bluuebunny/crossref_metadata_2025 huggingface dataset:
MON-529 The Impact of The Association of Unnecessarily Ordered Thyroid Ultrasounds (USGS) and Unnecessarily Requested Endocrinology Consultations
Authors: Veeramachaneni Ravali , Anbari Raghda Al , Marenych Nadiia , Patel Sabah , Moid Alvia , Theckedath Boby George , Barsano Charles P
Published: May 2020

We have previously reported that there is a strong association between unnecessarily ordered thyroid USGs and unnecessarily requested Endocrinology (Endo) consultations. Unnecessary consults consume time and resources, delay appropriate consults, and have even been proposed as a factor in the over-diagnosis of clinically innocuous thyroid cancers. We have examined the impact on the consumption of clinical resources.

The database consisted of 201 new Endo consults, each accompanied by a pre-consult thyroid USG. The consult requests were graded as appropriately requested (APPROP), optionally requested (OPT), or unnecessarily requested (UNNEC). The USG requests were likewise graded as APPROP, OPT, or UNNEC. The USGs were also graded on their degree of contribution to the request for a consultation, specifically, as having a significant role (SIGNIF), a minor role (MIN), or little or no role (NONE).

The impact of the UNNEC consults was categorized as (a) the initial Endo consult, a resource that would not have been utilized were an UNNEC consult not submitted, and (b) resources that probably would have been utilized were the UNNEC consults not submitted but would have been managed by and costed to the referring provider instead of to the Endo provider. Such resources included follow-up Endo visits and relevant USGs and blood tests,

Of the 201 consults with associated USGs, 156 (77.6%) consults were APPROP, 23 (11.4%) were OPT, and 22 (10.9%) were UNNEC. Conversely, 157 (78.1%) of the USGs were APPROP, 11 (5.5%) were OPT, and 33 (16.4%) were UNNEC. With respect to the association of consults with their accompanying USGs, Among APPROP requested consults, 87.8% of the associated USGs were also APPROP while only 7.7% were associated with UNNEC USGs. Among UNNEC requested consults, 31.8% of the associated USGs were APPROP while 68.2% were associated with UNNEC USGs.

Regarding the resource utilization borne by an Endo clinic as a consequence of the submission of 21 UNNEC consults for the two years after the initial consultation, each UNNEC consult had consumed, on average, 5.9 (1 + 2.6 + 2.3) [initial + Yr 1 + Yr 2 follow-ups] Endo clinic visits, 0.9 (0.5 + 0.4) USGs [excludes the USG associated with initial consultation] and 4.1 (2.2 + 1.9) blood work orders and reviews. No follow-up FNAs or thyroid surgeries were performed.

Endocrine care from any source would be best served by reducing both the unnecessary utilization and the unnecessary assignment of relevant resources.
MON-674 Diabetic Amyotrophy; A Rare Cause of Muscle Weakness
Authors: Abdallah Duaa , Langenhan Trek , Speer Jarod
Published: May 2020

Background: Diabetic amyotrophy is a rare complication of type 2 diabetes mellitus. There is little existing evidence contributing to projected outcomes for patients recovering from diabetic amyotrophy.Clinical Case: A 42 year-old man presented with lower extremity muscle pain and progressive proximal muscle weakness over 8 months. He developed asymmetrical muscle weakness in the lower extremities with diffuse pain and sensitivity to touch. He also had 80 pounds weight loss, diarrhea, and erectile dysfunction over the same time period. He had a past medical history of asthma, chronic migraines, and type II diabetes mellitus with A1c 7.1. His medications included high dose prednisone to treat his chronic migraines and asthma. Exam revealed generalized muscle atrophy, asymmetric proximal weakness, areflexia, with sensory loss in bilateral lower limbs.ESR, CRP, ANA, anti-HMG CoA reductase, CK, aldolase, SPEP, and myomarker panel were all within normal limits. Treponema pallidum and Bartonella serologies were negative. CSF evaluation was not suggestive of any demyelinating or neuromuscular disease. Full body STIR MRI demonstrated muscle edema in abductor, gluteus minimus, and paraspinal muscles bilaterally. EMG testing revealed acute to subacute active asymmetrical polyradiculoneuropathy and evidence of chronic proximal myopathy.Based on clinical presentation, EMG findings, and lack of evidence to support alternative diagnoses, he was diagnosed with diabetic amyotrophy and was started on IVIG and methylprednisolone with improvement in pain but very minimal improvement in weakness. Unfortunately, the expected clinical course following a diagnosis of diabetic amyotrophy is one of minimal improvement with treatment, as was the case in our patient.Conclusion: Diabetic amyotrophy is a rare complication of type 2 diabetes mellitus which typically presents with muscle weakness followed by severe pain in the thighs, hips, and buttocks. Compared with other neurologic complications of diabetes, amyotrophy is relatively uncommon, affecting approximately 1 percent of patients. This low prevalence and the broad differential for proximal muscle weakness makes it challenging to diagnose. It remains a diagnosis of exclusion, though EMG studies showing polyradiculoneuropathy in the proximal leg musculature is suggestive. Clinical improvement is slow and often incomplete. Physical and occupational therapy are a mainstay of treatment which may also include IVIG and steroids aimed at treating associated pain. Endocrinologists should have a high clinical suspicion for diabetic amyotrophy in the appropriate clinical context. When considering the diagnosis and discussing treatment options with patients, this case highlights the important role of endocrinologists discussing expectations associated with projected outcomes while attempting to manage diabetic amyotrophy.
SUN-370 Validation of a Deep Learning Based Algorithm to Diagnose Vertebral Compression Fractures
Authors: Page John , Moser Franklin , Maya Marcel , Prasad Ravi , Pressman Barry
Published: May 2020

Vertebral Compression Fractures are common in patients above age 50, but are often undiagnosed. Patients with one VCF are at higher risk of other osteoporotic fractures. Zebra Medical Imaging developed a VCF detection algorithm, utilizing a combination of traditional machine vision segmentation and convolutional neural network (CNN) technology, to detect VCFs from evaluating CT images of the chest, and/or abdomen/pelvis.

We conducted an independent and blinded validation study to estimate the operating characteristics of the Zebra VCF detection algorithm in identifying VCFs on de-identified data from previously completed CT scans of chest and/or abdomen/pelvis from 1200 women and men aged 50 or older who had those scans (for multiple reasons) at the clinics and hospitals affiliated with the Cedars Sinai Medical Center. Each set of scans were independently read by two of three board certified, practicing neuroradiologists to identify and grade VCF at each evaluable vertebra (using the semiquantitative scale of Genant and colleagues). When there was disagreement between radiologists, the respective scans were reviewed by a senior neuroradiologist who provided a final evaluation. The final determination of presence and severity of VCF by the neuroradiologists was used as the reference standard. The Zebra VCF detection algorithm evaluated the CT scans in a separate workstream from that used by the neuroradiologists (The algorithm and neuroradiologists were blind to each other’s evaluations).

The Zebra VCF algorithm was not able to evaluate CT scans for 113 patients. Of the remaining 1087 CT patients, 588 (54%) were women. Median age was 73 (range 51, 102; interquartile range 66, 81). The four neuroradiologists who evaluated the CT scans each had over 10 years of experience in neuroradiology. For the 1087 Zebra evaluated patients, 227 had at least one VCF (90 with mild VCF, 81 with moderate VCF, and 56 with severe VCF; 115 of the 1087 Zebra evaluated patients (10.6%) presented with two or more VCFs). The sensitivity and specificity of the Zebra VCF algorithm in diagnosing any VCF were 0.66 (95% confidence interval 0.59, 0.72) and 0.90 (95% confidence interval 0.88, 0.92) respectively; and for diagnosing moderate/severe VCF were 0.78 (95% confidence interval 0.70, 0.85) and 0.87 (95% confidence interval 0.85, 0.89) respectively.

The Zebra VCF algorithm works to identify approximately three-quarters of moderate to severe VCF in patients, aged 50 and above, who receive CT scans for other reasons. Implementing the Zebra VCF algorithm within radiology systems may help to identify patients at increased fracture risk and could support the diagnosis of osteoporosis, and thus be a valuable adjunct for population health.
SAT-303 3D Mapping of the Human Growth Hormone Locus Identifies Putative Regulatory Hubs for Genes Involved in Cellular Signalling and Cancer-Related Pathways
Authors: Jain Lekha , Fadason Tayaza , Schierding William , Vickers Mark Hedley , O’Sullivan Justin M , Perry Jo Kate
Published: May 2020

Growth hormone (GH) is a peptide hormone predominantly produced in the pituitary that is crucial for normal growth and metabolism. Downstream effects of GH are mediated through binding to the GH receptor (GHR) and consequent activation of key signalling cascades including JAK-STAT, MAPK, PI3K-Akt and mTOR. The GH locus is comprised of five evolutionarily related genes under the control of an upstream locus control region which coordinates tissue-specific expression of these genes in the pituitary and placenta (1). Compromised GH signalling and genetic variation in these genes has been implicated in various disorders including cancer. We hypothesised that polymorphisms which occur within the GH locus have the potential to impact on disease phenotypes by altering or disrupting gene regulation. We used the CoDeS3D (Contextualize Developmental SNPs using 3D Information) algorithm to analyse 529 common single nucleotide polymorphisms (SNPs) across the locus. This algorithm identifies colocalised Hi-C and eQTL associations to determine which SNPs are associated with a change in gene expression at loci that physically interact within the nucleus. We identified 181 common SNPs that interacted with 292 eGenes in 48 different tissues. 145 eGenes were regulated in trans. We performed pathway enrichment of identified eGenes and found these to be enriched in GH/GHR-related downstream cellular signalling pathways including MAPK, PI3K-Akt-mTOR, and ErbB signalling. Enrichment was also observed in the Wnt and Hippo signalling pathways. There was also a significant representation of these eGenes in pathways associated with hepatocellular, colorectal, breast and non-small cell lung carcinoma. 33 eQTL SNPs identified in our study were found to be of regulatory importance in a genome-wide Survey of Regulatory Elements (SuRE) reporter screen (2). In addition, 7 eQTL SNPs were located in known enhancer regions. Our data suggests that regions within the GH locus form regulatory hubs for multiple genes in cis and trans (intra and inter-chromosomal), many of which are involved in mediating GH function in normal and pathogenic states.

Reference: (1) Tsai et al. Nucleic Acids Res 2016, 44, 10, 4651 (2) van Arensbergen et al. Nat Genet 2019, 51, 7, 1160.
SUN-217 Skin Glucocorticoid Metabolism in Burn Injury: Towards Novel Treatments That Reduce Scarring
Authors: Tsai Kevin Hung-Yueh , Parungao Roxanne Janine , Shi Huaikai , Issler-Fisher Andrea , Wang Xiaosuo , Maitz Peter , Cooper Mark Stuart , Wang Yiwei
Published: May 2020

The most common and severe complication of burn injury is the development of excessive scarring/tissue fibrosis. No current treatments reduce scarring after burns. Prolonged exposure to high levels of glucocorticoids (Cushing’s syndrome) detrimentally impacts skin, leading to reduced collagen production and impaired wound healing. Skin can generate active glucocorticoids locally through expression and activity of the 11β-hydroxysteroid dehydrogenase type 1 enzyme (11β-HSD1). We hypothesised that local glucocorticoid activation by 11β-HSD1 is an important regulator of wound healing, fibrosis and scarring after burn injury. We additionally proposed that pharmacological manipulation of this system would improve outcomes of burn wound healing.

We examined glucocorticoid metabolism (by RT-PCR, immunohistochemistry and specific enzyme activity assays) in burn and non-burn skin from burn injury patients (n=14) and mouse models of burn injury (1cm2 full thickness burn in C57Bl/6 mice). We utilised mice with genetic or pharmacological deletion of 11β-HSD1 in skin to evaluate the effects of 11β-HSD1 on burn injury healing, wound fibrosis and skin properties (by atomic force microscopy and tensile property testing) after wound healing. We also developed slow release scaffolds containing therapeutic agents including inactive glucocorticoids (prednisone) that are selectively reactivated in skin cells expressing 11β-HSD1.

The expression of 11β-HSD1 in human and mouse skin increased substantially after burn injury (7.1+/-1.8 fold increase on day 4–9 post burn compared to non-burn skin, p<0.05). Early after injury, expression was primarily in immune cells but at later stages in fibroblasts. Mice with 11β-HSD1 deletion experienced faster wound healing post burn (17% reduced wound area at day 7 compared to wildtype, p<0.0001) but when healed these wounds had excessive collagen density and skin thickening, and abnormal collagen fibre organisation (assessed by Masson’s Trichrome staining). The post burn scars formed in 11β-HSD1 knockout mice demonstrated different skin elastic properties compared to those formed in wildtype mice. In wildtype mice application of scaffolds loaded with inactive glucocorticoid (prednisone) significantly impacted wound healing demonstrating the feasibility of using enzyme substrates to improve wound outcomes.

The findings demonstrate the importance of skin 11β-HSD1 in wound healing and scarring after burn injury and indicate ways in which excessive scarring might be prevented.
SAT-364 Brown Tumor of the Mandible in Severe Uncontrolled Primary Hyperparathyroidism
Authors: Gupta Suruchi K , Hou Runhua , Rosen Harold
Published: May 2020

Background: Brown tumors are a part of the complex “osteitis fibrosa cystica” which is a diffuse resorptive process of the bone resulting from uncontrolled hyperparathyroidism. Although these brown tumors were fairly common in the past1, the incidence of brown tumors is now extremely rare in the United States due to early diagnosis and treatment of hyperparathyroidism. Here we describe an unusual presentation for osteitis fibrosa cystica.

Clinical Case: A 38 year old woman was admitted to the hospital with rapidly growing facial swelling in June 2019. The swelling initially appeared in January 2019 and had rapidly increased in size since April 2019. The mass was malodorous, painful and interfered with oral intake. The patient smoked 1 pack per day for 13 years. A CT scan of the head and neck with contrast showed a 3.6 x 4.5 x 3.3 cm mass destroying the right mandibular body, involving the right platysma muscle and displacing the central and lateral incisor teeth and was concerning for malignancy. The initial impression was that this was likely a squamous cell carcinoma with local and perhaps distant metastases, complicated by humoral hypercalcemia of malignancy and she was admitted for management.

Upon admission, her calcium level was 14 mg/dL, albumin 4.1 g/dL, phosphorus 1.4 mg/dL PTH level was 890 pg/mL and vitamin D level was 22 ng/mL. Since the high PTH did not fit with hypercalcemia of malignancy, further evaluation was undertaken. A thyroid ultrasound showed a 4.6 x 1.8 x 1.5 cm isoechoic, heterogeneous lesion in the left lower pole, and Tc-99 sestamibi scan suggested parathyroid origin. The biopsy of the mouth lesion showed fibro histiocytic proliferation with multiple giant cells, negative for malignancy and consistent with a brown tumor. CT scan of the chest, abdomen and pelvis did not reveal any other masses or lytic lesions. . A skeletal survey showed another 2 cm lytic lesion in the proximal left humeral metaphysis which was not biopsied.

On parathyroidectomy, the patient was found to have an enlarged left inferior parathyroid gland measuring 3.3 x 3.0 x 0.8 cm weighing 7.093 grams. Intraoperatively PTH level decreased from 890 pg/mL to 69 pg/mL. Her calcium levels returned to normal post-operatively and she was discharged home. Pathologic examination report revealed the mass to be a parathyroid adenoma. The patient reports a reduction in the size of her mandible mass since the surgery.

Conclusion: Although uncommon, brown tumors can be seen in uncontrolled primary hyperparathyroidism. The mandible is a common site, though, as in this case, it is less common for it to be the only site affected

Reference:

1. Rosenberg, E. H. (1962). Hyperparathyroidism. A review of 220 proved cases with special emphasis on findings in the jaws. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 15(2), 84–94.
MON-141 Healthcare Services Utilization and Costs Associated with the Management of Patients Living with Acromegaly
Authors: Ribeiro-Oliveira Antonio , Munoz Kathryn A , Brook Richard Alan , Beren Ian A , Whalen John D , Yuen Kevin C j
Published: May 2020

Background: Acromegaly (ACRO) is a rare, chronic growth hormone hypersecretory disorder associated with increased morbidity and mortality. Limited information is available on the utilization and costs of healthcare by patients with ACRO.

Aims: To assess the impact of ACRO healthcare utilization and costs by locations of care (LoC).

Methods: A US database of prescription (Rx) drug and medical claims from Jan 2010 to Apr 2019 was analyzed. Patients with an ACRO diagnosis (Dx) were identified based on claims with ICD-9/-10 codes 253.0x/E22.0. The 12-month study period followed each patient’s first ACRO Dx in the database (the index date). ACRO patients included in the study had ≥ 2 ACRO Dxs > 30 days apart, or 1 ACRO Dx plus either a pituitary adenoma Dx or a pituitary surgery or radiosurgery claim during the study period. Costs were adjusted using the medical and Rx cost Consumer Price Indexes (CPIs). Study subjects were 18–65 yr old and had continuous eligibility during the study period. Eligible ACRO patients were matched with 20 subjects who did not have ACRO. Outcomes by LoC included costs, services, and likelihood of use and were compared using separate two-part regression models (logistic followed by generalized linear) for each outcome, controlling for demographic and job-related variables, region, and Charlson comorbidity index (CCI) scores. The likelihood models only used logistic regression. Data are shown as likelihoods or mean ± standard error. Findings are significant at P < 0.05.

Results: A total of 60 patients with ACRO and 1200 controls were compared. Compared with controls, patients with ACRO had a higher likelihood of using the physician’s office (100% vs 91%, P < 0.0001), inpatient (22% vs 3%, P < 0.0005), outpatient (89% vs 38%, P < 0.0001), laboratory (62% vs 31%, P < 0.0001), and “other” locations (e.g., ambulance and claims without a specific location code, 55% vs 23%, P < 0.0001). Services performed at each LoC were higher for patients with ACRO (P < 0.01, all except outpatient hospital). Total costs were higher for the ACRO cohort compared with controls ($25,770 vs $4,059, P < 0.05). Costs by LoC were consistently higher (all reported P < 0.001) for patients with ACRO compared to controls, with differences highest in the following settings: outpatient hospital/clinic ($9,611 ± $1,793 vs $1,355 ± $74), inpatient ($8,646 ± $2,388 vs $739 ± $115), physicians’ office ($4,762 ± $678 vs

$1,301 ± $43), other ($2,001 ± $583 vs $367 ± $29), and laboratory ($508 ± $93 vs $66 ± $4). Neither the costs nor likelihoods of treatment in the emergency department were significantly different between cohorts.

Conclusions: Compared with commercially insured people without ACRO, patients with ACRO had greater health care utilization, in all care locations, indicating a greater burden and higher costs of ACRO patients on the healthcare system.
SAT-585 Autoregulation of Adipose Tissue Development
Authors: Feldman Brian , Sayeed Mohd , Nakuluri Krishna
Published: May 2020

White adipose tissue not only serves as a reservoir for energy storage but also secretes a variety of hormonal signals and modulates systemic metabolism. A substantial amount of adipose tissue develops in early postnatal life, providing unique access to the formation of this important tissue. However, while a number of factors have been identified that can modulate the differentiation of progenitor cells into mature adipocytes in cell autonomous assays, it remains unclear which are connected to physiological extracellular inputs and are most relevant to tissue formation in vivo. We elucidated that mature adipocytes themselves signal to adipose depot-resident progenitor cells to direct depot formation in early postnatal life and gate adipogenesis when the tissue matures. Our studies reveal that, as the adipose depot matures, a previously unrecognized signal is generated in mature adipocytes that converges on progenitor cells to regulate the cytoskeleton and attenuate the rate adipogenesis in vivo. This signal toggles the adipose depots from developmental to tissue homeostatic levels of adipogenesis.
MON-646 Novel Use of GLP-1 Receptor Agonist Therapy in MODY-1 (HNF4A Mutation)
Authors: Broome David Tyler , Pantalone Kevin M , Mehta Adi Erach
Published: May 2020

Monogenic Diabetes (MODY) results from mutations or changes in a single gene, and currently account for about 1 to 4% of all cases of diabetes (1). Our group has previously published on the successful use of glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in three consecutive generations of a family with an HNF1A mutation (MODY-3) (2). Although GLP-1 RA therapy has been studied in patients with HNF1A mutations (MODY-3) (3), it has not been studied in patients with HNF4A mutations (MODY-1). In this father-son cohort, we demonstrate successful use of GLP-1 RA therapy in two patients with c.790:1 bp deletion of G; codon:264 mutations of HNF4A. The son first presented with neonatal hypoglycemia, then later developed diabetes and presented to our clinic at age 20, when genetic testing was performed and confirmatory for an HNF4A mutation. He was prescribed glimepiride and titrated to 4 mg twice daily, and two years later, his hemoglobin A1c (HbA1c) rose to 8.7%. He was switched to semaglutide 0.25 mg once weekly and was titrated to a maximum dose of 1 mg weekly over 8 weeks. The patient reports improvement in his post-prandial blood glucose values at this time, but HbA1c has not yet been repeated. The father had been diagnosed with monogenic diabetes in his early 20s and had been on sulfonylurea therapy until age 40, at which time he was transitioned to a regimen of long- and short-acting insulin therapy. Thereafter, he presented to our clinic in July, 2018 with a HbA1c of 9.6% and was transitioned to long-acting insulin once daily and liraglutide 0.6 mg once daily which was subsequently titrated to 1.8 mg once daily over 3 weeks. The patient tolerated this well and has been off short acting insulin since December 2018, with notable improvement in his HbA1c to 5.9% and marked improvement in his post-prandial glycemic control. To our knowledge this is the first report demonstrating the benefits of GLP-1 RA therapy in patients with the HNF4A mutations (MODY-1). Based on this report, it appears that GLP-1 RA therapy could be an effective therapy in patients with MODY-1.

1). Pihoker C, Gilliam LK, Ellard S, et al. Prevalence, characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. The Journal of Clinical Endocrinology and Metabolism. 2013;98(10):4055–4062.

2). Maricor Docena, Charles Faiman, Christine Stanley, and Kevin Pantalone (2014) Mody-3: Novel HNF1A Mutation and the Utility of Glucagon-Like Peptide (GLP)-1 Receptor Agonist Therapy. Endocrine Practice: February 2014, Vol. 20, No. 2, pp. 107–111.

3). Ostoft SH, Bagger JI, Hansen T, et al. Glucose-lowering effects and low risk of hypoglycemia in patients with maturity-onset diabetes of the young when treated with a GLP-1 receptor agonist: a double-blind, randomized, crossover trial. Diabetes Care. 2014;37(7):1797–17805.
OR21-06 Physician Management of Thyroid Cancer Patients’ Worry: Is It “Good” Enough?
Authors: Papaleontiou Maria , Zebrack Bradley , Reyes-Gastelum David , Hawley Sarah T , Hamilton Ann S , Ward Kevin C , Haymart Megan R
Published: May 2020

Introduction: Despite the excellent prognosis of most thyroid cancer patients, cancer-related worry is common. Additionally, patients report that being told by physicians that they have a “good cancer” invalidates their fears of having cancer and creates mixed and confusing emotions. However, it is not known what proportion of physicians try to reassure patients with the description “good cancer”.

Methods: Patients diagnosed with differentiated thyroid cancer in 2014–2015 from the Surveillance, Epidemiology and End Results Program (SEER) registries of Georgia and Los Angeles County were asked to identify endocrinologists and surgeons involved in managing their thyroid cancer. Physicians were surveyed using the modified Diliman method. They were asked to describe their thyroid cancer patients’ worry at time of diagnosis and what they tell them if worried. A multivariable logistic regression was conducted to identify physician characteristics associated with reporting thyroid cancer as a “good cancer”.

Results: Response rate was 69% (448/654). Overall, 40% were endocrinologists, 30% were general surgeons and 30% were otolaryngologists. A total of 8% of physicians reported that their patients are not worried or are a little worried at diagnosis, 27% that they are somewhat worried and 65% that they are quite or very worried. Ninety-one percent of physicians reported providing details on prognosis including information on death and recurrence to worried patients, 61% tell them their physicians are experienced in managing thyroid cancer, and 50% tell them that thyroid cancer is a “good cancer”. Factors associated with report of telling patients they have a “good cancer” included otolaryngology specialty [odds ratio (OR) 1.84, 95% confidence interval (CI) 1.07–3.17, compared to endocrinology), private practice setting (OR 2.57, 95% CI 1.42–4.75, compared to academic setting) and Los Angeles site (OR 2.23, 95% CI 1.46–3.45, compared to Georgia site). Physicians who perceived that their patients were quite or very worried at time of diagnosis were less likely to use this terminology (OR 0.55, 95% CI 0.35–0.84) and more likely to encourage patients to seek help outside of the physician-patient relationship (OR1.82, 95% CI 0.35–0.84), compared to patients not to somewhat worried.

Conclusion: Most physicians in our sample from two diverse geographic areas report perceiving patient worry as common at time of thyroid cancer diagnosis. They report addressing this worry with different strategies, including telling patients they have a “good cancer”. The benefit of such strategies on patient outcomes still needs further investigation.
SUN-578 Role of Linagliptin on CD34+ Endothelial Progenitor Cells and Arterial Stiffness in Renal Function Impaired Type 2 Diabetes Subjects
Authors: Awal Hassan , Domingues Cleyton , Dore Fiona , Kundu Nabanita , Ahmadi Neeki , Magan Fosso , Witkin Linda , Batistich Bethany , Safai Shauna , Amdur Richard , Sen Sabyasachi
Published: May 2020

Introduction: Endothelial Progenitor cells (EPCs) has been shown to be dysfunctional in both Type 2 Diabetes and Chronic Kidney Disease (CKD) leading to poor regeneration of endothelium and renal tubules. EPCs have been shown to be a robust cardiovascular disease (CVD) risk indicator. DPP4 inhibitor increase endogenous SDF1a which has been shown to increase CD34+ cells migration and thereby improve CVD risk. However, cellular mechanisms of DPP4i mediated improvement of CVD in patients with Type 2 Diabetes with established CKD is not established. Hypothesis: Linagliptin, a DPP4 inhibitor when added to insulin, metformin or both may recover endothelial function in a diabetic kidney disease (DKD) population. Methods: 31 subjects taking 1–2 grams of metformin and/or Insulin were enrolled in this 12 weeks, double blind, two-arm, randomized placebo matched trial, with 5 mg Linagliptin compared to placebo. Type 2 diabetes subjects (30–70 years old), HbA1c of 6.5–10%, and all stages of CKD were included. CD34+ cell number, migratory function, gene expression along with vascular parameters such as Arterial stiffness, biochemistry, resting energy expenditure and body composition were measured. Data were collected at week 0, 6 and 12. During trial HbA1C was maintained between 7–8% for all subjects. Every subject was used as their own control. A mixed model regression analysis was done with p value <0.05 considered significant. Results: A double positive CD34/CD184 cell count had a statistically significant increase (p<0.02) as determined by flow cytometry in treatment group though there was no statistically significant increase in CD34+ cell number, or colony formation units. Gene expression analysis on CD34+ cells showed reduced expression of TP53 (p<0.04). Arterial stiffness measures such as augmentation Index (p<0.04) along with augmentation pressure (p<0.02) were significantly reduced in the treatment group. A reduction in LDL: HDL ratio was noted in treatment group (p <0.04). No change in renal function was noted during the 12 week period.. We are currently analyzing urinary exosome based data to enquire further into renal function Conclusions: In DKD subjects, Linagliptin promotes an increase in CXCR4 expression on CD34+ progenitor cells with a concomitant improvement in arterial stiffness and LDL parameters within 12 weeks of intervention.
SAT-355 Severe Symptomatic Hypocalcemia Related to Cinacalcet Administration Introduction
Authors: Weaver Travis , Hoang Thanh Duc , Shakir Mohamed K M
Published: May 2020

BACKGROUND: Cinacalcet, a class of drug used to treat secondary hyperparathyroidism due to end-stage renal disease, is also indicated for the treatment of hypercalcemia in patients with parathyroid carcinoma. This drug acts as a calcimimetic agent by allosteric activation of the calcium-sensing receptor that is expressed in various tissues. Common side effects of cinacalcet include nausea, vomiting, diarrhea and weakness. Although mild hypocalcemia is a common side effect, severe hypocalcemia is rare.

Case Presentation: A 61-year-old man was evaluated for treatment of type I diabetes mellitus. He reported several months of progressive fatigue, muscle weakness, and paresthesia of his hands and feet. He was prescribed cinacalcet for a parathyroid disorder since 2014 and his previous physician increased the dose of cinacalcet about 2 months ago from 60mg daily to 120mg daily. Since that time his paresthesias have been more severe. Physical examination: normal vital signs, Chvostek’s and Trousseau’s signs were positive. Rest of the examination was normal. Laboratory: corrected serum calcium (Ca) of 6.7 mg/dL (ref 8.6–10.0), down from 7.6 mg/dL 2 months earlier. Additional laboratory: Ionized Ca 3.4 mg/dL (ref 4.5–5.6), PTH 68 pg/mL (ref 15–65), 25-OH vitamin D 37 ng/mL (ref 29–100), phosphorus 4.9 mg/dL (ref 2.5–4.5) and calculated GFR 97 mL/min. Cinacalcet was stopped. The patient was treated with calcium intravenously in the ICU resulting in normal serum calcium levels after 36 hours of treatment and complete resolution of symptoms. He was discharged on oral calcitriol and calcium supplementation, which was discontinued within 1 week of discharge.

Discussion:

In vast majority of cases hypocalcemia associated with cinacalcet therapy are mild and self-limited. Generally hypocalcemia develops within 16 weeks of starting therapy and resolves spontaneously within 2 weeks. This case is unusual in that the hypocalcemia occurred years after starting therapy and the patient experienced severe symptoms, undiagnosed for a prolonged period of time and required admission for close monitoring. Additionally, this patient was without the most common risk factor for cinacalcet-associated hypocalcemia which was secondary hyperparathyroidism, and he had normal renal function. The marked decrease in serum Ca levels may be related to his low baseline serum Ca levels and due to the recent increase in cinacalcet dose. However this has not always verified based on retrospective studies. Interestingly the cinacalcet dose was increased in up to 14% of patients with severe hypocalcemia (<7.5 mg/dL) and even in this population severe symptomatic hypocalcemia symptoms were rare. In conclusion, clinicians should closely monitor patients on calcimimetic drugs for hypocalcemic symptoms although mild asymptomatic hypocalcemia may resolve without intervention.
SAT-027 Comparison of Estradiol by Mass Spectrometry Versus Immunoassay in Women Undergoing Menopause: Study of Womens Health Across the Nation (SWAN)
Authors: Santoro Nanette F , Auchus Richard Joseph , Greendale Gail , Lasley Bill L , McConnell Daniel S , Randolph John F , Martin Deborah , Crawford Sybil
Published: May 2020

Serum estradiol (E2) concentrations in midreproductive women are easily measured using a variety of conventional immunoassays (IA). However, when women approach and traverse menopause, E2 eventually drops below levels where IA lacks sufficient sensitivity to accurately measure E2. Liquid chromatography and tandem mass spectrometry (LC/MS/MS) has become the standard method for assessing steroid hormones, especially when circulating concentrations are low. We evaluated the relationship between IA and LC/MS/MS E2 measurements in a cohort of women taken from the Study of Womens Health Across the Nation (SWAN) to assess the degree of agreement between the two methods and to determine the level of E2 at which IA becomes unreliable.

Methods: 315 serum samples that had been previously measured for E2 using IA were re-analyzed using LC/MS/MS performed by one of the authors (RA). In this original set, E2 levels that were below the limit of assay detection (LLD, 6 pg/ml) were interpolated as a random number between 0 and the LLD. Agreement between all 315 samples was assessed using both Pearson and Spearman correlation. The analysis was repeated excluding the subset of specimens that were below the lower limit of detection (LLD) for the IA E2 assay (6 pg/ml; N=176), and a third set of correlations was obtained for specimens that measured <15 pg/ml by IA but were above the 6 pg/ml LLD (N=82).

Results: The overall dataset (N=315) demonstrated excellent agreement between IA and LC/MS/MS with a Pearson’s r and Spearmans r of 0.98 AND 0.60, respectively. When the subset of 176 samples above the LLD were assessed, Pearson’s r was 0.98 and Spearman’s r was 0.81. In contrast, when specimens measuring 6–15 pg/ml by IA were compared to LC/MS/MS, Pearson’s r was -0.03 and Spearman’s r was 0.09, indicating a complete loss of relationship between the two methods.

Conclusions: The IA used by SWAN (England, Clin Chem 2002; 48: 1584) and LC/MS/MS demonstrate excellent correlation for E2 measurements above 15 pg/ml. However, circulating concentrations of E2 below 15 pg/ml were not accurately measured using IA.
SUN-011 Beyond PCOS - Ovarian Neoplasms Presenting with Hirsutism and Virilization
Authors: Chakravorty Shourjo , Hoard Brandon , Cosentino Gina , Friday Karen E , Uwaifo Gabriel Ikponmosa
Published: May 2020

BACKGROUND: PCOS is the most common cause of hirsutism in women of reproductive age. The presence of virilization in addition to hirsutism should alert to the possibility of less common causes of hyper-androgenization (HA) in this population including otherwise uncommon functional ovarian neoplasms (FON). We present 3 cases of women initially thought to have PCOS in whom virilization was the prime clue to the correct diagnosis of FON. Clinical Case series: Case 1 is a 40yr old woman with obesity and dysmetabolic syndrome referred for hirsutism presumed due to PCOS. She had noted symptoms over 2–3 yrs with amenorrhea and associated infertility. Examination revealed marked hirsutism and virilization with Ferriman-Galleway score (FGS) of 20. Lab tests confirmed marked male range HA. Multiple imaging tests revealed no adrenal or ovarian mass lesions. FDG-PET scan finally revealed a left ovarian focus for which she has left oophorectomy that revealed a 1cm Leydig cell tumor, Her HA resolved post-op and spontaneous periods resumed. Case 2 is a 45yr old woman referred with possible PCOS who had 5 mth history of progressive hirsutism and generalized hypertrichosis, dull lower abdominal pain and amenorrhea. Examination revealed marked hirsutism with generalized hypertrichosis and virilization. FGS was 25 and clitoral index was 935mm2. Lab tests confirmed marked male range HA and abdominopelvic imaging show no adrenal lesions but a 5.2cm left ovarian mass. Left salpingo-oophorectomy revealed a steroid cell tumor and postoperatively her androgen levels normalized. Case 3 is 37 yr old woman with SLE and obesity with prior gastric bypass referred with presumed PCOS but presenting with 1 yr history of progressive hirsutism. She was initially thought to have non classical CAH and treated with oral glucocorticoids with no symptom improvement. Examination revealed marked hirsutism, virilization with elevated FGS and clitoromegaly. Lab tests showed marked male range HA but multiple imaging studies revealed no apparent adrenal or ovarian lesions. Patient had no fertility interests and so had elective total hysterectomy and bilateral salpingo-oophorectomy. Histopathology revealed a 2.5cm left ovarian Leydig cell tumor not apparent at surgery and post op her androgen levels normalized. Conclusion: The distinction between PCOS which is ubiquitous and FON which is rare hinges on careful history and examination. Rapid onset hirsutism with virilization should prompt suspicion of FON. Marked male range HA (total serum testosterone >250ng/dl) is another “red flag” finding. Persistent radiologic search for such lesions should continue as they may not be immediately apparent on routine abdominopelvic imaging.
SUN-613 Association of Electrocardiograph Parameters and Diabetic Peripheral Neuropathy
Authors: Moon Seong Su , Lee Young-Sil
Published: May 2020

Aim: The purpose of this study was to assess the relation between Prolonged P wave duration with diabetic peripheral neuropathy in subjects with type 2 diabetes. Methods: We assessed the measures of electrocardiographic function in 105 in 147 Korean subjects with type 2 diabetes, who visited Dongguk University Hospital for regular health checkup using electrocardiogram (ECG). We measured several electrocardiogram parameters including ventricular rate, PR interval, QRS duration, QT, QTC and P wave duration. Subjects were grouped as without diabetic peripheral neuropathy (≤2) and with peripheral neuropathy (≥2) based on Michigan Neuropathy Screening Instrument Examination Score (MNSIES). Results: The population mean age was 61.50±11.17 years and 60.78% were men. The participants with DPN significantly found higher with age, MNSIES and P wave duration as compared to without DPN. The prevalence of drinking significantly found higher in participants with diabetic peripheral neuropathy. Furthermore, in a multiple regression analysis, MNSI examination score significantly showed positive association with prolonged P wave duration after adjustment with age, MNSIES and drinking alcohol(β, 1.123; 95% CI, .109∼2.138; p=.030). Conclusions: The current study revealed an association between prolonged P wave and MNSI examination score.
SUN-412 Graves’ Disease Displayed as a Risk Factor of Vertebral Fracture Even in Premenopausal Women
Authors: Notsu Masakazu , Yamauchi Mika , Sugimoto Toshitsugu , Kanazaki Keizo
Published: May 2020

Background

Hyperthyroidism is a known risk factor for osteoporosis and fractures especially in older men and postmenopausal women. However, it remains unclear whether younger patients with Graves’ diseases are at a higher risk of fracture compared to healthy individuals.

Objective

This study aimed to clarify whether premenopausal women with Graves’ disease represents a risk factor for vertebral fracture (VF).

Patients and Methods

We enrolled 30 premenopausal women (mean age, 32 ± 10 years) who were diagnosed with Graves’ disease at our institution between April 2007 and December 2017. We also enrolled 40 healthy control women who visited our hospital. The control subjects were confirmed to have no endocrine disease or any condition that might affect bone metabolism. None of the study subjects had taken drugs known to influence bone and calcium metabolism such as vitamin D, bisphosphonates, or glucocorticoids. Also, none has taken an oral contraceptive. Serum and urinary biological parameters, alkaline phosphatase (ALP), glycosylated hemoglobin (HbA1c), creatinine, serum calcium, total cholesterol, intact parathyroid hormone, free triiodothyronine (Free T3), free thyroxin (Free T4), thyroid-stimulating hormone (TSH) and urinary type I collagen cross-linked N-telopeptides (NTX; a bone resorption marker) were compared between the groups. Bone mineral density (BMD) of the lumbar spine and femoral neck was determined using dual-energy X-ray absorptiometry and vertebral fractures were diagnosed from lateral X-rays of the thoracic and lumbar spine. The chi-square and unpaired t-tests for two groups comparison were utilized to determine the statistical significance (P < 0.05). Multiple logistic regression analyses were proceeded after adjustments for variables.

Results

Patients with Graves’ disease displayed the higher ALP, eGFR, Ca, free T3, free T4 and urinary NTX levels, and lower body mass index (BMI), Alb, total cholesterol and intact PTH compared to controls.

The prevalence of VFs was significantly higher in patients with Graves’ disease (20.0%) than in controls (2.5%, <0.05). Such association remained significant even after adjustment for age, BMI, ALP, eGFR and free T3, but except for BMD. Among premenopausal patients with Graves’ disease, the values of several parameters, such as BMI, ALP, HbA1c, serum Ca, intact PTH and BMD and the prevalence of thyroid related antibodies did not differ significantly between those with and without VF; subjects with VF were older and exhibited lower free T3, free T4 and urinary NTX levels compared to subjects without VF. The mean value of lumbar BMD T score in subjects with VF among premenopausal patients with graves’ disease was -1.0, indicating osteopenia.

Conclusions

VF risk could be elevated even in the premenopausal women with Graves’ disease, although the BMD risk levels is not equivalent to that of osteoporosis.
SAT-271 Block and Replace Therapy Successfully Improved Symptoms in Recurrent Cyclic Cushing’s Disease
Authors: Kamigaki Risa , Kameda Hiraku , Iesaka Hiroshi , Izumihara Rimi , Ohe Yuki , Chiba Koki , Ono Wataru , Shigesawa Ikumi , Kameda Reina , Nomoto Hiroshi , Cho Kyuon , Nakamura Akinobu , Miyoshi Hideaki , Atsumi Tatsuya
Published: May 2020

BACKGROUND: Cyclic Cushing’s disease is rare and treatments have not been established for post-surgical recurrent cases. Here, we report a patient with recurrent cyclic Cushing’s disease, whose subjective symptoms improved by administration of metyrapone and hydrocortisone. Clinical Case: A 45-year-old woman had exhibited face and peripheral edema, hyperphagia, weight gain, hair loss and limb numbness since September X-10. In May X-9, her ACTH and cortisol levels were high (87.8 pg/mL and 28.8 µg/dL, respectively), and she was referred to our department. A brain MRI revealed a pituitary adenoma of 7mm in diameter. Because blood ACTH and cortisol levels turned normal and typical Cushingoid features were absent at the admission to our department, cyclic Cushing’s disease was suspected. Later in September, because subjective symptoms recurred accompanied with blood cortisol level elevation, she was diagnosed as cyclic Cushing’s disease with the examinations including inferior petrosal sinus sampling. Transsphenoidal surgery was performed in November, and immunohistology confirmed ACTH-producing pituitary adenoma based on ACTH positivity. After the surgery, endocrine test results were normalized and subjective symptoms were ameliorated. In March X-3, the blood ACTH level increased again; however, no subjective symptoms were observed. From May X, she had experienced limb numbness, hyperphagia and weight gain again. MRI showed no apparent recurrence, but endocrine tests showed the activity of Cushing’s disease. Urinary free cortisol (UFC) increased to 300–400 µg/day in a 1-week cycle, indicating the recurrence of cyclic Cushing’s disease. Metyrapone treatment was initiated, and the patient was finally discharged after block and replace therapy with metyrapone 2,000 mg/day and hydrocortisone 15 mg/day. After metyrapone treatment, subjective symptoms improved and UFC was normalized. Conclusion: Block and replace therapy with metyrapone and hydrocortisone may be effective for recurrent cyclic Cushing’s disease, especially in cases with a very short cycle.
SAT-520 Unusual Case of Hypothyroidism Possibly Due to Dialysis Leading to Van Wyk Grumbach Syndrome (VWGS)
Authors: Chummar Jenice , Salemi Parissa
Published: May 2020

BACKGROUND: Van Wyk Grumbach Syndrome (VWGS) is characterized by precocious central puberty in the setting of juvenile chronic primary hypothyroidism with symptom regression following thyroxine replacement.

Clinical Case: A 2 year old girl with dysplastic kidneys and chronic renal disease had been treated by her nephrologist with growth hormone for poor growth. She was referred to Endocrinology for evaluation of bloody dialysate thought to be retrograde menstrual flow. Pelvic US showed bilateral large cystic adnexae possibly ovarian cysts versus septated collections of dialysate fluid. Hormone measurements showed pubertal levels of LH 0.4mIU/mL and FSH 5.4mIU/mL, with a relatively low Estradiol 5.3pg/mL. Brain MRI showed impressive pituitary enlargement measuring 1.3cm craniocaudally. Additional laboratory testing was notable for a low normal free T4 fT4 0.9ng/dL and markedly elevated TSH>1000uIU/mL and Prolactin 835ng/mL. Thyroid US showed thyroid enlargement, and echogenic and hyper vascular gland. Anti-thyroid antibodies titers were normal, AM cortisol and IGF1 were also normal for age. We speculate that this case of profound hypothyroidism was due to dialysis, as thyroid function improved after the child underwent renal transplantation. Levothyroxine was discontinued 5 months after renal transplantation. Elevated TSH may induce a form of pseudopuberty as the TSH alpha subunit is similar to that of LH and binds to the LH receptor to stimulate the ovaries with cyst formation.

Conclusion: In VWGS, primary hypothyroidism with elevated TSH induces central precocious puberty. This child’s bloody diasylate was likely the result of transient central precocious puberty associated with uncontrolled primary hypothyroidism with elevated TSH and prolactin. Although the literature on dialysis suggests minimal thyroid hormone losses, this case shows the importance of monitoring thyroid hormones in dialysis patients. Early recognition of VWGS and initiation of thyroid hormone replacement can lead to resolution of symptoms.