bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-297 Development of a Local Reference Range for Hypertonic Saline-Stimulated Copeptin
Authors: Brooks Emily K , Bachmeier Caroline , Vorster Juanita , Sorbello Jane , Peer Faseeha C , Chikani Viral P , Dimeski Goce , Ungerer Jacobus , Pretorius Carel , Inder Warrick John
Published: May 2020

Differentiating between primary polydipsia and central diabetes insipidus (DI) can be challenging. The water deprivation test has traditionally been used to diagnosis DI, however has poor diagnostic accuracy (1). Direct measurement of anti-diuretic hormone (ADH) is limited clinically. Copeptin is the C-terminal glycoprotein moiety of ADH prohormone, and correlates well with plasma ADH. Unlike ADH, copeptin is easy to measure (2).

Hypertonic saline stimulated copeptin measurements have recently been described for the diagnosis of central DI. A copeptin cut-off of >4.9 pmol/L has a diagnostic accuracy of 96.5% for distinguishing primary polydipsia from central DI (3). A copeptin assay has recently been established in our laboratory. Validation of hypertonic saline-stimulated copeptin concentrations in our local population is needed before this test can be used with confidence in patients presenting to our institution with polyuria-polydipsia syndrome. The aim of this study was to develop a local reference range for hypertonic saline-stimulated copeptin in healthy volunteers.

Twenty healthy volunteers (10 male and 10 female) were recruited. Subjects underwent a hypertonic saline test, as previously described (3). Hypertonic saline (3%) was administered as an initial 250 mL bolus followed by 0.15 mL/kg/minute until a target serum sodium of ≥150 mmol/L was reached. At this time, blood was drawn for copeptin.

Twelve healthy volunteers (7 females; 5 males) have undergone the study to date. Median age was 28 years (range 26-50); median body weight 75.7 kg (range 57.9 -94.5); median baseline plasma sodium 138 mmol/L (range 136 - 140) and median serum osmolality 289.5 (range 281-297). Median peak sodium was 152 mmol/L (range 150-154) with osmolality 314.5 mmol/kg (range 306-320). Median volume of hypertonic saline infused was 1583 mL (1230-2177) and median hypertonic saline stimulated copeptin was 29.2 pmol/L (9.6-167.4). Overall symptom burden was 5/10 (range 3/10-9/10). There were no serious adverse events.

Development of a local reference range for hypertonic saline stimulated copeptin measurements will assist in interpretation of the test in our local population of patients presenting with polyuria-polydipsia syndrome.

References

1. Fenske W, Quinkler M, Lorenz D, Zopf K, Haagen U, Papassotiriou et al. Copeptin in the differential diagnosis of the polyuria-polydipsia syndrome- revisiting the direct and indirect water deprivation tests. JCEM. 2011;96:1506-1515

2. Timper K, Fenske W, Kuhn F, Frech N, Arici B, Rutishauser J et al. Diagnostic accuracy of copeptin in the differential diagnosis of the polyuria-polydipsia syndrome: a prospective multicenter study. JCEM. 2015;100:2268-2274

3. Fenske, W, Refardt J, Chifu I, Schnyder I, Winzeler B, Drummond J. A copeptin-based approach in the diagnosis of diabetes insipidus. NEJM. 2018;379:428-439
SAT-657 The Gut Microbiome Regulates Host Glucose Homeostasis via Peripheral Serotonin
Authors: Keating Damien
Published: May 2020

The gut microbiome is an established regulator of aspects of host metabolism, such as glucose handling. Despite the known impacts of the gut microbiota on host glucose homeostasis, the underlying mechanisms are unknown. The gut microbiome is also a potent mediator of gut-derived serotonin synthesis, and this peripheral source of serotonin is itself a regulator of glucose homeostasis. Here, we determined whether the gut microbiome influences glucose homeostasis through effects on gut-derived serotonin. Using both pharmacological inhibition and genetic deletion of gut-derived serotonin synthesis, we find [1] that the improvements in host glucose handling caused by antibiotic-induced changes in microbiota composition are dependent on the synthesis of peripheral serotonin.

[1] The gut microbiome regulates host glucose homeostasis via peripheral serotonin. Proc Natl Acad Sci U S A. 2019 Oct 1;116(40):19802-19804. Martin AM, Yabut JM, Choo JM, Page AJ, Sun EW, Jessup CF, Wesselingh SL, Khan WI, Rogers GB, Steinberg GR, Keating DJ.
SAT-664 Fluctuating Blood Glucose in an Infant with Newly Diagnosed IPEX Syndrome
Authors: Gottesman Bethany , Gottschalk Michael
Published: May 2020

Background: In the IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked) syndrome, Type 1 diabetes mellitus is the most common endocrine complication and usually occurs with a variable presentation from immediately at birth to within the first few months of life.

Clinical case: A four-month-old male presented for evaluation of failure to thrive, eczema, and diarrhea. In the ED, his glucose value was 246 mg/dL with beta-hydroxybutyrate of 0.29 mmol/L (0.00-0.30). Within eight hours and without insulin, he became hypoglycemic and required dextrose-containing fluids to maintain euglycemia; he was quickly made NPO and started on TPN due to excessive stool output. For nearly two weeks he required no insulin while receiving 84g of dextrose per day (21 g/kg/day) in TPN. He developed bloody stools on the day that he started receiving Tacrolimus and IVIG and required transfer to the ICU, and an insulin need of 1 unit/kg/day developed with this worsening of his systemic illness. After the bloody stools resolved, immunosuppression with Rituximab was initiated. Once bowel function improved, Pedialyte and formula were slowly reintroduced and for three weeks his insulin requirement varied from 0.2-0.4 units/kg/day. In his seventh week of hospitalization his insulin was discontinued due to hypoglycemia, and at the time of discharge he had been without insulin for ten days on ad lib formula feeding.

Hemoglobin A1c on admission was 10.2%, and repeat was 10.3%. A fructosamine level was obtained to evaluate the discrepancy between the initial HgbA1c and being euglycemic. It was 269 umol/L (190-270), equivalent to an approximate HgbA1c of 6.5%, suggesting that hyperglycemia resulting in an elevated HgbA1c occurred early in his life and had improved in the days to weeks prior to admission. Further testing revealed an elevated GAD-65 antibody of >250 IU/mL (<5) but normal ICA 512 and insulin autoantibody.

His clinical picture was consistent with IPEX syndrome, confirmed with rapid whole genome sequencing showed a pathogenic hemizygous c.1010G>A p.Arg337Gln variant in the FOXP3 gene.

A HgbA1c performed prior to discharge, eight weeks after the initial, was 6.6%. This spontaneous resolution of hyperglycemia in IPEX, with insulin needs developing only when he had worsening systemic illness as demonstrated by bloody stools, has yet to be described.

Conclusion: Hyperglycemia fluctuated in the first few months of life in a patient with IPEX syndrome, likely related to severity of systemic illness and control of enteropathy.
SUN-598 Phenotypic Study of Meso-Somatous (Roch-Leri) Lipomatosis
Authors: Lemaitre Madleen , Espiard Stéphanie , Humbert Linda , Boury Samuel , Lion Georges , Vantyghem Marie-Christine
Published: May 2020

Background: Lipomatosis is a condition in which multiple lipomas are present on the body. Different entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, MEN1, benign symmetric lipomatosis (Madelung or Launois-Bensaude disease), Dercum’s Disease, familial lipodystrophy, hibernomas, epidural lipomatosis, familial angiolipomatosis, and meso-somatous lipomatosis (LMS) still called Roch-Leri lipomatosis. LMS is characterized by the presence of many discrete, encapsulated lipomas of 2 to 5 cm, painless, at the level of the trunk and forearms. The aim of the present study was to determine the clinico-biological phenotype of LMS, as compared to controls. Patients and methods: In this single-center study (NCT01784289), 18 healthy controls (C) and 11 LMS were included after examining the cohort of 76 patients referred for suspected lipodystrophic syndrome between 2009 and 2019 in the Endocrinology Department of a University Hospital. Clinical (sex, age, weight, BMI, blood pressure (BP), alcohol consumption), metabolic (fasting blood glucose (FBG) and insulin levels, lipid balance, ASAT, ALAT, GammaGT, leptin), immuno-inflammatory (CBC, lymphocyte immunophenotyping), and anthropometric (% of body fat in DEXA, steatosis and intra-abdominal / total abdominal fat ratio (IAF / TAF) in MRI) were evaluated. Results: The following parameters, expressed as % or median, differed significantly between LMS vs. C groups, respectively: weight 100 vs. 69kg (p<0.01), BMI 30.8 vs. 22.7 (p<0.01), systolic BP 140 vs. 115 (p<0.01) and diastolic BP 80 vs. 70 mmHg (p<0.05), gammaGT 74 vs. 18 IU / L (p<0.01), fasting insulin levels 7.3 vs. 4.7 microIU / mL (p<0.05), leptin 28 vs. 5 ng / mL (p<0.01), CD3 (867 vs. 1444 / mm3 (p<0.01), CD4 499 vs 866 / mm3 (p<0.05), CD8 227 vs. 546 (p<0.05), fat mass 41 vs. 22 (p<0.05). Three LMS patients had hepatic steatosis and 3 a first-degree family member with LMS. Percentage of men (63% vs. 52%, FBG, lipid levels, ASAT, ALT, CBC, IAF / TAF (0.25 vs 0.19) did not differ significantly. The number of lipomas was > 5 in 82% of LMS patients and lipomas were localized first to the forearms (82%), then the thighs (73%) and the abdomen (55%). At diagnosis, the age of LMS patients was 20 years old; 55% of the LMS patients had a BMI above 30 and 45% above 25. No patient had excessive alcohol consumption. Five had a history of auto-immuneor inflammatory disease: 1 hyperthyroidism, 1 hypothyroidism, 1 multiple sclerosis, 1 vitiligo, 1 Raynaud syndrome. Conclusion: LMS mainly affects overweight men and is associated with hypertension, hyperinsulinism, increased gammaGT and a decrease in CD3, CD4 and CD8 lymphocytes, suggesting an immune dysregulation, all the more so that 45% had an associated auto-immune/inflammatory disease.
SAT-212 Management of VHL-Associated Pheochromocytoma in Pregnancy
Authors: Reikes Andrew Reed , Desai Ruchi
Published: May 2020

Background: The appropriate treatment of pheochromocytoma during pregnancy is crucial because, while its incidence is rare (0.007%), it is associated with increased maternal and fetal mortality1.

Clinical Case: A 32 year old Caucasian primigravida female presented with intrauterine pregnancy at 25 weeks for evaluation and management of a 9 mm left adrenal mass. The patient was previously diagnosed at age 10 with Von-Hippel Lindau (VHL) syndrome and genetic testing was positive for a VHL gene mutation (Type 2C VHL). At age 14, she underwent laparoscopic adrenalectomy to excise a right sided pheochromocytoma. At age 20, imaging revealed an enhancing left adrenal mass with imaging characteristics consistent with pheochromocytoma and with catecholaminergic labs that were normal or only mildy increased to 1.5 times upper normal range. Pre-partum the patient had been experiencing periodic episodes of headaches and palpitations. She reported experiencing baseline levels of palpitations and sweating with new onset of pre-syncope and hypotension during her pregnancy. Labs revealed normal serum levels of fractionated free metanephrines. Alpha adrenergic blockade, beta adrenergic blockade, and surgery were considered but deemed unnecessary as the patient was asymptomatic, imaging indicated the left adrenal mass was stable in size, and the patient wished to avoid lifelong adrenal replacement therapy. The patient’s blood pressure and heart rate were monitored closely throughout pregnancy and the use of alpha blockade or beta blockade was not needed. The patient had an uncomplicated induced delivery at 39 weeks. MRI with contrast of abdomen performed 10 months postpartum confirmed the presence of an enhancing 8 mm lesion on the inferior pole of the left adrenal gland with imaging characteristics again consistent with pheochromocytoma.

Conclusion: This case demonstrates that a conservative approach of monitoring blood pressure and heart rate can be sufficient and appropriate for management of some patients with pheochromocytoma and VHL during pregnancy.

Citation:

1.

ENDOCRINOLOGY IN PREGNANCY: Pheochromocytoma in pregnancy: case series and review of literature in: European Journal of Endocrinology Volume 177 Issue 2 (2017).
SUN-615 Does Patient Location (Urban or Rural) Influence Risk Factors and Incidence Rate for 30-Day Readmission for Diabetic Ketoacidosis?
Authors: Varghese Ron Thomas , Jacob Diana G , Khasawneh Khaled , Kamoga Roy , Mehta Neal
Published: May 2020

Introduction Nearly 1 in 10 individuals in the US have Diabetes Mellitus [1]. One potential preventable complication is Diabetic Ketoacidosis (DKA). Urban and rural patients may have different mortality [2]. Better understanding of the risk factors for readmissions of DKA will allow the development and implementation of specific patient-centered interventions to decrease future readmissions. We determined the 30-day all-cause readmission rate for adults (age >= 18) admitted with a principal diagnosis of DKA and compare the risk factors for urban and rural patients. Methods We utilized Agency of Healthcare Research and Quality’s (AHRQ) 2014 Nationwide Readmission Database to identify admissions with a principal diagnosis of DKA related ICD-9 diagnosis (250.10, 250.11, 250.12, and 250.13) associated with both Type 1 and Type 2 Diabetes Mellitus. Applicable admissions were all adults (age >= 18) with an index hospitalization between January 1 to November 30, 2014. Patients who died during index admission and those with missing covariates were excluded. The 2013 NCHS Urban-Rural Classification System was used to classify if originating from an urban or rural location. All-cause readmission within 30-days of DKA were analyzed. Predictors for readmission were determined using logistic regression model. Results A total of 65,249 patients met criteria for inclusion. Of which, there was 12,561 readmissions (19.25 %) within 30-days of the index admission. Patients originating from urban locations had a readmission rate of 19.36% compared to 18.56 % for patients from rural locations (p=0.07). Multivariate analysis showed patients from either rural or urban location each had a higher likelihood of readmission if their disposition was home health or AMA, younger age (<65), female, Medicare as payer, LOS 7-14 days, absence of obesity, and presence of renal failure. In addition, disposition to short term hospital increased the odds for readmission from rural patients. Conclusion Almost 1 in 5 patients discharged with a principal diagnosis of DKA will be readmitted within 30 days. No difference was noted in rates of readmissions for patients originating from urban or rural locations. Risk factors are similar with further research needed to better understand the drivers of readmission. References: [1] CDC: National Diabetes Statistics Report (2017) [2] Ferdinand AO, et al. (2017). Diabetes-Related Hospital Mortality in Rural America: A Significant Cause for Concern. Policy Brief #3. Southwest Rural Health Research Center
MON-155 Retrospective Cross-Sectional Study to Assess the Utility of 30 vs 60 Minutes Serum Cortisol Value Attained During a Short Synacthen Test (SST)
Authors: Butt Muhammad Imran , Amer Lama Ghassan , Aljamei Hadeel Salah , Riazuddin Muhammad , AlZuhairy Nouf , Abufarhaneh Mohammad , Alahmed Reem , AlRajhi Eman , AlNassar Anhar , Khan Muhammad Sohaib Ejaz , Aljayar Dina Mahmoud , Abothenain Fayha Farraj , Devol Edward Bentz
Published: May 2020

Background

SST is done to assess adrenal gland function by measuring basal serum cortisol followed by injecting 250 μg of Synacthen (ACTH) & measuring cortisol at 30 & 60 minutes.

Design

All patients over 14 years (adulthood age in the region) who had undergone a SST from January 2010 to December 2017 were included. Patients who underwent pituitary surgery in preceding 2 months, on exogenous steroids, opioids & oral contraceptives were excluded. Stimulated cortisol of 550 nmol/L or more achieved at 30, 60 minutes or both was classified as a normal response.

Results

965 patients were identified from pharmacy, medical & laboratory records. 116 patients were excluded and 849 were included in the analysis.

Mean age was 50.5 ± 20.45 years. Mean weight was 67 ± 21 Kg. 54% patients were female. Mean basal, 30 and 60 minutes cortisol values after ACTH injection were 394 ± 286.58 nmol/L, 722 ± 327.11 nmol/L, 827 ± 369.30 nmol/L respectively. 715 patients (84 %) had a normal response and 134 patients (16 %) had suboptimal response. Primary and secondary adrenal insufficiency was diagnosed in 10% and 35% respectively. No ACTH value was available in 55% of the patients.

Suboptimal response was observed at 30 minutes in 9.49% (n=72) of the patients: all crossed 550 nmol/L threshold at 60 minutes. Mean change of cortisol level from baseline to 30 minutes was 240 nmol/L in this particular sub group which was higher than the mean change of 152 nmol/L observed in patients who failed the test overall up to 60 minutes. No patient with optimal response at 30 minutes had suboptimal response at 60 min.

Morning basal cortisol threshold of 226 nmol/L or over had 80% sensitivity, 71 % specificity & 93% positive predictive value to detect a normal SST (P-value <.0001).

Conclusion

60 minute cortisol correctly identified all normal and abnormal results. Relying only on 30 min value resulted in significant false positive results.

Morning basal cortisol over 226 nmol/L should be considered reliable threshold for adequate adrenal function particularly when clinicians have low pretest probability for hypoadrenalism.
SUN-378 Unilateral Primary Aldosteronism as an Independent Risk Factor for Vertebral Fracture
Authors: Sakamoto Ryuichi , Yokomoto-Umakoshi Maki , Umakoshi Hironobu , Matsuda Yayoi , Hiromi Nagata , Fukumoto Tazuru , Ogata Masatoshi , Ogawa Yoshihiro
Published: May 2020

Context: Primary aldosteronism (PA) is known to increase vertebral fracture (VF), although the detailed mechanism remains to be elucidated. PA consists of two subtypes: the unilateral and bilateral subtype. Patients with unilateral PA, who usually have a higher plasma aldosterone concentration than those with bilateral PA, exhibit a more severe clinical phenotype. We hypothesized that PA subtype affects the prevalence of VF.

Objective: To evaluate whether unilateral PA is associated with the prevalence of VF.

Design: Cross-sectional study in a single referral center.

Patients: We identified 210 hypertensive patients whose clinical data were available for case-detection results. One hundred and fifty-two patients were diagnosed with PA using captopril challenge tests.

Measurements: The prevalence of VF according to PA subtype.

Results: We included 113 patients with PA who were subtype classified according to adrenal vein sampling, of whom 37 patients had unilateral PA and 76 patients had bilateral PA, whereas 58 patients had non-PA. We excluded 39 patients with PA who were not subtype classified. Patients with PA had a higher prevalence of VF (28% [32/113]) than those with non-PA (12% [7/58]; p = 0.020). Moreover, unilateral PA had a higher prevalence of VF (46% [17/37]) than bilateral PA (20% [15/76]; p = 0.021). There was no significant difference between bilateral PA and non-PA. Unilateral PA was an independent risk factor for VF after adjusting for age and sex (odds ratio, 3.16; 95% confidence interval, 1.12-8.92; p = 0.017). Among patients with unilateral PA, serum cortisol concentrations after 1 mg dexamethasone suppression test were higher in those with VF (1.32 ± 0.67 g/dl) than those without (0.96 ± 0.33 g/dl; p = 0.048).

Conclusions: Unilateral PA is an independent risk factor for VF, which is associated with autonomous cortisol secretion. Thus, careful management is required to prevent the development of VF in patients with unilateral PA.
SUN-431 Case Finding Versus Routine Screening of Thyroid Dysfunction in Pregnancy
Authors: Al Qarni Ali Ahmed , Alamoudi Reem Mohammad , Shahid Khalida , Almanei Amal , Alotaibi Muneera , AlAhmed Jawharah
Published: May 2020

Background:

Thyroid dysfunction in pregnancy is associated several adverse outcomes. This has triggered a debate about whether universal screening should be implemented. Despite recommendations against universal screening, the clinical practice of many caregivers may differ. We aimed to assess the sensitivity of using targeted high-risk case finding for diagnosing thyroid dysfunction in pregnancy compared to routine screening in pregnant Saudi women, and to evaluate if gestational diabetes (GDM) specifically affected the risk.

Methods:

A cross-sectional study in two hospitals under the Ministry of National Guards Health affairs of Saudi Arabia; King Abdulaziz Hospital, Al-Ahsa, and Imam Abdulrahman bin Faisal Hospital, Dammam. Pregnant ladies attending the Family medicine, Obstetrics and Gynecology, and Endocrinology clinics in both hospitals were assessed by the caring physician based on a check list for risk stratification for thyroid dysfunction as per the 2012 Endocrine society clinical practice guidelines for management of thyroid dysfunction in pregnancy. Presence of one risk factor defined high risk. All patients had a routine serum TSH measured as universal screening is commonly practiced in both institutions, the physician doing the risk stratification was not aware of the TSH result. Sensitivity and specificity for the case finding approach was calculated using and abnormal TSH value as the gold standard for presence of thyroid dysfunction. The institutions lab reference TSH 0.35 – 4.94 mIU/L was used as cutoff.

Results:

1571 pregnant women were included in the study; mean age 29.3± 6.2 years, 396 (23.5%) were primigravida. The mean TSH value was 1.898 ± 1.459 mlU/L. 1178 (75%) pregnant women had an indication for screening based on presence of at least one risk factor, of which 95 (8.1%) tested abnormal for TSH. 393 women had no risk factors, of which 379 (96.4%) had normal TSH, (Chi square 9.3, p-value 0.002). [Sensitivity 87.2%, (95%CI 79.4% – 92.8%), Specificity 25.9%, (95%CI 23.7% – 28.3%)]. Total abnormal TSH values was 109 (6.9%), 43 were abnormal high (i.e. hypothyroid); of which 40 screened positive by case finding approach [Sensitivity 93.02%, (95%CI 80.9% – 98.5%), Specificity 25.52%, (95%CI 23.4% – 27.8%)]. Moreover, 178 (11.3%) women screened positive for GDM at some stage in pregnancy out of which only 5 (2.8%) had an abnormal TSH value, while of the 1393 pregnant women who screened negative for GDM 1289 (92.5%) had a normal TSH value, (Chi square 5.3, p-value 0.02). [Sensitivity 4.6%, (95%CI 1.5% – 10.4%), Specificity 88.2%, (95%CI 86.4% – 89.8%)].

Conclusion:

Targeted high-risk case finding predicts thyroid dysfunction in pregnant Saudi women with high sensitivity supporting its utility in screening our pregnant population. Gestational diabetes is highly prevalent in Saudi women, but does not increase risk of thyroid dysfunction in pregnancy.
SAT-569 Management of Severe Gestational Hypertriglyceridemia
Authors: Borja Anne , Khandelwal Meena , Morgan Farah
Published: May 2020

Background: Severe gestational hypertriglyceridemia is a dangerous and life threatening illness. Management can be difficult due to the limited data on safety of medical therapy during pregnancy. We present a case of severe gestational hypertriglyceridemia.

Case Presentation: A 29 year old woman, G4P2012 at 23w3d, with a past medical history of gestational diabetes, nontoxic thyroid nodule, and hypertriglyceridemia presented to the emergency room for abdominal pain and nausea. She has no known family history of lipid disorders. Her last pregnancy was complicated by acute pancreatitis due to hypertriglyceridemia. Between pregnancies, her triglyceride level was >900 mg/dL and gemfibrozil therapy was advised, however reported nonadherence. In current pregnancy and after counseling, she was prescribed omega-3 acid ethyl esters (Lovaza) 2 grams twice a day and referred to maternal fetal medicine. Triglyceride level on admission was 3640 mg/dL, and she admitted to poor adherence to Lovaza. Liver function tests were within normal limits. She was started on an insulin drip, as well omega-3 fatty acids 4g daily. However, the triglyceride level remained elevated despite 72 hours on the insulin drip and it was subsequently discontinued. Plasmapheresis was discussed but deferred given no evidence of pancreatitis. Gemfibrozil 600mg twice a day was added to the omega-3 fatty acids which were titrated up to 2g three times a day. On her day of discharge, her triglyceride level was 2200 mg/dL and abdominal pain had resolved. She was maintained on gemfibrozil and Omega-3 fatty acids, with plans to increase them by 1g per week to reach a goal of 10g per day with a goal triglyceride level <1000mg/dL. Pre-gestational diabetes was tightly controlled with insulin. She was also seen by the nutritionist for counseling of a low fat diet and was followed very closely as an outpatient. Although the omega-3 fatty acids were titrated to 8g per day, the triglyceride level remained ~2000mg/dL. She remained asymptomatic and delivered a healthy baby boy weighing 3446 grams at 36 weeks 4 days, with no complications. She continues follow up with endocrinology with triglycerides 6 months later being 1618 mg/dl.

Conclusion: We present a patient with severe gestational hypertriglyceridemia with a known history of pancreatitis. Due to the rarity of this condition, there is limited data on the safety of treatments for hypertriglyceridemia in pregnant women. This case demonstrates the use of gemfibrizol is appropriate when the hypertriglyceridemia threatens the health of the mother and baby. Further studies are needed to establish efficacy and safety of the use of these treatments in pregnant patients.
SUN-337 Low Dose Ethinyl Estradiol in Women with Cystic Fibrosis Does Not Preserve Bone Mass
Authors: Wu Malinda , Hunt William R , Tirouvanziam Rabindra , Putman Melissa Susan , Tangpricha Vin
Published: May 2020

BACKGROUND: Cystic fibrosis-related bone disease (CFBD) affects 26% of adults with cystic fibrosis (CF). CFBD increases the risk for fractures, which in turn limits patients’ ability to effectively perform daily therapies necessary to maintain health. Factors contributing to CFBD include nutritional deficiencies, inflammation, glucocorticoid use, CF-related diabetes and untreated hypogonadism. Hypogonadism in CF is thought to be functional, although the distribution of etiologies of female hypogonadism in the modern era of CF therapies is unknown. Estrogen supplementation is commonly prescribed in the form of oral contraceptives to women with low bone mineral density (BMD). At our CF center, the average dose of ethinyl estradiol prescribed to women is 20 mcg. Recent evidence suggests that oral estrogen is ineffective for restoring bone health in women with functional hypogonadism and specifically that doses < 30 mcg oral ethinyl estradiol are inadequate. It is unknown if estradiol supplementation will restore and/or maintain BMD in women with CFBD.

METHODS: The purpose of this study was to examine the skeletal health of a cross-section of premenopausal women seen at a single CF center taking 20 mcg or less of ethinyl estradiol daily (low-dose estrogen) compared to women not taking estrogen supplement. As screening for an IRB-approved intervention study, we collected health information by chart review.

RESULTS: In a 12-week period, 98 women were seen in CF clinic. Of women 18 - 50 years old with CF and a documented DXA, 37 women were not taking estrogen supplement (mean age 30.8 ± 5.9 years) and 6 women were taking low-dose estrogen (mean age 30.4 ± 7.1 years). There were not statistically significant differences in other baseline characteristics known to modify CFBD. Women not taking estrogen had higher lumbar spine z-score: -0.04 ± 1.0, compared to women taking low-dose estrogen, z-score: -0.7 ±, 0.5 (p-value 0.01). Women not taking estrogen had higher BMD at the lumbar spine: 1.02 ± 0.1 g/cm2, compared to women taking low-dose estrogen: 0.95 ± 0.1 g/cm2 (p-value 0.03). Similar trends were seen at the total hip and femoral neck (p-values > 0.05).

DISCUSSION: In this retrospective single-center chart review, women not taking estrogen supplement compared to women taking low-dose estrogen supplement had higher BMD. This was statistically significant at the lumbar spine, the DXA site with mostly trabecular bone. Estrogen deficiency causes trabecular bone loss, which can be restored with estrogen supplementation. These findings raise concern that low-dose estrogen supplementation for women with CF is inadequate for optimal bone accrual and may be detrimental. The ideal route and dose of estrogen supplementation for skeletal health of premenopausal women with CF still needs to be clarified.

REFERENCES: CFF Patient Registry 2017; Aris JCEM 2005; Ackerman JCEM 2019; Anabtawi J CF 2019; Hughan J CF 2019
SAT-348 Primary Hyperparathyroidism Presenting as Acute Necrotizing Pancreatitis and Diabetic Ketoacidosis in Type 2 Diabetes
Authors: Knight John O’Connell , Haw Jeehea , Vellanki Priyathama
Published: May 2020

INTRODUCTION: The association between diabetic ketoacidosis (DKA) and acute pancreatitis (AP) is well established. Hypercalcemia from primary hyperparathyroidism (PHPT) is a rare cause of AP, accounting for less than one percent of cases. The constellation of PHPT, AP, and DKA as an initial presentation of diabetes is not known.

CASE PRESENTATION: A 33-year-old male with minimal prior healthcare contact presented to the ER with acute encephalopathy after three weeks of polyuria and polydipsia, and later abdominal pain, nausea, and vomiting. He was hyperglycemic to 1310 mg/dl with an anion-gap metabolic acidosis (pH 7.12, serum bicarbonate of 7 mEq/L, anion gap of 33) and elevated beta-hydroxybutyrate to greater than 9 mmol/L, and was profoundly dehydrated with hyperosmolarity to 354 mOsm/kg. He was hypercalcemic to 14.0 mg/dl with elevated parathyroid hormone of 260.7 pg/L. CT of the chest, abdomen, and pelvis revealed acute necrotizing pancreatitis. He was treated with insulin, aggressive fluid resuscitation, and supportive measures, with resolution of encephalopathy, DKA, AP, hyperosmolarity, and kidney injury. Calcium and parathyroid hormone remained elevated, with further workup suggesting PHPT as the etiology of his hypercalcemia.

DISCUSSION: Associations between PHPT and AP, and between AP and DKA, are established in the literature, but few cases of DKA from hypercalcemia-induced AP have been described. Our patient highlights the importance of the etiologic workup in both DKA and AP, as both carry high mortality and have high rates of recurrence. Further study is needed to better characterize the relationship between DKA, AP, and PHPT to better inform early diagnosis and prevention efforts.
SAT-478 A Case of Congenital Thyroid Hemi-Agenesis- Caution for Complications!
Authors: Patel Sabah , Krutilova Petra , Gilden Janice L
Published: May 2020

Introduction: Congenital Thyroid hemi-agenesis is an uncommon clinical entity. We present a case highlighting the importance of awareness of this condition and the need to evaluate and manage co-existing hypothyroidism and risk of malignancy. Case: A 20 year old female known to have Hashimoto’s thyroiditis (non-adherent to levothyroxine), and hemi-agenesis of left lobe of thyroid gland, presented with right-sided thyroid enlargement. She was clinically euthyroid. Physical exam: enlarged right sided thyroid gland with palpable anterior cervical lymphadenopathy. Left lobe could not be palpated. TFTs were notable for TSH 4.98 uIU/ml (0.358-3.74) and Free T4 0.79 ng/dl (0.76-1.46) consistent with sub-clinical hypothyroidism while Anti TPO antibody was positive at 8332.8 U/mL (0 - 60). CBC negative for leukocytosis. US thyroid: left-sided thyroid agenesis with intact isthmus and enlargement of right lobe of the thyroid 7.7 cm x 1.6 cm x 2.6 cm with 2 sub-centimeter hypoechoic solid nodules and 2 enlarged lymph nodes 1.5 cm and 2.3 cm (not found in US thyroid 2 years ago) Levothyroxine was re-started. ENT evaluation determined that her lymphadenopathy was benign and consistent with Hashimoto’s thyroiditis. Subsequent TFTs improved. Discussion: Thyroid Gland embryogenesis occurs in the 4th week of fetal life. Subsequent abnormal bilobal differentiation of the thyroid gland is presumed to be the etiology of congenital hemi-agenesis. Its prevalence in several studies is estimated to be between 0.05-0.25%. It is symptomatic pre-dominantly in females and may have familial origin with vast majority of cases having left hemi-agenesis with intact isthmus. It is helpful to know that most symptomatic patients have compensatory hypertrophy of the remnant lobe. It is important to remember that compensatory enlargement of the remnant lobe in the setting of hypothyroidism may be a sign of insufficient endogenous thyroxine production and/or replacement. Although rarely symptomatic, hemi-thyroid remnant may need to be evaluated for co-existing hyperthyroidism, hypothyroidism, carcinoma and multinodular goiter among others, with hypothyroidism thought to be the most common. US thyroid is a useful modality to help guide the evaluation of patients with hemi-agenesis. Awareness of this congenital condition is key in preventing unnecessary evaluations and interventions. Non-resolving lymphadenopathy in Hashimoto’s thyroiditis must be evaluated for lymphoma, however, based on studies, no additional risk of malignancy was identified in patients with underlying thyroid hemi-agenesis. References: Y.H. Wu, R.O. Wein, B. Carter Thyroid hemiagenesis: a case series and review of the literature Am J Otolaryngol, 33 (3) (2012), pp. 299-302
OR08-06 Increased Carotid Intima Media Thickness in Pediatric Type 1 Diabetes Is Associated with Disease Duration
Authors: Cohen Michal , Oren Meirav , Gendelman Raya , Yaseen Hiba , Weiss Ram , Ilivitzki Anat , Zuckerman-Levin Nehama , Khamaisi Murir , Shehadeh Naim
Published: May 2020

Background & Objective

Patients with type-1-diabetes (T1D) are at risk of long-term micro and macrovascular complications causing significant morbidity and mortality. Overt complications are not common in childhood; however, subclinical impairments in endothelial function, may be found. Better understanding of the timeline for the appearance of diabetic complications and identifying individuals at increased risk is key for developing prevention strategies. We aimed to study endothelial function and it’s determinants in adolescents with T1D at different time points from diagnosis.

Methods

Forty adolescents 11-20 years of age with T1D followed at our pediatric diabetes clinic and 18 healthy control subjects were included. Two groups of patients were recruited based on time from T1D diagnosis; 20 individuals were diagnosed 2-4 months prior to the study visit and 20 at least 7 years prior to the visit. Investigations included: i) medical and demographic data ii) anthropometrics iii) fasting blood samples iv) EndoPAT testing of endothelial function and heart rate variability (Itamar Medical Ltd., Israel) v) Carotid intima media thickness (CIMT).

Results

Mean age differed slightly between groups being 14.1±2.0years in individuals with recent-onset T1D, 16.2±2.5 in those with prolonged T1D, and 14.8±2.3 in the control group (p=0.02). There were no significant differences in pubertal stage or in BMI z-score between groups. Thirty-three (57%) females participated. No patient suffered from diabetic complications. Mean CIMT was significantly higher in individuals with prolonged T1D (0.49±0.07mm) compared to control subjects (0.43±0.05mm; p=0.013) and did not differ significantly between patients with recent-onset T1D (0.45±0.07mm) and controls. This difference remained significant when age and sex were included in the model. EndoPAT measures of endothelial function and heart rate variability did not differ significantly between groups. Mean HbA1c at the time of the visit differed between groups (6.7%±0.7, 9.6%±1.8, 5.4%±0.3, p<0.001). However, the average of HbA1c reflecting the 6-7 months prior to the visit did not differ significantly between subjects with recent onset T1D (9.8%±1.3) and those with prolonged T1D (9.5%±1.7). LDL was higher in subjects with prolonged T1D (114±28mg/dl) compared to either controls (93±26mg/dl) or recent onset T1D (88±19mg/dl),p=0.002. Diastolic blood pressure was higher in subjects with prolonged T1D (70±6mmHg) than in controls (61±6, p=0.007).

Conclusions

Our results demonstrate disease duration to be an important factor in the development of subclinical arterial damage in the pediatric age group. Early in the course of T1D, CIMT results were similar in patients and control subjects, suggesting an important window for prevention. Larger studies could shed light on the precise timeline of endothelial impairment.
MON-530 Local Lymph Node Metastasis Is Less Common in RAS- Mutated Thyroid Cancer Compared to BRAFV600E- Mutated Thyroid Cancer
Authors: Endo Mayumi , Nabhan Fadi , Brock Pamela , Roll Katie , Sipos Jennifer Anne , Ringel Matthew David
Published: May 2020

Introduction: Somatic mutations of RAS- and BRAFV600E- are the most common driver mutation in thyroid cancer (TC) and in the majority of cases, these are mutually exclusive1,2. Clinical characteristics of TC with either RAS or BRAFV600E mutation is not systemically studied.

Methods: This is a retrospective study at the Ohio State University (OSU) from 1/2000 to 12/2018. Data were extracted from OSU Endocrine Neoplasia Repository (ENR). Medullary thyroid cancer was excluded. The treating physician determined patient management. Statistical analysis was performed with the chi-square test for categorical values and Mann-Whitney U test for continuous unpaired values. Two-sided P values of less than 0.05 were considered statistically significant.

Results: Out of 320 patients, 152 patients had a positive mutational profile. Of these, 128 patients had a BRAFV600E mutation and 14 had a RAS mutation. Details of RAS mutation were as follows; NRASQ61K (n=2), NRASQ61R (n=1), HRASQ61R (n=1), HRASQ61K (n=1), NRAS without further details (n=9). Local lymph node metastasis was significantly less in RAS mutated cancer (58% vs 16%, p<0.05). Lymph node metastasis was limited to N1a in all RAS group, whereas 38% of BRAFV600E had N1b status. The number of positive lymph nodes were significantly fewer in the RAS group (mean 0.42 vs. 9.1, p=0.003). None of the patients in RAS group developed subsequent local neck recurrence, whereas 19% of BRAFV600E group developed a recurrence (p=0.05). Bone metastasis was more common in RAS compared to BRAFV600E group (21% vs 6%, p=0.04) but there were no differences in other distant metastases. Presence of extrathyroidal extension was significantly higher in BRAFV600E compared to RAS group (58 % vs 8%; p=0.04). Classic variant papillary thyroid cancer was the most common histologic diagnosis with both mutations, however, follicular-variant papillary thyroid cancer was more common in RAS than BRAFV600E group (29% vs 8%, p=0.04) and follicular thyroid cancer was only seen in the RAS group (25% vs 0%, p<0.05). There was no difference in gender, age at diagnosis, disease status after initial therapy, RAI treatment, RAI dosage, and mortality between the groups.

Conclusion: Thyroid cancer associated with a RAS-mutation has less tendency to metastasize locally and has a higher incidence of bone metastasis compared to thyroid cancer with BRAFV600E-mutation. Individualized clinical follow up may be indicated depends on their mutational profile.

References:

1. Cancer Genome Atlas Research N. Integrated genomic characterization of papillary thyroid carcinoma. Cell. 2014;159(3):676-690.

2. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-2326.
SAT-572 Extremely Elevated Plasma Lipoprotein X Level Secondary to Alcoholic Cholestasis
Authors: Nelson Carolyn Ann , Ahmad Zahid , Garg Abhimanyu
Published: May 2020

Background

Marked elevations of plasma lipoprotein X (Lp-X) levels have been reported in patients with cholestasis due to primary biliary cirrhosis, pancreatic cancer, hepatitis C, and quetiapine. We now report a patient with extreme elevation of plasma Lp-X due to alcohol-induced cholestasis.

Case Presentation

A 44 year-old African American male presented with painless jaundice and fatigue for one week. He denied nausea, vomiting, diarrhea, change in stool or urine color, or weight loss. He consumes 720-1080 mL of beer (2-3 cans) every night and admitted to heavier alcohol consumption in the past. On physical examination he had scleral icterus and hepatomegaly but no xanthomas or xanthelasmas.

His serum total cholesterol was 1,126 mg/dL (normal range, 120-199 mg/dL), triglycerides were 238 mg/dL (50-150 mg/dL), calculated LDL-cholesterol was 1,072 mg/dL (<100 mg/dL), and HDL-cholesterol was 6 mg/dL (>39 mg/dL). His serum AST, 162 IU/L (10-50 IU/L); ALT, 79 IU/L (10-50 IU/L); alkaline phosphatase, 1,058 IU/L (40-129 IU/L); total bilirubin, 18.8 mg/dL (0.2-1.3 mg/dL); direct bilirubin, 13.5 mg/dL (0-0.3 mg/dL); and gamma glutamyl transferase, 4,583 IU/L (8-61 IU/L) were markedly elevated. His blood alcohol level was 34 mg/dL (not detected), sodium 124 mmol/L (135-145 mmol/L), and platelet count was 84,000/µL (150,000-459,000/µL). His TSH 2.89 µIU/mL (0.4-4.5 µIU/mL), UA without proteinuria, HBV immunized, HCV negative, and anti-mitochondrial antibody negative. CT abdomen revealed hepatic steatosis and gallbladder swelling without evidence of obstruction. MRCP showed cirrhosis without primary sclerosing cholangitis. Serum lipoprotein electrophoresis confirmed the presence of Lp-X. On day 3 of hospitalization, his cholestasis improved and his serum total bilirubin 10.0 mg/dL, direct bilirubin 7.4 mg/dL, AST 108 IU/L, ALT 66 IU/L, and alkaline phosphatase 663 IU/L had improved. The patient was advised to abstain from all alcohol consumption. Telephone follow up 2 months later with his wife revealed that he had stopped drinking alcohol and that his jaundice had resolved.

Conclusions

Although alcohol-induced cholestasis is a well-recognized entity, such presentation with extreme elevations of Lp-X has not been previously reported. In such patients, it is important to establish whether extreme hypercholesterolemia is due to LDL or Lp-X since, as opposed to LDL, Lp-X elevations are not considered to be atherogenic.
SAT-675 Relapsing Diabetic Ketoacidosis During Stepdown from Intensive Care Unit
Authors: Zakai Yusha , Dagogo-Jack Samuel
Published: May 2020

BACKGROUND: DKA is a life-threatening and expensive complication of diabetes, costing $5.1 billion annually. Recurrent DKA accounts for ~ 20% of DKA admissions. Here we present 2 patients with relapsing DKA during transition from ICU to the medical floor. CASE-1: A 61-year-old previously healthy man presented with 3-day of generalized weakness and nausea. Review of systems was positive for polyuria and polydipsia. His brother has T2D. Examination: afebrile, HR 166/min, BP 146/104mmHg, dry oropharynx. Labs: Serum glucose 689mg/dl, Na 126mmol/L(136-145mmol/dl), K 4.8mmol/L(3.5-5.1mmol/L), Cl 78mmol/L(98-107mmol/L), bicarbonate 8mmol/L(21-32mmol/L), creatinine 4 mg/dl(0.7-1.3mg/dl), Anion gap(AG) >20(5-20), HCT 57.6%(38.8-48%), A1c 10.4%, c-peptide 1.5ng/ml(0.8-3.8ng/ml). Urine: ketones++. A diagnosis of new-onset diabetes presenting with DKA was made. Patient was admitted to ICU and insulin and saline were infused per protocol. Because the AG closed promptly and bicarbonate improved to 20mmol/L, insulin drip was stopped in the ICU and patient was transferred to medical floor. Evaluation on the medical floor 4 hours later showed bicarbonate of 14 mmol/L and AG >20. Due to deterioration, patient returned to the ICU for management of recurrent DKA. After stabilization in ICU, patient returned to the medical floor and was successfully discharged on basal-bolus insulin the next day. CASE-2: A 35-year-old with history of T2D presented with 1-day of nausea and vomiting. Review of systems was positive for polyuria and polydipsia. Home medications: metformin, glipizide and glargine. Examination: afebrile, HR 104/min, BP 154/97mmHg and tender abdomen. Labs: Serum glucose 411mg/dl, Na 137mmol/L, K 4.6mmol/L, Cl 103mmol/L, bicarbonate 17mmol/L, Creatinine 0.9 mg/dl, AG 22, BHB 6.98 mmol (0.0-0.89mmol), A1c 9%. Patient was admitted to ICU for DKA management. Bicarbonate improved to 20 mmol/L, so insulin drip was stopped in the ICU and patient was transferred to medical floor. Evaluation after 6 hours showed bicarbonate of 17mmol/L and AG of 20. Because of the decreasing bicarbonate and increasing AG, a diagnosis of recurrent DKA was made and prompt insulization was restarted. Patient responded to the regimen and was discharged home on basal-bolus two days later. CONCLUSION: Recurrent DKA due to abrupt cessation of IV insulin prolonged these patients’ hospitalization. The practice of overlapping IV insulin with SQ insulin for >30 min prevents dissipation of insulin action during resolution of DKA. Half-life of IV insulin is 3 min, so SQ insulin must be given before cessation of the insulin drip to prevent the relapse. Omission of this practice, as occurred in these patients unfortunately, caused relapse in DKA and prolonged hospitalization. Education of ICU staff on proper insulin management is warranted to prevent healthcare cost: the cost of a DKA hospitalization was $26,566 in 2014.
SUN-618 Decision Analysis for Glucagon-Like Peptide Receptor Agonists vs. Sodium-Glucose cotransporter2 Inhibitors in Type 2 Diabetes Mellitus
Authors: khazaali Ali Al , Mckee Alexis , Sharma Anjul , Albert Stewart
Published: May 2020

Background: Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i) demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD), and renal outcomes (RO). Objective. Evaluation of data to assist in the prescribing decision with regard to severity of illness and risk for adverse events.

Study Design: Systemic review of the major CVOT and previous meta-analyses.

Main Outcome Measures: Analysis of six trials on GLP-1 RA and 4 trials on SGLT2i, showed both drug classes reduced MACE and CVD compared to controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: (relative rate, rr MACE= 1.09, 95%CI;0.98,1.22, p= 0.129; rr, CVD =1.04, CI;0.87,1.24, p=0.657). Hospitalization for heart failure (HHF) improved with SGLT2i (rr=0.68, CI; 0.61,0.76, p<0.001) but not with GLP-1 RA, (rr = 0.94, CI; 0.86,1.03, p=0.17). Both GLP-1 RA and SGLT2i showed significant reduction in RO (GLP-1RA, rr=0.83, CI; 0.75,0.912, p=<0.001, SGLT2i, rr=0.0.67, CI; 0.57,0.79, p=0.001) without a preferential difference between the classes (GLP-1 RA vs SGLT2i, relative difference (rd) =0.005, CI;-0.011,0.021, p=0.532, number needed to treat (NNT)=200). Serious adverse events (SAE) for SGLT2i were predominantly mycotic genital infections in women (number needed to harm (NNH) =13 and diabetic ketoacidosis NNH=595. Gastrointestinal intolerance was the major SAE in the GLP1-RA class (NNH=35).

Conclusion: Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and RO. SGLT2i have advantages over GLP-1 RA in reduction in HHF especially in those with more severe cardiovascular disease risk.