bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-139 Development of a Culturally Competent Skills and Knowledge Assessment Tool for Patients with Diabetes
Authors: Hakimian Stephanie , Karam Susan , Pardilla Kim , Coyne Kasey , Touma Emilie K , Larsen Diane , Holl Jane L , Wallia Amisha , Grace Prince
Published: May 2020

Training of diabetes (DM) skills is critical to assure competency of DM survival skills (e.g. glucose testing) for immediate self-care. While DM assessments exist, we sought to develop a culturally acceptable DM Skills and Knowledge Assessment (DM-SKA) tool. A systematic search of Pubmed/Medline and Scopus (1980-2017) of assessments for DM knowledge was performed. 24 studies were identified, only 33% reported minority populations. Studies were classified by topic: measurement of DM skills, objectives of DM training, assessments of DM education, and other non-patient assessments. Content from existing assessments was adapted to create a 12 question DM-SKA to address 6 domains: DM, blood glucose and self-monitoring, support services, identification management of hypo and hyperglycemia, and insulin administration. To assess cultural acceptance, cognitive evaluations were conducted in individual user sessions and focus groups. The DM-SKA had a baseline Flesch reading score of 81.3 (low complexity language) and Flesch-Kincaid reading grade level of 5.3. Of 39 approached, 85% (N=33) participated (6 inpatients refused, feeling “overwhelmed”). Participants were diverse, including 8 clinicians, 10 patients/caregivers, and 15 laypersons; 46% were non-Hispanic whites, 33% non-Hispanic blacks, 12% Hispanics, and 9% Asian Americans. Mean age of patient/caregiver/laypersons was 57.8±17 (44% > age 65) and 40.1±12 years for clinicians (12.5% > age 65). All clinicians reported that appropriate DM skill domains were included and felt patients would complete the tool. All patients/caregivers and laypersons (N=25) verbalized adequate comprehension of each question; 96% reported willingness to complete the DM-SKA if provided and 88% reported their family, friends or someone in their community would be willing to complete it. However, both providers (N=2) and patients (N=2) reported concerns about assessment format and delivery [e.g. “testing” or “quiz”]. Some younger (<65 years) patients/caregiver/laypersons (N= 4) reported concerns about potential willingness of elderly family members to complete the tool. However, acceptability of the DM-SKA was noted from all participants >65 years. Vision problems and older age were identified as potential barriers. Of those offered the assessment (N = 25), 5 (20%) participants needed assistance [N=2 vision, N=3 English as second language]. Mean DM-SKA score was 10.2±1.7 of 12. Incorrect answers mostly occurred for questions with multiple correct answers. The DM-SKA has acceptable literacy characteristics, cognitive validity, and cultural acceptability by racial/ethnic minority populations, including elderly persons. Future work includes integration into clinical workflows and incorporation of patient preferences.
MON-363 Massive Bony Exostoses and Diffuse Osteosclerosis Secondary to Hepatitis C: Case Report
Authors: Shelden Daniel , Choksi Palak
Published: May 2020

Introduction:

Acquired osteosclerosis due to hepatitis C is a rare complication. While there are previously published case reports of this condition, to our knowledge this is the first case reported with diffusely increased osteosclerosis and prominent bony exostoses.

Clinical Case:

A 52-year old woman was evaluated in the Metabolic Bone Clinic for non-radiating left hip pain and visibly prominent hard, non-tender masses at the lateral aspect of her bilateral hips and proximal humerus. She denied history of fragility fractures, radiation exposure, risk factors for sexually transmitted diseases or substance abuse. Laboratory evaluation showed vitamin D deficiency with a value of 18 ng/mL (reference range: 25-100 ng/mL), elevated alkaline phosphate of 426 IU/L (reference range: 30-116 IU/L) and markedly increased serum C-telopeptide with a value of 1901 pg/mL (reference range: <1008 pg/mL). Plain radiographs showed multiple exostoses at the pelvis, hip, and shoulders. MRI showed extensive thoracic spine endplate sclerosis and increased sclerosis throughout the pelvis and proximal femurs. Massive calcifications adjacent to the greater trochanters were also identified. A total body bone scan revealed intensely increased uptake in multiple bones consistent with a “super scan.” Bone biopsy showed sclerotic bone with extensive remodeling. Computed tomography of the chest, abdomen, and pelvis was negative for malignancy. Given the symmetric nature of these lesions and diffusely increased uptake, the diagnosis of metabolic bone disease was considered. Further testing revealed hepatitis C Ab positivity confirmed with HCV Quant PCR 1553475 IU/mL (reference range: undetected). Pathologic findings were attributed to hepatitis C and treatment for hepatitis c was initiated with subsequent improvement in alkaline phosphate to 273 IU/L.

Clinical Lessons:

Osteosclerosis represents a little-known complication of hepatitis C. It is postulated that hepatitis C itself or other unknown agents may stimulate hepatic growth factors that increase osteoblast action. The radiographic and bone scan findings are classic for acquired osteosclerosis seen as increased cortical thickening with an intensely increased uptake in multiple bones. It frequently affects the lower extremity and this condition may take years to develop. Bone formation markers such as alkaline phosphate are typically elevated and bone biopsies show increased rates of remodeling as seen in our patient. While bisphosphonates may improve the serum markers for bone formation, they have not been shown to reverse or halt the progression of skeletal changes. Thus far, there has been a single case report showing improvement in sclerosis following treatment for hepatitis C with ribavirin and interferon. Natural history, progression and treatment of this condition have not been well established.
MON-480 Isolated Hyperthyroxinemia - Does Everyone Needs Treatment?
Authors: Bashir Bilal , Banerjee Moulinath , Bharaj Harnovdeep Singh , Krishnan Simmi , Khan Atir , Williams Carolyn , Basu Ambar
Published: May 2020

Background: Raised free thyroxine (T4) with normal thyroid stimulating hormone (TSH) levels should be identified and interpreted with caution. Some of these conditions do not need treatment. We present three cases with similar biochemical abnormalities from three different causes.

Case 1: A 62-year-old clinically asymptomatic lady was referred to us with Free T4 34.9 pmol/L (10.0 – 24.0 pmol/L), TSH 0.81 mU/L (0.2 – 5.0 mu/L) and negative TSH receptor antibodies (<0.9 IU/L). She was trialled on antithyroid drugs for 6 months. Her Free T4 stayed elevated between 29.0 – 35.0 pmol/L with normal TSH. We worked up for assay interference by running tests on two analysers, Roche Cobas e801 and Siemens ADIVA Centaur CP, both yielded similar results. Alpha1 glycoprotein subunits and SHBG were normal with clinical euthyroid status making TSHoma less likely. Serum protein electrophoresis did not detect any abnormal albumin. We were unable to perform equilibrium dialysis due to non-availability of facility at our centre. Due to strong clinical suspicion and family history of thyroid dysfunction that never needed a treatment, we tested her genetically for familial dysalbumineic hyperthyroxinemia (FDH) using mutation surveyor and fluorescent sequence analysis showed her to be heterozygous for c.725G>A ALB variant confirming diagnosis of FDH.

Case 2: A 65-year-old clinically asymptomatic lady, was referred to us with Free T4 28.8 pmol/L (10.0 – 24.0 pmol/L) and TSH 2.50 mU/L (0.2 – 5.0 mu/L). Given inappropriately normal TSH levels, we repeated her TFTs using 3 different analysers, Roche cobas e801, Siemens ADIVA centaur CP and Abbot ARCHITECT i1000SR. Roche and Siemens assays yielded similar results, however Abbot assay showed normal thyroid function tests with TSH 1.01 mu/L (0.4-5.0 mu/L) and free T4 18.7pmol/L (9.0-19.0 pmol/L), confirming assay interference. As Siemens and Roche uses streptavidin-biotin immobilizing system while Abbot uses a magnetic bead-based capture system, the abnormal results could be due to biotin interference.

Case 3: A 65-year-old lady, clinically asymptomatic was referred to us with Free T4 29.2 pmol/L (10.0 – 24.0 pmol/L) and TSH 1.59 mU/L (0.2 – 5.0 mu/L), 3 months after stopping amiodarone, which she took for 3 weeks for atrial fibrillation. This was thought to be due to amiodarone, owing to its long half-life of 58 days. We repeated thyroid function tests in 3 months from first clinical encounter i.e. 6 months after stopping amiodarone that showed Free T4 24.2pmol/L and TSH 2.30 mU/L and repeated further 3 months later that were normal, confirming amiodarone induced abnormal biochemical profile requiring no treatment.

Conclusion: Hyperthyroxinaemia with normal TSH need to be interpreted with caution as illustrated above. Some of them do not need treatment and inappropriate interpretation can potentially cause anxiety for the patient and harm due to unnecessary treatment.
MON-604 Conscious and Pre-Conscious Attentional Bias to Food in Patients Submitted to Bariatric Surgery
Authors: Friedman Rogerio , Heredia Mariana L D C , Weydmann Gibson
Published: May 2020

Obesity is the result of a positive energy balance. Cognitive biases have been shown to co-occur with obesity, highlighting the hypothesis that certain cognitive functions increase the risk for obesity. Attentional bias (AB) to food stimuli is one of the cognitive components that seem to contribute to the onset and course of obesity. The treatment of obesity still represents a major health challenge. The most effective treatment for severe obesity is bariatric surgery (BS). Patients with higher degrees of adiposity – the so-called “superobese” (SO), whose body mass index (BMI) is ≥ 50 kg/m2 - seem to lose more weight after BS than the non-SO patients. On the other hand, SO patients are more likely to regain weight. Differences in behavior and cognition before and after BS may explain weight regain differences. The aim of this study was to assess food AB in a sample (n = 59) submitted to Roux-en-Y gastric bypass (RYGB) and to compare food AB between the subjects who were SO before surgery, and those who were non-SO. 59 patients underwent anthropometric assessment, clinical interview, psychometric questionnaires, and AB behavioral assessment. Participants were mostly white (n = 46, 78%), had incomplete elementary school (n = 23, 39%), did not work (n = 31, 52.5%), and were in socioeconomic class C1 (n = 24, 40.7%). BMI before BS was 49.70 ± 1.25 kg/m² (mean ± S.D.). The last available BMI after surgery (assessed within 30 days from the assessments) was 33.60 ± 7.31 kg/m². The mean postoperative follow-up time at assessment was 47.76 ± 3.04 months. Most participants were above the cutoff points for binge eating disorder (n = 54, 91.5%) and impulsivity (n = 45, 76.3%). The overall sample showed food AB ​​(16.30 ± 7.09) when food stimuli were exposed during 2000 msec, suggesting a conscious attention towards food stimuli (t (58) = 2.303, p = .025, d = 0.29). SO and non-SO were compared using post-operative time as a covariate. Food AB was significantly higher in SO (24.06, SEM 8.55) than in non-SO (-12.98, SEM 8.11) when food stimuli were exhibited during 500 msec, indicating a pre-conscious attention to food stimuli in SO (F (2, 106) = 5.124, p = .008, η²partial = .083). At 500 msec, AB value was significantly different from 0 only in SO (t= 2,763, p = .010, d = 0.53, n=27), indicating an AB to food stimuli when attention orientation was less possible. Overall, the food AB observed in the whole sample indicates that all patients show a conscious attention toward food stimuli after BS, which may influence weight maintenance. Notwithstanding, the result was different when SO and non-SO were compared considering the post-operative time. The longer the time elapsed since surgery, the higher the food AB at 500 msec in SO. Given that SO patients have a higher risk of weight regain, these data suggest that a non-conscious AB after bariatric surgery may be one of the inductors of food ingestion, thus predisposing to weight regain.
SUN-126 Distinct Molecular Phenotypes of Non-Diseased Breast Adipose Tissue of Pre-Menopausal Obese and Non-Obese Women May Underlie Differing Breast Cancer Risks
Authors: Alhallak Iad , Wolter Keith G , Simmen Frank A , Ward Richard Jon , Petty Stacy A , Simmen Rosalia C M
Published: May 2020

Obesity is a major risk factor for many chronic diseases including postmenopausal breast cancer. Paradoxically, breast cancer susceptibility is inversely linked to obesity in pre-menopausal women. Adipose tissues are active endocrine organs that play major roles in tumor development and progression; however, fat depots at different anatomical sites are biologically and functionally distinct and their singular influence on breast epithelial biology remains unclear. To study the early events by which breast adiposity may provide a microenvironment predisposing normal breast epithelial cells to tumorigenesis, we collected breast tissue from pre-menopausal (n=10/group) non-obese (NO, BMI=27.6±0.8) and obese (O, BMI=44.5±2.8) women of comparable ages (NO: 36.1± 3.3; O: 40.0±2.0) with no breast cancer and undergoing elective breast reduction surgery. Breast adipose tissue and corresponding glandular cells were analyzed histologically and evaluated for expression of genes (adipokines, cytokines, steroid hormone signaling) by QPCR and proteins (proliferation, apoptosis, inflammation) by IHC. Adipocyte size distributions from NO and O breasts did not differ (P=0.9). However, adipose mRNA levels for pro-inflammatory cytokines (IL-6, IL-8, CSF-1, MCP-1) and adipokines (LEP, CFD) were higher for O than NO (P<0.05). AdipoQ, ER-α, and ER-β transcript levels were lower for O than NO (P<0.05), while those for CYP19 and PTGS2 showed reverse trends (O>NO, P<0.05). In the corresponding glandular cells, NO had higher mRNA levels for IL-6, IL-8, ER-α, and ER-β than O (P<0.05). Immunostaining with anti-Ki67 antibodies indicated that O glandular cells were 3-fold less proliferative than those for NO, consistent with their lower Cyclin D1 mRNA levels (P<0.05). Galectin-1, a pro-fibrotic protein, showed predominant myo- vs. luminal epithelial localization, with staining intensities for O tending to be higher (P=0.07) than for NO. Perilipin immunostaining was specific for adipocytes and did not differ for O and NO. A non-targeted approach using a Human Cytokine Array (R&D Systems) was employed to further evaluate the inflammation status of O vs. NO adipose. The analyses confirmed the higher expression of IL-8, Leptin and CFD (by QPCR) in O vs. NO and identified C-reactive protein, EMMPRIN, Trefoil Factor-3, Cystatin-3 and Macrophage Migration Inhibitory Factor-1 as greater in O than NO (~2-fold). Our findings demonstrate marked differences in gene and protein expression patterns of O and NO breast adipose tissue, which were accompanied by a suppression of proliferation of O relative to NO breast epithelium. We speculate that early exposure of the breast epithelium to a highly inflammatory environment fueled by breast adiposity may promote a senescent state that confers protection from pre-menopausal breast cancer.
SUN-748 Functional Characterization of Estrogen-Regulated LncRNA16 in ER+ Breast Cancer
Authors: Yang Barbara , Ramos Enrique Ivan , Choudhari Ramesh , Zilaie Mina , Sanchez-Michael Laura A , Sedano Melina , Gadad Shrikanth
Published: May 2020

Long noncoding RNAs (lncRNAs) have been demonstrated to be involved in diverse cellular processes as important regulators, such as in cancer. However, their roles in breast cancer biology are greatly unknown so far. In our study, integrated analysis of subcellular fractionation RNA-seq with gene expression profile from human reproductive tissues yielded a comprehensive catalog of estrogen-regulated reproductive tissue-specific lncRNAs. We selected long intergenic noncoding RNA 16 (LINC16) for further study as it was the top upregulated lncRNA by estrogen and associates with clinical outcome. Analysis of RNA-seq data from different human tissues, we found that LINC16 is highly expressed in testis and followed by other reproductive organs, cervix and uterus. Interestingly, interrogation of expression data from human cancer tissues showed LINC16 is highly expressed in breast cancer compared to other cancers. We have determined the 5’ and 3’ ends of LINC16 and its exon/intron structure, and cloned LINC16 to study its function in molecular and cell-based assays. Our preliminary results suggest that LINC16 plays a critical role in ERα-dependent pathways.
MON-248 Tachycardia and Myocardial Injury Induced Natriuresis - a Rare Clinical Encounter
Authors: Bashir Bilal , Basu Ambar , Lomas John-Paul , Little Steven , Banerjee Moulinath
Published: May 2020

Introduction:

Hyponatremia in the context of cerebral salt wasting secondary to intracranial events has well been described due to increased release of natriuretic peptides. We describe a case of natriuresis leading to acute symptomatic hyponatremia associated with tachyarrhythmia and myocardial infarction.

Case:

A 72-year-old lady was admitted with atrial fibrillation with rapid ventricular rate between 130-150 beats per minute, troponin positive chest pain, with high sensitivity troponin T of 1307 ng/L (<14 ng/L) and managed as type II myocardial infarction. 12 hours after admission she became acutely confused, agitated, associated with visual hallucinations and myoclonic jerks. On Examination she was dehydrated and there were no focal neurological features. Investigations showed acute hyponatremia with serum sodium (Na+) of 117 mmol/L (135 - 145 mmol/L) which 12 hours earlier, on admission, was 137 mmol/L, serum osmolarity 249 mosm/kg (275 - 295 mosm/kg), urine osmolarity 486 mosm/kg, urinary sodium of 160 mmol/L, pro-NTBNP 6575pg/ml (<450 pg/ml), 9am serum cortisol 575 nmol/L (140 - 690 nmol/L), TSH 4.72 mu/L (0.2 - 5.0 mu/L), FT4: 18.6pmol/L (10.0 - 24.0 pmol/L) and normal chest x-ray. She was treated with hypertonic saline (2.7%) 200ml followed by 0.9% saline infusion that corrected her serum sodium levels to 136 mmol/L over next 48-72 hours along with clinical symptoms gradually went back to normal. Repeat pro-NTBNP after recovery was 3153 pg/ml. Echocardiography showed normal left ventricular systolic function with normal atrial size and moderate mitral regurgitation with pulmonary artery pressure of 30mmHg. Based on acute onset hyponatremia and raised urinary sodium, we proposed diagnosis of hyponatremia secondary to salt wasting and we believe that in absence of acute intracranial pathology and raised pro-NTBNP, renal salt wasting was induced by acute rise in natriuretic peptides of cardiac origin either secondary to myocardial infarction or tachyarrhythmia. Paroxysmal SVT is a known cause of transient polyuria after termination but is not known to cause hyponatremia. Although well described in context of intracranial events, this is the first case of myocardial injury or tachyarrhythmia induced natriuresis leading to acute hyponatremia.

Conclusion:

Salt wasting due to natriuretic peptides is not exclusive to intracranial events. Any cardiac event leading to sudden increase in natriuretic peptides can lead to natriuresis which if prolonged enough can lead to acute symptomatic hyponatremia.

Reference:

1. Yee AH, Burns JD, Wijdicks EF. Cerebral Salt Wasting: Pathophysiology, Diagnosis, and Treatment. Neurosurgery Clinics of North America, 21(2), pp.339-352.

2. Tan SY, Nolan J, Craig K, Swainson CP. Supraventricular tachycardia, right atrial pressure, atrial natriuretic peptide and polyuria—a necessary sequence? J Int Med 1993; 233: 415-17.
SAT-360 Out of Sight, out of Mind: PHEX 3’-UTR C.*231A>G X-Linked Hypophosphatemia in Adults: A Case Study of One Family Pedigree with a Widely Variable Phenotype
Authors: Williams Alexander , Black Margo , Dahir Kathryn
Published: May 2020

Title: Out of Sight, Out of Mind: PHEX 3’-UTR c.*231A>G X-Linked Hypophosphatemia in Adults: A Case Study of One Family Pedigree with a Widely Variable Phenotype

X-linked hypophosphatemia (XLH) is an inherited form of hypophosphatemia that is part of a group of disorders that leads to impaired bone mineralization, which can manifest as rickets in children and osteomalacia in adults. Mutations in PHEX, DMP1, ENPP1, and activating mutations in FGF23 have each been shown as genetic causes for XLH. PHEX is a zinc metallopeptidase which reduces expression of FGF23 through mechanisms that are not fully understood. Inactivating mutations in the PHEX gene cause elevated levels of FGF23, resulting in renal phosphate-wasting, impaired conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D and impaired bone mineralization with osteomalacia. Though the clinical significance of FGF23 levels is not clearly understood, it has also been shown that FG23 increases with age.

XLH has a reported prevalence of 3.9–5 per 100,000. We speculate that this may be under recognized and that diagnosis may be delayed for many years in those with mild forms of XLH due to non-specific symptoms. Diagnosis may be complicated by normal or low-normal serum phosphorus levels. Adults may be mistakenly diagnosed with ankylosing spondylitis, polyarthritis, osteoarthritis, diffuse idiopathic skeletal hyperostosis and other disorders that cause stiffness. Some clinical manifestations of XLH in adults include dental disease, skeletal and spinal disease, sensorineural hearing loss, kidney stones, renal impairment, and hyperparathyroidism. The PHEX 3’-UTR c.231A>G near the polyadenylation signal has been previously described to cause milder severity in men and seemingly unaffecting women, but data for comparison is limited.

We present a large, multigenerational family with a mutation in the PHEX gene (3’-UTR c.*231A>G) demonstrating variable penetrance in the pedigree. Of the members positive for the mutation, the most common symptoms were sensorineural hearing loss, enthesopathy, and dental disease. Most had normal or low-normal phosphorus levels in both genders. Two patients had prior diagnoses of ankylosing spondylitis/ seronegative spondyloarthropathy. In general, males with the mutation had more severe symptoms than females. However, females with a severe phenotype and low phosphorus was also observed. The disease burden was cumulative over time and correlated with serum phosphorus levels. Musculoskeletal symptoms were increased in the members over the age of 60.

Sources:

Chesher, Douglas et al. Outcome of Adult Patients with X-Linked Hypophosphatemia Caused by PHEX Gene Mutations. Vol. 41. Dordrecht: Springer Netherlands, 2018. Web.

Zhang, Cong et al. Clinical and Genetic Analysis in a Large Chinese Cohort of Patients with X-Linked Hypophosphatemia. Vol. 121. Elsevier Inc, 2019. Web.
MON-376 Head to Toe Hyperparathyroidism - Impending Hyperparathyroid Crisis and Subsequent Crystal Arthropathies
Authors: Thomson Alastair , Shresta Sujata , Hope Lisel Marva
Published: May 2020

The myriad of presentations associated with PHP are well established, however gout is not commonly associated with this disease. Additionally, it is unusual to see multiple threatening and potentially debilitating complications occur concurrently in one patient.

An asymptomatic elderly male with hypertension presented to the PCP for the first time and was found on routine blood work to have a serum creatinine of 4.03 mg/dl, a serum calcium of 12.1mg/dl, and a PTH of 831.7ng/L. Subsequent Tc-99 Sestamibi scanning suggested that the source was both a single right inferior parathyroid adenoma and an ectopic mediastinal adenoma. At the initial encounter the patient’s hypercalcemia was treated with IV fluid resuscitation and calcitonin then subsequently cinacalcet. Renal ultrasound at that time showed normal sized kidneys with several cysts, and phosphate levels ranged from 2.0-3.9 mg/dl (range 2.5-4.5mg/dl. The patient’s serum calcium was controlled at 10.44mg/dl, and his renal function improved to a serum creatinine of 3.08mg/dl. Prior to discharge patient developed acute left knee pain, and was found to have an inflammatory arthritis, with urate crystals seen. The patient was diagnosed with an acute gout flare, which responded well to colchicine and was discharged. The patient eventually underwent parathyroidectomy, which showed a large 4cm left superior parathyroid as well as a large right superior parathyroid gland extending into the mediastinum. Pathology was consistent with parathyroid hyperplasia. After surgery, the patient developed hungry bone syndrome, with an admitting serum level calcium of 6.05mg/dl, serum magnesium of 2.00mg/dl, serum phosphorus of 2.8mg/dl, and serum potassium of 5.1mg/dl, with clinical features of tetany and weakness that resolved after two days with calcium and calcitriol administration. He again had an acute monoarticular arthritis prior to discharge that had both urate and calcium pyrophosphate crystals in the joint fluid and again responded well to colchicine and glucocorticoids. He was eventually discharged on vitamin D and calcium supplementation, with cinacalcet and colchicine.

This case illustrates the multiple clinical teaching points that exist in primary hyperparathyroidism, including both types of presentation and potential complications. It also expresses the need to be vigilant of some rarer clinical features, such as potential hyperparathyroid crisis and multiple enlarged parathyroid glands. Physicians should also be wary of both gout and CPPD, as well as complications that occur post parathyroidectomy such as hungry bone syndrome.
SUN-550 CARF Through Its Lipid Lowering Effect May Play a Pivotal Role in the Development of Non-Alcoholic Fatty Liver Diseases
Authors: Hasan Kamrul M , Parveen Meher , Pena Alondra , Sinha-Hikim Amiya P , Friedman Theodore C
Published: May 2020

CARF (Collaborator of ARF), a member of ARF-MDM2-p53 pathway and an emerging multifunctional protein, regulates cellular fate in response to various stresses including oxidative DNA damage and replicative stresses. However, its role in metabolic syndrome (MS) and associated diseases has not been studied. This study, using our well established in vivo and in vitro model systems, examines the role of CARF in the development of non-alcoholic fatty liver disease (NAFLD). Indeed, we have found that, compared to control, CARF expression along with Sirt1, pAMPK and pACC (common biological markers of NAFLD) was significantly decreased in the nicotine and high-fat-diet (HFD) in combination or HFD alone induced fatty livers. Additionally, CARF expression was down regulated in palmitate (PA)-treated HepG2 cells, an in vitro model of steatosis, suggesting that CARF expression is negatively regulated in MS, such as NAFLD. Our study further revealed that shRNA mediated knockdown or lentiviral mediated over expression of CARF induced or reduced endogenous fat accumulation, respectively, in HepG2 cells. We also found that overexpression of CARF lowered the exogenous fat accumulation in PA treated HepG2 cells. RNA seq analysis after CARF knockdown in HEK-293T cells further revealed that genes associated with lipid metabolism and triglyceride (TG) synthesis such as diacylglycerol O-acyltransferase2 (DGAT2), acyl-CoA synthetase long-chain family member 4 and 6 (ACSL4, ACSL6) were upregulated in CARF-depleted cells. Likewise, we also found increased expression of DGAT2 in CARF-depleted HepG2 cells, which enhanced TG synthesis. Intriguingly, consistent with the lipid lowering effects of metformin, an antidiabetic drug, we further found that CARF expression along with pAMPK and Sirt1 were significantly increased in metformin-treated HepG2 cells. However, we also found increased pACC levels in CARF over-expressing cells which was further enhanced in metformin-treated cells, suggesting, for the first time, that CARF may contribute to lipid lowering effect of metformin by inhibiting lipogenesis. We conclude that CARF has a lipid lowering effect in hepatocytes and its down regulation in response to MS perturbs lipid metabolism that may lead to the development of NAFLD.
SAT-646 Do Diabetes and Hypertension Mobile Apps Overlap?
Authors: Wong Jonathan , Wu Gloria , Leung Brian , Lau Chap-Kay K , Momen Donia
Published: May 2020

Background: Mobile health apps have 3.7 billion downloads yearly. The interest in patient-generated data is increasing yearly. Diabetes and cardiovascular apps occupy a significant part of the eHealth space. However, diabetic patients could have both diabetes (DM) and hypertension (HTN), and hypertensive patients may have prediabetes or diabetes as well. Do these eHealth apps meet the needs of the patient with both diabetes and hypertension?

Purpose: Do Diabetes apps ask questions about blood pressure control and do Hypertension apps ask questions about diabetes management?

Methods: Using the search term “diabetes,” and similarly, using the search term “blood pressure” (BP), Google Play Store was accessed for two lists of the most downloaded, free DM and BP Android apps. Inclusion criteria: 1) downloads > 100,000, 2) free, 3) medication adherence (push notification), 4) FBS/HbA1c, 5) lipids. For the diabetes apps, we evaluated them for Diabetes Self-Management Education Support Guidelines (DSMES), in addition to renal and CV complications. For the BP apps, we evaluated them for BP, ACC/AHA guidelines, weight, BMI, Diet, Na+ intake, K+ intake, exercise log, alcohol intake, and medication log. Exclusion criteria: purely educational apps, no data on downloads or rankings. Results: 10 diabetes mobile apps in descending order were: 1) mySugr, 2) Onetouch Reveal, 3) Ontrack Diabetes, 4) Diabetes, 5) Health2Sync - Diabetes Care, 6) Diabetes Connect, 7) Glucose Buddy Diabetes Tracker, 8) Diabetes:M, 9) Blood Glucose Tracker, and 10) OneDrop Diabetes Management. We found 10/10 tracked FBS/HbA1c; 18.2%-81.8% had DSMES; 1/10 log entry of “heart palpitation;” 0/10 renal complications; 7/10 medication reminders. 10 blood pressure apps in descending order were: 1) BP (Szymon), 2) BP Watch, 3) BP Log My Diary, 4) BP Diary (openit.inc), 5) BP Log (bpresso.com), 6) BP Diary (FRUCT), 7) BloodPressureDB, 8) Cardio Journal, 9) BP (OrangeKit), 10) BP Diary (Health&Fitness Tracker). We found 10/10 BP logs; 2/10 ACC BP guidelines; 3/10 HbA1c/FBS; 1/10 lipid log; 0/10 diet, Na+ intake, K+ intake; 2/10 exercise log; 8/10 push notification for medication adherence. Discussion: eHealth apps emphasize the use of patient generated health data to manage chronic disease and cost containment. This small study shows that for the most popular, free diabetes and hypertension apps, few follow all the guidelines from the ADA or ACC/AHA.

Conclusion: The Diabetes apps follow the DSMES guidelines more than the Hypertension apps follow the ACC/AHA guidelines. In the future, there is room for improvement for eHealth apps and the management of diabetes and comorbid conditions such as hypertension.
SAT-188 An Unusual Case Of Intra-adrenal Purely Norepinephrine Secreting Pheochromocytoma
Authors: de Souza Tamara Gizelle , Ayala Alejandro , Jara Mark Anthony , Hannoush Zeina Carolina
Published: May 2020

Background: In 40% of pheochromocytoma/paraganglioma (PPGL) cases a causal germline mutation in a well-defined gene can be identified. The remainder are sporadic. The most common hereditary syndromes are NF1, MEN2 and VHL. Paragangliomas usually produce exclusively norepinephrine (NE) and are more likely to metastasize than adrenal tumors. Exclusively NE producing adrenal tumors are extremely rare and almost always associated with VHL or SDH syndromes (1).

Clinical Case: A 45-year-old South Asian woman with a 5-year history of HTN controlled on losartan presented emergently complaining of chest pressure. Cardiovascular workup was unrevealing. CT chest showed an incidental 3.2 x 2.4 cm lipid-poor left adrenal adenoma. No further follow-up done at that time. Two years later she presented with recurring episodes of chest pressure and uncontrolled HTN on amlodipine, metoprolol and losartan. She denied panic attacks, diaphoresis and other symptoms of anxiety. She denied personal and familial history of clinical features seen in NF1, MEN 2, VHL or SDH. Plasma metanephrines were 26 (<=57 pg/mL) and free normetanephrine 902 (<=148 pg/mL). 24-hour urine metanephrine was 178 (58-203 mcg/24h), normetanephrine 2422 (88-649 mcg/24h) and total metanephrine 2600 (182-739 mcg/24h) confirming the diagnosis of a solely NE secreting PPGL. MRI abdomen showed a well-circumscribed 3.3 cm lipid-poor left adrenal mass. MIBG scan and SPECT CT showed a focal area of intense radiotracer uptake corresponding to a 3.2 x 2.5 cm mass within the left adrenal gland. No extra-adrenal activity was demonstrated. Alpha blockade was started with doxazosin and the patient asked to salt/fluid load. She underwent left adrenalectomy. Pathology revealed a 5 x 2.5 x1.1 cm intra-adrenal pheochromocytoma; Chromogranin (+), synaptophysin (-), MIB1 low reactivity < 5%, S100 positive in sustentacular cells, keratin (-), EMA (-), Inhibin (-). Genetic testing for VHL, SDHD, SDHB, SDHC and MAX has been ordered per guidelines. One month post-operatively the patient had no symptoms of adrenergic overactivity and normal plasma metanephrine levels.

Clinical Lessons: This rare case of norepinephrine-only secreting pheochromocytoma is made even more unusual by absence of features of autosomal dominant hereditary syndromes. This may be sporadic or present a novel VHL, SDHD, SDHB, SDHC or MAX germline mutation (2).

1.

Eisenhofer, G., et al., Distinct gene expression profiles in norepinephrine- and epinephrine-producing hereditary and sporadic pheochromocytomas: activation of hypoxia-driven angiogenic pathways in von Hippel–Lindau syndrome. 2004. 11(4): p. 897.

2.

Ercolino, T., et al., Uncommon clinical presentations of pheochromocytoma and paraganglioma in two different patients affected by two distinct novel VHL germline mutations. Clinical Endocrinology, 2008. 68(5): p. 762-768.
SAT-289 Evidence That Combined Pituitary Hormone Deficiency Frequently Has a Digenic/Oligogenic Etiology
Authors: Jee Youn Hee , Gangat Mariam , Yeliosof Olga , Temnycky Adrian , Vanapruks Selena , Gourgari Evgenia , Yanovski Jack Adam , Link Kathleen , Ten Svetlana B , Baron Jeffrey , Radovick Sally
Published: May 2020

Congenital hypopituitarism usually occurs in a child without a family history of pituitary disease. Explanations for such sporadic occurrence include: 1) monogenic inheritance (recessive or de novo), 2) digenic/oligogenic inheritance, and/or 3) nongenetic factors. To help distinguish these possibilities, we studied 9 children with hypopituitarism (HP)(small anterior pituitary gland, ectopic posterior pituitary, and either isolated GH deficiency (n=1) or combined with other pituitary hormone deficiencies(n=8)), with non-consanguineous parents and no family history of pituitary disease. SNP array analyses confirmed paternity and non-consanguinity and excluded significant copy-number variation. Exome sequencing was performed in probands and parents. Candidate variants (coverage >10, confirmed by examining BAM files, population frequency <1%, <2 homozygous subjects in gnomAD, and pathogenic prediction by at least 2 out of 3 prediction algorithms (SIFT, MutationTaster, PolyPhen2)) were identified. Children with non-familial non-endocrine idiopathic short stature (ISS) (n=19, sequenced at the same laboratory followed by simultaneous data processing with HP patients), served as a control group. To assess the frequency of genetic (mono-, di-, or oligogenic) HP cases, we identified heterozygous variants (regardless of inheritance) in 42 genes previously reported to be associated with pituitary development. The average number of variants per proband was greater in HP than in ISS (1.1 vs 0.26, P = 0.04). Similarly, the number of probands with at least 1 variant in a pituitary-associated gene was greater in HP than in ISS (67% vs 21%, P = 0.035). These data suggest that sporadic hypopituitarism is frequently genetic. To assess the number of monogenic cases, we counted the number of candidate variants (in any gene in the genome, to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence with a monogenic etiology (de novo mutation, autosomal recessive, X-linked recessive). There were fewer monogenic candidates in subjects with HP than ISS (1.6 vs 2.6 candidates/proband, P = 0.03). These data are consistent with approximately 1.6 non-causative variants/proband in both groups plus approximately 1 causative monogenic variant in ISS vs approximately 0 causative monogenic variants in HP. Candidate variants in genes previously reported to explain the phenotype were identified in 0 out of 9 trios with HP and in 8 of 19 trios with ISS (42%). These findings suggest that a monogenic inheritance is less common in HP than in ISS. In conclusion, the findings suggest that sporadic congenital hypopituitarism is frequently genetic but infrequently monogenic, implying a likely digenic/oligogenic etiology.
SUN-473 Primary Hyperparathyroidism and Papillary Thyroid Carcinoma, Association or Coincidence?
Authors: Nandu Nitish Singh , Gilden Janice L
Published: May 2020

Background: The Parathyroid glands originate from the Pharyngeal pouches, Inferior from the third and superior from the fourth. Rarely these glands migrate to the thyroid gland, isthmus or thymus and become ectopic. Primary Hyperparathyroidism (PHPT) is a common cause of hypercalcemia in ambulatory patients. It is also more frequent in women and increases with age. Its treatment is often surgical removal of the affected parathyroid gland. We present a case of an ectopic parathyroid adenoma hidden within the thyroid lobe, treated by thyroid lobectomy ultimately leading to the diagnosis and management of Papillary thyroid carcinoma. Case report: A 73-Year-old female with DM, HTN, hyperlipidemia, osteoporosis was referred to the Endocrine clinic for a history of fractures to the right upper and lower extremities after trivial falls, She was subsequently evaluated for metabolic bone disease, noted to have a PTH 78 (n=14-64 pg/ml) with a total serum calcium 9.7 (n=8.6-10.4 mg/dl), 25-OH Vit-D 14 (n=30-100 ng/ml), urinary calcium to creatinine ratio 20 (n=10-320 mg/g). The parathyroid scan showed persistent activity in the area of the inferior margin right thyroid lobe, suggesting a parathyroid adenoma. She had a parathyroidectomy and during the procedure, the parathyroid gland was unable to be visualized. Hence the Right inferior thyroid lobe was removed. The pathology also showed papillary thyroid carcinoma and the patient had a total thyroidectomy. Discussion: The relationship between PHPT and Papillary thyroid carcinoma still remains unclear. Our patient demonstrated a rare circumstance, wherein the presence of a parathyroid adenoma within the thyroid gland has led to early diagnosis and timely treatment of papillary thyroid carcinoma. Few authors reported thyroid malignancy as the most prevalent cancer among patients with PHPT as the primary disorder. While others report concurrence as a coincidental pathology. Nevertheless, we emphasize the importance of surveillance for thyroid pathology in patients with PHPT that can provide better overall patient outcomes.

References: 1. Vargas-Ortega, G., et al. (2018). “Symptomatic Primary Hyperparathyroidism as a Risk Factor for Differentiated Thyroid Cancer %J Journal of Thyroid Research.” 2018: 6. 2. Miccoli, P., et al. (2006). “Incidental thyroid carcinoma in a large series of consecutive patients operated on for benign thyroid disease.” ANZ J Surg 76(3): 123-126. 3. Bentrem, D. J., et al. (2002). “Is preoperative investigation of the thyroid justified in patients undergoing parathyroidectomy for hyperparathyroidism?” Thyroid 12(12): 1109-1112.
MON-455 Papillary Thyroid Carcinoma in the Thyroglossal Duct
Authors: Franco Katty Manrique , Manrique Helard Andres , Yauri William Lapa , Villanueva José Solis
Published: May 2020

BACKGROUND

In the thyroglossal duct (TD) there are remains of thyroid tissue in 1-40%. Thyroid cancer diagnosed in this duct is an uncommon finding, with a prevalence of less 1% and must meet these criteria: identify the TD, locate remains of carcinoma in it; absence of cancer in the thyroid gland and presence of thyroid follicles in the TD. We present a patient with thyroid cancer in the TD.

CLINICAL CASE

63-years-old-woman. 18 months ago, she noted a submandibular tumor associated to asthenia, weight loss and tremor. On physical examination: 3cm tumor, increased consistency, near to the hyoid bone and 1.5cm left cervical adenopathy. Blood analysis: TSH 0.01 (0.2-4.5) and FT4 5.53 (0.9-1.7). Hyperthyroidism was diagnosed and she started Tiamazol 10mg/bid and propanolol 20mg/tid.

Thyroid US: diffuse goiter. Soft tissue US: heterogeneous mass 39x15x26mm in midline of suprathyroid region suggestive of neoformative process.

Cervical CT scan: solid, heterogeneous, neoformative tissue, located in the midline, infiltrating prelaringeal muscles in contact with hyoid bone. Cervical adenopathy in group II on right side and group III and IV on the left side. Increase in thyroid gland volume.

FNA US guided of suprathyroid tumor was performed: cytology compatible with papillary thyroid carcinoma, Bethesda VI. FNA left adenopathy: compatible with metastasis papillary carcinoma.

Midline tumor exeresis in relation to a TD (Sistrunk surgery), total thyroidectomy plus left lymph node dissection group IIA, IIB, III, IV and V was performed.

Surgical findings: Right lobe thyroid 4x3x2cm with 1cm nodule on the upper pole. Left thyroid lobe 6x4x2cm with multiple nodules, the largest one in upper pole, 2cm. Multiple adenopathies. A 3x3x1cm tumor with irregular edges, hard consistency, adhered to the hyoid bone was removed.

The histology was compatible with papillary thyroid carcinoma in the TD. Thyroid gland was informed as simple goiter.

150ug of levothyroxine was initiated. Six months later, she receives 100mCi I131. The total body scan was positive for thyroid remnant in cervical region. TSH 0.8 FT4 1.71. Thyroglobulin (TG) 13.98 and AntiTG 400.

One year later, new total body scan was negative. TG 10,3 and antiTG 816. New thyroid US showed group III cervical adenopathy 4x7x3mm. Biopsy was compatible with metastasis of papillary thyroid carcinoma. The patient is awaiting a new surgery for lymph node dissection.

CONCLUSION

Sistrunk surgery and total thyroidectomy plus lymphadenectomy should be the treatment of choice in thyroid cancer in TD, followed by ablative therapy. This attitude improves long-term follow-up and reduces the risk of recurrence.

BIBLIOGRAPHY

1.

Granado A, et al. Cáncer del conducto tirogloso. Acta Chir Catal, 8 (1987), 37-44

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Echenique E. Thyroid cancer arising in a thyroglossal duct cyst. Cir Esp. 2000 67 (6) 567-71.
SAT-513 Thyroid Disease And Infrared Imaging Of Eyelids
Authors: Luu Shannon , Wu Gloria , Leung Brian , Momen Donia , Lau Chap-Kay K
Published: May 2020

Background: Thyroid eye disease is thought to present as proptosis and/or severe conjunctival chemosis. Severe dry eye disease and its symptoms of non-specific eye pain and foreign body sensation in the eye can be overlooked as an early biomarker of thyroid disease. New infrared imaging can be used to evaluate dry eye and eyelid gland anatomy. Infrared imaging and detailed history of thyroid eye symptoms may lead to subsequent testing of thyroid function and more referrals to thyroid specialists.

Purpose: Using infrared photography to evaluate dry eye complaints in patients: do they have thyroid disease?

Methods: A retrospective chart review (2017–2019) of patients with dry eyes, eyelid imaging with infrared photography and thyroid lab testing was performed. Infrared photography with 820 nm wavelength (Heidelberg Spectralis, Heidelberg, Germany). Percentage loss of Meibomian glands was identified for each eye, then analyzed, per patient. The control population consisted of patients with no dry eye complaints, no thyroid testing or thyroid history. Exclusion criteria: patients over the age of 90 years and patients with a history of glaucoma, diabetes, cataract surgery, and eyelid surgery. Age matching was done (±5 years).

Results: n=48 patients, avg age=57.73 years (sd=16.81, range 21–85 years). Thyroid patients: n=24 patients, male=10, female=14, avg age= 57.12 years (sd=16.65, med=55.5, range 23–83 years). Controls: n=24 patients, male=9, female=15, avg age=58.33 years (sd=17.30, med=58, range 21–85 years). Loss of Meibomian glands: thyroid=40.94%, control=5.10% (p<0.0001, t-test). Dry eye complaints: thyroid = 16/24, control = 0/24 (p<0.0001, x2).

Discussion: Meibomian glands are glands in the upper and lower eyelids. These glands provide the lipid component of the tear film, thus slowing the evaporation of the tears and stabilizing the tear film with each blink. Meibomian gland loss would explain the dry eye symptoms in an abnormal thyroid patient population. Infrared photography can be performed with a #87 camera lens filter (cost = $65). The loss of Meibomian glands may be an early sign for thyroid disease.

Conclusion: Infrared photography may be helpful in identifying severe dry eye, thus leading to increased awareness of thyroid eye disease symptoms in our patients in ophthalmology, endocrinology, and primary care.
SAT-428 Sex-Specific Risk Gene of Graves’ Disease
Authors: Zhao Shuangxia , Chen-Yan Yan
Published: May 2020

Graves’ disease is one of the most common forms of autoimmune thyroid disease, with several susceptibility single nucleotide polymorphisms identified by the case-control association studies. In this study, we aim to determine whether any observed differences in genetic associations are influenced by sex in Chinese Han populations. A total of 8,835 patients with Graves’ disease and 9,936 sex-matched healthy controls were enrolled in the study. We conducted sex specific analysis among 20 Graves’ disease susceptibility loci confirmed by two-stage association analysis. A significant sex-gene interaction was detected primarily at rs5912838 on Xq21.1 between the GPR174 and ITM2A gene, whereby men patients with Graves’ disease possessed a significantly higher frequency of risk alleles than women. Interestingly, men patients with Graves’ disease had a higher cumulative genetic risk than women. Our findings suggest one potential sex-specific link of Graves’ disease on Xq21.1, which could increase our understanding of the pivotal mechanisms behind Graves’ disease and ultimately the provision of possible therapeutic targets.