bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-LB78 TSH Is a Negative Modulator of Hippo Transcriptional Effectors
Authors: Fernández-Méndez Celia , Santisteban Pilar 
Published: May 2020

Abstract
Hippo signaling pathway regulation by hormonal signals acting through G-coupled receptors has been widely described. Modulation of processes such as tissue growth or differentiation by this pathway critically relies on the location and levels of its major effectors: the cofactors YAP/TAZ and the family TEAD of transcription factors. Despite this well-defined regulatory mechanism, little is known about the Hippo pathway in the thyroid gland. Thyrotropin (TSH), main factor for thyroid follicular cells differentiation, plays its role by interacting with its G-protein-coupled receptor (TSHR). High serum TSH levels are associated with hypothyroidism, characterized by a change in thyroid follicle morphology and inflammation of the thyroid gland. This led us to study if TSH could modulate the Hippo pathway.Rat thyroid follicular cells (PCCl3) were treated with TSH and forskolin, an adenylyl cyclase activator. By immunofluorescence and western blot, levels and subcellular location of the Hippo Pathway components were assessed in different conditions. An increase of the Hippo kinase MST1/2 and LATS1/2 was observed after TSH and forskolin treatments, corresponding to a downregulation of the transcriptional mediators of the pathway TAZ, YAP and Tead1. Especially remarkable is the translocation of YAP/TAZ from the nucleus, which involves a decrease in their activity.Next, we validated the results in an in vivo model generating hypothyroidism in 3-month-old male C57BL/6J by adding MMI (2-Mercapto-1-Methylimidazole) and perchlorate (KClO4) to their drinking water. After 2 weeks of treatment, we euthanized the animals, validated higher TSH serum levels and performed analysis of the Hippo components in the thyroid by immunohistochemistry. A reduction in the levels of the Hippo effectors TAZ, YAP and Tead1 was found in the thyroid slices from hypothyroid mice, confirming the in vitro results. In addition, evaluation of a human thyroid tissue microarray, including Hashimoto disease samples, led to a validation of the previously described TSH role.Hereby, we report a crosstalk by which TSH is increasing the kinase axis of the Hippo pathway thus decreasing the activity of its main transcriptional effectors in the nuclei. Future research of the role of these transcriptional effectors will be carry out to discern if their decrease could be associated with the morphology changes linked to hypothyroidism.
SAT-LB305 Concurrent Peri-Adrenal Paraganglioma and Renal AngiomyolipomaComplicated by Toxic Multinodular Goiter
Authors: Sathavarodom Nattapol 
Published: May 2020

Abstract
A 40 years old woman presented with headache, palpitation and diaphoresis by the past 3 months, and then developed progressive dyspnea on exertion and chest pain 2 weeks ago. She also lost 5 kg of her body weight during the past 6 months. She ever had multinodular goiter and lobectomy was done 12 years ago, after that she lost to follow up. At meantime, toxic multinodular goiter was suspected and high level of free T4, T3, and suppressed thyrotropin were demonstrated. Furthermore, thyroid scan revealed heterogenous tracer uptake at her thyroid bed. Methimazole was started, however her blood pressure and heart rate were all uncontrolled. Pheochromocytoma was suspected and markedly elevated of both urinary normetanephrine and metanephrine were confirmed. Computed tomogram revealed a huge, right supra-renal mass. In addition, hypodensity mass were found at upper pole of right kidney, and the results of 131I-Metaiodobenzylguanidine scintigraphy showed increased tracer uptake at upper abdomen. Right adrenalectomy and partial nephrectomy were performed. The final pathological diagnosis was sympathetic paraganglioma, and angiomyolipoma which confirmed by immunohistochemical staining. We present here an unusual case of concurrent periadrenal paraganglioma and renal angiomyolipoma which was complicated by autonomous toxic multinodular goiter.
MON-057 MODY Diagnosis: Missed Opportunity to Avert Insulin Therapy. A Case Series
Authors: Paulo Remberto , Kirmani Salman , Matlock Kristal Anne , Bowlby Deborah A , Headley Terry 
Published: May 2020

Abstract
BACKGROUND Prevalence of MODY is 1.2% in pediatric diabetes population. SEARCH study reported most of these patients were misdiagnosed as T1DM or T2DM up to 36% and 51% respectively (1). GCK (MODY 2) and HNF1A/HNF4A (MODY3) are the most common forms of MODY. Despite improvement in testing strategy (panel testing instead of step-wise approach) and cost, MODY testing remains underutilized. These conditions do not require insulin therapy, and MODY 2 patients may even be discharged from clinic after diagnosis. We present 4 cases and valuable lessons learned.
MODY 2 Case 1. 4 yo M referred for hyperglycemia in the 300s during surgery. A1c 6.4%. FBG at home 150s, asymptomatic. MGM and MGM’s siblings have diabetes. Diabetes autoantibodies (DAA) negative. C-peptide 5.4 (NL 0.78 - 5.19 ng/ml). MODY panel (GeneDx) showed heterozygous mutation in GCK gene (c.70 C&gt;T). Patient remains off insulin, family reassured and advised to undergo genetic testing.
MODY 2 Case 2. 8 yo M diagnosed at local ED with “T1DM” after presenting with polyuria, polydipsia, and random BG 237. A1c 6.7%, C-peptide 1.9, started on basal-bolus insulin. MODY panel (sent a year later when patient was found to have low insulin requirement, negative DAA) showed pathogenic variant in GCK gene. Weaned from insulin, A1c unchanged (6.3–7%). Mother found to have same mutation. MODY 3 Case 1. 16 yo F referred by PCP who started her on insulin a year prior after an incidental finding of hyperglycemia. A1c was 7.5% at diagnosis. Mom, MGM have diabetes, unknown type (MGM thin by report). DAA neg, C-Peptide 1.74. MODY Panel showed HNF1A heterozygous gene mutation for RI31Q. She was switched to Glyburide, blood glucose 90s. MODY 3 Case 2. 10 yo M referred from the ED for “T1DM” (weight loss, fatigue, A1c 7.6%) started on basal-bolus insulin, but lost to follow up for a year. Brother has MODY 3. DAA neg, C-Peptide 3.1. Targeted gene sequencing showed HNF1A gene mutation. He was switched to Glyburide, A1c improved to 6.7%. However, patient became noncompliant as teenager, A1c now 9.3%.
CONCLUSION MODY remains underdiagnosed. A high index of suspicion should be maintained in nonobese, DAA-negative patients diagnosed with DM before 25yo. Although DAA and genetic testing can be costly, diagnosis can dramatically alter diabetes management as illustrated in all 4 cases, and overall cost of management may be lower in the end. Patients with MODY 2 do not develop vascular complications associated with diabetes, nor require pharmacotherapy. MODY 3 patients may be safely switched to sulfonylurea monotherapy, though degree of diabetes control depends on compliance with medication. Testing gives relatives previously misdiagnosed the opportunity to improve their own quality of life. More education for health care providers is warranted for prompt diagnosis and appropriate management of this condition.
Reference:1. Pihoker, et al. JCEM 2013; 98:4055–62
SAT-LB107 Insulin Sensing by Astrocytes Is Critical for Normal Thermogenesis and Body Temperature Regulation
Authors: Hill Jennifer Wootton , Manaserh Iyad H 
Published: May 2020

Abstract
The important role of astrocytes in the central control of energy balance and glucose homeostasis has only recently been recognized. Changes in thermoregulation can lead to metabolic dysregulation, but the role of astrocytes in this process is not yet clear. Therefore, we generated mice congenitally lacking insulin receptors (IR) in astrocytes (IRKOGFAP mice) to investigate the involvement of astrocyte insulin signaling. IRKOGFAP mice displayed a significant decrease in energy expenditure and a striking decrease in basal and fasting body temperature. When exposed to cold, however, they were able to mount a thermogenic response. Brown adipose tissue in IRKOGFAP mice exhibited increased adipocyte size, more apoptosis, loss of innervation, and decreased βAR3 expression levels. These findings identify a novel role for astrocyte insulin signaling in the development of normal body temperature control and sympathetic activation of BAT. Targeting insulin signaling in astrocytes has the potential to serve as a novel target for increasing energy expenditure.
SUN-LB111 Comparison of Phenotype and Metabolic Abnormalities Among Familial Partial Lipodystrophy Due to LMNA or PPARG Variants
Authors: Vasandani Chandna , Li Xilong , Sekizkardes Hilal , Brown Rebecca , Garg Abhimanyu 
Published: May 2020

Abstract
Familial partial lipodystrophy (FPLD), a rare autosomal dominant disorder, is characterized by marked loss of subcutaneous (sc) fat from the extremities, and predisposition to insulin resistance, diabetes mellitus, dyslipidemia and hepatic steatosis. FPLD2 and FPLD3 due to causal variants in LMNA and PPARG, respectively, are the two most common subtypes. Due to extremely rare prevalence of FPLD3 and limited reports in the literature, whether there are phenotypic differences between the two subtypes remain unclear. Therefore, we compared the anthropometric measurements and prevalence of metabolic abnormalities among 32 FPLD3 subjects (4 M, 28 F; mean ± SD age, 41 ± 17.2 y; body mass index (BMI), 26 ± 4.0 kg/m2) with 271 FPLD2 subjects (66 M, 205 F; age, 37.4 ± 17.0 y; BMI, 26 ± 5.0 kg/m2) from two referral centers in the United States. As compared to those with FPLD2, FPLD3 subjects had borderline higher prevalence of hypertriglyceridemia (66% vs 84%; P = 0.063), but significantly higher prevalence of diabetes (44% vs 72%; P = 0.004), past history of acute pancreatitis (13% vs 52%; P &lt;0.001), and polycystic ovarian syndrome (26% vs 52%; P = 0.011). As compared to FPLD2, FPLD3 subjects had similar fasting triglyceride levels (median 208 vs 255 mg/dL; P=0.15), but lower high-density lipoprotein cholesterol levels (median 37.5 vs 30 mg/dL; P = 0.001), higher fasting glucose (median 95 vs 115 mg/dL; P = 0.05) and HbA1c (median 5.7 vs 7.0 %; P = 0.005) levels. Regional body fat was measured by dual energy X-ray absorptiometry in 19 FPLD3 and 105 FPLD2 subjects. In comparison to FPLD2, FPLD3 subjects had higher total fat (median 21.6% vs 26.1 %; P = 0.018); upper limb fat (median 20.3% vs 27.3%; P = 0.003) and lower limb fat (median 16.0% vs 20.8%; P = 0.007). Skinfold thickness measurements by calipers also revealed less severe fat loss from both the upper and lower extremities in FPLD3 subjects compared to FPLD2 subjects. As compared to FPLD2, FPLD3 subjects had significantly higher triceps skinfold thickness (median 5.5 mm vs 7.5 mm; P = 0.015); and thigh skinfold thickness (median 5.8 mm vs 11.3 mm; P = 0.001). There were no significant differences in the prevalence of fatty liver, plasma alanine aminotransferase and aspartate aminotransferase levels in the two subtypes. We conclude that compared to FPLD2 subjects, those with FPLD3 have milder lipodystrophy phenotype but paradoxically present with more severe metabolic complications, especially diabetes, dyslipidemia and polycystic ovarian syndrome. It is likely that this discrepancy could be due to early recognition of FPLD2 because of severe fat loss versus initial diagnosis of FPLD3 subjects due to severe metabolic complications leading to discovery of milder fat loss.
SUN-LB63 Optic Disc Edema in Patients With Craniofacial Fibrous Dysplasia / McCune-Albright
Authors: Raborn Layne , Pan Kristen , Fitzgibbon Edmond J , Collins Michael , Boyce Alison 
Published: May 2020

Abstract
Background: Fibrous Dysplasia (FD) is a mosaic disorder that involves fibro-osseous lesions in bone. In the presence of coexisting extra-skeletal features, it is termed McCune-Albright Syndrome (MAS). Optic disc edema (ODE) is a potentially serious finding that may progress to optic disc ischemia and nerve atrophy. We sought to determine the prevalence and identify risk factors for the development of ODE in the NIH FD/MAS cohort. Methods: A retrospective review was conducted and identified 7 patients with craniofacial FD/MAS with a diagnosis of ODE. Controls were patients with a normal eye examination and without potentially confounding ophthalmologic conditions. The cohort consisted of 73 patients with craniofacial FD, 7 (10%) of whom were diagnosed with ODE. Results: Radiographic and statistical analysis identified Chiari I malformation (CM1) and mass lesions, including aneurismal bone cysts (ABCs) and arachnoid cysts, as significant risks for developing ODE (odds ratio [OR] 48.8; 95% confidence interval [CI], 5.3 to 633.1; p &lt; 0.01) and (OR 16.3; 95% CI, 2.8 to 81.9; p &lt;0.01) respectively. There was no significant association of ODE with endocrinopathies, medications, optic canal diameter or intracranial volume.Conclusion: ODE can be found in association with craniofacial FD and may be the initial presenting symptom of intracranial mass lesions or CM1, which has previously been shown to be at an increased prevalence in the FD/MAS cohort. Patient with craniofacial FD/MAS and intracranial mass lesions or CM1 are at an increased risk of developing ODE and require close monitoring.
SUN-162 Isolated Primary Pigmented Micronodular Adrenal Disease. Unilateral or Bilateral Adrenalectomy? Two Cases Report
Authors: Chevais Anastassia , Beltsevich Dmitry , Ladygina Daria 
Published: May 2020

Abstract
Background: Isolated primary pigmented nodular adrenal disease (i-PPNAD) is a particular case of micronodular bilateral hyperplasia (MiBAH) leading to Cushing syndrome (CS). We present two patients with i-PPNAD who undergone unilateral adrenalectomy with different disease outcomes.
Case 1: A 56 yo man presented with typical signs and symptoms of CS, including central weight gain, proximal muscle weakness, hypertension and marked osteoporosis. A biochemical investigation showed an assessment of late-night salivary cortisol - 23 nmol/l (n &lt;9), 24h urinary free cortisol (UFC)- 1206 nmol/24h (n-60–413). The 1 mg DST showed post-DST cortisol 617 nmol/l (n&lt;50). ACTH concentration was suppressed at 1.1 pg/ml (n-7–66). Adrenal CT-scan was normal. PPNAD was assumed and the screening for Carney complex components was negative. After left adrenalectomy, histological examination confirmed the diagnosis of PPNAD. However, biochemical remission wasn’t achieved: postoperative UFC-860 nmol/24h. Thus, the right adrenalectomy was conducted.
Case 2: A 40 yo female presented with long term drug-corrected (beta-blockers, ACE inhibitor) arterial hypertension, menstrual dysfunction and clinical features of CS (central obesity, proximal muscle weakness, hirsutism), without osteoporosis. Baseline hormonal evaluation documented slightly increased level of salivary cortisol- 9,8 nmol/l (n &lt;9), post 1 mg DST cortisol - 470 nmol/l (n&lt;50) and ACTH-concentration below detection &lt;1 pg/ml (n-7–66). However, UFC was normal – 215 nmol/l (n-60–413). Abdominal CT-scan revealed micronodular hyperplasia of the left adrenal and was suggestive of possible right adrenal gland hyperplasia. We performed left adrenalectomy. In the early postoperative period, adrenal insufficiency was diagnosed and thus it required hydrocortisone replacement.
Discussion: We obtained two opposite results: in case 1, an expected remission after unilateral adrenalectomy was not achieved, while patient No.2 developed adrenal insufficiency, which was a more favourable prognostic sign and attested to the successful outcome of surgical treatment. A possible explanation of the ineffectiveness of surgical intervention in patient No.1 was primary more severe hypercortisolism. It is also necessary to take into account that according to the CT data of the patient No.1, both adrenal glands were within normal ranges and did not differ from one another, while in the patient No.2, the lesion was more prominent on the right side.
Conclusion: Diagnostic of i-PPNAD and choice of intervention can be precarious, consequently more studies are needed to define to which patients unilateral adrenalectomy could be an efficient treatment modality. It is possible to perform unilateral adrenalectomy with subsequent assessment of cortisol levels, in case of lack of remission the contralateral adrenalectomy is required.
SAT-570 Should Severe Hypertriglyceridemia Also Be Considered as a Contraindication for Use of Glucagon like Peptide 1 (GLP-1) Agonists?
Authors: Guzman Amelia 
Published: May 2020

Abstract
Background: Reported cases of acute pancreatitis have been associated with the use of GLP-1 agonists for treatment of diabetes mellitus. Hypertriglyceridemia is a well-established but underestimated cause of acute and recurrent pancreatitis. At the present time, there is insufficient data to know if there is a casual relationship. Clinical Case: A 46 y.o. male with past medical history of coronary artery disease, hyperlipidemia, type 2 diabetes mellitus, hypertension, and morbid obesity, was admitted to the hospital with severe abdominal pain radiating to the back associated with non-bilious vomiting, for 1 day. Patient endorsed that 4 years ago he was diagnosed with hypertriglyceridemia. Physical exam findings were notable for a distended abdomen with mild epigastric tenderness, heart rate at 120 bpm, and a body mass index of 37 kg/m2. Active medications include: atorvastatin 40 mg PO daily, fenofibrate 45 mg PO daily, metformin 1,000 mg PO twice a day, glipizide 5 mg PO daily, levemir 60 units SQ twice a day, and most recently he had been started on dulaglutide 0.75 mg SQ weekly. Initial tests were consistent with acute pancreatitis and diabetic ketoacidosis: lipase 944 U/L (n 8.0 - 78 U/L), anion gap 18 mEq/L (n 5 - 13 mEq/L), creatinine 1.6 mg/dL (n 0.72 - 1.25 mg/dL), glucose 479 (n 60–100 mg/dL), β-Hydroxybutyrate 5.3 mmol/L (n &lt;0.3mmol/L), urine glucose &gt;1,000 mg/dL (n Negative mg/dL), urine ketones 20 mg/dL (n Negative), Triglycerides (TG) 5,374 mg/dL (n &lt;150 mg/dL) and Hgb A1C 11.9% (n &lt;5.7%). CT abdomen and pelvis without contrast revealed moderate acute pancreatitis. Patient was admitted to the intensive care unit and was started on intravenous insulin, atorvastatin 80 mg PO daily and fenofibrate 145 mg PO daily. Despite optimization of lipid-lowering agents, TG remained above 2,000 mg/dL. Decision was made to start patient on plasmapheresis until TG was &lt;500 mg/dL. Patient’s TG improved to 370 mg/dL after second treatment. Patient’s dulaglutide was discontinued and patient was advised to avoid GLP-1 agonist use, indefinitely. One-month post discharge patient’s TG level was 370 mg/dL. Conclusion: Pancreatitis should be considered in patients on GLP-1 agonists, that present with persistent severe abdominal pain (with or without nausea), and its use should be discontinued in such patients. Use of GLP-1 agonists should be avoided in subjects with severe hypertriglyceridemia. Further research should be made in order to determine if GLP-1 agonists should be contraindicated in patients with severe hypertriglyceridemia, as both increase risk for pancreatitis.
SUN-385 Differential Effects of Abaloparatide and Teriparatide on Hip Cortical Volumetric BMD by DXA-Based 3d Modeling
Authors: Winzenrieth Renaud , Ominsky Michael S , Wang Yamei , Humbert Ludovic , Weiss Richard J 
Published: May 2020

Abstract
The osteoanabolic agent abaloparatide (ABL) has been shown to significantly increase total hip BMD over an 18-month period in postmenopausal women with osteoporosis. However, it remains unknown if these gains predominantly occur in the cortical or trabecular compartments of the proximal femur, and how they may differ from the effects of teriparatide (TPTD). Therefore, a 3D modeling approach was applied to DXA images from patients in the ACTIVE trial to estimate cortical and trabecular changes in the proximal femur over 18 months of treatment with placebo (PBO), ABL, or TPTD. A subset of 750 patients, 250 from each of the treatment groups in ACTIVE (PBO, ABL, TPTD) with non-missing BMD data were randomly selected with data stratified by study site and patient race/ethnicity. Hip DXA scans at baseline and months 6 and 18 were subjected to DXA-based 3D modeling to evaluate volumetric BMD (vBMD) in the cortical and trabecular compartments, as well as cortical thickness and cortical surface BMD (sBMD) (3D-SHAPER v2.10.1, Galgo Medical, Spain). Pairwise group comparisons were made for percentage change from baseline data using P-values derived from contrast tests based on an MMRM model adjusting for BMI, age, value at baseline, and DXA scanner. At 18 months, total hip areal BMD was significantly increased in both the ABL and TPTD groups (P&lt;0.001 vs PBO), with gains from baseline significantly greater with ABL versus TPTD (4.2% vs 3.3%; P&lt;0.05). Similar increases from baseline were observed with ABL and TPTD for both trabecular vBMD (9%) and cortical thickness (1.5%) at month 18 (both P&lt;0.001 vs PBO). In contrast, cortical vBMD was significantly increased from baseline with ABL (1.3%) compared with PBO (-0.2%) and TPTD (0.4%) at month 18 (both P&lt;0.05 vs ABL). Cortical sBMD, the product of cortical thickness and vBMD, was also increased with ABL (+2.8%) versus both PBO (-0.2%) and TPTD (+1.8%) at month 18 (both P&lt;0.05). Although ABL and TPTD increased trabecular vBMD and cortical thickness similarly at the hip by DXA-based 3D modeling after 18 months, ABL significantly increased cortical vBMD and sBMD to a greater extent than TPTD. Additionally, ABL appears to increase cortical density relative to TPTD in clinically important regions of the proximal femur. Further studies may be warranted to investigate these differences and how they may impact hip strength.