher than those in EH group, and the levels of serum renin and minimum blood potassium were significantly lower than those in EH group (P < 0.05). Left ventricular diameter (LV), left atrial diameter (LA), interventricular septal thickness (IVS), left ventricular posterior wall thickness (LVPW), ascending aorta diameter (AAO), end-diastolic diameter (EDD), end-diastolic volume (EDV) and stroke volume (SV) in PA group were significantly higher than those in EH group (P < 0.05). It was significantly higher than that in EH group (P < 0.05). The correlation analysis of variables with statistical significance between the two groups showed that serum renin activity level was negatively correlated with LV, AAO, EDD and SV, and the lowest serum potassium level was negatively correlated with LVPW and AAO. CONCLUSION Compared with EH of the same age, course of disease and blood pressure level, PA patients are more likely to suffer from cardiac damage, which is manifested by heart growth, ventricular septal thickening and cardiac function decline, and is closely related to the inhibition of serum renin activity and serum potassium level. Clinical attention should be paid to early screening and treatment of PA and its complications in order to reduce the risk of cardiac death.Key words: primary aldosteronism; echocardiography; cardiovascular risk factors
MON-714 CRISPR / Cas9 Genomic Edition of the CDH2 Gene in Zebrafish Leads to Eye and Cardiac Malformation
Authors: Ventura Bianca Helena , Bissegatto Débora Delmonte , Arnhold Ivo J , Carvalho Luciani Renata Silveira
Published: May 2020

Introduction: The CDH2 gene encodes a transmembrane protein responsible for calcium-dependent cell-cell adhesion that participates in the process of embrionic development. Neural development is achieved by neuronal neurulation, migration and differentiation, as well as axon growth and synapse formation. During pituitary development, CDH2 was associated to the epithelium-to-mesenchymal transition, with cell migration from the marginal zone to the anterior pituitary gland, followed by terminal differentiation. Thus, a dysfunction in n-cadherins disrupts the architecture of the neural tube, cortical architecture of the embryonic brain and pituitary development. In a previous study in our laboratory, a patient was diagnosed with a homozygous variant located in the N-terminal region of CDH2 (p.Val289IIe) that culminated in congenital hypopituitarism and pituitary hypoplasia. Together, these observations indicate that cadherins, especially N-cadherin, play an indispensable role in the organization of neuroepithelial layers. Zebrafish has been widely used as a model for studies of gene functionality, as it has 70% genetic homology to humans, besides being a small animal with rapid development. Our goal was to generate a zebrafish knockout for the CDH2 gene, using CRISPR Cas9 genomic edition to study its importance during development and analyze this gene in patients with characteristics similar to those observed in zebrafish. Material and methods: Three guides were drawn for the CDH2 gene using crispor program. sgRNA, produced by in vitro transcription, and Cas9 protein were injected into one cell stage. All developmental parameters were observed under a microscope up to 96 hours post fertilization (hpf). Mortality rate were calculated at 24, 48, 72 and 96 hpf. The embryos were genotyped to confirm the deleterious allelic variant. CDH2 coding region was evaluated in 3 female siblings, born from consanguineous parents, presenting micro/anophtalmia and short stature. Exons 2 to 16 were sequenced by the Sanger method. Results: 352 eggs were injected and several deformities such as absence of somites, cardiac edema, spinal curvature, cranial malformation and microphthalmia or total absence of eyes were observed. The mortality rates were 26%, 31%, 40% and 62% at 24, 48, 72 and 96 hpf, respectively. The Sanger sequencing from DNA extracted from the whole animal presented deleterious effect classified as insertions, deletions and missense changes. No deleterious allelic variant was observed in the 15 analyzed exons in the 3 patients. Conclusion: The CDH2 gene is important for neurodevelopment and eyes formation in the zebrafish although pathogenic allelic variants in this gene was not found in the studied patients with short stature and eye abnormalities.
SUN-348 Growth Hormone Replacement in Adults During 8 Years Leads to Sustained Increase in Bone Mineral Density
Authors: Payer Juraj , Kužma Martin , Stojkovičová Daša , Smaha Juraj , Jackuliak Peter , Killinger Zdenko
Published: May 2020

Introduction: Adult growth hormone deficiency (AGHD) is associated with lower bone mass and likely with increased risk of fragility fractures. GH replacement leads to increase in bone mineral density (BMD).However, only few studies longer than 2 years exist. Aim: To assess long-term effect of recombinant GH replacement on BMD and bone turnover markers duringperiod of 8 years. Patients & Methods: Prospective follow-up of all (N=63) AGHD patients at one single center. All patients with adult GHD followed at single center. All participants were replaced with daily injection of recombinant human (rh) GH in IGF-1 normalizing regimen according to Endocrine Society Guidelines. Every 2 years, lumbar spine (L-spine) and total hip (TH) BMD using dual X-ray absorptiometry on Hologic Discovery device, was assessed. All patients were assessed for bone turnover markers; carboxy-terminal collagen crosslinks (CTx) and osteocalcin (OC), and 25(OH)D levels. Deficiencies of other pituitary axes were treated if necessary. All patients were supplemented with 800 IU /day of cholecalciferol and 1000-1200mg/day of calcium as recommended by International Osteoporosis Foundation. Results: Study group consisted of 38 males and 25 females (35 with adult onset (AO) /28 with childhood onset (CO); mean age at diagnosis 25,1 yrs) AGHD patients. All patients ended 8 years follow-up period without any treatment discontinuation during this period. Treatment was well tolerated, without any serious adverse event. IGF-1 has reached the normal ranges during first 6 months and remains normal during whole study period documenting good adherence to treatment (average dose of rhGH=0,4 mg/day). Both, L-spine and TH BMD increased significantly after 8 years of GH replacement (+8 % for L-spine BMD, +7,7% for TH BMD, both p<0,01). The highest peak of BMD was observed after 6 years of treatment. CTx increased by 35% (p<0,05) and remain stable, and no significant change in OC was observed during study period. Levels of 25(OH)D increased by 32% (p<0,05) from baseline. No clinical fractures were observed. Conclusion: Long-term GH replacement in adult GHD together with sufficient levels of vitamin D levels led to increase in BMD and CTx. This study supported fact that GH has sustained effect on bone mass and bone turnover and is safe and well -tolerated for the long time period.
SAT-309 Integrated Analysis of Pituitary Adenoma Using Novel Approach of Non-Target Proteomics Along with RNA-Sequencing Analyses
Authors: Gao Yue , Nagano Hidekazu , Horiguchi Kentaro , Hashimoto Naoko , Nakayama Akitoshi , Higuchi Seiichiro , Yamagata Kazuyuki , Yokoyama Masataka , Iwadate Yasuo , Tanaka Tomoaki
Published: May 2020

Objective: To clarify the relationship between proteomic expression and clinical feature of pituitary adenoma. Methods: We have previously developed non-target proteomics analysis, which enables to detect and quantify approximately 7,000 to 9,000 kinds of protein weave, in parallel with RNA-seq analysis, and then subjected to 14 cases of pituitary adenoma surgically removed at Chiba University Hospital. Bioinformatic evaluation including DEGs, heatmap and PCA analyses was performed to reveal underlying their molecular pathogenesis. Results: We successfully identified 789 differentially expressed proteins and 593 DEGs in non-target proteomics and RNA-seq, respectively. Intriguingly, PCA analysis demonstrated that tumors were clearly divided into 3 groups based on protein expression profile; functional pituitary adenomas consisting of two subtypes depending on Pit1 and T-pit linage, and non-functional tumors consisting of two distinct subtypes, with properties close to functional tumors and unique characteristics of hard tumor difficult to remove by endoscopic surgery. To address the underlying molecular biological functions in each group clustering analysis and heat-map were performed and we found that 3 groups were separated clearly with their own both gene and protein expression profile. Indeed, for instance, GO term of plasma membrane part was significantly enriched in hard tumor group, pathways of GH receptor signaling, GH hormone synthesis as in GH-positive group. Conclusions: We herein demonstrate that pituitary adenoma can be uniquely separated into certain categories through our novel non-target proteomics with coupling to RNA-seq, particularly providing novel group of hard tumor characteristics with enriched expression of both protein and mRNA in plasma membrane part. Thus our method would be beneficial and useful to elucidate underlying molecular pathogenesis for pituitary tumors, while further analysis is required.
SUN-212 Interference in Serum Androstenedione Measured by LC-MS/MS in Newborns Samples
Authors: Lima-Valassi Helena Panteliou , Takitane Juliana , Silva Márcia Rodrigues , Alves Atecla Nunciata Lopes , Hayashi Giselle Yuri , Hadachi Sonia Marchezi , Bachega Tania A , Mendonca Berenice Bilharinho
Published: May 2020

Introduction: Liquid chromatography followed by mass spectrometry (LC-MS/MS) is considered the gold standard method to measure steroids. Newborn screening for congenital adrenal hyperplasia (CAH) involves measurement of 17α-hydroxyprogesterone (17-OHP) in blood dried spots by immunoassay. Because this testing has high false-positive rates, serum samples to measure 17-OHP, androstenedione, 21-desoxicortisol and cortisol simultaneously by liquid chromatography-tandem mass spectrometry (LC-MS/MS) are used for confirmatory test in our laboratory. Objective: To report an interference in androstenedione levels measured by LC-MS/MS assay in serum samples from newborns. Patients and methods: The method for androstenedione measurements was based on protein precipitation followed by a semi-automated and multiplexed on-line solid phase extraction coupled reverse phase separation and detection of underivatized analyte by tandem mass spectrometry. Among 312 samples 82 presented unexpected androstenedione results considering that 17OHP levels were <5 ng/mL. These samples presented a high variability among 4 replicates (CV ranged from 20 to 133%). These samples also showed an inadequate ion ratio resulting in pseudo-elevated androstenedione, indicating a coeluition of an isobaric interferent. In routine samples from other patients this problem was not observed. Results: Since this fact suggests a possible interference in LC-MS/MS measurements and modification in chromatographic method was unable to resolve from the interference, alternative method for sample preparation was developed. Liquid-liquid extraction with diethyl ether was performed and eliminated the interference and provided substantial decrease in androstenedione values (9.3+12.94 ng/mL vs 5.2+9.59 ng/mL after extraction) with ion ration normalization and CV less 10% between replicates. The identity of this compound is still unknown. Therefore, it will be necessary additional studies to clarify this artifact. Conclusions: Although the measurement of androstenedione by reverse phase chromatography without derivatization followed by tandem mass spectrometry is the simplest and commonest approach to determine androstenedione, it is susceptible to interferences causing falsely elevated androstenedione levels in newborns.
SAT-669 CD40 Ligand Gene Mutation in Type 1 Diabetes Mellitus in a Saudi Consanguineous Family
Authors: Alzaman Naweed , Shamsi Monis Bilal , Samad Firoz abdul , Imam Syed Nazar , Alharbi Ghadeer , Zaitooni Deema
Published: May 2020

Introduction:

Type 1 Diabetes Mellitus (T1D) is a common autoimmune disorder. Investigating genetic factors that could turn the immune cells to auto-reactive are critical to our understanding of T1D. In this study genetic factors and the affected autoimmunity related molecular mechanisms in familial T1D with parental consanguinity were studied.

Materials and Method:

Whole Exome Sequencing (WES) was performed in a family with familial T1D. Sanger Sequencing was done to analyze segregation in affected and non-affected. Clinical and molecular aspects were also evaluated. Protein modeling and other in silico tools were used to identify probable impact of genetic abnormalities on the structure and function of protein.

Result:

We identified a novel homozygous substitution mutation at “c.379A>T:p.Iso127Val” in CD40 Ligand (CD40LG) gene in diabetic siblings by WES. This change was found to be segregating in the affected and non-affected individuals by Sanger sequencing. Parents and non-diabetic siblings were found to be heterozygous carriers of the nucleotide change. The c.379A>T is located within evolutionarily conserved locus of human genome. Functional prediction by Gene Ontology term analysis suggested that immune functions of CD40LG are compromised by this genetic change. Further, by protein-modeling analysis we identified that structure of ligand-binding domain of CD40LG protein, with which it interacts with other immune cells, may also be affected. In silico analysis revealed significantly reduced spatial inter amino acid distance between the site of genetic change and the ligand binding domain in mutant CD40LG.

Discussion:

Apoptotic elimination of developing auto-reactive T-cells, having the potential to generate an autoimmune response against pancreatic cells, is critical to prevent T1D. This apoptotic removal mechanisms, occurs in thymus and is dependent on highly specific interaction of cell surface molecules as CD40LG on developing T-cells, and the corresponding cell surface molecules on Antigen Presenting Cells (APC). In the diabetic individuals investigated in our study, the mutation in CD40LG gene, caused significant structural damage to its protein, due to which these interactions between mutant CD40LG (present on T-cells) and the corresponding CD40 (present on APC) were probably affected. This loss of interaction between CD40LG bearing T-cells and APC, probably led to escape of auto-reactive T-cells in to immune system, which further generated autoimmune response against the pancreatic tissue, precipitating to T1D among these individuals.

Conclusion

Genetic investigation of cell surface proteins in autoimmune cells and understanding their mechanism for development of autoimmunity offers prospects for the development of new therapeutic strategies in the approach to probable early diagnosis of T1D.
MON-009 GLUT1-Mediated Glycolysis Facilitates GnRH-Induced Secretion of Luteinizing Hormone
Authors: Nicholas Dequina , Knight Vashti , Tonsfeldt Karen , Terasaka Tomohiro , Molinar-Inglis Olivia , Stephens Shannon Brooke Zoe , Trejo Joann , Kauffman Alexander S , Mellon Pamela L , Lawson Mark A
Published: May 2020

Reproduction requires intensive energy expenditure, and energy availability impacts the function of the reproductive endocrine HPG-axis. Accordingly, the reproductive axis is suppressed during hypoglycemia. Circulating blood glucose can directly interact with gonadotropes within the highly vascular pituitary. Therefore, it is possible that gonadotropes may sense energy availability via the presence of glucose in the circulation and integrate this status with input from GnRH neurons to regulate hormone production. Gonadotropes dominantly express glucose transporter 1 (GLUT1) and increase glucose uptake in response to GnRH. Thus, we hypothesized that gonadotropes engage glycolysis in response to GnRH stimulation due to the high energy demand of protein synthesis required for LH production. We developed an approach to sort and successfully culture primary gonadotropes from wild type mice. Using this approach, we performed extracellular flux analysis and found that gonadotropes respond to GnRH by inducing GLUT1-mediated glycolysis that is independent of mitochondrial respiration. Knock-down of GLUT1 expression in the LβT2 gonadotrope cell line, glucose restriction, or treatment with the competitive inhibitor of glycolysis, 2-DG, diminished GnRH-induced LH secretion, indicating GLUT1 expression is necessary for maximal GnRH-induced LH secretion. We confirmed this observation in primary female mouse gonadotropes by limiting glucose availability which resulted in diminished basal LH and FSH secretion. Lastly, GLUT1 expression in the pituitary correlates with GnRH receptor expression and is increased during the LH surge in a mouse model. These results implicate glucose uptake through GLUT1 as permissive for gonadotrope secretion of LH and therefore reproductive function, especially the LH surge. We conclude that GLUT1-mediated glucose uptake is an important rate-limiting step in gonadotropin synthesis and operation of the HPG-axis.
SAT-540 Primary Aldosteronism Represents Earlier Myocardial Fibrosis Than Essential Hypertension by T1 Mapping
Authors: Wu Tao , Ren Yan , Cheng Wei , Wang Wei , Zhou Fangli , Chen Yucheng , Zhou Xiaoyue , Sun Jiayu
Published: May 2020

Introduction:

Primary aldosteronism (PA) is associated with cardiovascular disease and has increased cardiovascular morbidity. Several studies had demonstrated that PA shows more serious myocardial fibrosis compared with essential hypertension (EH) using late Gadolinium-enhanced (LGE) imaging [1, 2]. However, the early myocardial change may not be detected by LGE. Recently, cardiac MRI T1 mapping emerged to be a sensitive technique in detecting early changes of myocardium quantitatively. Our study aimed to demonstrate the early myocardial change in PA patients by applying the T1-mapping technique.

Method:

81 (male: 25; age: 48±12 years) PA[3] and 44 (male: 21; age: 47±14 years) EH patients diagnosed by the Department of Endocrinology and metabolism according to the 2016 TES guidelines for PA were recruited from September 2018 to May 2019. All the subjects underwent cardiac MRI examinations on a 3T MRI scanner (MAGNETOM Trio a Tim System, Siemens Healthcare, Erlangen, Germany), including steady-state free-precession (SSFP) cine imaging and modified Look-Locker inversion recovery (MOLLI) imaging for T1 mapping. Functional parameters were obtained from cine images by the Argus software (Siemens Healthcare, Erlangen, Germany).The mid-ventricular native T1 value was acquired using the QMass software (Medis, Leiden, The Netherlands). Native T1 value and cardiac function parameters were analyzed between the two groups. Differences of continuous variables were analyzed by Student’s t-test or Mann-Whitney U-test, and the relationships between native T1 value and physiological variables were analyzed by multiple linear regression method.

Results:

The age (PA: 48±12 years vs EH: 47±14 years; p=0.720) and BMI (PA: 25.06±3.73 vs EH: 25.17±2.83; P=0.874) between two groups had no significant differences. The PA group had a significant higher aldosterone/renin ratio (ARR) than those in the EH group (114.6 (48.7-474.8)ng/dl:ng/ml.h vs 7.6 (4.2-13.8) ng/dl:ng/ml.h; p<0.001). All functional parameters including LVEDVI (PA: 78.66 (72.4-90.6) ml/m2 vs EH: 75.8 (64.3-85.8) ml/m2; p=0.054); LVESVI (PA: 31.7 (26.2-38.4) ml/m2 vs EH: 29.3 (24.9-36.2) ml/m2; p=0.152); LVEF (PA: 59.9 (53.3-65.0)% VS EH: 59.2(55.3-65.6)%; p=0.679); LVmassi (PA: 58.5(47.7-67.7) g/m2 vs EH: 54.9 (47.6-60.1) g/m2; p=0.463) had no differences between the two groups. However, native T1 values were higher in PA group than those in EH group (1227±40ms vs 1203±45ms). The multiple linear regression analysis showed that gender (Beta=-27.678, p<0.001) and PA (Beta=-17.287, p=0.031) were independently related to the native T1 values.

Conclusion:

PA patients represent more severe and earlier myocardium damage and this might be related to cardiovascular morbidity. The T1-mapping technique in cardiac MRI is more sensitive to evaluate the left ventricular function and to detect the myocardial fibrosis in PA patients.
MON-097 Continuous Glucose Monitoring in Youth with Type 1 Diabetes; Parental Anxiety and Parent Defined Outcomes: Results of Follow up Surveys
Authors: Alkhaled Lina , O’Riordan MaryAnn , MacLeish Sarah A , Hazen Rebecca , Wood Jamie
Published: May 2020

Continuous glucose monitors (CGMs) can be helpful in management of type 1 diabetes (T1D). Our objectives were to explore parental reason for adding CGM to their child’s T1D management and to describe potential barriers to starting CGM. Prior to CGM initiation, the primary caregiver of a child with T1D completed validated questionnaires including Fear of Hypoglycemia Scale (FOH), State-Trait Anxiety Inventory (STAI), Problem Areas in Diabetes Scale (PAID), and an investigator developed questionnaire assessing primary reason for starting CGM. Surveys were repeated 3-8 months after adding CGM.

The results of the initial surveys reported elsewhere suggest that the most common reason for starting CGM is to improve glycemic control. Out of 32 participants who completed initial surveys and intended to start CGM on their child, only 43% (N=14) started using CGM during the 3-8 month follow up period. Reasons for not starting CGM included: not having the chance to start the process of having it approved by insurance in 64% (N=9), and difficulties getting insurance to approve CGM in 28% (N=4). One participant reported that despite insurance coverage, out of pocket expense was too much.

Wilcoxon Rank Sum tests were used to compare demographic variables between those that started and those that did not start CGM. Medians were used to report the results. There were no statistically significant differences between children who did and did not start CGM in terms of age (9.3 vs. 11.4 yrs, P=0.3), baseline HbA1c (8.1% vs. 9.4%, P=0.1), and diabetes duration (3.0 vs. 4.3 yrs, P=0.6).

In summary, despite parental interest in CGM initiation for their children with type 1 diabetes, there remains a significant barrier to implementation from delays in getting insurance approval. Revision of policies related to CGM coverage in youth need to be revised and systems in place to expedite approval.
MON-261 Pituitary Abscess Presenting as Pituitary Macroadenoma Causing Hypopituitarism and Acute Meningitis; A Wolf in Sheep’s Clothing
Authors: Jalil Fatima , Azim Sidra , Kantorovich Vitaly
Published: May 2020

Background: Pituitary abscess (PA) is a rare but life-threatening cause of suprasellar (SS) lesion and pituitary hormonal deficiencies with an incidence of 0.2% - 1.1%. Clinical Case: A 65-year woman with history of transient ischemic attacks, presented with double vision for 3 months (mon) and sudden onset, severe headache. She was diagnosed with cranial nerve (CN) VI palsy. MRI brain showed 1.7 cm SS mass suggestive of pituitary macroadenoma abutting optic chiasm. Visual field testing was unreliable due to underlying visual defects. She had progressive improvement in her diplopia. She was referred to Endocrinology for worsening fatigue. Physical exam was unremarkable. Pituitary hormonal work up showed secondary hypothyroidism with TSH 1.17 mIU/L (0.4-4.5), free T4 0.6 ng/dL (0.8-1.8); hypogonadotropic hypogonadism with FSH 12 mIU/ml (23-116.3), LH 1.7 mIU/ml (10-54.7), estradiol <15 (<31); elevated prolactin due to stalk affect with prolactin level of 83.3 ng/mL (3-30). She had normal IGF-1 of 154 ng/mL (41-279), ACTH 12 pg/mL (6-50), cortisol 14.1 mcg/dL (4-22) and mildly low sodium 134 mmol/L (135-146). Levothyroxine 50 mcg daily was started. The MRI brain at 2 mon and 6 mon follow up showed stable 1.8 cm peripherally enhancing SS mass. She was planned for elective pituitary adenoma resection but prior to that that was emergently admitted to ICU with high grade fever, confusion, seizures, severe hyponatremia with sodium of 122 mmol/L (135-146) and a concern for meningitis. She had a dental crown placed 3 weeks ago. MRI brain showed increase in size of the cystic component of SS mass. She was started on empiric IV antibiotics and high dose steroids. She underwent trans-sphenoidal surgery (TSS), and actually found to have a pituitary abscess. Gram stain of purulent material was positive for neutrophils. Pathology showed pituitary gland with focal infarct and surrounding acute on chronic inflammation and fibrosis. The intra-operative abscess cultures grew Cutibacterium (Proprionibacterium) acnes. She is planned to receive 6 weeks of IV antibiotics. Conclusion: We present a case of pituitary abscess presenting as a SS mass causing hypopituitarism. It was presumed pituitary macroadenoma due to the sub-acute onset and lack of progression. She developed acute deterioration in sensorium leading to concern for meningitis and PA requiring timely diagnosis and management with trans-sphenoidal resection and IV antibiotics. Definitive diagnosis of PA is usually made post-operatively. 60% of patients with PA and new onset hypopituitarism may require long term hormone replacement. References: 1. Agyei JO, Lipinski LJ, Leonardo J. Case Report of a Primary Pituitary Abscess and Systematic Literature Review of Pituitary Abscess with a Focus on Patient Outcomes. World Neurosurg. 2017 May;101:76-92
MON-700 Protective Effects of Smoking? Improved In-Hospital Mortality in Smokers Admitted for Diabetic Ketoacidosis
Authors: Nasserifar Shabnam , Ho Kam Sing
Published: May 2020

PURPOSE: To determine the relationship between tobacco smokers and the rate of hospital readmission within 30 days, mortality, morbidity, and health care resource utilization in patients admitted to the hospital in the United States with diabetic ketoacidosis (DKA). METHOD: A retrospective study was conducted using the AHRQ-HCUP National Inpatient Sample for the year 2014. Adults (≥ 18 years) with a principal diagnosis of DKA and a secondary diagnosis of tobacco dependence or active smokers were identified using ICD-9 codes as described in the literature (1). The primary outcome was in-hospital mortality. Secondary outcomes include readmission rate, length of hospital stay (LOS), total hospitalization costs. Propensity score (PS) using the next neighbor method without replacement with 1:1 matching was utilized to adjust for confounders (2). Independent risk factors for readmission were identified using multivariate logistic regression model (3). RESULTS: In total, 186,824 hospital admissions with a primary diagnosis of DKA were identified, of which 32.44% (47,382) had TD. In-hospital morality among the smoking cohort (0.39%, SD 0.03) was lower than the non-smoking cohort (0.32%, SD 0.04) during the first hospitalization. Similar effects were observed after propensity match - 0.33% (SD 0.18) vs 0.27% (SD 0.03). The mortality rate during next hospitalization was also lower in the smoking cohort (0.72%, SD 0.03) in comparison to their counterpart (1.16%, SD 0.01). Smokers had a higher readmission rate of 17.6% (SD 0.57) than non-smokers (9.6%, SD 0.25). The length of stay among smokers and non-smokers were similar after propensity match - 3.12 days (SD 0.03) vs 3.06 days (SD 0.09), p=0.42, respectively. Total hospital cost was also similar between the two groups, $6,898 (SD $82) vs $7,100 (SD $203), p=0.32, respectively. Based on multivariate logistic regression, female and high Charlson comorbidity index were associated with higher 30-day readmission rate; whereas private insurance and high household income were associated with reduced readmission rate. CONCLUSION: Smoking has been associated with improved survival in patients with DKA (4). Previous studies have shown that glucose concentration were significantly lower at fasting and 120 min in current smokers than non-smokers. However, the effects of cigarette smoking on glucose metabolism and insulin resistance are still disputed.
SAT-279 Crooke’s Cell Adenoma- an Aggressive Form of Cushing’s Disease
Authors: Radovanovic Natasa , Alexa Yuen , Tabatabaie Vafa
Published: May 2020

Introduction: Cushing’s disease is a condition of cortisol overproduction caused by an ACTH-producing tumor. Corticotroph cells surrounding an ACTH-producing tumor usually undergo Crooke’s hyaline change, where cytokeratin filaments accumulate in the cytoplasm in response to glucocorticoid excess. These changes are thought to be a mechanism of feedback inhibition and thus facilitate a suppression of ACTH. However, in a subtype of ACTH-secreting tumors known as Crooke’s cell adenomas (CCA), the ACTH-producing cells also undergo these hyaline changes. This would be expected to suppress hormone secretion but these cells are still able to release significant amounts of ACTH.

Case presentation: A 32-year-old woman presented to the hospital after an episode of syncope. On head MRI, she was found to have a 2 cm sellar mass with optic chiasm compression. Labs showed low TSH, free FT4, T3, FSH, and LH. She was also pre-diabetic with an HgbA1c of 6.2%. Her baseline cortisol of 20.6 µg/dL did not suppress after 1 mg of dexamethasone. After receiving 4 mg of dexamethasone, her cortisol suppressed to 5.2 µg/dL. She was diagnosed with hypopituitarism except for cortisol and a likely ACTH-producing pituitary macroadenoma. She completed a transsphenoidal pituitary resection and pathology revealed Crooke’s hyaline changes with immunohistochemical stains positive for ACTH. The immunostain for the proliferation marker Ki67 showed a relatively low proliferation index. Her course was complicated by diabetes insipidus. She was ultimately discharged on 20 mg hydrocortisone each morning, 10 mg hydrocortisone each afternoon, desmopressin 0.05 µg daily, and levothyroxine 125 µg daily. Two weeks later, the patient was sent to the emergency room by her endocrinologist for hyperglycemia up to 288 mg/dL. She was also found to be newly diabetic with an HgbA1c of 6.5%. A fasting morning cortisol was collected during her admission and showed a cortisol level of <1.0 µg/dL, proving she was cured of Cushing’s disease. However, she will need close endocrinology follow up and MRI imaging of her pituitary for this aggressive type of pituitary adenoma.

Discussion: We have come across an interesting case of a young woman who presented for syncope and was found to have a pituitary macroadenoma with pathology consistent with CCA. This type of ACTH-producing tumor is known for aggressive patterns including high rates of recurrence with rates of up to 60% reported in literature, persistent disease after surgery, malignant transformation, and metastases. Despite presentation and symptoms similar to those of other ACTH-producing adenomas, the dangerous pattern of Crooke’s cell adenomas necessitate long-term follow-up in affected patients.
MON-923 MENIN Gene Mutation: Unity Amidst Diversity
Authors: Rais Nadeem M , Kumar Anshul , Jain Swetha , Scaria Vinod , Prakash Savinitha , Mathur Sandeep Kumar , Joshi Apoorva
Published: May 2020

Introduction

The MEN 1 syndrome is an enigmatic disorder, manifesting a wide spectrum of disorders, in members of a family, harbouring the same gene mutation. We present one such family, with a MENIN gene mutation with marked diversity in the clinical presentation

Clinical cases

1992: RB (Age: 13) presented with accelerated puberty, galactorrhoea and a lactotroph adenoma. Treated with Bromocriptine, followed by hypophysectomy and radiotherapy. He was on hormone replacement for hypopituitarism.

1996: He gained 21 kg of weight and had recurrent episodes of convulsions with unconsciousness.He had hypoglycaemia (13mg/dl; N >70), with hyperinsulinemia (58uIU/ml; N<25). MRI abdomen showed a mass (3.4 x 3.0 cm) over the tail of the pancreas for which a distal pancreatectomy was done (HPE: Neuroendocrine tumour).

2013: He had pain in the lower limbs with hypercalcemia (11.4mg%; N: 8.5-10.5) and hyperparathyroidism (329 pg/ml; N: 10-61) (MIBG Scan: parathyroid adenomas treated by bilateral inferior parathyroidectomy).

2016: He had hypoglycaemia with hyperinsulinemia with multifocal pancreatic NETs. These were enucleated at surgery.

2017: He developed Zollinger Ellison syndrome with raised basal gastrin levels (Gastrin: >200ng/ml; N<180) and multiple duodenal ulcers (Treatment: Pantoprazole). He simultaneously had recurrent hyperparathyroidism and underwent a total parathyroidectomy with allograft. The allograft initially showed evidence of hyperparathyroidism followed by hypoparathyroidism.

His father VB (Age: 56) was seen by us in 1996 for skin lesions and a malignant thymic carcinoid, to which he succumbed to, shortly after the surgery. His aunt, SB (Age: 18), has a lactotroph adenoma with severe insulin resistance characterised by obesity, acanthosis nigricans and hyperandrogenism.

2009: His paternal uncle PB (Age: 54) had a pituitary macroadenoma. He underwent a hypophysectomy and was lost to follow up.

2018: PB had massive haemoptysis. A bronchoscopy showed nodules in the right lung which on biopsy revealed a NET. The whole body scan showed a hilar and mediastinal mass along with metastatic disease to the adrenals, liver, spine, skull and rectum. The histopathology examination revealed a malignant carcinoid

Clinical lesson

Whole exome sequencing of the two of the affected members showed mutations of the MENIN gene at exon 2 c.G2492T:p.G831V; g. chr10. This common mutation in the family was associated with a wide spectrum of diverse clinical manifestations which include the classic disease, malignant carcinoids of the lung and acromegaloid variant of Type A insulin resistance with hyperandrogenism. These observations suggest the unity amidst diversity in the enigmatic syndrome that encompasses MEN1.
SAT-004 Prevalence of Abnormalities of Glucose Metabolism in Teenage Indian Girls with PCOS
Authors: Talwar Vipan
Published: May 2020

Background:Polycystic ovary syndrome (PCOS) is one of the common endocrine disorders affecting young women and has been associated with an increased risk of impaired glucose tolerance and type 2 diabetes mellitus. However, there are very few studies on glucose abnormalities in Indian adolescent girls with PCOS. This study was conducted to determine the prevalence of abnormal glucose metabolism in this patient population. Method: Study group comprised of 106 young females aged 13–18 years. None of them were on metformin at the time of initial visit. Clinical examination along with Anthropometric evaluation was done and along with routine hormonal assessment they underwent a standard 75-g oral glucose tolerance test (OGTT). American Diabetes Association (ADA) criteria were used for diagnosis of diabetes (2 hr value>200mg/dl), Impaired glucose tolerance (2 hour value > 140 -199 mg/dl) and Impaired fasting glucose (blood glucose level of 100–125 mg/dl) Results:Out of 106 girls with PCOS diagnosis;1 girl met criteria for diagnosis of type 2 diabetes mellitus (0.9%).15 had impaired glucose tolerance (14.1%). In addition, 2 girls with impaired glucose tolerance were also noted to have impaired fasting glucose (1.9%).Abnormalities of glucose metabolism had significant correlation with BMI(p-0.02),Waist circumference (p-0.01) and testosterone levels (p-0.02). Conclusions:In our series of adolescent PCOS subjects, we report the prevalence of abnormal glucose metabolism to be 14.1% which is quite significant. Based on our results, we recommend that all adolescent girls with a diagnosis of PCOS should undergo formal oral glucose tolerance testing. Further studies are necessary in this field, so as to make guidelines regarding the timing and frequency of this testing, as well as its utility in the clinical management of these girls.