bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-500 Viral-Induced Autoimmune Hyperthyroidism in an Adult Patient Without Established Thyroid Disease
Authors: Das Dhriti , Linares Andrea , Bertolotti Cesar , Cortes Anais
Published: May 2020

Introduction: Subacute thyroiditis is a self-limited inflammation of the thyroid associated with recent upper respiratory tract viral infection. Graves’ disease has also been associated with viral illness.

Clinical Case:A 55-year-old female presented to the emergency department complaining of sore throat, cough, and shortness of breath. She also had fatigue, dyspnea on exertion, palpitations, and a family member who recently had bronchitis. She denied chest pain, weight changes, temperature intolerance, constipation, or diarrhea. She had never had similar symptoms before.

On initial evaluation, the patient was febrile at 101.2 °F, tachycardic at 156 beats per minute (bpm), and tachypneic at 33 breaths per minute. She was thin and her thyroid gland was tender upon palpation. She had eyelid lag, her skin was warm, and she was diaphoretic. Chest x-ray showed increased interstitial lung markings bilaterally. CBC showed anemia with hemoglobin of 9.7 g/dL (n<12 g/dL). Lactic acid was elevated to 2.00 mmol/L (n<1.9 mmol/L). D-dimer was 3020 ng/mL (n<230 ng/mL) and BNP was 961 pg/mL (n<100 pg/mL). An electrocardiogram showed sinus tachycardia at 140 bpm. Blood, sputum, and urine cultures were drawn, as were studies for viral respiratory pathogens. CT angiography of the chest and bilateral lower extremity venous ultrasound were ordered to rule out thromboembolism.

A point-of-care echocardiogram showed reduced ejection fraction of 20%. Thyroid function tests revealed TSH < 0.03 mIU/mL (range 0.5-5.0 mIU/L), free T4 of 4.5 ng/dL (n<2.15 ng/dL), and T3 251 ng/dL (n<200 ng/dL). Patient was started on an esmolol drip for heart rate control. CT angiogram of the chest was negative for thromboembolism but revealed a bilaterally enlarged thyroid gland with multiple small nodules. RNA for Respiratory Syncytial Virus (RSV) type A was detected by PCR. A thyroid ultrasound was done and revealed heterogenous echotexture with increased blast flow.

Thyroid antibody studies revealed thyrotropin receptor antibody of 26.5 IU/L (n<1.75 IU/L), thyroid-stimulating immunoglobulin 19.40 IU/L (n<0.55 IU/L), thyroglobulin antibody 235.6 IU/mL (n<0.9 IU/mL), and thyroid peroxidase antibody 11 IU/mL (range 0-34 IU/mL). Patient was started on methimazole 30 mg daily. A formal echocardiogram showed preserved ejection fraction of 50-55%. She was transitioned to oral propranolol. Patient’s shortness of breath and cough resolved, and she was discharged on methimazole 10 mg daily.

Conclusion:This case emphasizes the importance of measuring thyrotropin receptor antibodies in confirming Graves’ disease in a patient presenting with upper respiratory viral illness and supports the idea of viral-induced autoimmune thyroid disease.
MON-374 Management of 1,25-dihydroxyvitamin D (1,25-OHD) Mediated Hypercalcemia of Unknown Etiology
Authors: Menon Sruthi , Agarwal Swashti , Paul David L
Published: May 2020

Background: We describe the diagnostic dilemma and treatment challenges faced in a rare case of 1,25-OHD mediated hypercalcemia. Clinical Case: A 13 year old boy was admitted with severe hypercalcemia (calcium 15.5 mg/dl) in the setting of a non-specific rash, malaise, pancytopenia and acute kidney injury. He was incidentally also noted to have hypogammaglobulinemia a few months prior to presentation. Blood tests were suggestive of hypercalcemia mediated by 1,25-OHD (level >200 pg/ml; ref: 30-83 pg/ml). 25-hydroxy vitamin D was normal (29 ng/ml) and PTH was appropriately suppressed (<4 pg/ml). Workup for various etiologies including infectious, rheumatologic and oncologic diseases associated with ectopic production of 1,25-OHD was initiated. Hypercalcemia was initially managed with hyperhydration, furosemide and calcitonin. However after a brief period of improvement in hypercalcemia, levels started to rise again despite increasing calcitonin dose and frequency (secondary to tachyphylaxis). Kidney function also started to worsen. Extrarenal 1-alpha hydroxylase activity can be suppressed using steroid therapy, however it was contraindicated at the time given that malignancy and other infectious etiologies had not been excluded. At that point, a trial of zoledronic acid was done with subsequent resolution of hypercalcemia. However, this was only temporary given that the underlying disease process driving the production of 1,25-OHD had not been addressed. Various other treatment options were considered including a repeat dose of bisphosphonate, denosumab, ketoconazole and hydroxychloroquine, but since hypercalcemia was only mild, supportive measures were continued. An extensive workup revealed splenomegaly, lymphadenopathy, bilateral renomegaly and bilateral pulmonary ground glass opacities and nodules. Infectious workup and bone marrow biopsy were negative. Although non-specific, an elevated angiotensin converting enzyme (ACE) level (359 units/L; ref: 13-100 units/L) suggested an underlying granulomatous process. Renal biopsy showed non-caseating granulomas. The most likely unifying diagnosis was thought to be sarcoidosis, however presence of hypogammaglobinemia also raised suspicion for a granulomatous form of Common Variable Immunodeficiency (CVID) which, albeit rare, has previously been reported to be associated with hypercalcemia. Patient was started on empiric treatment with steroids and intravenous immunoglobulin following which calcium, 1,25-OHD and ACE levels normalized. Conclusion: Granulomatous form of CVID is a rare entity but should be considered in a patient presenting with 1,25-OHD mediated hypercalcemia and hypogammaglobulinemia. Treatment of this entity during an ongoing diagnostic workup can be challenging, particularly if the use of steroids is contraindicated due to potential interference with diagnostic investigations.
SUN-627 A Test for Variation in Insulin Concentrations at the Wilford Hall Ambulatory and Surgical Center
Authors: Jenkins Craig , Lovett Dennis P , Brinkman Joseph , Tate Joshua , Gibbons Thomas , Beckman Derrick , Jenkins Lydia , Wardian Jana
Published: May 2020

Background

Wilford Hall Ambulatory and Surgical Center is the Department of Defense’s largest outpatient ambulatory surgical center serving over 55,000 patients, and is the U.S. Air Force’s flagship medical facility for outpatient care.

As with the measurement of any medication concentration or lab value, there is some reasonable expectation that there may be some variability between the reported value and the objective measurement. However, expectations are that variability should be minimal in order to ensure reliable doses of medication. In the case of diabetes management, insulin concentration variability should be kept to a minimum for both its life-saving and stress-mitigating effects. Insulin in the correct doses is lifesaving for type 1 Diabetes, so understandably, the impact of degraded insulin is catastrophic. In both type I and type II diabetes, “diabetes distress” can lead to poor self management and is linked to higher A1C levels. A study published in 2017 testing insulin after receipt from their cold supply chain found shockingly low concentrations of insulin. Recent literature published in the Journal of Diabetes Science and Technology reported that insulin concentrations in randomly tested vials not only failed to meet a pre-established concentration standard per unit of insulin, but also had concerning variability. The prevalence of Diabetes in the Department of Defense population is approaching 20%, making the impact of degraded insulin concerning. There are expectations of variability in any medications prescribed, but the FDA states that the expected insulin concentration should be 95% or greater.

Methods

Overall, 40 vials representing two different types of insulin (20 vials of Novolog and 20 vials of Lantus) were collecting from the military pharmacy and transported to the clinical research laboratory for analysis. Following baseline analysis, half of the vials were stored in refrigerated conditions of 2-8 degrees Celsius; the other half were stored at room temperature according to manufacturer’s directions.

Results

At the laboratory, all vials underwent initial analysis to determine concentration at baseline. The Novolog insulin was found to have a concentration range of 105.1% to 107.7% and the Lantus insulin concentration was 99.0% to 103.9%. Thus, all vials met the minimum concentration of 95 U/ml at time of baseline testing. Vials will be tested weekly to determine if degradation occurs under refrigeration and at room temperature.

Discussion

Given the high cost of insulin and the high impact on the health of the person with diabetes, assurance of a minimum of 95 U/ml must be met. If this is not met, investigation of the cold supply chain should identify the source of the problem and address it. Our study demonstrates that Novolog and Lantus were meeting the minimum concentration upon receipt at the pharmacy.
SUN-912 The Rare Men of Mississippi Complications in the Diagnosis of Multiple Endocrine Neoplasia Type 1
Authors: Rashid Hytham , Clayton Tiarra , Bruckmeier Kurt , Drake Ben
Published: May 2020

Background: Multiple endocrine neoplasia type 1 (MEN1) is a rare, autosomal dominant disorder associated with tumors of the parathyroid glands, pituitary gland, and gastroenteropancreatic cells caused by mutations of the MEN1 tumor-suppressor gene. Thescarcity with which this syndrome is encountered makes diagnosis challenging in rural settings.

Clinical Case: A 34-year-old male presented to the Emergency Department complaining ofintermittent abdominal pain for the past year, that was associated with nausea, vomiting, and diarrhea. Past medical history was significant for hyperparathyroidism treated with parathyroidectomy, nephrolithiasis, and alcohol-induced chronic pancreatitis. Initial laboratory studies revealed elevated corrected calcium (11.5 mg/dL, n:7.6-10.6 mg/dL) with a subsequent elevated parathyroid hormone level (105, n:14-72 pg/mL). CT scan of the abdomen and pelvis revealed fatty liver changes, nonobstructive nephrolithiasis and pancreatic calcifications. Due to his recurrent symptoms, gastroenterology was consulted for esophagogastroduodenoscopy that revealed erosive esophagitis with multiple duodenal ulcers. The patient was started on a high dose Proton Pump Inhibitor IV and treated supportively. His symptoms improved within a few days. Additional studies were obtained including a gastrin level and H. pylori antigen testing that required sending out to an outside laboratory for analysis. He was discharged with close outpatient follow up scheduled, but then was readmitted two days later with recurrent symptoms. The patient was again treated with supportive care, and was able to provide additional family history revealing parathyroid and ulcer disease in both his father and paternal grandmother, which triggered suspicion for multiple endocrine neoplasia type 1. His gastrin level returned, and was found to be elevated (489 pg/mL, n < 100) with a negative H. pylori antigen, supporting the diagnosis of MEN1. Further diagnostic testing was performed, revealing an elevated serum chromogranin A level (117 ng/mL, n < 15) and abnormalities on MEN1 genetic testing. An Octreotide scan was then performed, showing a single intense area of uptake near the caudate lobe of liver. At this time, he was transferred to a tertiary medical center for further evaluation and management.

Conclusion: This case illustrates the significance of suspicion for multiple endocrine neoplasia and the value of a complete history. Additionally, while a serum chromogranin A level can be nonspecific, it can be obtained in an outpatient setting to help differentiate neuroendocrine pathology from other etiologies. Though the symptoms of MEN1 patients can mimic many other disease processes, recognition of symptoms is critical for medical communities to provide swift treatment.
SUN-022 Metformin-Fish Oil Adjunct Therapy Improves apoB-Remnant Lipoprotein and Triglyceride Levels in Women with Polycystic Ovary Syndrome
Authors: Proctor Ethan , Weaver Olivia , Ghosh Mahua , Maximova Katerina , Proctor Spencer , Vine Donna
Published: May 2020

Background: Polycystic ovary syndrome (PCOS) is highly associated with the metabolic syndrome (MetS): obesity, insulin resistance and atherogenic dyslipidemia. Women with PCOS-MetS are at higher risk of developing ischemic cardiovascular disease (CVD) and Type-2 Diabetes. First-line intervention in PCOS-MetS includes targeting diet and lifestyle, and metformin is commonly prescribed to treat insulin resistance, however these interventions have shown limited effectiveness to improve dyslipidemia. At present there are limited safe and efficious options to target atherogenic dyslipidemia in young women with PCOS. Fish oil (FO) and Icosapentyl ethyl supplementation have been shown to reduce fasting TG, apoB and to improve ischemic CVD outcomes. The efficacy of FO or as an adjunct therapy to metformin to improve ApoB-remnant lipemia in PCOS-MetS is unknown. The aim of this pilot study was to determine the effect of metformin, FO and FO-metformin combination treatment on fasting and non-fasting plasma TG and apoB-remnant lipoprotein metabolism in patients with PCOS-MetS.

Methods: Participants diagnosed with PCOS aged 18-30yrs received dietary counselling and were randomly assigned to receive FO (n=8), metformin (n=7) or FO-metformin (n=12) treatment for 12 wks. Plasma lipids (TG and cholesterol), ApoB48 and ApoB100 lipoprotein metabolism were assessed in the fasting and non-fasting state using a standardized high-fat meal test.

Results: At baseline, the fasting plasma TG, ApoB48 and ApoB100 was 238.0 ± 21.0 mg/dL, 9.00 ± 1.12 ug/ml and 290 ± 18.00 mg/dL. FO and FO-metformin decreased fasting plasma TG by 10% and 30% compared to the metformin treatment group (7%). Fasting ApoB48 was reduced 45%, 16% and 19% in FO-metformin, FO and metformin treatment groups, respectively. Non-fasting plasma TG and apoB48 lipoprotein area under the curve were reduced by 30% in the FO-metformin treatment group.

Conclusion: These pilot findings demonstrate FO-metformin adjunct therapy may have greater efficacy to improve atherogenic apoB-dyslipidemia compared to metformin or FO alone in high-risk patients with PCOS-MetS. A larger clinical trial is warranted to determine the long term effects of FO-metformin intervention on apoB-dyslipidemia and atherosclerotic cardiovascular disease indices.
SUN-142 Clinical Characteristics of Patients Diagnosed with Functional Neuroendocrine Tumors Treated at a Tertiary National Referral Center in Mexico
Authors: Enríquez-Román Arlette , Reza-Albarran Alfredo A , Iniguez-Ariza Nicole M
Published: May 2020

Neuroendocrine tumors (NET) represent up to 0.5% of all new cancers and can be functional or non-functional. Epidemiologic data on NET in Mexico is very limited. To delineate the clinical characteristics of patients with functional NET at a tertiary national referral center in Mexico we performed a retrospective cohort study (January 1987-June 2019). The target study population was adults with functional NET with biochemical and histopathological confirmation. Results: 126 patients with functional NET were included in this study. The median follow-up was 47.4 months (IQR 10.8 to 93.7). Most were female (64.3%). The mean age at diagnosis was 46.3 ± 14.48 years. The most frequent insulinomas (59.5%), followed by (12.7%) carcinoid tumors, gastrinomas (11.1%), ACTHomas (10.3%), VIPomas (2.4%) glucagonomas (2.4%) and PPomas (1.6%). Nineteen subjects (15.1%) had genetic syndromes, mainly MEN1 (89.5%); and 8.7% had other neoplasms, most frequently non-functional gastrointestinal (GI) carcinoids (36.3%) and thyroid cancer (18.8%). The median duration of symptoms prior to diagnosis was 24 months (IQR 7.75 to 48). The most common locations were, the GI tract (86.5%), whereas 7.1% were outside the GI tract and 6.4% were of unknown primary origin. Functional NETs outside GI tract were localized primarily in lungs

(66.6%). Functional pancreatic NETs occurred more commonly in the tail (39.6%). 24.6% had locoregional or distant metastasis during follow-up. The most frequent metastatic sites were liver (86.5%), regional lymph nodes (59.8%) and bone (13.5%). The most common treatment was surgery (87.3%, with 13.6% ≥2), followed by 18.3% somatostatin receptor analogues and 11.1% cytotoxic chemotherapy. Most subjects (73%) had complete remission with first line therapy, but 14.1% had recurrence at a median of 50.7 months (IQR 15.4 to 97.6). Subjects with an incomplete remission progressed after a median of 14.85 months (IQR 10 to 38.9). Conclusions: The clinical characteristics of functional NET treated at a tertiary center in Mexico are similar to those in other population and geographic locations described in the literature.
SUN-356 Burosumab Resulted in Greater Clinical Improvements Compared with Higher-dose Conventional Therapy in Children with X-linked Hypophosphatemia (XLH)
Authors: Imel Erik A , Chen Angel , Chang Ting , Roberts Mary Scott , Ward Leanne Marie
Published: May 2020

In XLH, excess circulating FGF23 causes hypophosphatemia, rickets, lower limb deformity, and impaired growth and mobility. An active-controlled, phase 3 trial (CL301; NCT02915705) showed treatment with burosumab, a fully human monoclonal antibody against FGF23, resulted in significantly greater improvements in all of these outcomes in children with XLH, compared with continuing oral phosphate and active vitamin D as conventional therapy (Pi/D) per established guidelines. In a post-hoc analysis, we compared children who received burosumab vs those who received an average 64-week oral phosphate daily dose >40 mg/kg (higher-dose Pi) vs ≤40 mg/kg (lower-dose Pi). Sixty-one children with XLH (1–12 years-old) were randomized 1:1 after a 7-day Pi/D washout to receive burosumab (n=29) starting at 0.8 mg/kg subcutaneously Q2W or to resume Pi/D (n=32) titrated by their investigator, for 64 weeks. Eligibility criteria included Rickets Severity Score (RSS) ≥2.0 despite prior Pi/D treatment. Of the 32 subjects randomized to Pi/D, 12 received average higher-dose Pi and 20 received average lower-dose Pi (as specified above). The primary endpoint was rickets healing, using the Radiographic Global Impression of Change (RGI-C) Scale. At week 64, the improvement in the least square (LS) mean (LS mean [±SE; 95%CI]) RGI-C Global Score for rickets was greater on burosumab (+2.06 [0.072; 1.92, 2.20]) compared with either higher-dose (+1.02 [0.241; 0.55, 1.50]) or lower-dose (+1.04 [0.162; 0.73, 1.36]) Pi. The mean decrease in the total RSS from baseline was also greater on burosumab (-2.23 [0.117; -2.46, -2.00]) compared with higher-dose (-0.87 [0.264; -1.39, -0.35] or lower-dose (-1.09 [0.180; -1.45, -0.74]) Pi. Similarly, the mean RGI-C Lower Limb Deformity Score was greater on burosumab (+1.25 [0.170; 0.92, 1.59]) compared with either higher-dose (+0.32 [0.188; -0.05, 0.69]) or lower-dose (+0.26 [0.146; -0.02, 0.55]) Pi. Adverse events including hypersensitivity and injection site reactions, were more frequent with burosumab, and were mild to moderate in severity overall. No discontinuations occurred. In conclusion, children with XLH treated with burosumab had greater improvements in rickets and lower limb deformity compared with subjects receiving higher or lower doses of Pi.
SUN-675 Breast Cancer Treatment Causes Diabetes
Authors: Silparshetty Santh V S , Bhatt Bankim
Published: May 2020

Introduction: Alpelisib (BYL719) a PI3K p110alpha inhibitor, was recently FDA approved to treat postmenopausal women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA gene mutation positive, advanced or metastatic breast cancer following progression on endocrine-based regimen. A major side effect of this cancer therapy is severe hyperglycemia. Case Report: 78 year old female with prediabetes, presents with 5 days of polyuria, polydipsia, blurred vision, severe fatigue and pre-syncope. Random blood glucose at home was >500mg/dL. She has a history of ER, PR positive and HER2 negative invasive adenocarcinoma of right breast with bone metastases that has progressed on chemotherapy, radiation therapy and hormone therapy. Her PI3KCA gene mutation was positive and she was started on alpelisib a week prior to hospitalization. Physical examination revealed heart rate 98/min, blood pressure 160/74mmHg, BMI 21, dry oral mucosa and reduced skin turgor. Urinalysis showed >1000mg/dL glycosuria. Random plasma glucose was 354mg/dL. Creatinine was 1.07mg/dL (baseline 0.70mg/dL). She was resuscitated with IV saline and started on glimepiride 2mg oral twice daily, glargine 5 units at bedtime with correctional insulin regimen. Despite therapy, plasma glucose remained 180-350mg/dL. Discontinuation of alpelisib, rapidly improved her plasma glucose. Discussion: PI3K (phosphatidylinositol 3 kinase) activation by insulin is a key step in whole body glucose metabolism. PI3K inhibition leads to glycogen breakdown in liver and marked insulin resistance by reduced glucose uptake in skeletal muscle and adipose tissue. Treatment options using oral agents or insulin are limited in these patients. As more patients with cancer are approved for treatment with PI3K inhibitors, clinicians need to be more aware of the mechanism of hyperglycemia to effectively manage it. More evidence based consensus is needed on management of hyperglycemia with PI3K inhibition.
SAT-398 The Use of Imaging in Primary Hyperparathyroidism
Authors: Broome David Tyler , Naples Robert , Bailey Richard , Bena James F , Scharpf Joseph , Skugor Mario
Published: May 2020

Primary hyperparathyroidism is characterized by excessive dysregulated production of parathyroid hormone (PTH) by 1 or more abnormal parathyroid glands. Preoperative localization is important for surgical planning in primary hyperparathyroidism. Previously, it had been published that ultrasound (sensitivity of 76.1%, positive predictive value of 93.2%) and nuclear scintigraphy (Sestamibi-SPECT) (sensitivity of 78.9%, and a positive predictive value of 90.7%) are first line imaging modalities1. Currently, the imaging modality of choice varies according to region and institutional protocol. The aim of this study was to evaluate the imaging modality that is associated with an improved remission rate based on concordance with operative findings. A secondary aim was to determine the effect of additive imaging on remission rates. This was an IRB-approved retrospective review of 2657 patients with primary hyperparathyroidism undergoing surgery at a tertiary referral center from 2004–2017. Analyses were performed with SAS software using a 95% confidence interval (p<0.05) for statistical significance. After excluding re-operative and familial cases, 2079 patients met study criteria. There were 422 (20.3%) male and 1657 (79.7%) female patients with a mean age of 66 (+12.2) years, of which 1723 (82.9%) of patients were white and 294 (14.1%) patients were black. Ultrasound (US) was performed in 1891 (91.9%), sestamibi with SPECT (sestamibi/SPECT) in 1945 (93.6%), and CT in 98 (4.7%) patients. Of these, 1721 (82.8%) had combined US and sestamibi/SPECT. US was surgeon-performed in 94.2% of cases and 89.9% of the patients underwent a four gland exploration. Overall, US concordance was 52.4%, sestamibi/SPECT was 45.5%, and CT was 45.9%.US and sestamibi/SPECT both had an improved remission rate if concordant with operative findings, while CT had no effect (US p=0.04; sestamibi/SPECT p=0.01; CT p=0.50). The overall remission rate was 94% (CI=0.93–0.95), however, increasing the number of imaging modalities performed did not increase the remission rate (p=0.76) or concordance with operative findings (p=0.05). Despite having low concordance rates, US and sestamibi/SPECT that agreed with operative findings were associated with higher remission rates. Therefore, when imaging is to be used for localization, our data support the use of US and sestamibi/SPECT as the initial imaging modalities of choice for preoperative localization.

1Kuzminski SJ, Sosa JA, Hoang JK. Update in Parathyroid Imaging. Magn Reson Imaging Clin N Am. 2018;26(1): 151–166.
SAT-016 Analytical Performance and Clinical Value of AMH Testing
Authors: Sluss Patrick M , Palomaki Glenn , Kumar Ajay , Morrison Anthony , Kalra Bhanu , ALPADI KANNAN
Published: May 2020

The clinical uses for of anti-Mullerian hormone (AMH) measurements have risen dramatically over the past 5 years. This increase has been driven by the release of fully automated immunoassay systems with European and FDA approval of AMH measurements for assessing ovarian reserve in women presenting at fertility clinics. Most recently the MenoCheck® AMH method was cleared by FDA as an aid in determining menopausal status in women over the age of 40. Arguably much, of the increased use of AMH measurements is due more to greater test availability for infertility than to strong data supporting its clinical utility. Furthermore, few clinicians realize that the current methods for measuring AMH utilize antibodies with difference specificities, non-commutable calibrator materials, and significantly difference analytical performance characteristics.

This presentation will summarize the analytical validation of MenoCheck® AMH methodology and results of the assessment of clinical value. This method is calibrated with recombinant human AMH in a non-covalent complex associated with the cleaved N-terminal portion of the AMH prohormone protein (the major circulating form of AMH) and demonstrates commutability with native human AMH. Validation studies conformed with published Clinical Laboratory Standards Institute guidelines. Values generated by the method were not commutable to other widely available methods based on method comparison studies using control materials or unadulterated serum from normally cycling women. Clinical value assessment was possible only because of a limit of quantitation enabling measurement of AMH in the majority of perimenopausal women. SWAN study specimens carefully annotated with relevant clinical information, including date of their final menstrual period, were available from women sampled and examined during their menopausal transition. The impact of method-specific differences among the various assay systems and their implications for intended clinical use of AMH testing will be discussed. Clinicians and translational investigators must consider these technical specifications when ordering and interpreting results from AMH testing.
SAT-LB137 Rescue of Misfolded G-Protein Coupled Estrogen Receptor, GPER, from the Endoplasmic Reticulum via Natural and Synthetic Estrogens
Authors: Rouhimoghadam Milad , Dong Jing , Thomas Peter , Filardo Edward Joseph
Published: May 2020

GPER bears structural and functional characteristics shared by members of the G-protein coupled receptor (GPCR) superfamily, the largest class of cell surface receptors, with more than 800 members encoded in the human genome. GPER is localized predominately in intracellular membranes, in many but not all cell types, and its surface expression is modulated by steroid hormones and during tissue homeostasis. An intracellular staining pattern is not unique among GPCRs, which deploy a diverse array of posttranslational regulatory mechanisms to determine cell surface expression, effectively regulating cognate ligand binding and activity.

Here, we show nascent GPER undergoes strict quality control via endoplasmic reticulum associated degradation (ERAD) requiring direct poly-ubiquitinylation of GPER and valosin-containing protein VCP/p97-mediated segregation of misfolded proteins from the ER membrane to the cytoplasm for delivery to the 26S proteasome. Specifically, we find that inhibition of p97 using the pharmacological compound, CB-5083, or by doxycycline-inducible p97 shRNA results in the accumulation of immature glycosylated GPER in the ER. Inhibition of proteasome function facilitates anterograde trafficking with the transport of nonfunctional GPER to the plasma membrane as indicated by no increase in specific estrogen binding using 3H-17β-estradiol in a radioreceptor assay. The forward trafficking of misfolded GPER requires transit through the Golgi as treatment with brefeldin A (BFA) prevents GPER plasma membrane expression. Substitution of all three lysines (K333, K342, and K357) encoded in the cytoplasmic tail of GPER with arginines blunts its polyubiquitinylation and allows GPER to evade degradation by quality control but does not result in increased plasma membrane expression suggesting that additional structural motifs encoded within GPER control its anterograde trafficking. In contrast, functional GPER is recovered at the plasma membrane of human SKBR3 breast cancer cells treated with either 17β-estradiol or the GPER selective antagonist, G15, in the presence of cycloheximide resulting in increased surface GPER. Thus, our findings suggest that estrogens, both natural and synthetic, can function as pharmacochaperones capable of promoting the correct folding of GPER and enhanced expression of functional GPER at the plasma membrane.
SAT-LB104 Maternal Non-Nutritive Sweeteners Consumption Perturbs Development of Melanocortin Circuits Causing Long-Term Metabolic Alterations in the Offspring
Authors: Park Soyoung , Jang Alice , Lowy Josephine , Bouret Sebastien G
Published: May 2020

Maternal Non-Nutritive Sweeteners Consumption Perturbs Development of Melanocortin Circuits Causing Long-Term Metabolic Alterations in the Offspring Soyoung Park1, Alice Jang1, Josephine Lowy1, Sebastien G Bouret2 1Developmental Neuroscience & Diabetes and Obesity Programs, Children’s Hospital Los Angeles, University of Southern California, Los Angeles, USA. 2 Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Centre, UMR-S 1172, Lille, 59000, France.

With the growing prevalence of obesity and diabetes, including among pregnant women, non-nutritive sweeteners (NNS) have been widely used as an alternative to sugar in the attempt to deliver a sweet taste without excessive caloric load. However, there is little evidence regarding their biological effects particularly during critical periods of growth and development. In this study, we aimed to investigate whether maternal NNS consumption causes long-term neurodevelopmental and metabolic perturbations in the offspring. Adult female wild-type mice were exposed to either water (control), aspartame (0.03%), or rebaudioside A (0.02%) throughout pregnancy and lactation. Adult male, but not female, offspring from both aspartame- and rebaudioside A-exposed dams displayed increased adiposity and developed glucose intolerance. Moreover, maternal NNS consumption impaired pro-opiomelanocortin axonal projections to the paraventricular nucleus of the hypothalamus as well as reduced parasympathetic innervation of pancreatic islets. Taken together, our data indicate that maternal NNS consumption causes neurodevelopmental abnormalities in the offspring that may contribute to lifelong metabolic dysregulations.
MON-371 The Case of Dueling Femurs
Authors: Patel Richa , Berlioz Ana Ramirez , Chinnakotla Bhavana , Kurukulasuriya Lilamani Romayne Goonetilleke
Published: May 2020

Introduction: Paget’s disease of the bone is characterized by excessive osteoclastic bone resorption followed by formation of disorganized bone; which is often focal. Bone pain and deformities are common features and it often leads to complications such as pathological fractures, deafness or neurologic deficits. Elevated bone turnover markers and alkaline phosphatase reflect ongoing exaggerated bone resorption and osteoblastic activity. We present an unusual scenario of post-menopausal osteoporosis and Paget’s disease occurring in the same patient.

Clinical Case: 86-year-old female with history of Type 2 Diabetes Mellitus, Hypertension,

Hypothyroidism, degenerative joint disease of lumbar spine with prior interbody fusion and laminectomy was referred to our clinic by Orthopedics for evaluation of newly diagnosed Paget’s disease. 2 months ago, she noticed severe right hip pain limiting daily activities. She denied any history of falls, fractures or family history of Paget’s. Physical exam was notable for tenderness to right sacro-iliac joint and right femoral trochanteric region. Work up included MRI of Lumbar spine and Pelvis, Pelvis X-ray, DEXA scan and routine blood work.

Interestingly, her DEXA scan showed T score of +2.9 in Right hip and -3.1 in Left hip. On Pelvis X-ray cortical thickening, coarse trabecula and osteoarthritic changes were noted in right femur and hip, consistent with Paget’s disease. Left femur showed strikingly thinner cortices compared to the right, due to underlying osteoporosis. MRI of lumbar spine and pelvis was consistent with polyostotic Paget’s involving L3-L5, Sacrum and Right femur. Nuclear bone scan showed areas of uptake including anterior calvarium, lumbar spine, right hip, right femur, 8th rib, left mid tibia and 1st metatarsal of left foot. Since the distribution of uptake seemed atypical for Paget’s, a skeletal survey was obtained which was negative for bone lesions suggestive of malignancy.

Laboratory testing revealed serum calcium 9.8mg/dL(8.4–10.2), 25-Hydroxy Vitamin D 30ng/dL(20–30), PTH 45.6pg/mL (15–65), Alkaline Phosphatase 370U/L (35–104), Procollagen I intact N-terminal 516mcg/L (16–96) and N-Terminal Telopeptide (NTX) 126.4 nM BCE (6.2–19).

Patient received one dose of IV Zoledronic acid with modest improvement in hip and lower back pain. She continues to take Calcium carbonate 600mg twice daily and vitamin D3 1000IU once daily. We plan to see her in follow up in 3 months with repeat levels bone turnover markers.

Conclusion: This is a unique case of Paget’s disease and osteoporosis, two very different diseases of metabolic bone disorder spectrum found in one patient. Treatment of Paget’s disease is indicated for pain reduction, prevention of fractures and deformities and to prevent disease progression in weight bearing areas. Bisphosphonates can target pathology of both diseases by reducing osteoclastic bone resorption.
SAT-LB60 Discordant Biological Parameters of Remission in Acromegaly Do Not Increase the Risk of Hypertension or Diabetes: A Study With the Liege Acromegaly Survey Database
Authors: Amodru Vincent , Petrossians Patrick , Colao Annamaria , Delemer Brigitte , Maione Luigi , Neggers Sebastian J C M M , Decoudier Benedicte , Kamenicky Peter , Castinetti Frederic , Hana Vaclav , Pivonello Rosario , Carvahlo Davide , Brue Thierry Christian , Beckers Albert M , Chanson Philippe , CUNY Thomas
Published: May 2020

Introduction: Acromegaly is a rare disease due to growth hormone (GH)-secreting pituitary adenoma. GH and IGF-1 levels are usually congruent, indicating either remission or active disease, however a discrepancy between GH and IGF-1 may occur. We aimed to evaluate the outcome of acromegalic comorbidities in patients with congruent GH and/or IGF-1 levels vs discordant biochemical parameters. Methods: Retrospective analysis of the data of 3173 patients from the Liège Acromegaly Survey (LAS) allowed to include 190 patients from 8 tertiary referral centers across Europe, treated by surgery, with available data concerning diabetes mellitus (DM) and hypertension (HT) both at diagnosis and at last follow-up. We recorded for all the patients the number of antihypertensive and antidiabetic drugs used at the first evaluation and at last follow-up. Results: Ninety-nine patients belonged to the REM group (Concordant parameters), sixty-five patients were considered as GHdis and 26 patients were considered as IGF-1dis. At diagnosis, 63 patients (33.1%) had HT and 54 patients had DM (28.4%). There was no statistically significant difference in terms of number of anti-HT and anti-diabetic drugs at diagnosis versus last follow-up (mean duration=7.3+/-4.5years) between all 3 groups. Discussion: The results highlight that the long-term outcome of acromegaly does not tend to be more severe in patients with biochemical discordance in comparison with patients considered as in remission on the basis of concordant biological parameters, suggesting that patients with biochemical discordance do not require a closer follow-up.
SUN-LB133 Analysis of Clinical Characteristics and Gene Mutation in Four Cases of Gitelman Syndrome
Authors: Yao Bin
Published: May 2020

Gitelman syndrome is an autosomal recessive renal tubular disorder characterized by renal salt wasting with secondary hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria. GS was found to be caused by mutations in SLC12A3 encoding the thiazide-sensitive sodium chloride cotransporter (NCCT) on the apical membrane of distal convoluted tubule. The prevalence worldwide is estimated at approximately 1:40,000, making it one of the most frequent inherited renal tubular disorders. To date, over 400 mutations scattered throughout SLC12A3 have been identified in GS patients. The majority of patients are compound heterozygous for SLC12A3 mutations, but a significant number of GS patients are found to carry only a single SLC12A3 mutation. The type of the SLC12A3 mutation may be a determinant factor in the severity of GS. The purpose of this study is to analyze clinical characteristics and gene mutation in four cases of GS.

Methods: Four patients with closely resembling Gitelman syndrome was selected.

Results: Six SLCl2A3 gene mutations were found in these four patients. There were one SLCl2A3 homozygous mutation in case 1 and case 3, and two SLCl2A3 heterozygous mutations in case 2 and case 4, respectively. This six gene mutations include missense mutations, frameshift mutations, and nonsense mutations. Four patients were diagnosed with Gitelman syndrome. Case 4 is the most severe with severe hypokalemia, accompanied by ventricular arrhythmias, which may be related to the presence of two SLC12A3 gene mutations in the patient.

Conclusions: Four patients in this study were diagnosed with Gitelman syndrome based on their clinical characteristics and genetic testing results. For patients with hyperreninemia and hyperaldosteronism, chronic hypokalemia with renal K wasting and metabolic alkalosis, and hypomagnesemia, and hypocalciuria need to exclude Gitelman syndrome.

Key words: Gitelmen Syndrome, Mutations, SlC12A3 gene
SAT-LB65 A Rare Existence
Authors: Bedia Jiselle Aimee Yaplito , Gomez Maria Honolina S
Published: May 2020

Primary hyperparathyroidism is a common endocrine disorder of metabolism usually due to a parathyroid adenoma. Although, the clinical presentation of primary hyperparathyroidism has changed from Albright’s description of a disease of bones and stones, the central target organs affected by this disorder continue to be the skeleton and kidneys. With the advent of routine biochemical screening, the typical diagnosis of primary hyperparathyroidism is no longer accompanied by overt skeletal and renal involvement. Majority of the cases of primary hyperparathyroidism are due to parathyroid adenomas. Giant glands were defined as greater than the 95th percentile, characterized as glands weighing > 3.5 grams.

This present case in a 54-year old female is a rare case of primary hyperparathyroidism secondary to a giant parathyroid adenoma measuring 10.7 x 8.0 x 40.0 cm and weighing 145 grams, the largest giant parathyroid adenoma reported to date, with co-existent silent thymoma, multinodular goiter and osteosclerosis of the vertebral spine, metaphorically known as the “rugger-jersey spine”. The association between thymoma and parathyroid adenoma is rare, and only 3 cases have been reported in the literature. We characterized the correlation of preoperative imaging, intraoperative location, and postoperative course, including significant postoperative hypoparathyroidism, as compared to other patients with PHPT to determine whether giant adenomas represent a clinical entity with distinct clinical characteristics.

Keywords: primary hyperparathyroidism, giant parathyroid adenoma, rugger-jersey spine, thymoma

Abbreviation

PHPT

Primary hyperparathyroidism
MON-LB002 Compounded Testosterone Preparations Raise Testosterone Levels to Premenopausal Ranges in Postmenopausal Women With Hypo-Sexual Desire Disorder (HSDD)
Authors: Olson Beatriz Rodriguez
Published: May 2020

Introduction

Testosterone (T) in women declines with age. T levels cannot differentiate women with or without HSDD. T therapy approximating upper physiologic premenopausal levels improves all domains of sexual desire, libido, and decreases sexual distress1,2. As of 2020, there are no FDA-approved T preparations for women. Male preparations of T are frequently used off-label to treat HSDD. No peer-reviewed data exists on T levels achieved with compounded testosterone preparations from a single reliable source. This study assesses efficacy of four compounded T preparations to raise T levels, using typically recommended doses. T was obtained from a single Pharmacy Compounding Accreditation Board (PCAB)-certified pharmacy.

Methods

Twenty-six matched baseline and post-treatment T levels were obtained as part of standard care for post-menopausal women (age 61±6 years) 3 months after being prescribed T for HSDD. T was obtained from the Women’s International Pharmacy. T doses were 0.5-2.0 mg/day, 6 days a week, using 4 methods of administration based on patient’s preferences: 1) cutaneous cream to skin (CS) behind the knees (n=12); 2) intravaginal suppositories (IVS) (n=5); 3) intravaginal oil-capsules (IVoil-C) (n=7); and 4) vulvar cream (VC) (n=2). Mean T dose was 1.5±0.6 mg/day. All patients gave consent for use of their T data, and were compliant with treatment for a week prior to testing. Measures of total T were performed by MS/LC, and of free T by equilibrium dialysis. Normal ranges for total T is 15-70 ng/dl and free T is 0.5-6.5 pg/ml. Paired T-tests comparisons between baseline and treatment values where done within each group where n was sufficient. (*p<0.05, **p<0.01).

Results:

Baseline and treatment total T (ng/dl) were 18.3±3.6 and 55.3±5.2** for CS, 19.8±4.3 and 56.6±15.9 for IVS (p=NS), 23.0±3.2 and 89.2±23* for IVoil-C, and 25.0±3.0 and 182±47 for VC. Baseline and treatment free T (pg/ml) were 1.18±0.26 and 4.16±0.6** for CS, 1.12±0.2 and 3.46±1.3 for IVS, 1.60±0.2 and 5.95±1.2* for IVoil-C, and 1.36±0.4 and 9.45±1.2 for VC. Testosterone administration by CS or IVoil-C significantly increased testosterone levels to the upper normal premenopausal range in women with HSDD.

Conclusion

Treatment of HSDD in postmenopausal women with compounded T via CS or IVoil-C, at doses of 0.5-2.0 mg, effectively raises T levels to upper premenopausal range. Vaginal oil capsules may be particularly useful in avoiding accidental hormone contact by other household members. A FDA-approved form of T replacement would be a welcome treatment for women with HSDD.

1. Islam RM et al. Lancet Diabetes-Endocrinology (7):754-66, 2019.

2. Davis SR. Climacteric, 22:5,429-434, 2019.
MON-LB038 Isolated Hypoaldosteronism Due to Autoimmune Adrenalitis in a Patient With Autoimmune Polyglandular Syndrome
Authors: Grover Dheera , Cao Chenxiang , Rao Sarika
Published: May 2020

BACKGROUND

At the initial presentation of autoimmune adrenal insufficiency, most patients present with hormonal deficiencies from all three layers of adrenal cortex. However, isolated aldosterone deficiency causing a true partial adrenal insufficiency in the setting of autoimmune adrenalitis remains underrecognized.

CASE REPORT

A 67-year old female patient with a known history of diabetes mellitus type 1 since the age of 13 and morphea, presented with progressively worsening symptoms of confusion and hallucinations, fatigue, and loss of appetite over the past 5 years. During this time, she has had frequent and recurrent episodes of mild intermittent hyponatremia with hyperkalemia requiring intravenous fluids and ingested salt tablets, especially when she felt more symptomatic. On her initial evaluation here, she presented with hyponatremia (125 mmol/l, n: 135-145 mmol/l), low osmolality (264 mOsm/kg, n: 275-295 mOsm/kg), and normal potassium level (3.6 mmol/l, n: 3.6-5.2 mmol/l). Further investigations drawn at the same time revealed a low aldosterone (<4 ng/dL), normal renin (5.3 ng/mL/hr, ref 2.9-10.8), normal serum cortisol level (and normal response to Cortrosyn stimulation), though all in the setting of positive antibodies against 21-hydroxylase. Pan-imaging revealed no evidence of malignancy that can be causing ectopic SIADH production. Additional testing showed presence of auto antibodies contributing to pernicious anemia and thyroid disease. Treatment was started with fludrocortisone 0.1 mg tablet daily and she was advised to take the salt tablets only if she has any symptoms. The patient’s symptoms have resolved 8 months since this diagnosis, with normalized sodium and potassium levels.

CONCLUSION

Autoimmune primary adrenal insufficiency usually affects all three layers of the adrenal cortex, where patients present with deficiencies in cortisol and aldosterone. Isolated hypoaldosteronism has rarely been reported, however because it can cause life-threatening hyponatremia, it is an important entity to recognize. It is important to work up in such patients as they may be in the initial stages of autoimmune Addison’s disease and can progress to developing cortisol deficiency, though the time course to this progression is not well known.
SAT-LB75 Thyroid Peroxidase Antibody Positivity Predicts Relapse Free Survival Following Anti-Thyroid Drug Treatment for Graves Disease
Authors: Muir Christopher Alan , Greenfield Jerry Richard , Weissberger Andrew , Jones Graham R D , Samaras Katherine
Published: May 2020

Objective: Graves disease is an autoimmune disease characterized by production of autoantibodies directed against the thyroid gland. Thyrotropin-receptor antibodies (TRABs) are clearly pathogenic, but the role of thyroid-peroxidase antibodies (TPOAb) in Graves disease is unknown. Design: We retrospectively studied whether TPOAb positivity reduced risk of relapse following anti-thyroid drug treatment in newly diagnosed Graves disease. Results: During follow-up of 204 patients with TRAB positive Graves disease, 107 (52%) relapsed following withdrawal of anti-thyroid medication. Mean age was 40.0 years and 82% were female. The average duration of anti-thyroid drug (ATD) treatment was 23.5 months and was not different between patients who relapsed and those with sustained remission. Absence of TPOAb significantly increased risk of Graves relapse (OR 2.21) and displayed a trend towards shorter time to relapse. Male sex and younger age were additional factors significantly associated with increased risk of relapse. Conclusion: TPO-antibody positivity significantly improves odds of remission following ATD treatment in newly diagnosed Graves disease.