bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-663 The Impact of Anxiety on the Successful Management of a Type I Diabetic Patient
Authors: Janakiram Nikhila 
Published: May 2020

Abstract
Background: Patients with both type 1 diabetes mellitus (T1DM) and generalized anxiety disorder (GAD) are known to be at increased risk for hypoglycemic events, long-term hyperglycemia, weight gain and vascular disease. However, little research has been conducted regarding management of anxiety in patients with T1DM.
Clinical case: A 27 year old female with T1DM (controlled on an insulin pump), GAD, PTSD, and history of benzodiazepine abuse presented to the emergency department after experiencing multiple panic attacks the day of admission. Recently, patient had multiple bouts of emesis in addition to decreased oral intake. On admission, blood sugar was 54, which increased to 164 after administration of 1 amp of dextrose-50. Patient was obtunded and unable to provide much history. Overnight, insulin was not given due to patient’s poor oral intake. The following morning, patient had one cup of juice for breakfast. Accu-check shortly after revealed a blood glucose level over 500 and patient developed diabetic ketoacidosis (DKA) and was admitted to the ICU on our hospital DKA protocol. Once anion gap closed, patient was transferred out of the ICU for continued management of her diabetes. Patient went on to have multiple panic attacks for the duration of her hospitalization which were controlled with scheduled diazepam, valproic acid, lorazepam and quetiapine. Psychiatry was consulted and found that a major contributing factor to her developing recurrent DKA was her struggle with anxiety surrounding the responsibilities of managing her diabetes and its associated complications including gastroparesis and neuropathy. Further conversation revealed that her psychiatrist had passed away a few months prior to admission and that she had not established care with a new psychiatrist yet.
Discussion: Given the life changing nature of T1DM, it is not uncommon for these patients to have difficulty coping with the daily challenges required to optimally treat their condition. It can be frustrating when the slightest shift in caloric intake or exogenous insulin leads to life-threatening situations such as DKA. The above case sheds light on the profound medical consequences and setbacks that poorly controlled anxiety can have on diabetic patients. Therefore, recognizing the impact of anxiety on our patients with diabetes is critical in preventing further complications, especially microvascular, macrovascular and potentially other life-threatening events.
MON-537 Primary Adrenal Insufficiency During Tyrosine Kinase Inhibitors Treatment in Advanced Thyroid Cancer Patients
Authors: Valerio Laura , Matrone Antonio , Agate Laura , Bottici Valeria , Viola David , Cappagli Virginia , Giani Carlotta , Molinaro Eleonora , Elisei Rossella 
Published: May 2020

Abstract
Objective: Tyrosine kinase inhibitors (TKIs) are used for the treatment of metastatic differentiated (DTC), poorly differentiated (PDTC) and medullary (MTC) thyroid cancer. Several adverse events (AEs) have been reported in almost all patients (pts) treated with TKIs. One of the less known AE related to the use of these drugs is the primary adrenal insufficiency (PAI).
Methods: We analyzed the basal and stimulated adrenal function, ACTH levels, adrenal antibodies and electrolytes levels in 82 thyroid cancer pts treated with TKIs (vandetanib and cabozantinib in MTC pts, lenvatinib and sorafenib in DTC and PDTC pts) and we correlated these results with the clinical-pathological features of our pts.
Results: In our series, 25/82 (30.5%) pts showed a PAI after stimulation test with a progressive ACTH increase in 14/25 (56%) pts. Thirteen/25 (52%) pts with PAI were DTC, 8/25 (32%) pts were MTC and 4/25 (16%) pts were PDTC. Sixteen/25 (64%) pts were treated with lenvatinib, 8/25 (32%) were treated with vandetanib and 1/25 (4%) was treated with cabozantinib at the time of stimulation test. In 5/25 (20%) pts PAI occurred within 12 months from the TKIs treatment initiation, in 9/25 (36%) within 36 months and in 11/25 (44%) after 36 months of treatment. Eighteen/25 pts with PAI were older than 55 years. Twenty/25 (80%) of these pts were treated with cortisone acetate replacement therapy with the improvement of fatigue in a small part of these while other 5 pts were untreated due to the mild degree of PAI and the absence of specific symptoms (i.e fatigue). Moreover, in our pts the evaluation of adrenal antibodies was negative and the electrolytes levels were in the normal range. We also correlated the presence of PAI with the clinical-pathological features of our pts but we didn’t observe any significant correlation.
Conclusions: We observed that PAI, mainly subclinical, can occur during TKIs treatment in thyroid cancer pts. The appearance of fatigue, the typical symptom of PAI, could be multifactorial in these pts due also to the direct effect of TKIs treatment. Thus, in these cases is very difficult to recognize the cause of fatigue and to decide the appropriate treatment (cortisone acetate replacement therapy vs TKIs dose reduction). Moreover, the time of PAI appearance is variable since it can be early (&lt;12 months) or late (&gt;36 months) after TKIs treatment initiation and the adrenal function must be monitored during all TKIs treatment period. More studies are needed to know the pathophysiology of this “adverse event” during TKIs treatment and to improve the acknowledgments regarding the differential diagnosis and treatment of these pts, regardless of symptoms.
SAT-107 Improved Adult Height in Brazilian Turner Syndrome Patients Treated with Growth Hormone
Authors: Scalco Renata Da Cunha , Braz Adriana Farrant , Malaquias Alexsandra C , Antonini Sonir Roberto Rauber , Guerra-Junior Gil , Mendonca Berenice Bilharinho , Jorge Alexander A L 
Published: May 2020

Abstract
Background: Short stature is the most frequent clinical manifestation in Turner syndrome (TS), occurring in 98% of these patients. Growth hormone was shown to improve adult height in TS patients from diverse genetic backgrounds. However, there are few studies on adult height in TS patients from developing countries, where the diagnosis is frequently delayed.
Objective: To compare adult height between GH-treated and untreated TS patients.
Patients and methods: 120 GH-treated and 109 GH-untreated TS patients from 3 referral hospitals in Brazil were evaluated. The most common reasons for not treating TS patients with GH were late diagnosis or GH unavailability. Data on karyotype, parents’ height, puberty development and GH treatment were obtained from their medical records. Adult height was determined when growth velocity was inferior to 1cm/year during a minimum follow-up period of 12 months.
Results: The frequency of 45,X karyotype was similar between the groups (48.7% vs. 41.9% in GH-treated vs. GH-untreated TS patients, respectively, P= 0.639). GH-treated TS patients started GH therapy at a chronological age (CA) of 11.2 ± 3.7 yr, bone age of 9.3 ± 3.1 yr, height SDS (British 1965 standards) -3.1 ± 1.1. GH mean dose was 48µg/kg.d and GH treatment duration was 5.4 ± 3.0 yr. Estrogen replacement was started late, at CA of 14.3 ± 2.0 yr in GH-treated and at 14.9 ± 1.9 yr in GH-untreated patients, and the rate of spontaneous puberty was similar between the groups (GH-treated 16.8% vs. GH-untreated 22,8%, P=0.304). Adult height was significantly higher after GH treatment (150.1 ± 5.8 cm vs. 143.3 ± 7.2 cm in GH-treated vs. untreated TS patients, respectively, P &lt; 0.001), even with a small but significant difference in target height between the groups (158.2 ± 4.8 vs. 159.8± 4.5 cm in GH-treated vs. untreated TS patients, respectively, P= 0.015). More than half of the TS GH-treated patients reached normal adult height (equal or higher than 150.2 cm), whereas only 15.6% of GH-untreated patients reached it.
Conclusion: Despite the delayed diagnosis of TS patients in our cohort, GH treatment was associated with a significant height gain, and the TS GH-treated group was around 7 cm taller than the GH-untreated group.
OR24-01 Mutational Study of the GPR119 Receptor Binding Site
Authors: Rosales Matthew D , Dean Frank , Kotsikorou Evangelia 
Published: May 2020

Abstract
The GPR119 receptor, a class A G-protein coupled receptor located in the pancreatic β cells, induces insulin production when activated. Due to its specific activity, the pharmaceutical industry has identified GPR119 as a target for the treatment for type 2 diabetes. The lack of a GRP119 crystal structure has hindered the study of the receptor so our laboratory developed GPR119 active and inactive homology models. Docking studies with the inactive receptor model indicated that two leucine residues facing the binding pocket, L5.43(169) and L6.52(242), may be involved in ligand activation. Additionally, a serine at the extracellular end of the pocket, S1.32(4), may help orient of the ligand in the binding pocket via hydrogen bonding. To gain further insight into the role of these residues and the receptor activation mechanism, molecular dynamics (MD) simulations and in vitro cAMP assays of the wild type and mutant receptors were employed. The software NAMD employing the CHARMM force field was used to carry out MD simulations of the active receptor model bound with the agonist AR231453 embedded in a hydrated lipid bilayer. Preliminary results indicate that L6.52(242), located on transmembrane helix (TMH) 6, does not face directly into the binding site and does not interact with the ligand, while L5.43(169), located on TMH5, does face into the binding site, potentially interacting directly with the ligand. Also, S1.32(4), because of its extracellular location, is solvated instead of interacting with the ligand. The in vitro studies overall support the MD simulations. The mutations L6.52(242)M and L6.52(242)A appear to have minimal to no effect on agonist-induced cAMP production, compared to the wild type. In contrast, the L5.43(169)M and L5.43(169)A mutations decrease the potency of activation by AR231453, indicating that L5.43(169) changes the shape of the binding pocket, affecting ligand binding and activation. Finally, the cAMP assays show that the S1.32(4)A mutant also shows decreased activity compared to the wild type, implying that the ligand may be losing a hydrogen bonding interaction when S1.32(4) is mutated to alanine.
SAT-144 Cooperative Mechanism of SREBP-Dependent Cholesterol Synthesis Pathway and P53 on Malignant Formation in Breast Cancer
Authors: Nakayama Akitoshi , Yokoyama Masataka , Nagano Hidekazu , Sakuma Ikki , Hashimoto Naoko , Higuchi Seiichiro , Yamagata Kazuyuki , Tanaka Tomoaki 
Published: May 2020

Abstract
p53 is mutated more than half of human cancers, and mutant p53, a gain of function, can actively have functional consequences with tumorigenesis. However, its action of molecular mechanisms, particularly in vivo conditions, has not been fully are clarified. Here, we generated KO and KI (R280K) breast cancer cell lines for p53 using CRISPR/Cas9 system, and then performed a three-dimensional culture model. We found that the introduction of mutant p53 was solely able to mediate the transformation to poor architectural structure. Interestingly, our findings in statin-effect along with cholesterol synthesis pathway, especially isoprenoid dependency, revealed that this pathway is necessary and sufficient for the regulation of malignant architecture in SREBP2-dependent manner with cooperatively being controlled by mutant p53 on 3D-cultured breast cancer. Furthermore, in accordance with the malignancy progresses, SREBP2 was accumulated in nuclear and nuclear membrane portion with enhancement in malignant formation. In addition, we found that mutant p53 interacts with SREBP2, and consistently mutant p53 was associated with DHCR7 promoter in parallel with binding pattern of SREBP2. Thus, our results provide the novel insight into the mutant p53, a gain of function, and its linkage to poor architectural structure in 3D-cultured breast cancer cells via SREBP2-dependent isoprenoids regulation as potential therapeutic targets.
SAT-166 Advantage and Trustworthy of Cortisol and Dexamethasone Evaluation in Different Biological Matrices in Patients with Adrenal Masses
Authors: Lionetto Luana , Maggio Roberta , Lardo Pina , Bernardini Donatella De , Cipolla Fabiola , Capi Matilde , Simmaco Maurizio , Petrangeli Elisa , Toscano Vincenzo , Pugliese Giuseppe , Stigliano Antonio 
Published: May 2020

Abstract
Biochemical function of adrenal masses is currently based on 1mg post-overnight dexamethasone suppression test (pDST). Several approaches are recently developed, in order to reduce false positive/negative samples, only in retrospective series. They are based on the correlation of some different parameters, i.e. late-night salivary cortisol (LNSC) vs serum and salivary cortisol pDST; LNSC vs serum and salivary cortisol and serum dexamethasone pDST; LNSC and cortisone vs serum cortisol and salivary cortisol and cortisone pDST. Although these findings offer a better diagnostic performance, several conditions are still disappointed. No information is traceable about the harvest time of diurnal salivary and serum samples and no study include neither the levels of salivary nor urinary dexamethasone pDST. Aim of our study is to combine all these strategies in order to avoid the underestimated biases and obtain more precise information about the true “cortisol condition” of the patients.
To reach this purpose we assess both cortisol and dexamethasone concentrations in several samples: saliva at 11PM before the drug administration, diurnal saliva and serum at 8AM and also the urine collection from 11PM to 8AM. Analytes levels are measured using a validated liquid chromatography-tandem mass spectrometry method. In this study we included 20 subjects without morphological adrenal alteration (MRI assessment), dyslipidemia, hypertension and impaired glucose tolerance (healthy controls) and 20 patients with adrenal incidentaloma showing different cortisol levels ranging from normal to ACTH-independent hypercortisolism. In both series, LNSC were similar to salivary cortisol pDST, even if they were greater in the patients with adrenal incidentalomas and subclinical cortisol secretion. Serum dexamethasone levels were in reference ranges, while salivary and urinary dexamethasone found in these matrices require additional sample numbers in order to establish appropriate cut-offs. Our preliminary results suggest that the combination of these findings could represent an improvement to assess the individual cortisol status.
MON-189 Evaluation of Adrenal Insufficiency and Recovery in Rheumatology Patients on Long-Term Glucocorticoid Therapy
Authors: Sagar Rebecca , Mackie Sarah , Stewart Paul Michael , Abbas Afroze 
Published: May 2020

Abstract
Background
Long-term glucocorticoid (GC) therapy is commonly used to treat rheumatological conditions. This may result in tertiary adrenal insufficiency, as a result of suppression of the HPA axis, when GC doses are weaned/withdrawn. There is little published data about tertiary adrenal insufficiency in this group. This study aims to further evaluate prevalence, characteristics and recovery of adrenal insufficiency in these patients at a large UK teaching hospital.
Methods
We retrospectively identified patients seen in outpatient clinics between January 2014 and September 2019 who had received tapering doses of long-term GC to treat their underlying condition (largely patients with polymyalgia rheumatica, giant cell arteritis or other vasculitis) and had either had a 9am cortisol or short synacthen test (SST). Data were collected using a standardised proforma.
Results
There was a total of 238 patients, median age of 71 years with a female preponderance (75%). Mean duration of glucocorticoid use was 63.3 months. Mean peak dose of glucocorticoid was 29.2mg.
142 patients had 9am cortisol as the first line test to assess adrenal function. 65% of these were considered sub-optimal based on local protocol (cortisol &lt;350nmol/L). 38% of these patients went on to have SST, of which 56% continued to show evidence of sub-optimal cortisol production. All patients where baseline 9am cortisol was &lt;100nmol/L failed to reach stimulated cortisol of &gt;500nmol/L on SST, whereas 31% failed SST if 9am cortisol was 250-350 nmol/L.
In total 138 SSTs were performed of which 51% (n=70) were abnormal (cortisol &lt;500nmol/L post synacthen). When baseline cortisol was &lt;100nmol/L on SST, all patients had a suboptimal peak response. However, where baseline cortisol on SST was &gt;350 nmol/L only 3% had a sub-optimal peak cortisol.
32 of these patients with an abnormal baseline SST went on to have a repeat SST within 2 years. 50% (n=16) continued to be suboptimal. Of the 32 patients, 38% (n=12) were switched to hydrocortisone with 33% showing complete adrenal recovery, average time to recovery of 25 months. 62% (n=20) patients did not switch, with 60% demonstrating recovery within the same time period (p=0.05). Mean ACTH levels in patients who had sub-optimal SST were 23.1 ng/L (n=19). ACTH levels were not different between those who recovered and those who did not (p=0.23).
Conclusion
Our study suggests that tertiary adrenal insufficiency is highly prevalent in this cohort of patients with rheumatological conditions requiring long-term glucocorticoid therapy. A 9am cortisol threshold of greater than 350nmol/L excludes most patients with adrenal insufficiency. These data also suggest no significant difference in adrenal recovery if switched to hydrocortisone versus continuing on prednisolone. ACTH levels were not fully suppressed in patients with adrenal insufficiency and did not predict recovery.
SAT-650 Novel Insights into the Entero-Insular Axis in Fibrocalcific Pancreatic Diabetes: An Isoglycemic Intravenous Glucose Infusion (IIGI) Study from India
Authors: verma shivendra , Gupta Riddhi Das , Anoop S Shajith , Thomas Nihal 
Published: May 2020

Abstract
In tropical countries including India, one of the common causes for young onset diabetes mellitus (DM) is “Fibro Calcific Pancreatic Diabetes” (FCPD) characterized by progressive pancreatic destruction. Despite this, glucagon has been found to be elevated in FCPD (1,2). The L-Cells in gut produce glucagon like peptide- 1 (GLP-1) and oxyntomodulin which are products of glucagon gene, thus raising probability of extra-pancreatic glucagon in FCPD. To test this hypothesis we performed 75grams oral glucose tolerance test (OGTT) followed by IIGI on separate days on nine FCPD and six healthy subjects. The latter procedure ensured matched glucose levels achieved during OGTT. Glucagon and incretins were measured at nine pre-specified time points. We found an increase in L-Cell products: GLP-1 (44.5±9.2pM vs. 12.4±4.5pM, p=0.02) and Oxyntomodulin (1252±350pg/ml vs. 859.8±165pg/ml, p=0.43) along with significant rise in glucagon during OGTT (98.8±13pg/ml vs. 63.4±7pg/ml, p=0.03) despite flat basal & stimulated C-peptide (0.43±0.14ng/ml and 1.09±0.3ng/ml, respectively) and Pancreatic polypeptide (12.3±0.0pg/ml and 14.7±1.7pg/ml, respectively) levels.
Paradoxically, gastric inhibitory polypeptide (GIP) levels were low in FCPD (106.8±40.3pg/ml vs. 557.8±96.4pg/ml, p=0.003). We speculate that the hyperglucagonemia is extra-pancreatic (L-Cell) in origin and may also contribute to the dichotomous incretin response in FCPD.
References:
1. Yajnik CS, Shelgikar KM, Naik SS, Kanitkar SV, Orskov H, Alberti KG, et al. The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test. Diabetes Res Clin Pract. 1992 Feb;15(2):149-56.
2. Dasgupta R, Naik D, Thomas N. Emerging concepts in the pathogenesis of diabetes in fibrocalculous pancreatic diabetes. J Diabetes. 2015 Nov;7(6):754-61.
MON-693 Strongyloides Stercoralis Hyper Infestation Syndrome in Type 2 Diabetes: An ANCA Positive Case Report from India
Authors: Dash Kalpana , Tippisetty Surekha , Kolukula Vamsi Krishna 
Published: May 2020

Abstract
A 53-year old male patient with T2D and hypertension for 13 years, presented to Apollo Sugar Clinic, Raipur with recurrent abdomen pain, but no vomiting, constipation, diarrhea or fever. The patient has a past history of asthmatic bronchitis, recurrent eosinophilia, and one month prior to hospitalization, recovered from erythematous maculopapular serpentine rash measuring 6.0 x 1.5 cm over the abdomen post anti-allergic treatment. The patient was neither suffering from immunosuppressive condition nor was on immunosuppressant therapy, had normal vitals but the laboratory findings revealed high total leukocyte count and raised absolute eosinophil count (52%). The provisional diagnosis was made as hypereosinophilic enteritis in a long-standing T2D and hypertension. Immunological tests antinuclear antibody (ANA) and antineutrophil cytoplasmic antibodies (ANCA) resulted in positive ruling out vasculitis. Stool examination detected rhabditiform larvae of S Stercoralis and diagnosed as Strongyloides hyper infestation syndrome. The patient was managed with IV antibiotics, IV fluids, IV insulin and when abdomen pain reduced started with the oral diet. To remove larvae load, unlike routine treatment, the patient was put on albendazole and ivermectin for three consecutive days. After 15 days follow-up patient was completely asymptomatic; at 6 weeks TLC, stool test, ANCA and ANA titer were negative indicating no parasite load. These antibodies detected could be due to molecular mimicry triggered by parasite antigens which may help in diagnosing and monitoring the disease course. ANA and ANCA positive results have been rarely reported in the past for S stercoralis. This unique case of S stercoralis infestation in T2D may enlighten the health care physicians to investigate for this infestation in immunocompromised T2D patients with pain abdomen. Precise diagnosis with timely management can prevent steroid therapy due to eosinophilic enteritis which can be harmful to the patients.