bluuebunny/crossref_metadata_2025_split huggingface dataset:
MON-198 Cosyntropin Stimulation on Adrenal Venous Sampling Obscure Surgically Curable Primary Aldosteronism
Authors: Kobayashi Hiroki , Abe Masanori , Kurihara Isao , Ichijo Takamasa , Takeda Yoshiyu , Yoneda Takashi , Katabami Takuyuki , Wada Norio , Naruse Mitsuhide 
Published: May 2020

Abstract
Context: While it has been shown that ACTH stimulation during adrenal venous sampling (AVS) for primary aldosteronism (PA) leads to correct lateralization, others showed opposite results. Whether to use ACTH stimulation during AVS for the subtype diagnosis of PA remains unsolved. Objectives: Our purpose of this study is to evaluate the clinical implications of ACTH stimulation during AVS in terms of surgical outcomes. Design and settings: Among JRAS cohort, we allocated 314 patients with both basal and ACTH-stimulated AVS data who underwent adrenalectomy to 3 groups: basal lateralization index (LI)≥2 with ACTH-stimulated LI ≥4 on the ipsilateral side (Unilateral (U) to U group, n=245); basal LI &lt;2 with ACTH-stimulated LI ≥4 (n=15); basal LI≥2 with ACTH-stimulated LI &lt;4 (U to Bilateral (B) group, n=54). We compared surgical outcomes among the groups. Results: Compared with the U to U group, the U to B group had poor clinical and biochemical outcomes and low rates of adrenal adenoma as a pathological finding. All patients in the U to Bgroup with clinical and biochemical benefits however had adrenal adenoma as a pathological finding and could be well differentiated from those with poor surgical outcome via basal LI, but not ACTH-stimulated LI. A receiver operating characteristic curve analysis demonstrated that the cut-off value of 8.3 showed the specificity of 84% for the prediction of good surgical outcome in U to B group.These results were similar even when we defined each group based on a cut-off value of 4 for basal LI. Although, the basal plasma aldosterone concentration (PAC) in the adrenal veins on both dominant and non-dominant sides among patients with better surgical outcome in the U to B group were not significantly different from those in the U to U group, there was a significant difference in the ACTH-stimulated PAC on the dominant side. Conclusions: We demonstrated novel findings showing that patients in the U to B group were shown to be comprised of 2 groups with good and poor surgical outcomes, and basal LI was useful in identifying PA patients with good surgical outcome in U to B group. The low expression level of MC2R receptor on aldosterone-producing adenoma (APA) might be the explanation of the weak response in aldosterone level in a proportion of surgically curable APA cases. These findings point to the important fact that ACTH stimulation on AVS obscure surgically curable cases of PA.
MON-472 A Case of Resistance to Thyroid Hormone with Concurrent Hashimoto’s Thyroiditis and Post-Surgical Hypothyroidism
Authors: Bernthal Julie , Kim Sarah , Grock Shira 
Published: May 2020

Abstract
Introduction: Resistance to thyroid hormone (RTH) is a rare defect that results in impaired sensitivity to thyroid hormone. While most commonly caused by mutations in the thyroid hormone receptor beta (THRβ) gene, in 15% of patients with the RTH phenotype, no mutation is identified.1 This entity is known as non-thyroid hormone receptor RTH (nonTR-RTH). Patients with RTH have an increased risk of autoimmune thyroid disease with a reported odds ratio of 2.36.2 Hashimoto’s thyroiditis or other etiologies of hypothyroidism add a layer of complexity to RTH as such individuals may require high doses of levothyroxine to overcome hormone resistance.
Clinical Case: A 36-year-old male was referred for abnormal thyroid function tests. He denied symptoms of thyroid dysfunction. Physical examination was notable for a goiter. Weight was 83 kg. Initial labs revealed TSH 6.8 mcIU/mL (0.3-4.7 mcIU/mL), free T4 2.0 ng/dL (0.8-1.7 ng/dL), free T3 491 pg/dL (222-383 pg/dL), and thyroid peroxidase antibody &gt;600 IU/mL (≤20 IU/mL). Additional work-up demonstrated elevated free T4 by equilibrium dialysis 2.5ng/dL (0.9-2.2 ng/dL) and elevated TSH with HAMA treatment 5.96 mIU/L (0.40-4.50 mIU/L), thereby ruling out familial dysalbuminemic hyperthyroxinemia and HAMA interference. Alpha-subunit of 0.30 ng/mL (&lt;0.55 ng/mL) and normal pituitary MRI did not support a TSH-secreting adenoma. Quest Diagnostics RTH Gene Sequencing was negative for a mutation in the THRβ gene. The patient was subsequently diagnosed with nonTR-RTH. Thyroid ultrasound showed multiple thyroid nodules, including a 1.8 cm hypoechoic, complex nodule in the left inferior gland and a 1.7 cm isoechoic nodule in the right inferior gland. Fine needle aspiration of the left nodule was suspicious for papillary thyroid carcinoma and the right nodule showed lymphocytic thyroiditis. The patient underwent total thyroidectomy and pathology demonstrated a benign left nodule and an incidental 0.3 cm right papillary thyroid carcinoma. The patient started levothyroxine 150 mcg daily (1.8 mcg/kg) post-operatively with subsequent TSH of 18.1 mcIU/mL. His dose was increased to 200 mcg daily (2.4 mcg/kg) and TSH was still elevated at 11.7 mcIU/mL. His levothyroxine dose was subsequently increased to 250 mcg daily (3 mcg/kg) and TSH is outstanding.
Conclusions: This case highlights the diagnostic challenge in nonTR-RTH. It also demonstrates the complex management of patients with RTH and concurrent hypothyroidism. Such patients need close monitoring and aggressive titration of levothyroxine to achieve desired hormone levels.
1. Dumitrescu AM, Refetoff S. The syndromes of reduced sensitivity to thyroid hormone. Biochim Biophys Acta 2013;1830:3987-4003.
2. Barkoff MS, Kocherginsky M, Anselmo J, Weiss RE, Refetoff S. Autoimmunity in patients with resistance to thyroid hormone. J Clin Endocrinol Metab 2010;95:3189-93.
SAT-114 Loss of DHEA-Targeting SULT2b1b Sulfotransferase Exacerbates Aggressive Traits of Prostate Cancer
Authors: Song Chung Seog , Park Sulgi , Jiang Shoulei , Osmulski Pawel , Marck Brett T , Matsumoto Alvin M , Morrissey Colm , Gaczynska Maria E , Mostaghel Elahe A , Chatterjee Bandana 
Published: May 2020

Abstract
The prostate-expressed sulfotransferase SULT2B1b (SULT2B) regulates intracrine androgen homeostasis by mediating 3β-sulfation of DHEA, thus reducing the precursor pool in the androgen biosynthesis pathway. We explored how loss of SULT2B might influence prostate cancer progression. Results show that SULT2B ablation in castration-resistant prostate cancer (CRPC) cells, generated by stable RNA interference or gene knockout, led to robust activation of the ERK1/2 Map kinase survival signal and induction of epithelial to mesenchymal transition (EMT). EMT activation was concluded on the basis of increased levels of vimentin (a mesenchymal protein) and the EMT-activating transcription factors SNAI1 (Snail) and TWIST1, shown by Western blotting, mass spectrometry and single-cell mass cytometry. Loss of SULT2B was associated with enhanced motility and invasive activity of CRPC cells in vitro and their growth escalation in vivo as xenografts. Higher invasion and metastasis potential of SULT2B-ablated CRPC cells was further indicated by results that these cells are less adhesive (i.e. easily detachable) and less stiff (i.e. more pliable) based on atomic force microscopy analysis of individual cells. Notably, AKR1C3, an aldo-keto reductase, which is elevated frequently in advanced prostate cancer, showed marked upregulation in SULT2B-deficient cells. AKR1C3 regulates androgen receptor (AR) signaling by promoting androgen biosynthesis and functioning as an AR-selective coactivator. While levels of AR and DHT did not change, AR activity was elevated, since PSA and FKBP5 mRNA induction by DHT-activated AR was several fold higher in SULT2B-silenced cells. The DHT-metabolizing AKR1C2 aldo-keto reductase was also upregulated, which likely accounts for a steady-state androgen level despite elevated AKR1C3 expression. Phosphorylation of ERK decreased in AKR1C3-silenced cells, signifying a causal link between AKR1C3 upregulation and ERK1/2 activation. SULT2B was undetectable immunohistochemically in tissue microarrays of clinical CRPC metastases, while SULT2B-negative samples showed AKR1C3-positive immunostaining. Primary prostate cancer exhibited variable, Gleason score independent SULT2B levels -- varying from strong positive to significantly reduced or undetectable. The reciprocal expression pattern for SULT2B and AKR1C3 in clinical CRPC suggests that AKR1C3 upregulation, ERK1/2 activation and increased aggressive traits of SULT2B-ablated cells, observed in vitro in cell models, may be clinically significant. Pathways regulating the inhibitory SULT2B-AKR1C3 axis may inform new avenue(s) for delaying disease progression in SULT2B-deficient prostate cancer.Funding Support: 1I01BX000280, VA (BC); W81XWH-14-1-0606, DOD (BC); IK6 BX004207, VA (BC); P50 CA97186, NIH & W81XWH-12-1-0208, DOD (EAM)
SUN-681 Does Short Term Intensive Insulin Therapy in Newly Diagnosed Type 2 Diabetes Mellitus Delay Eventual Insulin Dependence
Authors: Patil Madhuri , Gunasekaran Uma 
Published: May 2020

Abstract
In patients with type 2 diabetes mellitus (T2DM), dysfunction of β-cells starts years before the diagnosis of T2DM and rapidly worsens after overt hyperglycemia. Use of short-term intensive insulin therapy (STIIT) at the time of diagnosis of overt hyperglycemia has shown clinical recovery of β-cells for up to 2 years. A systematic literature review of studies looking for the effect of STIIT, used within two years of diagnosis of T2DM, on the duration from relapse of hyperglycemia to eventual insulin dependence is presented in this abstract.
The key phrases ‘type 2 diabetes mellitus’, ‘short-term insulin therapy’, ‘β-cell failure’, and ‘permanent insulin dependence’ were used to search English literature. For simplicity the duration of diabetes in these studies was divided into three periods: Period 1- Diagnosis of T2DM to initiation of STIIT, Period 2- End of STIIT until relapse of hyperglycemia i.e. total glycemic remission period, and Period 3- Relapse of hyperglycemia to permanent dependence on insulin therapy. Studies were excluded if all of their participants had diagnosis of T2DM for more than 2 years at the time of inclusion, i.e., if period 1 was more than 2 years.
Six clinical trials involving STIIT were identified (Period 2). No studies that examined the clinical course of T2DM in their patients beyond the relapse of hyperglycemia (Period 3) were identified.
This literature review identified a lack of data about this important clinical question- do ‘recovered’ β-cells from STIIT exhibit a better response to non-insulin therapies after the end of period 2 and, hence, delay the secondary β-cell failure in period 3? There is a need to conduct studies with longer follow up to characterize the differences in the disease course between patients treated with STIIT and patients treated with non-insulin therapies. This can help us understand scope of STIIT beyond the initial functional remission of β-cells.
SUN-333 Burosumab Improves Bone Density in Patients with X-Linked Hypophosphatemia
Authors: Murari Keerti , Insogna Karl Leonard 
Published: May 2020

Abstract
Background: X-linked hypophosphatemia (XLH) causes rickets in children and osteomalacia in adults due to lifelong renal phosphate wasting that is mediated by high circulating levels of FGF-23. Burosumab, is a recently approved fully human monoclonal antibody that blocks FGF23, thereby correcting the renal phosphate leak, improving mineral metabolism and reducing osteomalacia by 50-75% in adults [1]. Whether this results in measurable changes in skeletal mass and microarchitecture is unclear. Objective: We examined the impact of burosumab on regional bone mineral density (BMD) and trabecular bone scores (TBS) in study subjects involved in two phase III clinical trials of burosumab.
Methods: In these trails subjects received burosumab 1 mg/kg every 4 weeks. Some patients received placebo for the first 6 months of one trial so we considered their month 6 data as their baseline. Most of the patients had been treated at some point in the past with calcitriol and phosphorus. DXA and TBS were obtained at baseline and then after 6, 12 and 18-24 months of drug treatment. Paired t-tests and ANOVA were performed to assess changes in L-spine BMD, Total Hip BMD and TBS.
Results: 25 subjects with XLH (mean age 38.9 years, 56% female) were enrolled in these studies. Paired data were available in 23 subjects at 6 months, 15 subjects at 12 months and 18 subjects at 18-24 months. Compared to baseline, there were significant increases in L-spine BMD at all time points by paired analysis: 6 months (+6.0%, p=&lt;0.0001), 12 months (+6.95%, p=&lt;0.0001), 18-24 months (+6.13%, p=0.0005). Although there was no significant difference in total hip BMD at 6 months when compared to baseline, there were significant increases at 12 months (+6.72%, p=0.0005) and a further increase at 18-24 months (+10.02%, p=0.0029). When all available subjects were analyzed by one-way ANOVA, there was a significant effect of time of treatment on these regional BMD measurements. There was no change in trabecular bone score over the course of treatment.
Conclusion: Treatment with burosumab is associated with a marked improvement in BMD, particularly in the hip. Since the hip is a frequent site of fracture in XLH, the effect of burosumab at this site is of considerable clinical relevance. The lack of an effect on TBS may relate to the fact that this measurement is much less sensitive to therapeutic interventions than BMD assessed by DXA.
References:
[1] JBMR. 2019. https://doi.org/10.1002/jbmr.3843.
SAT-577 Severe Asymptomatic Hypertriglyceridemia
Authors: Rodriguez Daniel , Drame Awa 
Published: May 2020

Abstract
Background
Case reports of patients with severely elevated serum triglyceride levels (&gt;1000 mg/dL) have been documented where Insulin infusions, heparin and plasmapheresis have demonstrated rapid and successful decrease in serum Triglyceride levels. The benefits of one approach versus the other to prevent major complications such as cardiovascular events or acute pancreatitis has not been well investigated. We present the case of a patient with severely elevated serum triglyceride levels without any manifestations.
Case Description
A 53-year-old male presented from his primary care provider’s office due to elevated Triglycerides levels over 6000 as per outpatient lab work. Inpatient labs were unattainable initially due to hemolysis secondary to the severely high lipid content. Patient was admitted to the medical ICU for closer monitoring and initiated on an insulin drip. Two days after insulin initiation patient’s triglyceride levels returned as 2,887 with a total cholesterol count of 848. His insulin drip was continued until his TAG levels were less than 1000. Upon discharge his levels were less than 600.
Discussion
Most patients with hypertriglyceridemia are asymptomatic. However, in patients with levels above 1000 mg/dL, the risk of pancreatitis or cardiovascular event is of concern. Hypertriglyceridemia may account for 1 to 14 percent of cases of acute pancreatitis. Treatment is largely based upon symptoms and complications. In the event of pancreatitis or other cardiovascular complication, plasmapheresis is usually recommended. If asymptomatic, Insulin may be used. Insulin promotes synthesis of lipoprotein lipase which functions to hydrolyze triglycerides, and has been shown to be an effective lowering agent in the treatment of such individuals. Case reports of Heparin being used as a lipid lowering agent have also been documented, but was not used in our particular patient.
Normal triglyceride plasma levels are defined as less than 150 mg/dL. Mild hypertriglyceridemia typically ranges between 150-499 mg/dL, moderate between 500-866 mg/dL, and severe is defined as levels greater than 886 mg/dL. Plasma triglyceride levels above 1000 mg/dL occur in fewer than 1 in 5000 individuals. It is said that patients with TAG levels above 2000 mg/dL almost always have both a secondary and a genetic form of Hypertriglyceridemia. For this reason it is very important to identify these patients as early as possible to treat appropriately. Our patient was a known alcohol abuser, yet without the presence of some polygenic familial disorder, the likelihood of our patient having TAG levels &gt;6000 mg/dL, is very unlikely.
SUN-683 Was Metformin the Culprit for This Lactic Acidosis?
Authors: Vemparala Pranathi , Krishnamurthy Mahesh 
Published: May 2020

Abstract
Introduction
Metformin is the first-line drug for treatment of Type 2 diabetes. A meta-analysis of 70,490 patient-years of metformin use reported no lactic acidosis. We present a case of a patient who developed lactic acidosis while on Metformin; with other contributing factors.
Case Description
A 72-year old male with dementia, diabetes, hypertension, hypothyroidism and “muscular dystrophy” was admitted with encephalopathy. Medications included levothyroxine, donepezil, insulin glargine and metformin. A Brain CT scan revealed frontal lobe atrophy and lacunar infarcts. Admission blood work revealed lactic acidosis of 5.6. Sepsis workup was negative. Metformin was discontinued, and the patient improved with intravenous hydration. Upon discharge, Metformin was restarted. Follow-up lactic acid was normal. After a subsequent hospitalization with similar presentation and peak lactic acid of 4.7, metformin was stopped altogether. The patient was referred to a neuromuscular specialist and a diagnosis of Mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) was made. The “muscular dystrophy” was likely mitochondrial disease. A third hospitalization (while not on Metformin) saw a peak lactic acid of 2.8. We concluded that the lactic acidosis was secondary to MELAS, but Metformin had caused the significant spikes seen during the first two hospitalizations.
Discussion
Mitochondrial disorders must be in the differential diagnosis for patients diagnosed with muscular dystrophy. The hallmark of MELAS syndrome is stroke-like episodes that result in hemiparesis, hemianopia, or cortical blindness. Other features include seizures, recurrent headaches, vomiting, short stature, and muscle weakness. Patients with mitochondrial diseases also have a high incidence of diabetes. Lactic acidosis occurs during stress. DNA testing is the gold standard for diagnosis.
Conclusion
Metformin is contraindicated in patients with mitochondrial disease and diabetes due to the predisposition for lactic acidosis. This is not part of the current package inserts for prescribers and patients- and we strongly recommend inclusion of this language.
SUN-688 Pancreatic Cancer in Longstanding Diabetes
Authors: Suarez Janine 
Published: May 2020

Abstract
Background
Pancreatic Cancer carries one of the highest mortality rates in the US and it is established that there is a relationship between Pancreatic Cancer and Type 2 Diabetes Mellitus. We present a case of a woman with longstanding T2DM who developed Pancreatic Cancer and worsening of her T2DM.
Case Presentation
86 year old female was brought to the ER by her family due to jaundice and scleral icterus. Additionally, her blood glucose levels had been uncontrolled in the previous month despite good control for years. Her AST was 871 and ALT was 827, Alkaline Phosphatase was 591, and Total Bilirubin was 13.9, mainly direct with a value of 11.11. The patient had a CT Abdomen and was found to have a mass in the head of her pancreas. She underwent an Endoscopic Ultrasound and FNA biopsy. Cytology results were consistent with Pancreatic Adenocarcinoma. The mass was unresectable and it was recommended she transition to hospice. Regarding her T2DM, she was diagnosed 15 years ago and prior to the last month, her glucose had been well controlled on Metformin and Glipizide, never requiring Insulin. HbA1C 1 year prior was 6.7 and HbA1C during the admission was 8.5. During the month preceding her pancreatic cancer diagnosis, her family noticed her blood glucose levels were running higher than usual. During her admission, her glucose continued to range from 178-315 even though she was on Lantus 12 units nightly and an Insulin Sliding Scale before meals.
Discussion
Although a relationship between Pancreatic Cancer and T2DM has been found, recent studies have shown that this relationship is bidirectional and complex. Several reports have shown that there is a risk association that the shorter the duration of T2DM the higher the average risk association between Pancreatic Cancer and T2DM. Several cohort and case-control studies of patients diagnosed with Pancreatic Cancer show that 25-50% of patients will have developed T2DM within 1-3 years before their diagnosis of Pancreatic Cancer and 85% of patients diagnosed with Pancreatic cancer have impaired glucose tolerance. The mechanism of action of T2DM causing Pancreatic Cancer includes insulin resistance, hyperinsulinemia, hyperglycemia, and chronic inflammation and it is proposed that this pathogenesis is more of a humoral process rather than local tumor destruction of the gland. A factor supporting this is that insulin and C-Peptide levels are reported to be higher in patients with Pancreatic Cancer and T2DM.
Conclusion
Unexplained elevation in HA1C should prompt clinicians to run a differential diagnosis of factors that can induced hyperglycemia. This case highlights the importance of recognizing pancreatic malignancy as a possible cause of worsening hyperglycemia in T2DM.