bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-489 The Weary Beating Heart: Complications of Severe Hypothyroidism in a Mentally Ill Patient
Authors: Pagan Nikita Limara Rabelo , Serrano Melanie Quintana , Malave Mary J Rodriguez , Reyes Meilyn 
Published: May 2020

Abstract
Myxedema coma is a severe form of hypothyroidism representing a endocrinologic emergency. It requires prompt identification and management, as mortality rates exceed 50%. Its rarity stems from early recognition and thyroid medication availability. Its presentation can be non-specific, making it a challenging diagnosis.
This is a 67-year-old male inmate who was brought to the ED due to hypoactivity. He had a long-standing history of bipolar disorder, and hypothyroidism receiving oral levothyroxine.
On evaluation, patient had slowed mentation, GCS 14/15, sluggish reactive pupils, macroglossia, diffuse non-pitting edema, and delayed relaxation of the deep tendon reflexes in the extremities. Vital signs were abnormal; T: 35.2 °C, RR: 10 rpm, SpO2: 84 %, BP: 137/89 mmHg and HR: 42 bpm without chronotropism. 12-lead ECG revealed a complete atrioventricular block (AV block), with non-conductive P waves and idioventricular rhythm. Patient became hemodynamically unstable, transcutaneous pacemaker was placed. Dopamine infusion was initiated for adequate mean arterial pressure. Subsequently, a femoral transvenous pacemaker was performed. However, neurological deterioration prompted mechanical ventilation.
Exploring reversible AV block etiologies, laboratory results were markedly elevated for TSH at 184.775 ng/mL and decreased T4 at 1.5 ng/mL. Lithium levels were therapeutic.
Myxedema coma was identified and timely treatment was provided with intravenous thyroid hormone replacement, intravenous hydrocortisone, and supportive care. Patient was transferred to an ICU where TSH was monitored. After 5 days of receiving IV thyroid hormone replacement therapy, TSH improved. However, patient remained dependent on transvenous pacemaker, for which permanent pacemaker had to be placed. With further therapy, patient’s neurological status improved leading to extubation, and subsequent discharge.
Thyroid hormones play a vital role in the electrical current of the heart; hence, disturbances may potentiate cardiac arrhythmias. Sinus bradycardia and QT interval prolongation are commonly seen. As the severity of hypothyroidism progresses, high-grade AV block may be encountered, being third degree AV block the most challenging and severe.
Patients with high-degree AV block in the setting of reversible etiologies, commonly, do not need a permanent pacemaker. On the contrary, our patient developed complete dependence of the pacemaker for adequate cardiac synchrony, despite adequate replacement therapy.
With this case, we illustrate the importance of a thorough evaluation in patients with AV block of unknown origin, with special attention to reversible etiologies. Thyroid function abnormalities should be promptly identified and managed for better outcomes. Furthermore, it may decrease cardiac death risk and the need for invasive procedures, such as permanent pacemaker placement.
MON-131 Mortality and Glycemic Control Among Patients with Leukemia and Diabetes Mellitus: A Case-Control Study
Authors: Wiedmeier Erin , Mountjoy Luke , Verona Patricia , Kosiorek Heidi , Buras Matthew , Coppola Kyle , Cook Curtiss Bela , Karlin Nina 
Published: May 2020

Abstract
Background: Unlike with solid organ cancers, little data is available on how diabetes mellitus (DM) and hematologic malignancies interact to affect survival and glycemic control. We examined the impact of DM on survival in patients with leukemia and the effect of leukemia on glycemic control. Materials and Methods: Patients with leukemia with and without DM were matched 1:1 (2007–2017), 70 matched pairs (total N=140 pts) were included in the analysis. We compared characteristics between cases and controls and assessed survival with the Kaplan-Meier method and Cox proportional hazards model. Mixed models compared hemoglobin A1c (HbA1c) and glucose levels over time. Results: The median age of patients at diagnosis was 56 (18–94); 60% were male and 89% had acute leukemia. Among those with DM, HbA1c was only recorded in 25 of 70 patients during the year following cancer diagnosis and was 6.8%. There was no change in HbA1c values over time in these DM patients. Mean glucose was significantly different between DM and non-DM patients (p&lt;0.001). Time (days since leukemia diagnosis) was significant (p&lt;0.001) and there was a significant interaction effect (p=0.01). Glucose values increased in the DM patients during the year following diagnosis, while remaining stable in those without DM. Median follow-up time was 23.2 months. Three-year survival was estimated at 46% for DM patients versus 45% in non-DM pts by Kaplan Meier method (p=0.79). Hazard ratio (stratification for matched pairs) was 1.05 (95% CI: 0.57 - 1.94; p=0.88). Three-year relapse-free survival was estimated at 34% for DM patients versus 43% for non-DM patients (p=0.58). Hazard ratio (stratification for matched pairs) = 1.10 (95% CI: 0.61–1.98; p=0.76). Conclusions: DM did not adversely impact survival in patients with leukemia. Leukemia and its treatment did not affect glycemic control. This should be reassuring to hematologists and endocrinologists who treat patients with leukemia and diabetes.
MON-066 17B-hydroxysteroid dehydrogenase Type 3 Deficiency: An Under-Recognized Cause of 46,XY DSD in the United States?
Authors: Whitehead J , Yerkes Elizabeth , Johnson Emilie , Chen Diane , Goetsch Allison , Leeth Elizabeth , Finlayson Courtney Anne 
Published: May 2020

Abstract
Title: 17β-hydroxysteroid dehydrogenase type 3 deficiency: An under-recognized cause of 46,XY DSD in the United States?
Introduction: The 17β-hydroxysteroid dehydrogenase type 3 (17BHSD3) enzyme, expressed in the testes, converts androstenedione (A) to testosterone (T). 17BHSD3 deficiency causes a 46,XY difference of sex development (DSD), or intersex condition, characterized by lack of prenatal virilization followed by marked virilization at puberty due to peripheral conversation of A to T by other 17BHSD isoenzymes. Diagnosis is suspected with an abnormal T:A ratio of &lt;0.8 and confirmed by HSD17B3 sequencing and deletion/duplication analysis. 17BHSD3 deficiency may present similarly to complete or partial androgen insensitivity syndrome (CAIS, PAIS) due to undervirilization in infancy, and to 5α-reductase deficiency due to virilization during puberty. Previously, only 12 cases of this autosomal recessive disorder have been reported in the US. We report 3 cases of 17BHSD3 deficiency diagnosed at a single pediatric center in the US.
Clinical Cases: Patient A had atypical genitalia at birth and a presumed diagnosis of PAIS though sequencing of AR was normal. He underwent multiple genital surgeries throughout childhood, had significant psychiatric and behavioral concerns, and was referred to our multidisciplinary clinic at age 16 years. Additional diagnostic testing revealed a T:A ratio of 0.29 consistent with 17BHSD3 deficiency; confirmatory genetic testing was deferred per family preference.
Patient B was noted to have testicular tissue present at age 3 years during an inguinal hernia repair and was diagnosed with CAIS. She presented to our institution at age 14 years with clitoromegaly. T:A ratio was 0.29 and genetic testing revealed a pathogenic splice site variant in HSD17B3. She requested gonadectomy due to unwanted virilization inconsistent with her female gender identity. Following gonadectomy at age 16 years, she began estrogen treatment and vaginal dilations.
Patient C presented to our institution at age 18 years with pubertal delay and primary amenorrhea. She was noted to have palpable gonads and clitoromegaly. Evaluation revealed a 46,XY karyotype and a T:A ratio of 0.32. She was raised as a girl and identified as female. She requested gonadectomy to avoid further virilization, after which she began estrogen for pubertal induction. She deferred confirmatory genetic testing.
Conclusions: Previous studies noted 17BHSD3 deficiency to be rare in the US, but the presence of 2 suspected and 1 confirmed diagnoses at a single US institution suggests it is likely more common and may be misdiagnosed as other types of DSD. Differentiating 17BHSD3 deficiency from other causes of 46,XY DSD is essential to inform accurate counseling about sex designation, gender identity, gonadal function, malignancy risk, potential fertility and heritability.
SAT-234 Association Between Hypogonadotrophic Hypogonadism and NARP Due to Mitochondrial Disease
Authors: Shariff Amal , Naranjo Maria Belen , Kumar Salini Chellappan , Liao Huijuan 
Published: May 2020

Abstract
Introduction: Hypogonadotropic hypogonadism is a common disorder encountered in endocrine practice with a prevalence of 1 in 10,000 men (1). We describe a patient with possible mitochondrial mutation causing him to have concurrent central hypogonadism and NARP syndrome (neuropathy, ataxia, retinitis pigmentosa). Case: 65 year old male with central hypogonadism diagnosed at age 17 was on testosterone replacement therapy off and on since then. He was diagnosed with NARP at age 49. On exam, he was OX3, BP 147/83mmHg, HR 63 bpm, wt 185lbs. Pupils were sluggish to light. Unable to assess visual fields as patient is legally blind. No gynecomastia. Cardiac and pulmonary exam were normal. Testicles were soft and the volume was 12mL. Prostate was enlarged, non tender and without nodules. He had ataxic gait, abnormal finger to nose test and strength was normal. LH &lt;0.2 mIU/ml (N 1.2 - 10.6 mIU/ml), FSH &lt; 0.2 mIU/ml (N 0.7 - 10.8mIU), total testosterone as low as 12ng/dL when off and 260ng/dL (N 250-1110ng/dL) while on testosterone IM. CBC, CMP, prolactin, ACTH, cortisol, Igf-I, TSH and PSA wnl. MRI brain showed cerebellar atrophy and normal pituitary. Discussion: NARP is a mitochondrial disorder characterized by neuropathy, ataxia and retinitis pigmentosa primarily affecting the nervous system. NARP results from point mutation at base pair 8993 of the mitochondrial genome in the ATPase 6 gene. Symptoms typically consist of proximal neurogenic muscle weakness, sensory neuropathy, ataxia, and retinitis pigmentosa. According to Al-Gadi et al, hypogonadism has been reported in mitochondrial disease (2). RRM2B is a nuclear-encoded mitochondrial maintenance gene. Mitochondrial DNA depletion due to ar-RRM2B mutations have been reported in association with hypogonadism. A mutation of m.8561C&gt;G in MT-ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotrophic hypogonadism has also been reported in a case report of two patients (3). Upon literature review, no prior cases of hypogonadotropic hypogonadism in patients with NARP have been reported. The impairment of the hypothalamic-pituitary axis appears to manifest in severe mitochondrial phenotypes. For example, the association of central hypogonadism with Kearns Sayre Syndrome (KSS). Given that both disorders are related to mitochondrial dysfunction, we propose that the hypogonadism may be linked to NARP syndrome. References Rohayem, J.et al. (2016), Causes of hypogonadotropic hypogonadism predict response to gonadotropin substitution in adults. Andrology Al-Gadi.et al. (2018). Endocrine Disorders in Primary Mitochondrial Disease. JES Kytövuori, L. et al. (2016, August 8). A novel mutation m.8561C&gt;G in MT- ATP6/8 causing a mitochondrial syndrome with ataxia, peripheral neuropathy, diabetes mellitus, and hypergonadotropic hypogonadism.
SAT-509 Sudden Onset of Malabsorption
Authors: Mroueh Gabriela , Burks James K 
Published: May 2020

Abstract
Celiac disease (CD) is an immune-mediated enteropathy caused by a reaction to gliadin which responds to a restriction to dietary gluten. It has been traditionally recognized in children and young adults, although, recently, detection in the elderly population has increased. CD occurs in 2–5% of patients with autoimmune hypothyroidism, and is more prevalent in this group than in the general population
An 82-year-old Caucasian woman with primary hypothyroidism and a BMI of 16 is referred to our endocrinology clinic for help with the management of hypothyroidism. She had a history of well controlled hypothyroidism on weight-dosed levothyroxine for many years until several months prior when she developed sudden onset of diarrhea and weight loss. Since then, her thyroid function tests showed an elevated TSH despite medication adherence. Her levothyroxine dose was steadily increased to 300 mcg daily and yet, her TSH still remained elevated. Laboratory work up was done which revealed elevated transglutaminase antibodies, suggesting the diagnosis of CD. The patient refused an endoscopy for a tissue diagnosis. Even though the patient has been diagnosed with CD, she has trouble following a gluten free diet and still has intermittent diarrhea and high levothyroxine requirements.
Although lack of medication adherence is common, it is important to exclude gastric or intestinal causes of malabsorption in patients with high thyroid replacement requirements. Elderly patients often have paucity of symptoms, so high clinical suspicion is necessary to diagnose these patients.
MON-623 Pattern of C-Peptide Response to Oral Glucose Tolerance Test: Interest and Cut-Off Values
Authors: Bonnet-Serrano Fidéline , Jaoude Mathieu Abou , Gobeaux Camille , Bouzerara Amina , Mosnier-Pudar Helen , Laguillier-Morizot Christelle , Guibourdenche Jean 
Published: May 2020

Abstract
Introduction: Oral glucose tolerance test (OGTT) allows classification of subjects in 3 groups, depending on glycaemia 120 minutes after 75g glucose ingestion: normal (glycaemia &lt; 1.4 g/L), glucose intolerant (1.4-2 g/L) and diabetic (&gt;2g/L). Five insulin profiles following OGTT associated with different incidence rates of diabetes over 10 years of follow-up have also previously been described (Kraft J et al, Laboratory Medicine, 1975; Hayashi T et al, Diabetes Care.2013). Insulin measurement is very sensible to hemolysis and can advantageously be replaced by C-peptide determination. However, little is known about C-peptide reference values and response to OGTT.Material and Methods: 128 patients were included to evaluate glyceamia (COBASe801® ROCHE Diagnostics, France), insulin and C-peptide (LiaisonXL®, Diasorin, France) responses to OGTT.Results: According to Hayashi classification, 23 (18%) patients of the whole cohort harbored a physiological insulin response corresponding to profile I (peak of insulin during OGTT at 30 min and higher insulin level at 60 vs. 120 min). Others presented 5 pathological profiles: 14 (11%) patients were classified in profile II (peak of insulin at 30 min and lower or equal insulin level at 60 vs. 120 min), 56 (44%) in profile III (peak of insulin at 60 min), 26 (20%) in profile IV (peak of insulin at 120 min and lower insulin level at 30 vs. 60 min), and finally 9 (7%) in profile V (peak of insulin at 120 min and higher or equal insulin level at 30 vs. 60 min). Only 4 different mean C-peptide profiles emerged from the subgroups previously defined by insulin profile, mean C-peptide profile being substantially similar to mean insulin profile. The only major difference relied on a similar C-peptide profile corresponding to a growing curve from T0 to T120 in both patients with insulin profile IV and V. Mean and 95% confidence interval of C-peptide value at the different times of OGTT were also calculated in the subgroup of patients with both normal glycemic and insulin (pattern I) responses to propose reference values: respectively T0: 0.53 (0.26-0.77); T30: 2.2 (1.24-3.29); T60: 2.26 (1.36-3.68); T120: 1.88 (0.84-2.62) nmol/L. Conclusion: C-peptide response to OGTT profile seems to give globally the same information as insulin profile and should therefore also be predictive of the risk type 2 diabetes in case of hemolyzed samples. The slight differences observed between insulin and C-peptide profiles can be explained by their different metabolic pathways, insulin being quickly degraded in the liver and C-peptide undergoing a longer renal elimination. This work also allows us to propose for the first-time reference values for C-peptide at the different times of OGTT using Liaison XL®.
MON-130 Improving the Accuracy and Reliability of Free Thyroxine (FT4) Measurements Through the CDC Clinical Standardization Programs (CSP)
Authors: Ribera Ashley , Poynter Krista , Sugahara Otoe , Zhang Li , Danilenko Uliana , Vesper Hubert 
Published: May 2020

Abstract
Reliable free thyroxine (FT4) measurements are essential for assessing thyroid function and for correctly diagnosing and treating thyroid disorders. Thyroid hormones play an important role in normal brain development of the fetus, and abnormal FT4 during pregnancy is associated with adverse pregnancy outcomes. Standardization of FT4 measurements, is critical to improving the accuracy and reliability of current methods and thus to improve diagnosis, treatment and prevention of thyroidal illnesses. Currently, there are no serum-based reference materials available for FT4 to assess the accuracy and reliability of FT4 assays. CDC CSP is collaborating with the International Federation of Clinical Chemistry and Laboratory Medicine, and the Partnership for the Accurate Testing for Hormones to address these issues through development of an accurate and sensitive higher-order Reference Measurement Procedure (RMP) for FT4 that will be used to assign target value to serum-based materials. The CDC CSP FT4 reference method is using equilibrium dialysis in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS). FT4 in serum is isolated from the binding proteins in 1 mL equilibrium dialysis cells for 4 hours at 37oC. FT4 is further isolated by extractions prior to LC-MS/MS analysis. To determine the concentration of FT4 in serum, certified primary reference materials are used to prepare calibration materials. Chromatographic separation is achieved using a C18 reverse phase column with a gradient of methanol and water with 0.1% formic acid. Quantification by selective reaction monitoring is performed in the positive mode using electrospray ionization. Two transitions are monitored for each analyte and internal standard, and triplicate injections are used to minimize instrument instability. The within- and between-day imprecision for the CDC RMP are 2.2–3.9% and 1.8–2.6%, respectively. By comparisons with the RMPs at Ghent University in Belgium, Radboud University Medical Center in the Netherlands, and the Reference Material Institute for Clinical Chemistry Standards in Japan, the CDC RMP reported a bias within +2.5% of the mean for all labs. Factors affecting measurement accuracy were investigated, to maximize recovery for optimum performance of the method. FT4 was detectable in all samples, and thus, suitable for analysis of hypo-, eu-, and hyperthyroid patients. A comparison among hypo-, eu-, and hyperthyroid patients of a commercially available immunoassay and the CDC RMP indicated a mean bias of -37.7%. The CDC CSP has also evaluated the RMP for accurate measurement of FT4 in pregnant individuals. This candidate reference method for FT4 in serum demonstrates good accuracy and precision, and can be used as a viable base for accuracy to which routine methods for FT4 can be compared. 1. Van Houcke, S.K., et. al. Clin. Chem. Lab. Med. 2011, 49, 1275–1281.
MON-650 Glucocorticoid- Induced Hyperglycemia, Higher Mortality and Morbidity? a Retrospective Analysis
Authors: Delfs Neele , Struja Tristan , Gafner Sandra , Muri Thaddäus , Bächli Ciril , Mueller Beat , Schuetz Philipp , Blum Claudine 
Published: May 2020

Abstract
Introduction: Glucocorticoid (GC)-induced hyperglycemia is a frequent side effect in hospitalized patients. Guidelines recommend treat-to-target treatment between 6-10 mmol/l with insulin, but patient-specific outcome has not been well-studied.
Methods: In this retrospective data analysis, all patient records of a Medical University Clinic from January 2014 to April 2018 were screened for GC administration. We investigated the incidence of hyperglycemia in hospitalized patients after administration of at least 10 mg prednisolone equivalents daily and a minimal length of stay of 3 days. The primary combined endpoint consisted of mortality, cardiovascular events, and infections until 30 days after admission.
Results: 2424 hospitalized patients received systemic GCs and met the inclusion criteria, of which 511 patients (21%) had an underlying diagnosis of diabetes. The overall incidence for GC-induced hyperglycemia was 33.5% (812 patients) and 3.7% of patients (n=89) had at least one documented hypoglycemia during the hospital stay. Compared to normoglycemic patients, GC-induced hyperglycemia was associated with a 40% increase in the risk for the combined primary endpoint (unadjusted odds ratio 1.39, 95%CI 1.16-1.66). This was also true after adjusting the analysis for age, Charlson comorbidity index and GC dose (adjusted odds ratio 1.68, 95% CI 1.25-2.26). Hypoglycemia was also associated with a doubling in the risk for the combined primary endpoint (odds ratio 1.95, 95% CI 1.2-3.17).
Discussion/Conclusion: Mortality, cardiovascular events and rate of infections were markedly higher in patients with GC-induced hyperglycemia compared to normoglycemic patients. Hypoglycemia was infrequent, but also associated with higher risk for adverse outcome. Future studies should evaluate whether glucose control with novel treatment modalities has a beneficial effect on clinical outcomes in patients with GC-induced hyperglycemia.